What is the structure and function of the nervous system? - Chapter 2

The goal of cognitive neuroscientists is to figure out what the 89 billion neurons of the human brain do and how their collective action enables us to function.

What are the cells of the nervous system?

The nervous system is composed of two main classes of cells: neurons and glial cells. The neurons are the basic signaling units that transmit information throughout the nervous system. They vary in form, interconnectivity and location. Glial cells serve various functions in the nervous system, providing structural support and electrical insulation to neurons and modulating neuronal activity.

Glial Cells

There are roughly as many glial cells as there are neurons in the human brain, the central nervous system has three types of glial cells: astrocytes, microglial cells, and oligodendrocytes.

Astrocytes: are large glial cells with round or radially symmetrical forms, they surround neurons and are in close contact with the brain's vasculature. They make contact with blood vessels, which permits the astrocyte to transport ions across the vascular wall.

The astrocytes create the Blood Brain Barrier. This lies between the tissues of the central nervous system and the blood. The BBB makes sure certain microscopic objects, such as bacteria, can't diffuse into the blood vessels. The astrocytes also have an active role in brain function. They may either directly or indirectly regulate the reuptake of neurotransmitters.

The glial cells also form the substance myelin in the nervous system. In the central nervous system the oligondendrocytes form the myelin, in the peripheral nervous system the Schwann Cells perform this task. Myelin is a good electrical insulator, preventing loss of electical current across the cell membrane. It increases the speed and distance that information can travel along a neuron.

The microglial cells are very small and irregular shaped. They devour and remove damaged cells.

The Neurons

A neuron consists out of the standard components found in almost all cells. They have a cell membrane, sometimes called a soma that encases the cell body. It contains the nucleus, endoplasmic reticulum, cytoskeleton, mitochondria, Golgi apparatus and other organelles. The neuron itself sits in a bath of salty extracellular fluid, which is made up out of a mixture of ions (positive or negative electrical charge; potassium, sodium, chloride and calcium).

Neurons possess two unique cellular components: the dendrites and the axon. The dendrites are branching extensions of the neuron that receive inputs from other neurons, they can have varied and complex forms depending on the task and location of the neuron. Most dendrites also have specialized processes called spines, little knobs attached to the surface of the dendrites. The axon is a dingle process that extends from the cell body. Electrical signals travel along the length of the axon to its end, axon terminals, where the neuron transmits the signal to other neurons or other targets. The transmission of the signal occurs in the synaps. Some axons can branch to form a axon collaterals that can transmit signals to more than one cell.

Neurons receive, evaluate, and transmit information, this is called neuronal signaling. Information is received by the neuron at its input synapses, passes through the cell body, via the axon, to the output synapses on the axon terminals. Within the neuron information moves from input synapses to output synapses through changes in the electrical state of the neuron caused by the flow of electrical currents within the neuron and across its membrane. Most neurons are both presynaptic - when their axon's output synapses make connections to other neurons or targets - or postsynaptic - when other neurons make a connection at the input synapses onto their dendrites or elsewhere on the receiving neuron.

How does the neuron generate signals, and what are these signals? To answer these questions you first have to understand several things about a neuron:

1. Energy is needed to generate the signals

2. This energy is in the form of an electrical potential across the neuronal membrane, this is defined as the difference between the voltage inside the neuron versus outside the neuron

3. These two voltages depend on the concentrations of potassium, sodium and chloride ions, as well as on the charged protein molecules both inside and outside the cell

4. When a neuron is in its resting state and not actively signaling, the inside of a neuron is more negatively charged than the outside, this difference is typically -70 mV, this is known as the resting membrane potential

Also, the neuron membrane is peppered with transmembrane proteins, these are of two main types: ion channels and ion pumps. Ion channels are proteins with a pore through the center and they allow certain ions to flow down their electrochemical and concentration gradient. Ion pumps use energy to actively transport ions across the membrane against the concentration gradient.

The extent to which a particular ion can cross the membrane is referred to as its permeability. This characteristic gives the neuronal membrane the attribute of selective permeability. The neuronal membrane is more permeable to K⁺ than Na⁺. Unlike most cells in the body, neurons are excitable, meaning that their membrane permeability can change, such proteins are called gated ion channels.

Regarding the ion pumps; Under normal conditions, the NA⁺ and the Cl^- concentrations are greater outside the cell, and K⁺ concentrations are greater inside the cell. Why don't the K⁺ just flow out of the cell until the concentrations are equal inside and outside the cell? Neurons use active transport proteins known as ion pumps. They pump Na⁺ out of the cell and K⁺ into the cell, but this costs energy. Each pump is an enzyme that hydrolyzes ATP to get that energy. The inside and outside voltages are different because the membrane is more permeable to K⁺ than to Na⁺. The force of the K⁺ concentration gradient pushing the ions out of the cell, leaving the inside of the cell slightly more negative than the outside. This difference creates another force called electrical gradient. Eventually, the force of the concentration gradient pushing K⁺ out of the cell through the channels is equal to the force of the electrical gradient driving the K⁺ in. When this happens there is said to be reached an electrochemical equilibrium.

The action potential

Neurons have evolved a clever mechanism to regenerate and pass along the signal received at synapses on the dendrite: the action potential. An action potential is rapid depolarization and repolarization of a small region of the membrane. Action potentials enable signals to travel for meters with no loss in signal strength, because they continually regenerate the signal at each patch of membrane on the axon. The action potential can regenerate itself by voltage-gated ion channels. The ion channels are also found along the axon. In myelinated axons, voltage-gated ion channels along the axon's length are restricted to the nodes of Ranvier

1. The depolarized membrane (-55mV) is the potential value for the threshold for initiating an action potential. When the threshold is reached the voltage-gated Na⁺ channels open and the ions flow rapidly into the neuron. This influx of positive ions further depolarizes the neuron, continuing the cycle by causing even more Na⁺ channels te open.

2. This is called the Hodgkin-Huxley cycle. This lasts about 1 ms and generates the large depolarization that is the first portion of the action potential. Then the K⁺ channels open, allowing the ion to flow out of the neuron to down its concentration gradient. This outward flow of positive ions shifts the membrane back toward its resting potential.

3. The opening of the K⁺ channels outlasts the closing of the Na⁺ channels, causing a second repolarizing phase of the action potential. This drives the membrane toward the equilibrium potential of K^+.. The membrane is temporarily hyperpolarized (-80 mV).

4. Hyperpolarisation causes the K⁺ channels to close, in reponse to which the membrane potential gradually returns to its resting state. (-70 mV).

5. During this transient hyperpolarisation state, the voltage-gated Na⁺ channels are unable to open, so not other action potential can be generated. This is called the absolute refractory period. This last only a couple of milliseconds and has two consequences:

   1. The neuron's speed for generating action potentials is limited to about 200 action potentials per second.

   2. The passive current that flows from the action potential cannot reopen the ion-gated channels that generate it. The result is that the action potential moves down the axon in one direction only, from the axon hillock to the axon terminal.

What holds the synaptic transmission?

Most neurons send a signal to the cells across the synapse by releasing chemical neurotransmitters into the synaptic cleft, gap between neurons at the synapse.

1. The action potential at the axon terminal leads to depolarization of the terminal membrane and opening of the voltage-gated ion Ca²⁺ channels.

2. This opening triggers small vesicles containing neurotransmitter to fuse with the membrane at the synapse and release transmitter into the synaptic cleft.

There are two types of postsynaptic receptors: ligand-gated ion channels - where neurotransmitter binding directly gates (opens) the ion channel, and the G protein-coupled receptors where biochemical signals indirectly cause the gating of the ion channels, this works via a second messenger.

The neurotransmitter

What makes a molecule a neurotransmitter?

• It is synthesized by and localized within the presynaptic neuron, and stored in the presynaptic terminal before release.

• It is released by the presynaptic neuron when action potentials depolarize the terminal

• The postsynaptic neuron contains receptors specific for it

• When artificially applied to a postsynaptic cell, it elicits the same response that stimulating the presynaptic neuron would.

Some neurotransmitters are amino acids: aspartate, GABA, glutamate, and glycerine. Other neurotransmitters are dopamine, norepinephrine, and epinephrine, serotonin and histamine. Another large group of neurotransmitters consists of slightly larger molecules and are called the neuropeptides; tachykinins, neurohypophyseal hormones, hypothalamic releasing hormones, opioid peptides and other neuropeptides. A particular neurotransmitter may have more than one type of postsynaptic receptor to which it binds, mediating different responses. The neurotransmitters that usually have an excitatory effect include ACh, catecholamines, glutamate, histamine, serotonin, and some other neuropeptides. The neurotransmitters that usually have inhibitory effect include GABA, glycine and some of the neuropeptides.

The two primary players in balancing act between excitation and inhibition are glutamate and GABA. Glutamate is released by the pyramidal cells of the cortex, therefor it is the most prevalent neurotransmitter and is found in most of the fast excitatory synapses in the brain and spinal cord. GABA is synthesized from glutamate. It is found in most of the fast inhibitory synapses across the brain.

Acetylcholine is present in the synapses between neurons and between neurons and muscles, where it has an excitatory effect and activates muscles.

The primary sites of dopamine production are the adrenal glands and a few small areas of the brain. This include the striatum, substantia nigra and hypothalamus. There are several dopaminergic pathways, each sprouting from one of the small brain areas and is involved in several functions including cognitive and motor control, motivation, arousal, reinforcement, reward etc.

Serotonin in the brain is released largely by the neurons of the raphe nuclei, in the brainstem. The serotonergic pathways are involved in the regulation of mood, temperature, appetite, behavior, muscle contraction, sleep and the cardiovascular and endocrine systems.

Norepinephrine or noradrenaline is the sympathic nervous system's go-to neurotransmitter. It is produced by neurons with cell bodies in the locus coerculeus - area in the brain involved in physiological reactions to stress and located in the brainstem, more precisely the pons. Outside the brain NE is released by the adrenal glands. There are two types of receptors for NE: alpha-1 and alpha-2, and beta. The alpha-2 receptors tend to have excitatory effects, the alpha-1 and beta receptors tend to have inhibitory effects.

Some neurons communicate via electrical synapses, which are very different from chemical synapses because there is no synaptic cleft that separates the neurons. The neuronal membranes touch at specializations called gap junctions, and the cytoplasms of the two neurons are essentially continuous. As a result, the two neurons are isopotential, meaning that electrical changes in one are reflected instantaneously in the other.

What is the overview of the nervous system structure?

Neural communication depends on patterns of connectivity in the nervous system, the neural 'highways' along which information travels from one place to another. But identifying those patterns is tricky because neurons are extensively connected in both serial and parallel circuits. Localized interconnected neurons form a microcircuit. They process specific kinds of information and can accomplish sophisticated tasks such as processing sensory information, generating movements and mediating learning and memory.

There are long-lasting connections between various brain regions, those are called neural networks, which are macrocircuits that are made up of multiple embedded microcircuits.

The two main divisions of the nervous system are: the central nervous system (CNS) consisting of the brain and spinal cord and the peripheral nervous system (PNS) consisting of nerves and ganglia outside the CNS.

The autonomic nervous system

The autonomic nervous system is involved in controlling the involuntary action of smooth muscles, the heart and various glands. It has two subdivisions: sympathetic and parasymphathetic branches. In general, the sympathetic system uses the neurotransmitter norepinephrine, and the parasympathetic system uses the neurotransmitters acetylcholine. The two systems frequently operate antagonistically.

The central nervous system

The CNS is made up of the brain and spinal cord, and each is covered with three protective membranes, the meninges. Between two membranes is the subarachnoid space filled with cerebrospinal fluid (CSF). Within the brain there are four large interconnected cavities called ventricles. The largest are the two lateral ventricels in the cerebrum, which are connected to the more caudal third ventricle in the brain's midline and the fourth ventricle in the brainstem below the cerebellum. The CNS neurons are bunched together in various ways, two of the most common organizational clusters are the nucleus and the layer. Nuclei are located throughout both the brain and the spinal cord. The cerebral cortex of the brain, on the other hand, has billions of neurons. The cerebellum is the other structure of the brain that is highly layered, containing billions of neurons, also having white and gray regions. The gray matter in these layers is composed of neuronal cell bodies, the white matter consists of axons and glial cells. Finally, axons may project from one cerebral hemisphere to the other in bundles that are called commissures. The largest of these interhemispheric projections is the main commissure crossing the hemispheres called the corpus callosum.

How does the brain get its blood supply?

The brain needs oxygen and energy, which its extracts from blood. Two sets of arteries bring blood to the brain: the vertebral arteries, which supply blood to the caudal portion of the brain, and the internal carotid arteries, which supply blood to wider brain regions. The primary purpose of increased blood flow is not to increase the delivery of oxygen and glucose to the active tissue, but rather to hasten removal of the resultant metabolic by-products of the increased neuronal activity.

A guided tour of the brain

The spinal cord

The spinal cord takes in sensory information from the body's peripheral sensory receptors, relays it to the brain, and conducts the outgoing motor signals from the brain to the muscles. The spinal cord runs from the brainstem at about the first spinal vertebra to its termination in the cauda equina. It is enclosed in the bony vertebral column that extend from the base of the skull to the fused vertebrae at the coccyx (tailbone).

The brainstem: medulla, pons, cerebellum and midbrain

We usually think of the brainstem as having three main parts: the medulla, the pons and the cerebellum, and the midbrain. The brainstem contains groups of motor and sensory nuclei, nuclei of widespread modulatory neurotransmitter systems, and white matter tracts of ascending sensory information and descending motor signals.

The brainstems most caudal region is the medulla, which is continuous with the spinal cord. It houses the cell bodies of 12 cranial nerves, providing sensory and motor innervations to the face. Functionally, the medulla is a relay station for sensory and motor information between body and brain, it is the crossroads for most of the body's motor fibers.

The pons is latin for 'bridge' and it is named that way because it is the main connection between the brain and the cerebellum. The pons is important for some eye movement as well as movements of the face and mouth. The reticular formation as three colomns of nuclei: raphe nuclei, parvocellular reticular nuclei, gigantocellular nuclei.

The cerebellum clings to the brainstem at the level of the pons. Most of the fibers arriving at the cerebellum project to the cerebellar cotex, conveying information about motor outputs and sensory inputs describing body position.

The midbrain lies superior tot he pons and can only be seen in medial view. Large fiber tracts course through the midbrain's ventral region from the forebrain to the spinal cord, cerebellum and other parts of the brainstem. The midbrain also contains some of the cranial nerve ganglia and the superior and inferior colliculus - they play a important role in perceiving objects and locating and orienting towards auditory stimuli.

The Diencephalon: thalamus and hypothalamus

The thalamus is almost exactly in the center of the brain and perched on top of the brainstem. It is divided in two parts: one in the right hemisphere and one in the left - that straddle the third ventricle. The thalamus has been referred to as the 'gateway to the cortex' because all of the sensory (except the olfactory nerve) modalities make synaptic relays in the thalamus before continuing to the primary cortical sensory receiving areas.

The main link between the nervous system and the endocrine system is the hypothalamus, which is the chief site for hormone production and control. It lies on the floor of the third ventricle. The hypothalamus controls the functions necessary for maintaining the normal state of the body: basal temperature and metabolic rate, glucose levels, hormonal state, sexual phase, cicadian cycle etc. It accomplishes much of this work through the endocrine system via control of the pituitary gland. The hypothalamus produces hormones as well as factors that can regulate those hormones.

The telencephalon: cerebrum

The telencephalon develops into the cerebrum which includes most of the limbic system's structures, the basal ganglia, the olfactory bulb, and the cerebral cortex - covering it all. WIllis observed that the brainstem appeared to sport a cortical border encircling it. The classical limbic lobe is made up of the cingulate gyrus of cerebral cortex that extends above the corpus callosum in the anterior-posterior direction and spans both the hypothalamus, the anterior thalamic nuclei, and the hippocampus (memory system).

MacLean named it the limbic system when he suggested to include the amygdala into the group, this is anterior to the hippocampus. The structures included in the limbic system are tightly interconnected with many distinct circuits and share the characteristic that they are the most capable of plasticity in the cortex.

The basal ganglia are a collection of nuclei bilaterally located deep in the brain beneath the anterior portion of the lateral ventricles, near the thalamus. They include: the caudate nucleus, putamen, globus pallidus, subthalamic nucleus and substantia nigra. The caudate nucleus and the putamen together are known as the striatum.

What holds the cerebral cortex?

The cerebral cortex is the outermost tissue of the cerebrum. The cerebral cortex sits over the top of the core structures that we have been discussing the last few paragraphs. The folds of the human cortex serve two important functions:

1. They enable more cortical surface to be packed into the skull, if the human cortex were smoothed out to resemble that of a rat, humans would need to have very large heads.

2. Having a highly folded cortex brings neurons that are located at some distance from each other along the cortical sheet into closer three-dimensional relationships. The axons that make the long-distance corticocortical connections run under the cortex through the white matter and do not follow the foldings of the cortical surface in their paths, so they project directly tot he neurons brought closer together because of the folding.

The cerebral cortex can be divided by four main divisions: the frontal, parietal, temporal and occipital lobe. The central sulcus divides the frontal lobe from the parietal lobe, and the Sylvian (lateral) fissure separates the temporal lobe from the frontal and parietal lobe.

How do you divide the cortex by cell architecture?

Cytoarchitectionics uses the microanatomy of cells and their organizations to subdivide the cortex. The cortex can now be divided in almost 200 defined areas. We use the Brodmann system to number the system and anatomical names for the cerebral cortex. This often seems very unsystematic, but the numbering has more to do with the order in which Brodmann sampled a region than with any meaningful relations between areas that may or may not exist.

When using microscopic anatomical criteria, it is also possible to subdivide the cerebral cortex according to the general patterns of the cortical layers. 90% of the cortex is composed of neocortex - cortex that contains six cortical layers or that passed through a developmental stage involving six cortical layers. The mesocortex is a term for the so-called paralimbic system.

How do you divide the cortex by function?

The different lobes in the cerebral cortex have a variety of functional roles in neural processing. Typically, cognitive brain systems are composed of networks whose component parts are located in different lobes of the cortex.

• The frontal lobe has two main functional subdivisions; the prefrontal cortex and the motor cortex. It receives input from the cerebellum and basal ganglia via the thalamus and the premotor area. It is mainly responsible for generating neural signals that control movement. The motor association areas modulate inhibition, planning and sensory guidance.

• The parietal lobe receives sensory information about touch, pain, temperature sense and limb proprioception via the receptor cells on the skin.

• The specific cortical regions of the somatosensory and motor cortices that process the sensations and motor control of specific parts of the body have been mapped out. The mapping of specific parts of the body to specific areas of the somatosensory cortex is known as somatotopy - but these maps are not set in stone and do not have necessarily distinct borders.

• The occipital lobe is related to vision. The visual information from the outside world is processed by multiple layers of cells in the retina and transmitted via the optic nerve to the lateral geniculate nucleus of the thalamus.

• Neural projections from the cohclea (auditory sensory organ in the inner ear) proceed through the subcortical relays to the medial geniculate nucleus of the thalamus and then tot the primary auditory cortex. The auditory cortex has a tonotopic organization which means that the physical layout of the neurons is based on the frequency of sound.

• A good portion of the neocortex that is netiher primary sensory cortex nor primary motor cortex is traditionally been termed as association cortex

• The more anterior region of the frontal lobe, the prefrontal cortex, is the last to develop and is evolutionary the youngest region of the brain. It is therefor also proportionately larger in humans compared to the brain of other primates. The main regions are: the dorsolateral PFC, the ventrolateral PFC, the orbitofrontal cortex and the medial PFC. It takes part in the more complex aspects of planning, organizing, controlling and executing behavior, also known as the executive functions.

• The paralimbic ares form a belt around the basal ganglia and medial aspects of the cerebral hemispheres and don't reside in a single lobe. Processing in these areas provides critical information about the relevance of a stimulus for behavior, rather than just its physical characteristics, which are provided by the sensory areas.

The advantage we have over other primates is that our brains are larger in absolute volume and weight; therefore, we have more neurons. In addition to neuron number, other aspects of brain structure might affect cognitive ability. But the number of neurons that an average neuron connects to actually does not change with increasing brain sizes. By maintaining absolute connectivity, not proportional connectivity, larger brains became less interconnected. But evolution came up with two clever solutions:

1. Minimizing connection lengths: short connections keep processing localized, with the result that the connection costs are less. Shorter axons take up less space, less energy is required for building and signaling is faster over shorter distance.

2. Retaining a small number of very long connections between distant rites: primate brains in general and human brains in particular have developed what is known as 'a small-world' architecture. It combines very short, fast local connections with a few long-distance connections to communicate the results of local processing. This design allows both a high degree of local efficiency and, at the same time, quick communication to the global network.

How does the development of the nervous system look like?

Fertilization of the egg is followed by a series of events that lead to the formation of a multicellular blastula, that is already begun to specialize. The early processes that go into forming the nervous system are called neurulation. As the nervous system continues to develop, the cells at the lateral borders of the neural plate push upwards. This causes the more central cells of the neural plate to invaginate to form the neural groove. As the groove deepens the cells form the neural tube.

At the end of 6 weeks, when there is a stockpile of cells, asymmetrical division begins. After every cell division, one of the two cells formed becomes a migratory cell destined to be part of another layer.

A host of behavioral changes takes place during the first months and yeard of life. Although the brain nearly quadruples in size from birth to adulthood, the change is not due to an increase in neuron number. A substantial amount of that growth comes from synaptogenesis - the formation of synapses, and the growth of the dendrites. At roughly the same time as the synaptogenesis the neurons in the brain are increasing the size of their dendrites. The synaptogenesis is followed by the synapse elimination, or pruning. The person you become is shaped by the growth and elimination of the synapses, which in turn are shaped by the world you're exposed to and the experiences you have.

What is the role of methods in cognitive neuroscience? - Chapter 3

Cognitive neuropsychology is the study of mental activities an information-processing problem. They seek to identify the internal processing that underlies observable behavior. A basic assumption is that people do not directly act on what they see and perceive in the world. Our ability to comprehend the information we are getting, depends on a complex interplay of processes. Cognitive psychologists design experiments to test hypotheses about mental operations by adjusting what goes into the brain and then seeing what comes out.

In summary, two key concepts underlie the cognitive approach:

1. Information processing depends on mental representations

2. These mental representations undergo internal transformations

What are mental representations?

We usually take for granted the idea that information processing depends on mental representations. Context helps dictate which representational format is most useful. You can use experiments to see if we have multiple representations of stimuli. Such experiments always have an independent variable, this is the manipulated variable. The dependent variable is the event you are evaluating. But, as you may have experienced, experiments generally elicit as many questions as answers.

What are internal transformations?

The second critical notion of cognitive psychology is that our mental representations undergo internal transformations. When you are taking action, you see and smell certain flavors and things and you brain transforms these sensations into perceptual representations, and, by processing them, enables you to decide on a course of action and to carry it out. So, cognitive psychology is all about how we manipulate representations.

Sternberg (1975) introduced an experimental task that bears show some similarity to the problem faced by an absentminded shopper. The job is comparing sensory information with representations that are active in memory. In each trial, the participant sees a set of letters to memorize. Then he sees a single letter and must decide whether this letter was part of the memorized set. Sternberg postulated that, to response on this task, the participant must engage in four primary mental operations:

1. Encoding: the participant must identify the visible target

2. Comparing: the participant must compare the mental representation of the target with the representations of the items in memory

3. Deciding: the participant must decide whether the target matches one of the memorized items

4. Responding: the participant must respond appropriately for the decision made in Step 3

Sternberg's basic question was how to characterize the efficiency of recognition memory. A highly efficient system might simultaneously compare a representation of the target with all of the items in the memory set. Or, the recognition process might be able to handle only a limited amount of information at any point in time. Sternberg realized that the reaction time data could distinguish between these two alternatives. If the comparison process can be simultaneous for all items - a parallel process - then the reaction time should be independent of the number of items in the memory set. But if the comparison process operates in a sequential, or serial, manner, then reaction time should slow down as the memory set becomes larger.

How do you study the damaged brain?

Cognitive psychologists assume that fundamental principles of cognition can be learned from this limited population but also recognize the importance of testing other populations. A core method in cognitive neuroscience involves testing a unique population - people who have suffered brain damage.

What are causes of neurological dysfunction?

Vascular disorders

Neurons need a steady supply of oxygen and glucose. These substances are essential for the cells to produce energy, fire action potentials, and make transmitters for neuronal communication. A cerebral vascular accident, or stroke, occurs when there is a sudden disruption of the blood flow to the brain. The most frequent cause of stroke is occlusion of the normal passage of blood by a foreign substance. Other types of cerebral vascular disorder can lead to ischemia (inadequate blood supply). The vascular system is fairly consistent between individuals; thus, a stroke of a particular artery typically leads to destruction of tissue in a consistent anatomical location.

Tumors

A tumor or neoplasm is a mass of tissue that grows abnormally and has no physiological function. Brain tumors are relatively common; most originate in glial cells and other supporting white matter tissues.

Degenerative and infectious disorders

Many neurological disorders result from a progressive disease. Here we focus on the etiology and clinical diagnosis of degenerative disorders. They have been associated with both genetic aberrations and environmental agents. A prime example is the Huntington's disease, the link in other degenerative disorders, such as Parkinson's and Alzheimer's disease, is weaker. The diagnosis of degenerative disorders is usually confirmed by MRI scans. Viruses can also cause progressive neurological disorders. HIV and AIDS have the tendency to lodge in subcortical areas of the brain, producing diffuse lesions of the white matter by destroying axonal fibers resulting in dementia.

Traumatic brain injury

The most common brain affliction that lands patients in a neurology ward is traumatic brain injury (TBI). Common causes of head injuries are car accidents, falls, contact sports, bullter or shrapnel wounds and bomb blasts. One consequence of the primary lesion from a TBI is edema (swelling) around the lesion. The limited space in the skull, due to the edema, causes an increase in the intracranial pressure, in turn reducing the perfusion pressure and flow of blood throughout the brain, resulting in inschemia and, in some cases, the emergence of secondary lesions.

Epilepsy

Epilepsy is a condition characterized by excessive and abnormally patterned activity in the brain. The cardinal symptom is a seizure, a transient loss of consciousness. An EEG (electroencephalography) can confirm seizure activity.

What a cognitive neuropsychologists wants to do is design tasks that will test specific hypotheses about brain-function relationships. Associating neural structures with specific processing operations calls for appropriate control conditions, the most basic control is to compare the performance of a patient or group of patients with that of healthy participants.

What methods are there to perturb neural function?

The release of neurotransmitters at neuronal synapses and the resultant responses are critical for information transfer from one neuron to the next. Though protected by the blood-brain-barrier (BBB) the brain is not a locked compartment. Pharmalogical studies may involve the administration of agonist drugs, those that have a similar structure to a neurotransmitter and mimic its action, or antagonist drugs, those that bind to receptors and block or dampen neurotransmission. There are several studies regarding the influence of drugs on the brain. But one major drawback of studies using drugs injected into the bloodstream is the lack of specificity.

The start of the 21st century went hand-in-hand with the climax of one of the greatest scientific challenges: the mapping of the human genome. Genetic disorders are manifest in all aspects of life, including brain function. By analyzing individual's genetic codes, scientists can predict whether the children of individuals carrying the Huntington disease gene will develop his debilitating disorder.

What are the invasive stimulation methods?

Given the risks associated with neurosurgery, researchers reserve invasive methods for studies in animals and for patients with neurological problems that require surgical intervention. An invasive approach is deep brain stimulation (DBS), a procedure in which surgeons implant electrodes in specific brain regions for an extended period to modulate neuronal activity. The most common application of this method is as a treatment for Parkinson's disease, a movement disorder resulting from the basal ganglia dysfunction.

Optogenetics has provided a reliable switch to activate neurons using viral transduction. Scientists inserted the ChR-2 gene into the part of the mouse's brain that contains the motor neurons controlling its whiskers. Once the light-sensitive ion channels were constructed and a tiny optical fiber was inserted in the same region, the neurons were ready to rock'n'roll.

What are noninvasive stimulation methods?

TMS or transcranial magnetic stimulation procused relatively focal stimulation of the human brain noninvasively. The area of neural activation depends on the shape and positioning of the TMS coil. There are numerous protocols, or ways in which stimulation can be manipulated. Researchers can administer TMS pulses at various intensities, timings, and frequencies. TMS has become valuable research tool in cognitive neuroscience because of its ability to induce 'virtual lesions'. But, TMS also has its limitations. With currently available coils, the area of primary activation has about a 1-cm radius and thus can activate only relatively superficial areas.

Researchers are constantly looking for new ways to noninvasively stimulate the brain. Transcranial direct current stimulation (tDCS) is a brain stimulation procedure that delivers a constant, low current to the brain via electrodes placed on the scalp. A current is send between an anode and a cathode. The neurons under the anode become depolarized, they achieve an elevated state of excitability, making them more likely to initiate an action potential when a stimulus or movement occurs. The transcranial direct current stimulation procedures changes in a wide range of sensory, motor and cognitive tasks.

Transcranial alternating current stimulation (tACS) is a newer procedure in which the electrical current oscillates rather than remaining constant as in tDCS. The experimenter controls the rate of tACS oscillation, providing another tool to modulate brain function. The direction and the duration of the tACS-induced effects can vary with the frequency, intensity and phase of the stimulation.

Transcranial static magnetic stimulation (tSMS) uses strong magnets to create magnetic fields that, as with TMS, perturb electrical activity and thus temporarily alter cortical function. Another emerging method, one that promises improved spatial resolution and the ability to target deeper structures, is transcranial focused altrasound (tFUS). This signal increases the activity of voltage-gated sodium and calcium channels, thus triggering action potentials.

What is the structural analysis of the brain?

We now turn to methods used to analyze brain structure. Structural methods take advantage of the differences in physical properties that different tissues possess.

CT or CAT, computerized tomography scanning was the first method to offer an in vivo look at the human brain. This method was actually an extension of X-rays. Although CT scanning continuous to be an extremely important medical procedure for clinical purpose, magnetic resonance imaging (MRI) is now the preferred method for whole-brain imaging because it provides images of much higher resolution. MRI scans provide a much clearer image of the brain than is possible with CT scans.

A variant of the traditional MRI is diffusion tensor imaging (DTI). This is used to study the anatomical structures of the axon tracts that form the brain's white matter, this method offers information about anatomical connectivity between regions.

What methods are used to measure neural activity?

The development of methods for single-cell recording was perhaps the most important technological advance in the history of neuroscience. By measuring the action potentials produced by individual neurons in living animals, researchers could begin to uncover how the brain responds to sensory information, produces movement and changes with learning. The primary goal of a single-cell recording experiments is to determine which experimental manipulations produce a consistent change in the response rate of an isolated cell.

A single cell is not responsive to all visual stimuli. A number of stimulus parameters might correlate with the variation in the cell's firing rate. An important factor is the location of the stimulus. All visually sensitive cells respond to stimuli in only a limited region of space. This region of space is that cell's receptive field. Neighboring cells have at least partially overlapping receptive fields. As such, cells form a topographic representation - in vision, we refer to topographic representations as retinotopic maps.

What holds the invasive neurophysiology in humans?

Surgeons may insert intracranial electrodes to localize an abnormality before its surgical resection. A invasive neurophysiological method used to study the human brain is electrocorticography (ECoG), where a grid or strip of electrodes is placed directly on the surface of the brain, either outside the dura or beneath it, and the activity of the populations of neurons is recorded for a sustained amount of time. In a second procedure, they remove the electrodes and perform the corrective surgery. Researchers can stimulate the brain with the electrodes, using them to localize and map cortical and subcortical neurological functions such as motor or language function. The time-varying record of the signals from the electrodes is an electrocorticogram.

What are the noninvasive electrical recording of neural activity?

The electrical potential produced by a single neuron is minute; it would be impossible to detect that signal from an electrode placed on the scalp. When populations of neurons are active, they generate a much larger composite of electrical signal. You can measure those with noninvasively by using electrodes placed on the scalp, a method known as electroencephalongraphy (EEG). Because normal EEG patterns are consistent among individuals, we can detect abnormalities in brain function from EEG recordings.

The data collected with an EEG can also be used to examine how a particular task modulates brain activity. The evoked response, or event-related potential (ERP) is a tiny signal embedded in the ongoing EEG triggered by the stimulus or movement. ERP's also provide an important tool for clinicians. The visual evoked potential can be useful in diagnosing multiple sclerosis, a disorder that leads to demyelination.

Related to EEG is magnetoencephalography (MEG), a technique that measures the magnetic fields produced by the brain's electrical activity. As with EEG, the MEG traces over a series of trials to obtain event-related signals, called event-related fields.

The marriage of function and structure: what is neuroimaging?

The most exciting advances for cognitive neuroscience have been provided by imaging techniques that enable researchers to identify the physiological changes in specific regions of the brain as people perceive, think, feel and act. The most prominent of these neuroimaging methods are positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). PET and fMRI do not directly measure neural events. Rather, they measure metabolic changes correlated with the neural activity. When a brain area is active, increasing the blood flow to that region provides it with more oxygen and glucose at the expense of other parts of the brain. PET and fMRI can detect this change in blood flow, known as hemodynamic response.

Positron Emission Tomography

PET activation studies use radioactive-labeled compounds to measure local variations in cerebral blood flow that correlate with mental activity. The radiologist injects a tracer into the bloodstream, which distributes it throughout the brain in step with its metabolic needs. A common tracer isotope used in PET studies is the oxygen-15 (¹⁵O), which has a half life of 122 seconds. Although all areas of the body use some of the radioactive oxygen, the fundamental assumption of PET is that there is increased blood flow to the brain regions that have heightened neural activity. Thus, PET activation studies measure relative activity, not absolute metabolic activity. The results are usually reported as a change in regional cerebral blood flow (rCBF) between the control and experimental conditions.

Functional magnetic resonance imaging

fMRI exploits the fact that local blood flow increases in active parts of the brain. Radio waves cause the protons in hydrogen aims to oscillate, and a detector measures the local energy fields emitted as the protons return to the orientation of the magnetic field created by the MRI scanner. The fMRI detectors measure the ratio of oxygenerated to deoxygenerated hemoglobin; this value is referred to as the blood oxygen level-dependent (BOLD) effect.

fMRI offers several advantages over PET. MRI scanners are much less expensive and easier to maintain, and fMRI uses no radioactive tracers, so it does not incur the additional costs, hassles, and hazards associated with handling these materials.

fMRI and PET differ in their temporal resolution. The PET imaging requires sufficient time for detecting enough radiation to create images of adequate quality. Because of this time requirement, the researchers must use block design experiments with PET. The researcher integrates the recorded neural activity over a 'block' of time during which the participant performs multiple trials of the same type.

fMRI can either use a block design, in which the experimenter compares the neural activation between experimental and control scanning phases, or an event-related design. Event-related fMRI improves the experimental design because the researcher presents the experimental and control trials randomly.

You can also use the MRI machine to measure other properties of brain tissue. One method, the magnetic resonance spectroscopy (MRS) offers a tool to obtain, in vivo, information about the chemical composition of tissues. From the MRS data, researchers can estimate the concentration of different neurochemicals in one brain area or the same neurotransmitter in multiple areas.

What are limitations of functional imaging techniques?

1. PET and fMRI have poor temporal resolution compared with single-cell recordings or ERP's. PET is constrained by the decay rate of the radioactive agent, and fMRI is dependent on the hemodynamic changes that underlie the BOLD response.

2. To relate function and structure, it is necessary to be able to map the data obtained with functional imaging methods such as fMRI and PET onto corresponding structural MRI scans. These methods work because brains, in general, have the same components, but, just like fingerprints, no two brains are the same. This variation presents a problem for comparisons of the functional imaging data across individuals.

3. There is also a difficulty arising on the interpretation of the data from a PET of fMRI study. The data sets are massive, presenting challenging statistical problems.

4. Even with proper statistical procedures, comparisons between different experimental conditions are likely to produce many differences.

What is a connectivity map?

The last years there has been a lot of work regarding developing tools, to understand how the brain supports any cognitive process, this is called a connectivity map. These maps, often referred to as connectomes, are visualizations of structural or functional connections within the brain. A brain network can be constructed from either structural or functional imaging data:

1. Define the network nodes. Data from MRI and fMRI are divided into nodes, visualized in a parcellation map.

2. Measure the correlation between all possible pairs of nodes, using the dependent variable of interest.

3. Generate an association matrix by compiling all pairwise associations between the nodes.

4. Visualize the correlations in connectivity map, one way to create these maps is to depict brain regions as nodes of a network and indicate connections as edges between them.

So, the connectivity maps capture the correlated patterns of activity between different brain regions. They also give a new opportunity and new methods for examining variation between individuals or groups.

What is computational neuroscience?

Creating computer models to simulate postulated brain processes is a research method that complements the other methods discussed in this chapter. A simulation is an imitation, a reproduction of behavior in an alternative medium. These simulated cognitive processes are commonly referred to as artificial intelligence (AI). Computer models are useful because we can analyze them in detail

Computer models differ widely in their representations. Symbolic models include units that represent symbolic entities. An alternative architecture that figures prominently in cognitive neuroscience is the neural network. Models can be 'lesioned' to test whether the resulting change in performance resembles the behavioral deficits observed in neurological patients. Lesioning thus provides a tool to assess whether the model accurately simulates a particular cognitive process or domain, and more important, to shed a light on the credibility of the model.

What are converging methods?

Cognitive neuroscience is a interdisciplinary field that draws on ideas and methodologies from cognitive psychology, neurology, neuroscience, and computer science. The great strength of cognitive neuroscience lies in the ways that diverse methodologies are integrated.

How do sensation and perception relate to each other? - Chapter 5

A patient PT had suffered a cerebral vascular accident, commonly known as a stroke. The unusual aspect was that he got really weird symptoms 4 months later. The most troubling was, he could not recognize the people around him. He had, for instance, no trouble seeing his wife, but when it came to identifying her, he was at a complete loss. He knew that her body parts - arms, legs, head - formed a person, but PT failed to see these parts as belonging to a specific individual. A striking feature was that PT impairment was that his inability to recognize objects and people was limited to the visual modality. As soon as his wife would speak a few words, he would recognize her.

What are senses, sensation and perception?

Perception begins when a stimulus from the environment such as sound, light, or touch, stimulates one of the sense organs such as the ear, eye or skin. The sense organs transduces the input into neuronal activity, which then goes to the brain for processing. Sensation is this initial activation of the nervous system, the translation of information about the environment into patterns of neural activity. The mental representation of that original stimulus, whether it accurately reflects the stimulus or not, is called a percept. Thus perception is the process of constructing a percept. Our senses are our physiological capacities to provide input from the environment to our neurological system. Our sense of sight is our capacity to capture light waves on the retina, convert them into electrical signals, and ship them on for further processing.

What is common processing across the senses?

Each system begins with some sort of anatomical structure for collecting, filtering, and amplifying information from the environment. Each system has also specialized receptor cells that transduce the environmental stimulus, such as sound waves, light waves, or chemicals, into neuronal signals. These signals are then passed along specific sensory nerve pathways: the olfactory signals travel via the olfactory nerve, visual signals via the optic nerve, auditory signals via the cochlear nerve, taste via the facial and glossopharyngeal nerves, facial sensation via the trigeminal nerve, and sensation for the rest of the body via the sensory nerves that synapse in the dorsal roots of the spinal cord. These nerves terminate their monosynaptically or disynaptically in different parts of the thalamus. From the thalamus, neural connections from each of these pathways travel first to what are known as primary sensory regions of the cortex, and then to secondary sensory areas.

What are the sensory receptors?

Across the senses, receptor cells share a few general properties. Receptor cells are limited in the range of stimuli they respond to, and as part of this limitation, their capability to transmit information has only a certain degree of precision.

• Range: each sensory modality responds to a limited range of stimuli. This range is not the same for all species. As limited as our receptor cells may be, we do respond to a wide range of stimulus intensities.

• Adaptation: this is the adjustment of the sensory system's sensitivity to the current environment and to important changes in the environment. Adaptation happens quickly in the olfactory system; one minute you can smell the freshly baked bread in the bakery, the next minute it is gone.

• Acuity: Our sensory systems are tuned to respond to different sources of information in the environment. How well we can distinguish among stimuli within a sensory modality, or what we would call acuity, depends on a couple of factors. Our visual acuity is better than most animals, but not better than an eagle's. Our acuity is the best in the center of the visual field, because the central region of the retina, the fovea, is packed with photoreceptors. We have to move our eyes frequently in order to focus on different parts of the visual scene. These rapid eye movements are called saccades.

What is the role of olfaction?

The ability to smell is essential for terrestrial mammals, helping them to recognize foods that are nutritious and safe. It now serves other important roles as well - for instance, knowing or detecting a hazard such as fire or airborne toxins. Olfaction also plays an important role in social communication: pheromones are excreted or secreted chemicals that trigger a social response in another individual of the same species when perceived by the olfactory system. Smell is the sensory experience that results from the transduction of odor molecules, or odorants, into neuronal signals sent to the olfactory cortex. These molecules enter the nasal cavity during the course of normal breathing or when taking a sniff.

The human sense of smell uses the input from odor receptors embedded in the mucous membrane of the roof of the nasal cavity to discriminate among odorants. There are tens of thousands of odorants and over a thousand types of receptors: most receptors respond to only a limited number of odorants, though a single odorant can bind to more than one type of receptor.

Another hypothesis is that the molecular vibrations of groups of odorant molecules contribute to odor recognition. This model predicts that odorants with similar vibrational spectra should elicit similar olfactory reponses, and it explains why similarly shaped olfactory molecules with dissimilar vibrations have very different fragrances.

The olfactory receptors are called bipolar neurons because appendages extend from opposite sides of their cell bodies. When odorant triggers a receptor, they send a signal to the glomeruli, the neurons in the olfactory bulb. The axons from the glomeruli then exit laterally from the olfactory bulb, forming the olfactory nerve. Their destination is the primary olfactory cortex, located at the ventral junction of the frontal and temporal cortices. The olfactory pathway is unique in two ways:

1. Most of the axons of the olfactory nerve project to the ipsilateral cortex.

2. The olfactory nerve arrives at the primary olfactory cortex without passing through the thalamus.

Also, research has shown that the primary olfactory cortex might be essential for detecting a change in the external odor and that the secondary olfactory cortex might be playing an important role in identifying the odor itself.

What holds gustation?

The sense of taste depends greatly on the sense of smell. Since these two senses interpret the environment by discriminating between different chemicals, they are referred to as the chemical senses. Gustation begins with the tongue. Across the surface of the tongue are different kinds of papillae present. They serve multiple functions; some are concerned with gustation, some with sensation, and some with the secretion of lingual lipase, an enzyme that helps break down fats. Whereas the papillae in the anterior region of the tongue contain just a few taste buds, the papillae found near the back of the tongue have hundreds to thousands of taste buds. There are five basic tastes: salty, sour, bitter, sweet and umami - the savory taste you experience when you eat steak or other protein-rich substances. All five tastes are present across the tongue.

The sensory transduction in the gustatory systems begins when a food molecule, or tastant, stimulates a taste receptor cell and causes it to depolarize. Each of the basic taste sensations has a different from of chemical signal transduction. Synapsing with the taste receptor cells in the taste buds are bipolar neurons. Their axons from a nerve that joints the other fibers to form the facial nerve. The next synapse in the gustatory system is on the ventral posterior medial nucleus (VPM) of the thalamus. Axons form the VPM synapse in the primary gustatory cortex. This is connected to secondary processing areas of the orbitofrontal cortex, providing an anatomical basis for the integration of tastes and smells.

The tongue does more than taste. Some papillae contain nociceptive receptors, a type of pain receptor. The output joints the trigeminal nerve. This nerve not only carries pain information, but also signals position and temperature. A gustotopic map has recently been identified in the primary gustatory cortex of the mouse brain, with considerable segregation of areas responsive to the five basic tastes. The perception of more complex tastes arises from the combination of these fundamental tastes, perhaps in the secondary gustatory cortex within the ortbitofrontal cortex.

What is somatosensation?

Somatosensory perception is the perception of all mechanical stimuli that affect the body, including the interpretation of signals that indicate the position of our limbs and the position of our head, as well as our senses of temperature, pressure, touch and pain. Somatosensory receptors lie under the skin and at the musculoskeletal junctions.

Touch is signaled through: Meissner's corpuscles, Merkel's cells, Pacinian corpuscles, and Ruffini corpuscles. Pain is is signaled by nociceptors, the least differentiated of the skin's sensory receptors. They come in three flavors:

• Thermal receptors that respond to heat or cold

• Mechanical receptors that respond to heavy mechanical stimulation

• Multimodal receptors that respond to a wide range of noxious stimuli, such as heat, mechanical insults, and chemicals

The afferent pain neurons may be either myelinated or unmyelinated. The myelinated fibers quickly conduct information about pain, the activation of these cells usually produces immediate action. Specialized nerve cells provide information about the body's position, or what is called proprioception. This enables the sensory and motor systems to represent information about the state of the muscles and limbs. Somatosensory receptors have their cell bodies in the dorsal-root ganglia. They enter the spinal cord via the dorsal root, some synapse on motor neurons in the spinal cord from the reflex arcs. Other synapse on neurons send axons up the dorsal column of th spinal cord to the medulla.

The initial cortical receiving area is called the primary somatosensory cortex, or S1. It contains a somatotopic representation of the body, called the sensory homunculus. The relative amount of cortical representation in the sensory homunculus corresponds to the relative importance of somatosensory information for that part of the body. For instance, the large representation of the hand is essential, given the great precision we need in using our fingers to manipulate objects and explore surfaces.

The secondary somatosensory cortex, or S2, builds more complex representations. Regarding to touch, the S2 neurons may code information about object texture and size.

Looking at the somatotopic maps may make you wonder just how much of that map is set in stone. If you work with numbers from quite some time, would you see changes in parts of the visual cortex that discriminate numbers? They did a research experiment using the somatosensory representation of the hand area of professional violin players. They found that the responses in the musicians' right hemisphere, which controls the left-hand fingers that manipulate the violin strings, were stronger than those observed in non musicians. So, you can say that somatosensory information exhibit plasticity, showing variation in extent and organization as a function of individual experience.

What is the role of audition?

The sense hearing, or audition, plays an important role in our daily lives. How does the brain process sound waves? How does the nervous system figure out what and where the sound comes from? The complex structures of the peripheral auditory system - outer, middle and inner ear - provide the mechanisms for transforming sounds into neuronal signals. Sounds waves arriving at the outer ear enter the auditory canal. In the canal, the sound waves are amplified, that they travel to the far end of the canal where they hit the tympanic membrane/ eardrum and make it vibrate. These low-pressure vibrations then travel through the air-filled middle ear and rattle three tiny bones: malleus, incus and stapes, which cause the oval window, to vibrate. The oval window is the door to the fluid-filled cochlea. In the cochlea there are tiny haircells located along the inner surface of the basilar membrane. The location of the hair cells on the basilar membrane determines the frequency tuning, the sound frequency that it responds to.

The spatial arrangement of the sound receptors is known as tonotopy, and the arrangement of the hair cells along the cochlear canal forms a tonotopic map. Natural sounds such as music or speech are made up of complex frequencies, thus a natural sound will activate a broad range of hair cells.

The central auditory system contains several synapses between the hair cells and the cortex. The cochlear nerve projects to the cochlear nuclei in the medulla. Axons from the cochlear nuclei travel up to the pons and split to innervate the left and right olivary nucleus. From the midbrain, auditory information ascends to the medial geniculate nucleus (MGN) of the thalamus, which projects to the primary auditory cortex (A1) in the superior part of the temporal lobe.

The computational goal of audition is to determine the identity (what) and location (where) of sounds. The brain must take the auditory signal and, using acoustic cues such as frequency and timbre, convert it into a perceptual representation that can be further combined with information from other systems, such as memory and language. We can discriminate between the sound of a banjo and that of a guitar, but we are still able to identify a 'G' from both as the same note, because the notes share the same base frequency.

A second important function of audition is to localize sounds in space. In solving the 'where' problem the auditory system relies on integrating information from two ears. Barn owls rely on two cues to localize sounds:

• the difference in when a sound reaches each of the two ears (the interaural time)

• the difference in the sound's intensity at the two ears.

What is vision?

Both audition and vision are important for perceiving information at distance, engaging in what is called remote sensing; we need not be in immediate contact with stimulus to process it. An organism can avoid a predator better when it can detect the predator at a distance.

Visual information is contained in the light reflected from objects. To perceive objects, we need sensory detectors that respond to the reflected light. As light passes through the lens of the eye, the image is inverted and focused to project on the retina. The deepest layers are composed of millions of photoreceptors that are protein molecules that are sensitive to light. They consist of rods and cones. The rods contain the photopigment rhodopsin, therefor they are more useful at night, when light energy is low. Cones contain photopsin, they require more intense levels of light, cones are therefor more active during daytime vision. There are three types of cones:

1. Cones that respond to shorter wavelengths, the 'blue' part of the spectrum

2. Cones that respond to medium wavelengths, the 'green' region

3. Cones that respond to the longer wavelengths, the 'red' part

Rods and cones are not distributed equally across the retina. The cones are densely packed near the fovea. Rods are distributed across the retina. The rods and cones are connected to bipolar neurons that synapse with ganglion cells, the output layer of the retina. The axons of these cells form a bundle, the optic nerve, that transmits information to the central nervous system. The axons that make up the medial half of each optic nerve cross to the opposite hemisphere and form an intersection at the optic chiasm. Axons in the optic nerve synapse on the lateral geniculate nucleus or LGN and from the LGN become the optic radiations that project to the primary visual cortex, or V1.

The visual system identifies the what and where of objects. Because of the optics of the eye, light reflecting off objects in the environment strikes the eye in an orderly manner. Neurons in the visual system keep track of where objects are located in space by responding only when a stimulus is presented in a specific region of space, named the receptive field. Visual cells from an orderly mapping between spatial location and the neural representation of that dimension. These tonotopic representations are called the retinotopic maps in vision.

The optimal stimulus becomes more complex as information moves through the system: cells in the retina and LGN respond best to small spots of light, while cells in V1 are sensitive to edges. Farther up in the system, the areas like V4 and TE, the optimal stimulus becomes much more complex, such as shapes or even faces. The visual cortex is made up of many distinct regions defined by their distinct retinotopic maps. The visual areas have functional differences that reflect the types of computations performed by cells within each area. For instance, cells in area V4 are more sensitive to color information, whereas the cells in V5 are sensitive to motion information.

Why has the primate brain evolved so many visual areas? One possibility is that processing works hierarchical. Each area, representing the stimulus in a unique way, successively elaborates on the representation derives by processing in earlier areas. Successive elaboration culminates in formatting the representation of the stimulus so that it matches information in memory. But there is a problem, there is no such thing as hierarchy.

An alternative hypothesis is based on the idea that visual perception is an analytic process. Each visual area provides a map of external space, each map represents different types of information. This hypothesis suggests that neurons within an area not only code where an object is located in visual space, but also provide information about the object's attributes.

What leads from sensation to perception?

At what stage of processing does this sensory stimulation become a percept, something we experience phenomenally? One way to study this question is to 'trick' our sensory processing systems with stimuli that cause us to form percepts that do not correspond to the true stimuli in the environment - to perceive illusions. Our percepts are more closely related to activity in higher visual areas that to activity in the primary visual cortex. A strong case for the hypothesis that perception is more closely linked to secondary sensory areas would require evidence showing that activity in these areas can be sufficient, and even predictive, of perception.

Before the advent of neuroimaging, much of what we learned about processing in the human brain came from the study of patients with lesions, including those with disorders of perception. For instance, describing the loss of the ability to perceive colors in the right visual field of a patient.

A rare disorder of color perception is a disorder that arises from disturbances of the central nervous system. These disorders are called achromatopsia. Individuals with these disorders are able to see and recognize objects color is not a necessary cue for shape perception. But, despite their relatively good visual recognition, achromatiopsia patients are likely to have some impairments in their ability to perceive shape, given that color-sensitive neurons show tuning for other properties as well, such as orientation. Lesions to areas in and around V4 can result in achromatopsia.

Another rare disorder has to do with a selective loss of motion perception, is called akinetopsia. The patients view of the world was akin to viewing the world as a series of snapshots, rather than seeing things move continuously in space, the patient saw moving objects appear in one position and then another. When pouring a cup of tea, she saw the liquid frozen in the air, failed to notice the tea rising in the cup, and was surprised when it would overflow. The impairment can be very dramatic when V5 is damaged in both left and right hemispheres.

What is multimodal perception?

Even though the information provided by each sense is distinct, the resulting representation of the surrounding world is not one of disjointed sensations, but of a unified multisensory experience. A particular powerful presentation of this distortion comes from the world of speech perception. Most people think of speech as an inherently auditory process: we decipher the sounds of language to identify phonemes, combining them into words, sentences, and phrases. However, the sounds we hear can be adjusted and influenced by visual cues. This is made clear in a compelling illusion called the McGurk effect, in which the perception of speech - what you believe you 'hear' - is influenced by the lip movements that your eyes see.

Some areas of the brain, such as the superior colliculus and the superior temporal sulcus, process information from more than one sensory modality, integrating the multimodal information to increase perceptual sensitivity and accuracy.

The patient JW experiences the world differently than most people. He tastes words, the word 'exactly' tastes like yogurt, and the word 'accept' tastes like eggs. Most conversations are pleasant tasting, but when JW is tending bar, he cringes whenever someone showsup because the name 'Derek' tastes like earwax. This phenomenon, in which the senses are mixed is called synesthesia. Tasting words is an extremely rare kind of synesthesia, more common kinds of synesthesia are when people hear words or music as colors, or see achromatic lettering (as in books or newspapers) as colored. Given that synesthesia is such a personal experience, researchers have had to come up with clever methods to verify and explore this unique phenomenon. That is why researchers came up with the Stroop-task. The stroop task requires the person to name the color of a written word. For instance, the word green is written with red ink, the participant is supposed to say 'red'. Synesthesia is associated with both abnormal activation patterns in functional imaging studies and abnormal patterns of connectivity in structural imaging studies.

What holds perceptual organization?

In 1949, Hebb thought that the brain was unchangeable after the early formative years. He suggested a theoretical framework for how functional reorganization, or cortical plasticity, might occur in the brain through remodeling of neuronal connections.

Brain regions that are typically associated with a particular sensory system become reorganized in individuals who lack that sensory system. For example, regions usually involved in visual processing become responsive to auditory and tactile stimuli in blind individuals. Much of the work involving cortical reorganization has focused on individuals who have complete loss of one sensory system, usually audition or vision.

Reorganization in the motor cortex has been found to depend on the level of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter. When GABA levels are high, activity in individual cortical neurons is relatively stable. If GABA levels are lower, the neurons respond to a wider range of stimuli. For example, a neuron that responds to the touch of one finger will respond to the touch of other fingers if GABA is blocked.

What is the role of engineering for compensation?

Cochlear implants are designed to help people with severe hearing problems for whom typical hearing aids does not help. Permanent hearing loss is usually the result of damage or loss of the hair cells in the cochlea, often due to aging or frequent exposure to loud noise. Hearing aids facilitate hearing by amplifying the signals carries by sound waves and thus increasing the intensity of the stimulus arriving at the sensory transducers in the ear. The benefits of cochlear implants can take some time to become optimal, likely because the brain has to learn to interpret the modified auditory input.

Retinal implants are designed for patients who are blind because of degenerative diseases that affect the photoreceptors, resulting in progressive vision loss. Even when the visual loss is very advanced, many cells in the retina remain intact. Therefor the researchers came up with a subretinal implant, which exploits the remaining photoreceptors, and a epiretinal implant, which bypasses the photoreceptor cells and directly stimulates the ganglion neurons on the retina.

Which matters are important in object recognition? - Chapter 6

What are the computational problems in object recognition?

When you think about object recognition, there are a few things to keep in mind:

1. Use terms precisely: When you talk about certain cases or patients it is very important for researchers to be precise about when using terms like perceive or recognize.

2. Object perception is unified: our sensory system uses a divide-and-conquer strategy, but the perception of objects is unified. Features like color and motion are processed along distinct neural pathways. Perception, however, requires more than simply perceiving the features of objects.

3. Perceptual capabilities are enormously flexible and robust: The city vista looks the same whether the view of both eyes or with only the left or the right eye. The percept of an image always stays the same, even if we stand on our head and the retinal image is inverted.

4. The product of perception is immediately interwoven with memory: object recognition is more than linking features to form a coherent whole. Part of memory retrieval is recognizing that things belong to certain categories.

Object constancy refers to our amazing ability to recognize an object in countless situations. When you show a drawing of a car, from a different view each time, a person has no problem identifying the object in each picture as a car, and discerning that all four cars are the same model. The visual information emanating from an object varies as a function of three factors: viewing position, illumination conditions, and context.

1. Viewing position: sensory information depends highly on your viewpoint, which changes not only as you view an object from different angles, but also when the object itself moves and thus changes its orientation relative to you. The human perceptual system is adept at separating changes caused by shifts in viewpoint from changes intrinsic to an object itself. The sensory system automatically uses any sensory cues and past knowledge to maintain object constancy.

2. Illumination: while the visible parts of an object may differ depending on how light hits it and where shadows are cast, recognition is largely insensitive to changes in illumination. A dog in the sun and a dog in the shade both register as a dog.

3. Context: objects are rarely seen in isolation. People see objects surrounded by other objects and against varied backgrounds. Yet we have no trouble separating, for instance, a dog from other objects on a crowded city street. Our perceptual system quickly partitions the scene into components.

Object recognition must accommodate these three sources of variability. But the system also has to recognize that changes in perceived shape may reflect actual changes in the object.

What are the multiple pathways for visual perception?

The pathways carrying visual information from the retina to the first few synapses in the cortex segregate into multiple processing streams. Much of the information goes to the V1 (primary visual cortex). Output from the V1 is contained primarily in two major fiber bundles, which carry visual information to regions of the parietal and temporal cortex - that are involved in visual object recognition.

There is the ventral (occipitotemporal) stream and the dorsal (occipitoparietal) stream. These two are also known as the what and where pathways. Ungerleider and Mishkin proposed hat processing along these two pathways is designed to extract fundamentally different types of information.

They hypothesized that the ventral stream is specialized for object perception and recognition, for determining 'what' we are looking at. The dorsal stream is specialized for spatial perception, for determining 'where' an object is, and for analyzing the spatial configuration between different objects in a scene. What and where are two basic questions to be answered in visual perception. To be more specific, the dorsal stream or 'where' is going upwards from the back of the brains to the front, the ventral stream is 'what' and is going downwards from the back of the brain to the front. If you want to use a mnemonic; dorsal comes first in the alphabet when you choose between dorsal and ventral, so dorsal is above and ventral is below.

The first data for the what-where dissociation of the ventral and dorsal stream comes from animal studies. Animals with bilateral lesions to the temporal lobe that disrupted the ventral stream had great difficulty discriminating between different shapes (the 'what' discrimination). But, these animals had no problems determining where the object was in relation to other objects, because this second ability depends greatly on the 'where' route. But the separation of the 'what' and 'where' routes is not limited to the visual system, for instance in audition.

What are the representational differences between the dorsal and ventral streams?

Neurons in both the temporal and parietal lobes have large receptive fields, but the physiological properties of the neurons within each lobe are quite distinct. 40% of these neurons have receptive fields near the central region of vision, the remaining cells have receptive fields that exclude the foveal region. These eccentrically tuned cells are ideally suited for detecting the presence and location of a stimulus, especially one that has just entered the field of view.

The response for neurons in the ventral stream of the temporal lobe is quite different. The receptive fields for these neurons always encompass the fovea, most of these neurons can be activated by a stimulus that falls within either the left or the right visual field. Cells within the visual areas of the temporal lobe have a diverse pattern of selectivity. In the posterior region cells show a preference for relatively simple features such as edges. Further along the process stream, they have a preference for much more complex figures; such as human body parts, apples, flowers or snakes etc.

What is the difference between perception for identification and perception for action?

Agnosia is an inability in processing sensory information even though the sense organs and memory are not defective. To be agnosic means to experience a failure of knowledge or recognition of objects, persons, shapes, sounds, or smells. When the disorder is limited to the visual modality, is it referred to as visual agnosia. This is a deficit in recognizing objects even when the processes for analyzing basic properties such as shape, color, and motion are relatively intact.

Patient DF is an extraordinary case. She couldn't name the right household items, made errors in labeling them. She usually gave crude descriptions of displayed objects. Picture recognition was even more disrupted. When DF was given an explicit matching task she failed miserably. She couldn't orientate the card the right way for fitting the lock. But when she was asked to insert the card into the slot, DF quickly reached forward and inserted the card into the lock. The explicit matching task couldn't succeed because DF could not recognize the orientation of the object because of the severe agnosia. But when DF was asked to insert the card, the shape and orientation information were available for the visuomotor task. So, the 'where' system appears to be essential for more than determining the locations of different objects; it is also critical for guiding interaction with these objects.

So, patients with selective lesions in the ventral pathway may have severe problems in consciously identifying objects, yet they can use the visual information to guide coordinated movement. Thus we see that visual information is used for a variety of purposes.

Optic ataxia holds that patients can recognize objects, yet they cannot use visual information to guide their actions. When someone with optic atraxia reaches for an object, she doesn't move directly toward it; rather, she gropes about like a person trying to find something in the dark. Optic atraxia is associated with lesions in the parietal cortex.

How do you see shapes and perceive objects?

Object perception depends primarily on an analysis of the shape of a visual stimulus, though cues such as color, texture and motion certainly also contribute to normal perception. But, even when the surface features are absent or applied inappropriately (think about an abstract painting), we are still able to recognize the object using perceptual ability to match the analysis of shape and form to an object, regardless of color, texture, or motion cues.

One way to investigate how we encode shapes is to identify areas of the brain that are active when we compare contours that form a recognizable shape versus contours that are just squiggles. There is an idea that perception involves a connection between sensation and memory in the brain. Researchers explored this question using a PET study designed to isolate the specific mental operations used when people viewed familiar shapes, novel shapes, or stimuli formed by scrambling the shapes to generate random drawings. Viewing both novel and familiar stimuli led to increases in regional cerebral blood flow bilaterally in lateral occipital cortex (LOC). Many others have also shown that the LOC is critical for shape and object recognition. People have an insensitivity to the specific visual cues that define an object, this is known as cue invariance. Thus, the LOC can support the perception of an elephant even when the elephant is blue and green, or an apple shape even when the apple is made of onyx and striped.

The functional specification of the LOC can also be tested with 6-month-old babies. To do this researchers use a fNIRS, functional near-infrared spectroscopy, which employs a lightweight system that looks similar to an EEG cap and can be comfortably placed on the infant's head. This system uses infrared light, that can project through the head and skull. The repetition suppression (RS) effect is hypothesized to indicate increased neural efficiency: the neural response to the stimulus is more efficient and perhaps faster when the pattern has been recently activated.

From shapes to objects

Multistable perception is an image where their is an object that you can see in a black-and-white view, such as a vase, but when you point your attention to another part of the image you see a different object. The vase can change profiles in two people facing each other, an then you can go back to the vase, back to the two people, on and on. This is an example of multistable perception. The stimulus information does not change at the points of transition from one percept to the other, but the interpretation of the pictorial cues does.

What is the role of the grandmother cell in ensemble coding?

How do we recognize specific objects? Are there individual cells that respond only to specific integrated percepts, or does perception of an object depend on the firing of a collection or ensemble of cells? In the latter case, this would mean that when you see a peach, a group of neurons that code or different features of the peach might become active, with some subset of them also active when you see a nectarine. A type of neuron that can recognize a complex object is called a gnotic unit, referring to the idea that the cell signals the presence of a known stimulus - an object, a place, or an animal that has been encountered in the past.

Researchers also discovered cells in the IT gyrus and the floor of the superior temporal sulcus (STS) that are selectively activated by faces. They coined the term grandmother cell to convey the notion that people's brains might have a gnostic unit that becomes excited only when their grandmother comes into view. Although it is tempting to conclude that there are cells like this that are gnostic units, it is important to keep in mind the limitations of such experiments:

• Aside from the infinite number of possible stimuli, the recordings are performed on only a small subset of neurons. This cell potentially could be activated by a broader set of stimuli, and many other neurons might respond in a similar manner.

• The results also suggest that these gnostic-like units are not really 'perceptual'. The cell could represent a concept of, for instance, a 'grandmother'.

One alternative to the grandmother-cell hypothesis is that object recognition results from activation across complex feature detectors. Granny, then, is recognized when some of these higher-order neurons are activated. According to this ensemble hypothesis, recognition is not due to one unit but to the collective activation of many units.

What are the top-down effects of object recognition?

Up to this point, we have emphasized a bottom-up perspective on processing within the visual system, showing how a multilayered system can combine features into more complex representations. This model appears to nicely capture the flow of information along the ventral pathway. But there is also an top-down way we are not forgetting. One model of top-down effects emphasizes that input from the frontal cortex can influence processing along the ventral pathway. The frontal lobe generates predictions about what the scene is, using this early scene analysis and knowledge of the current context. These top-down predictions can then be compared with the bottom-up analysis occurring along the ventral pathway of the temporal cortex, making for faster object recognition by limiting the field of possibilities.

Can you read minds?

We have seen various ways in which scientists have show us that you can manipulate the output and input of the visual cortex. These observations have led investigators to realize that it should, at least in principle, be possible to analyze the system in the opposite direction. That is, we should be able to look at someone's brain activity and infer what the person is currently seeing - a form of mind reading. This idea is referred to as decoding: the brain activity provides the coded message, and the challenge is to decipher it and infer what is being represented.

There are two issues:

1. Our ability to decode mental states is limited by our models of how the brain encodes information.

2. Our ability to decode will be limited by the resolution of our measurement systems.

How does the specificity of object recognition in higher visual areas work?

When we meet someone, we always look at that person's face. The face, particularly the eyes, of another person can provide significant cues about what is important in his environment. Also, looking at someone's lip when they are speaking can provide a lot more information about what that person is saying.

Is face processing special?

It seems reasonable to suppose that our brains have a general-purpose system for recognizing all sorts of visual inputs, with faces constituting just one important class of problems to solve. But multiple studies argue that face perception does not use the same processing mechanisms as those used in object recognition, but instead depends on a specialized network of brain regions. Do the processes of face recognition and nonfacial object recognition involve physically distinct mechanisms? Although clinical evidence showed that people could have what appeared to be selective problems in face perception, more compelling evidence of specialized face perception mechanims comes from neurophysiological studies with nonhuman primates. Neurons in various areas of the monkey brain show selectivity for face stimuli.

The similar specificity for faces is observed using fMRI studies in humans, including an area in the right fusiform gyrus parahippocampal place area (PPA). This area is specialized for processing information about spatial properties, for instance the difference between an indoor and outdoor scene, and the extrastriate body area (EBA) and the fusiform body area (FBA) have been identified as more active when body parts are viewed.

What are failures in object recognition?

Patients with visual agnosia have provided a window into the processes that underlie object recognition. By analyzing the subtypes of visual agnosia and their associated deficits, we can draw inferences about the processes that lead to object recognition. Although the term visual agnosia has been applied to a number of distinct disorders associated with different neural deficits, patients with visual agnosia generally have difficulty recognizing objects that are presented visually or require the use of visually based representations.

The current literature broadly distinguishes between three major subtypes of visual agnosia: apperceptive, integrative and associative.

1. Apperceptive visual agnosia: The recognition problem is one of developing a coherent percept: the basic components are there, but they can't be assembled. It's somewhat like going to Legoland, but instead of seeing buildings, cars, and monsters, you can only see piles of Lego bricks. The elementary visual functions - acuity, colorvision, and brightness - are still intact. The object recognition problems become especially evident when a patient is asked to identify objects on the basis of limited stimulus information, for instance when the object is shown as a line drawing or is seen from an unusual perspective.

2. Integrative visual agnosia: this is a subtype of the apperceptive visual agnosia, where people perceive the parts of an object but are unable to integrate them into a coherent whole. At Legoland they may see walls and windows, but not a house. A patient's object recognition problems became apparent when he was asked to identify objects that overlapped each other.

3. Associative visual agnosia: perception occurs without recognition. It is the inability to link a percept with its semantic information, such as its name, properties or functions. A patient can perceive objects with het visual system but cannot understand them or assign meaning to them. At Legoland she may perceive a house, and be able to draw a picture of that house, but still be unable to tell that it is a house or describe what a house is for.

Patients with agnosia are unable to recognize common objects. This deficit is modality specific. Patients with visual agnosia can recognize an object when they touch, smell, taste or hear it, but not when they can only see it. Therefor, visual agnosia can be category specific. Category-specific deficits are deficits of object recognition that are restricted to certain classes of objects. Linked to this there has been a debate in research about how object knowledge is organized in the brain. One theory suggests that it is organized by features and motor properties, and the other suggests specific domains relevant to survival and reproduction.

What is prosopagnosia?

Prosopagnosia is the term used to describe an impairment in face recognition. Given the importance of face recognition, propsopagnosia is one of the most fascinating and disturbing disorder of object recognition. Propsopagnosia is usually observed in patients who have lesions in the ventral pathway, especially occiptial regions associated with face perception and the fusiform face area. Some patients also have congenital propsopagnosia (CP), defined as a lifetime impairment in face recognition that cannot be attributed to a known neurological condition.

Hostilic processing is a form of perceptual analysis that emphasizes the overall shape of an object. This mode of processing is especially important for face perception. We can recognize a face by the overall configuration of its features, and not by the individual features itself.

Analysis-by-parts processing is a form of perceptual analysis that emphasizes the component parts of an object. This mode of processing is important for reading, when we decompose the overall shape into its constituent parts.

How do we achieve goals and meet needs? - Chapter 12

What is the anatomy behind cognitive control?

Cognitive control, sometimes referred to as executive functions, refers to the set of psychological processes that enable us to use our perceptions, knowledge and goals to bias the selection of action and thoughts from a multitude of possibilities. The behaviors thus enables can be described as goal-oriented behavior. Cognitive control requires the integrated function of many different parts of the brain. The remainder of the frontal lobe is called the prefrontal cortex (PFC), we will refer to four regions of the PFC: lateral prefrontal cortex (LPFC), frontal pole (FP), orbitofrontal cortex (OFC) and the medial frontal cortex (MFC). In this chapter we concentrate on two prefrontal control systems. The first system, which includes the LPFC, OFC and FP, supports goal-oriented behavior. The second control system, which includes the MFC, plays an essential role in guiding and monitoring behavior.

When compared to other primate species, the expansion of the prefrontal cortex in the human brain is more pronounced in the white matter than in the gray matter.

What are cognitive control deficits?

From a superficial look it is very difficult to detect a neurological disorder by someone. With more specific and sensitive tests, it becomes clear that frontal lesions can disrupt different aspects of normal cognition and memory, producing an array of problems. Such patients may persist in a response even after being told that it is incorrect - this behavior is called perseveration. Ironically, patients with frontal lobe lesions are aware of their deteriorating social situation, have the intellectual capabilities to generate ideas that may alleviate their problems, and may be able to tell you the pros and cons of each idea. With a PFC lesion, monkeys demonstrate a loss of goal-oriented behavior and the behavior becomes stimulus-driven. They also have a utilization behavior, humans have prototypical responses for guiding behavior. Deficits in cognitive control are also considered a hallmark of many psychiatric conditions, including depression, schizophrenia, OCD and ADHD. A hallmark of drug or alcohol addiction is the sense of a loss of control, the disruption of PFC function may underlie the characteristic problems addicts have in inhibiting destructive behavior.

What is goal-oriented behavior?

Researchers distinguish between two fundamental types of action. Goal-oriented actions are based on the assessment of an expected reward or value and the knowledge that there is a causal link between the action and the reward. In contrast to goal-oriented actions stand habitual actions. A habit is defined as an action that is no longer under control of a reward, but is stimulus driven; we can consider it automatic.

The PFC appears to be an important interface between the current perceptual information and stored knowledge, and thus constitutes a major component of the working memory system. Its importance in working memory was first demonstrated in studies where animals with prefrontal lesions performed a variety of delayed-response tasks. A working memory system requires a mechanism to access stored information and keep that information active. The prefrontal cortex can perform both operations. PFC cells could simply be providing a generic signal that supports representations in other cortical areas. Research shows that in terms of stimulus attributes, cells in the LPFC exhibit task-specific selectivity. We can conceptualize working memory as the interaction between a prefrontal representation of the task goal and other parts of the brain that contain perceptual and long-term knowledge relevant to that goal.

How does decision making works?

The theories about our decision-making processes are either normative or descriptive. Normative decision theories define how people ought to make decisions that yield the optimal choice. Very often, such theories fail to predict what people actually choose. Descriptive decision theories attempt to describe what people actually do, not what they should do. We reach decisions in many different ways. The distinction is that goal-oriented decisions are based on the assessment of expected rewards, whereas habits, are actions taken that are no longer under the control of the reward. A somewhat similar way of classifying decisions is to divide them into action-outcome decisions - where the decisions involves some from of evaluation of the expected outcomes, or stimulus-response decisions - if the outcome is consistent, it becomes a stimulus-response decision.

Decision making is about making choices that will maximize value. It is not, however, enough to think only about the possible reward level. We also have to consider the likelihood of receiving the reward, as well as the costs required to obtain that reward.

Some rewards, such as food, water and sex are primary reinforcers: they have a direct benefit for survival fitness. The secondary reinforcers such as money and status, are rewards that have no intrinsic value themselves, but become rewarding through their association with other forms of reinforcement. Value is represented in the brain of monkeys in the ACC, anterior cingulate cortex, the LPFC and the OFC. The subjective value of an item is made up of multiple variables that include payoff amount, context, probability, effort-cost, temporal discounting, novelty and preference. The classic finding in behavioral economics, temporal discounting, is the observation that the value of a reward is reduced when we have to wait to receive that reward. Overall, the neurophysiological and neuroimaging studies indicate that the OFC plays a key role in the representation of value.

Rewards are fundamental to the behavior of all animals. Much of the work on reward has focused on the neurotransmitter dopamine (DA). Dopaminergic cells are scattered throughout the midbrain, sending axonal projections to many cortical and subcortical areas. Schultz proposed a new hypothesis to account for the role of dopamine in reward-based learning. Rather than thinking of the spike in DA neuron activity as representing the reward, he suggested that it should be viewed as a reward prediction error (RPE), a signal represents the difference between the obtained reward and the expected reward. The RPE is used as a learning signal to update value information as expectancies and the valence of rewards change. The activity of some DA neurons provides a neuronal code of prediction errors.

How does goal planning work; how do you stay on a task?

Once humans choose a goal, we have to figure out how to accomplish it. Three components are essential for successfully developing and executing an action plan:

1. The goal must be identified and subgoals developed

2. In choosing among goals and subgoals, consequences must be anticipated

3. Requirements for achieving the subgoals must be determined

When an action plan is viewed as a hierarchical representation, it is easy to see that failure to achieve a goal can happen in many ways. The different activation patterns show that different subregions of the PFC are required for things like response selection or rule specification. A key idea of hierarchy, however, is that processing deficits will be asymmetrical. Individuals who fail at operations required for performance at the lower levels of a hierarchy, will also fail when given more challenging tasks. Making wise decisions with complex matters, such as long-term financial goals, requires keeping an eye on the overall picture. Therefor we must evaluate the different subgoals.

Goal-oriented behavior requires selecting task-relevant information and filtering out task-irrelevant information. Selection refers to the ability to focus attention on perceptual features or information in memory. The PFC has been conceptualized as the dynamic filtering mechanism through which the task-relevant information is activated and maintained in working memory. Cognitive control is also essential when we need to maintain multiple goals at the same time. This is especially needed when those goals are unrelated. With practice, the brain develops connectivity patterns that enable people to efficiently shift between different goals. The prefrontal cortex helps make action selection more efficient. This benefit of using experiences to guide action selection may also come at a cost in terms of considering novel ways to act, given a specific situation.

What are the mechanisms of goal-based selection?

Dynamic filtering of the PFC can influence the contents of information processing in at least to distinct ways. One is to accentuate the attended information. When multiple sources of information may come from the same location, we might selectively enhance the task-relevant information or inhibit the irrelevant information. Evidence for a loss of inhibitory control with frontal lobe dysfunction comes from electrophysiological studies. All people will have experienced similar situations, whereas you put your keys down somewhere, but you forgot where you put them. Goal-oriented behavior involves the amplification of task-relevant information and the inhibition of task-irrelevant information.

Patients who have lesions in the prefrontal region have difficulty with and loose their inhibitory control, for instance, they are unable to inhibit task-irrelevant information. That's why they are not good at keeping their eyes on one goal, and take in a lot of noise. The inhibition of action on the other hand constitutes of another form of cognitive control. The right inferior frontal gyrus and the subthalamic nucleus are important for this form of control.

How can you ensure that goal-oriented behaviors succeed?

Researchers proposed a psychological model of cognitive control, outlining the conditions under which the selection of an action might require the operation of a high-level control system, or what they referred to as a supervisory attentional system (SAS). These include the following situations:

• Planning or decision making is required

• Responses are novel or not well learned

• The required response competes with a strong, habitual response

• Error correction or troubleshooting is required

• The situation is difficult or dangerous

One might expect the task of a monitoring system to be like that of a supervisor, keeping an eye on the overall flow of activity, ready to step in whenever a problem arises. The last 30 years have witnessed burgeoning interest in the medial frontal cortex (MFC) and in particular the anterior cingulate cortex (ACC) as a critical component of a monitoring system. Damage to the ACC was associated with akinetic mutism, a disorder characterized by minimal movement including the absense of speech. The medial frontal cortex becomes engaged whenever a task becomes more difficult - the type of situations where monitoring demands are likely to be high.

Attentional hierarchy hypothesis

An early hypothesis centered on the idea that the medial frontal cortex should be conceptualized as part of an attentional hierarchy. The MFC occupies an upper rung on the hierarchy, playing a critical role in coordinating activity across attention systems.

Error detection hypothesis

When people make an incorrect response, a large evoked response sweeps over the prefrontal cortex just after the movement is initiated. This signal, referred to as the error-related negativity (ERN) when time-locked to the response, and the feedback-related negativity (FRN) when time-locked to feedback, has been localized to the anterior cingulate. We make errors when we are not paying much attention to the task at hand. This response is all generated by the medial frontal cortex.

Response conflict hypothesis

A key function of the medial frontal cortex is to evaluate response conflict. This hypothesis is intended to provide an umbrella account of the monitoring role of this region, encompassing earlier models that focused on attentional hierarchies or error detection. The medial frontal cortex is also engaged when the response conflict is high. Through its interactions with lateral regions of the prefrontal cortex, a monitoring system can regulate the level of cognitive control.