Foehring - Cortex

Question 1

Describe the prenatal devo of the cerebral cortex.

Answer 1

• Develops as outpocketings of Prosencephalon (most anterior/rostral part of neural tube), but is specifically a Telencephalic structure
  1. Two cerebral hemispheres form laterally on either side of the Telencephalon
• ~100d gestation: cerebral hemispheres grown over most of the rest of the brain -> at this age (until about 6 months), cortical surface is smooth or lissencephalic
• 9 mos (birth): surface of cortex covered in pattern of ridges and valles (gyri and sulci) -> gyrencephalic
  1. Reflects solution to packing problem bc larger head would pose problems during birth
• Cortex is of similar thickness over much of its extent

Question 2

What is the significance of brain size?

Answer 2

• Human brain about 3-4 lbs
• While brain size to body weight differences between species correlate overall with our perceptions of animal intelligence, clearly something else must be going on as well
• There has never been any credible correlation bt brain size and intelligence within humans or any animal species
• In other words, we don’t really know…

Question 3

What are the 4 cortical lobes?

Answer 3

• FRONTAL: from frontal pole to central sulcus
• PARIETAL: from central sulcus to imaginary line connecting preoccipital notch to parietooccipital sulcus
• OCCIPITAL: aforementioned line to occipital pole
• TEMPORAL

Question 4

What are the 3 histological kinds of cortex?

Answer 4

• Defined on the basis of histo:
  1. ALLOCORTEX: incl hippocampal formation, olfactory complex (3 layers)
  2. ISOCORTEX: 6 layers, at least some pt in devo
  3. MESOCORTEX: less regular, and may have 3-5 layers
• NOTE: in mature brain, some cortical areas emphasize particular layers, and o/layers may be DEC or absent

Question 5

What does this figure illustrate?

Answer 5

• Nissl (cell body) stain of the 6 layers of ISOCORTEX (aka, neocortex)
• Layers are named I to VI, going from pia surface to deep white matter
  1. LAYER I is cell poor, and different layers differ in size and density of cells
• NOTE: this example is from 1^o somatosensory cortex of a rat

Question 6

Describe the cellular composition of the 6 layers of isocortex.

Answer 6

• Layer I = molecular layer, and is poor in cells (in mature brain, only GABAergic interneurons)
• Layers II and III are continuous and hard to tell apart from e/o -> collectively, the superficial pyramidal cell layer (most common cell type)
• Layer IV has many small cells (looks like grains of sand) = granular layer
  1. Since layer IV is granular layer, I-III are known as supragranular layers (above granular), and layers V-VI subgranular layers (or infragranular)
• Layer V = deep pyramidal cell layer, and largest pyramidal cells are found here
• Layer VI contains multiple cell types, and is known as the polymorphic layer

Question 7

What are the 3 evolutionary types of cortex? From what are they formed?

Answer 7

• Defined in terms of evolutionary/embryo origin:
  1. PALEOCORTEX: incl olfactory cortex -> formed from lateral pallium
  2. ARCHICORTEX: incl hippocampal formation -> formed from medial pallium
  3. NEOCORTEX: synonymous w/isocortex -> formed from dorsal pallium

Question 8

What are the 3 major classes of neurons in the neocortex (soma shape scheme)?

Answer 8

• Based on soma shape + configuration of dendrites
• PYRAMIDAL: pear-shaped soma and single dominant apical dendrite (+ basal rosette of dendrites) -> send their axon deep to white matter (projection neurons)
  1. Project locally, to o/cortical, & subcortical areas
  2. Excitatory: glutamate or aspartate as 1^o NT
• NON-PYRAMIDAL: mostly GABAergic interneurons (local circuit neurons that only project locally in given area of cortex) -> typically multipolar (several similar sized dendrites radiating from soma) or bipolar (2 similar sized dendrites on opposites sides of soma)
• SPINY STELLATE CELL: another type of non-pyramidal neuron in layer IV of 1^o sensory cortex uses glutamate as its transmitter -> may be a subtype of pyramidal cell, but only project locally (local circuit interneuron)
• NOTE: as many as 45+ different cell types in neocortex, but only need to focus on 2 for this course

Question 9

What is the second classification system for neocortex neurons?

Answer 9

• Divides cells into spiny and aspiny (sparsely spiny)
• Dendritic spines are sites of excitatory synapses on dendrites that isolate individual synapses electrically and biochemically
• SPINY: pyramidal cell dendrites are covered with dendritic spines (spiny), as are dendrites of spiny stellate cells in layer IV (spiny)
• ASPINY: GABAergic interneurons are aspiny or very sparsely spiny

Question 10

Describe the cortical cell types based on soma shape, apical dendrite, spines, axonal projection, and transmitter.

Answer 10

• PYRAMIDAL: pear-pyramid shape, apical dendrite, spines, axonal projection to white matter, glutamate, excitatory
• SPINY STELLATE: pear-pyramid shape, NO apical dendrite, spines, local axonal projection, glutamate, excitatory (distinguishing features from pyramidal underlined)
• NON-PYRAMIDAL: variable shape, NO apical dendrite (multi- or bipolar), no or sparse spines, local axonal projection, GABA, INH
• Non-pyramidal cell types: chandelier, basket, neuroglia form, bipolar

Question 11

What is this? Describe its key characteristics.

Answer 11

• Typical neocortical PYRAMIDAL CELL: single, dominant apical dendrite, basal rosette of dendrites, and axon that leaves soma and projects deep to white matter, giving off collaterals on the way
• Variable density of spines along dendrites (highest density intermediate distance from soma)
• ATTACHED IMAGE: examples of human pyramidal cells (and dendrite with spines at higher power) filled w/dye (biocytin)

Question 12

What cells do you see here? Describe their key characteristics.

Answer 12

• NON-PYRAMIDAL cells: diverse, Golgi-filled neurons (>40 types in cortex)
• A, B = basket cells: in layers II, III, and V, and vary in size -> multipolar (many similar-sized dendrites), and axons have basket-shaped terminations surrounding somas of pyramidal cells
• D = chandelier cells: also named for their axonal terminations, whose cassettes contact initial segments of pyramidal neurons and collectively make the cell look like a chandelier
• F-G = various bipolar and bi-tufted cells -> have long dendrites and axons organized vertically as opposed to the more horizontal organization of basket and chandelier cells, and tend to innervate more distal dendrites of pyramidal neurons (compared to chandelier or basket cells)

Question 13

Where do the main inputs to the cortex come from/go?

Answer 13

• Dominant input to most cortical neurons from other cortical neurons -> excitatory pyramidal neurons are highly interconnected
• Main extrsinsic input to cortex = THALAMUS
  1. Specific: from thalamic nuclei that project to single cortical area, and typically concern a single modality -> ex. incl VL to motor cortex, VPL to somatosensory cortex, lateral geniculate to visual cortex, and medial geniculate to auditory
  a. Input from specific thalamic nuclei centered on layer IV (in 1^o sensory areas, synapse is on spines of spiny stellate cells)
  2. Non-specific: thalamic nuclei that integrate info from many sources that is important for general brain states and arousal -> ex. incl intralaminar and midline thalamic nuclei
  a. Projection is primarily to layer I (local interneurons and apical tuft of pyramidal cell apical dendrites)
• Another source of extrinsic input = widely projecting brainstem nuclei, which serve modulatory functions
  1. Incl: locus ceruleus (NE), raphe nuclei (5-HT), ventral tegmental area (DA), basal forebrain nuclei (Ach)
• NOTE: all of extrinsic inputs enter the cortex from the deep white matter and travel vertically

Question 14

Describe the cortical outputs.

Answer 14

• Pyramidal cells = principal cortical projection neurons
• LAYERS II-III: main sources of cortico-cortical connections, incl. association fibers that project ipsilaterally (local and long distance) and callosal projections (cross to equivalent areas of contralateral cortex via CC)
  1. Send some axons to subcortical telencephalon (esp. basal ganglia)
• LAYER V: project to various subcortical regions, incl spinal cord (corticospinal tract), pons (corticopontine), tectum (corticotectal), basal ganglia (corticostriatal)
• LAYER VI: primarily project to thalamus (same areas from whence afferent signals came) -> feedback loop is basis for thalamocortical rhythms observed in EEG
  1. Rhythms important in regulation of sleep-wake cycle, consciousness, and several pathological conditions (e.g., absence epilepsy)

Question 15

What makes up the cortical white matter? Describe some of the terminal projections.

Answer 15

• Made up of axons of cortical projection (pyramidal) neurons, which have several different targets.
  1. LAYERS II-III: primarily project to contralateral cortex (COMMISSURAL) or o/cortical areas on same side of brain (ASSOCIATIONAL); some also project to striatum (subcortical; in telencephalon)
  2. LAYER V: more hetero in their projections; those in more superficial part (5A) tend to be thinner, w/less robust apical dendrite, project to contralateral cortex and subcortical telencephalic targets like striatum (like layers II, III), meanwhile those in deeper parts (5B) more robust, and tend to project beyond telencephalon (e.g., spinal cord, tectum, pons, brain stem)
• IMAGE: subcortical projections

Question 16

What percentage of cells in most areas of the cortex are pyramidal?

Answer 16

80% (rest non-pyramidal)

Question 17

Briefly, how are pyramidal and non-pyramidal cells different?

Answer 17

• Pyramidal: excitatory (glutamate, aspartate), projection
• Non-pyramidal: GABAergic, INH, local circuit

Question 18

Most inputs to a given pyramidal cell are from…? What are the implications of this?

Answer 18

• Other pyramidal cells (excitatory) -> this system of mutual excitation would lead to unstable network if not for the less numerous, but very important INH interneurons
• Many neural diseases may reflect relatively subtle changes in the balance of excitation to INH in local cortical circuits (EX: epilepsy, which is characterized by abnormal excitability and synchrony between cells)
  1. More recently, alteration of this balance has been implicated in Autism, Alzheimer s disease, and various forms of mental retardation

Question 19

Briefly describe the interactions b/t cells in the cortex.

Answer 19

• Numerous local circuits (synaptically connected neurons) that work together on a particular task
• Influenced by extrinsic inputs from thalamus and brainstem modulatory systems + more distal cortical circuits -> white matter tracts are anatomical substrate for these interactions bt local circuits
• ATTACHED IMAGE: 2 human layer III pyramidal cells (leftmost 2) and 1 multipolar basket cell (rightmost) in close proximity in human temporal cortex
  1. Note the vertical arrangement of the pyramidal cells (pia is at top of photo) and more horizontal arrangement of the basket cell

Question 20

What is going on in this image? Describe the key features of these cells.

Answer 20

• Typical layer V pyramidal cell: apical and basal rosette of dendrites -> different orientation of these 2 types of dendrite allows sampling of different inputs
• Chandelier cell: terminal cassettes selectively contact basal dendrite and esp. axon initial segment of pyramidal cell -> allows GABAergic (INH) chandelier cell to powerfully INH output of layer V pyramidal cell (and thus the output of this local circuit) bc initial segment/first node of Ranvier is site of AP initiation
• Basket cell: axon terminals terminate as baskets that surround soma of pyramidal cell, allowing INH control at final summing point for synaptiv input from whole dendritic tree at soma -> particularly powerful INH influence on pyramidal cell and cortical output
• Bipolar (double bouquet) cell: also GABAergic and INH, but its primary axonal termination is on more distal braches of apical and basal dendrites, making these cells more influential on local signal processing in dendrites (where most excitatory input to pyramidal cells occurs on spines)
• NOTE: non-pyramidal cells show axonal arborization

Question 21

What is a cortical column?

Answer 21

• Cortex is composed of repeated modules called cortical columns (not exactly a column, but grouping and repeatability)
• All cells in a mini column (~30 microns diameter: 100-200 cells) encode similar features -> associations bt cells in mini columns may be dynamic and depend upon particular tasks
• Idea of a microcolumn or hyper-column (~0.5-1 mm diameter) would encompass all of the cells (several microcolumns) allied together for a particular function
• Current idea is that a macro column (~10,000 cells) is the basic functional unit

Question 22

Describe the anatomical nature of a cortical column.

Answer 22

• Specific (excitatory) thalamic input is to a small group of layer IV spiny stellate cells -> these excitatory layer IV cells in turn project to layer II, III pyramidal cells
• Layer II, III pyramidal cells project to layer V, VI pyramidal cells (excitatory), which are the excitatory output of the column
• Axons of layer V pyramidal cells project to o/columns locally, other areas of cortex, and subcortically)
• The anatomy of pyramidal cell axons, together with lateral inhibition by interneurons, set the dimensions of the column

Question 23

What is the radial unit hypothesis?

Answer 23

• All pyramidal cell members of developmental mini-column are ancestors of a single precursor cell in the ventricular zone of embryonic cerebral vesicles
• Precursors give rise to pyramidal cells and radial glia; radial glia migrate to layer I, and nuerons migrate along radial glia to their mature laminar location, where they fully differentiate
• Interneurons are NOT generated in the ventricular zone of cerebral vesicles, but rather derive from cells from medial ganglionic eminence (and caudal gang eminence), and migrate to neocortex to give rise to majority of cortical GABAergic interneurons
• According to this theory, a single functional column that responds to same receptive field in the periphery might consist of several ontogenetic radial columns originating from the adjacent proliferative units in the ventricular zone
• NOTE: columns can be defined based on anatomy or function, but anatomical and physiological columns do not always match

Question 24

Can functions be localized within the cortex?

Answer 24

Yes

Question 25

What are 3 ways cortical areas can be defined?

Answer 25

- By histology: Brodmann's areas - By connections: e.g., with thalamic nuclei - By function

Question 26

What are homotypic and heterotypic cortex? Provide some examples.

Answer 26

- HOMOTYPIC: areas of cortex where 6 layers are easy to see -\> _association areas_ (not 1^o motor or sensory; ex = prefrontal cortex) - HETEROTYPIC: individual layers reduced, enhanced so the 6 layers are less obvious 1. _1^o motor cortex_ (precentral gyrus): IV (granular layer) almost absent, so called the AGRANULAR CORTEX -\> layer V very large (lg pyramidal cells project to spinal cord, subcortical motor centers) 2. _1^o sensory cortex_ (visual, auditory, somato-sensory; ex: primary visual cortex): layer IV (the thalamic input zone) esp. large and layer V is relatively small -\> called GRANULAR CORTEX (or koniocortex = dust)

Question 27

What are Brodmann's areas?

Answer 27

- Based on variation in histology across the cortex: 52 distinct areas based on density and types of cells in each area - Many of these areas have since been determined to correspond to functional areas (e.g. primary motor or sensory)

Question 28

What is the difference bt unimodal and heteromodal association areas?

Answer 28

- UNIMODAL: concerned with a single modality, i.e., vision, auditory, motor - HETEROMODAL: concerned with more than a single modality, e.g., combo of vision and hearing

Question 29

Where are the primary motor, primary somatosensory, primary visual, and primary auditory cortices located?

Answer 29

- Primary motor = precentral gyrus (BA #**4**) - Primary somatosensory = postcentral gyrus, sup parietal lobule (BA #**3, 1, 2**; ant to post, post to central sulcus) - Primary visual cortex = banks of calcarine fissure (BA #**17**) - Primary auditory cortex = Heschl's transverse gyrus (BA #**41,42**)

Question 30

Describe the pathway for cortical integration of information for each sensory modality.

Answer 30

- For each sensory modality, there is a _1^o cortical area_ that receives input from the corresponding thalamic nucleus (e.g., lateral geniculate for vision) 1. Initial processing occurs here, so damage to 1^o sensory areas often leads to loss of perception of a given modality (e.g., loss of part of BA #17 = blindness in corresponding retinal field) - Further processing in _unimodal association areas_, where different aspects and sub-modalities of a stimulus are combined - Different modalities are combined at _heteromodal association areas_ - EX: most sensory experiences involve sight, sound, smells, and tactile sensation (+ emo and memories) -\> peripheral and subcortical mechs break apart all of these separate modalities, and each is processed in parallel in its own specific system up to the respective primary sensory cortices 1. The scene is somehow reassembled in the uni- and heteromodal association areas - NOTE: similar situation for motor processing (there are motor-assoc uni- & heteromodal association areas)

Question 31

Where are the cortical association areas?

Answer 31

- In each of the cortical lobes, incl frontal, parietal, occipital, and temporal - One can also view the hippocampal formation and amygdala (together with parts of the frontal lobe) as an additional limbic association area

Question 32

Most of the cortex is composed of what type of cortex/area?

Answer 32

- ASSOCIATION CORTEX - Color coding in this image indicates primary motor or sensory cortex (dark gray) vs. association areas (light gray) - Association areas _can be unimodal or heteromodal_: only a small % of cortex is primary motor or sensory

Question 33

Describe the inputs and outputs for each of the thalamic nuclei (table).

Answer 33

- Each area of the cortex (motor, sensory, association) receives input from a specific thalamic nucleus

Question 34

What Brodmann's areas are associated with the primary motor cortex, primary somatosensory cortex, and premotor cortex?

Answer 34

- Primary motor cortex = precentral gyrus (BA #4) 1. Premotor cortex = BA #6 (unimodal assoc area) - Primary somatosensory cortex = postcentral gyrus (BA #3, 1, 2, ant to post, post to central sulcus) 1. BA #5 and 7 (superior parietal lobule) unimodal association areas for somatesthesis - NOTE: correspondence bt BA (upper Figure), defined by histology, and functional areas (lower Figure) close, but not perfect

Question 35

Describe the cortical homunculus.

Answer 35

- Relative size of the cortical area concerned with a given part of the body corresponds to how fine a degree of motor control there is (area 4) or ability to discriminate bt pts on the body surface (3, 1, 2) - Disproportionate amount of cortical area devoted to the face and fingers, with much less area devoted to the back or legs

Question 36

How can the cerebral blood supply + the homunculus be used to localize a stroke?

Answer 36

- Can use knowledge of motor and somatosensory homunculi + territory of cerebral aa (attached) to localize a stroke to a particular artery - EX: lower limb on mid-sagittal surface = supplied by anterior cerebral artery 1. Upper limb on lateral surface of pre- or post-central gyri = supplied by middle cerebral artery

Question 37

Use the somatosensory cortex as an example of parallel and serial aspects of cortical processing.

Answer 37

- SERIAL PROCESSING: thalamic inputs carry somato-sensory info to 1^o somatosensory cortex in BA #3, 1, 2 1. Area 3 can be further subdivided into 3a (ant) and 3b (post), which e/have separate homunculi; 3a and 2 receive inputs from afferents in _mm and deep tissues_, while 3b and 1 receive cutaneous inputs (further subdivision by types of _cutaneous_ input, pain, flutter, vibration, etc.) - PARALLEL PROCESSING: areas 3, 1, 2 project to _areas 5, 7_ (unimodal somatosensory cortex), where info about different submodalities is combined -\> dynamic attributes (e.g., direction, speed of mvmt of objects on skin, texture) also analyzed here 1. This unimodal assoc area then projects to heteromodal areas in parietal, frontal, temporal cortices to further reconstruct the world - NOTE: how this occurs is still unclear -\> popular idea is that widely divergent areas of cortex may be bound by their synchronous oscillatory activity, esp. _gamma rhythm of the EEG_ (30-50 Hz)

Question 38

What are evoked potentials?

Answer 38

- Useful clinical tool for assessing somatosensory pathways - EX: in the attached image, electrical stimulation of surface of the hand was used to _map receptive fields_ (area of cortex that responds when a given area of the periphery is stimulated) onto 1^o somatosensory cortex

Question 39

What does this image illustrate?

Answer 39

- Shows how evoked potentials can can be used to demonstrate _use-dependent plasticity_ of receptive fields in the adult somatosensory cortex - In this pt born with syndactyly, lack of separation of the fingers resulted in little separation of the cortical map -\> after sx to separate the fingers (right), cortical map also changed, becoming more spread out 1. Example of _plastic change in the organization of adult cortex in response to an altered use pattern_; thought that similar, less drastic changes occur with learning and memory

Question 40

How might cortical reorganization explain the phantom limb phenomenon?

Answer 40

- One possibility is that due to loss of input from the limb, _adjacent cells in the cortical map take over_ the area that was originally concerned with the arm, for example - In the example shown here, the face representation took over the arm representation, resulting in referred sensations of the arm upon touching the face

Question 41

What is association cortex? Function by location?

Answer 41

- Most of the human neocortex: 1. Parietal: attention to physical world 2. Temporal: naming things (what is it?) 3. Prefrontal: overall executive behavior 4. Occipital: primarily visual system - NOTE: this is an oversimplification -\> considerable overlap in func, and func MRI studies suggest connections bt cortical areas may be more important for particular funcs, rather than strict localization of function to particular gray mater

Question 42

How can damage to the parietal association cortex lead to sensory neglect?

Answer 42

- Important for attention to the physical world - If parietal cortex (inf parietal lobule = angular and supramarginal gyri) damaged in dominant hemisphere (L side for R-handed ppl and also most L-handers), pts suffer from language disorders (aphasias) - Similar **injury to non-dominant hemisphere** causes SENSORY NEGLECT: pts ignore sensory experience on 1/2 of the body contralateral to the injury 1. Ex: might ask what is leg doing in bed with me when it is their own leg; also ignore objects in contralateral visual field - IMAGE: pt asked to draw objects, and only drew R half -\> **right parietal association cortex necessary for attention to the internal and external environment**

Question 43

What is the primary role of the temporal association cortex?

Answer 43

- Recognition and identification - Several areas in temporal lobe important for naming and recognizing objects - EX: person is shown an image of a face (attached), they respond w/activity in fusiform (occipitotemporal) gyrus of the temporal lobe -\> _lesions in this region cause deficits in recognition of objects and people_

Question 44

Describe the role and divisions of the prefrontal cortex. What happens if it is damaged?

Answer 44

- _Executive function_: largest component of the cortex, comprising nearly 1/3 of cortical volume - Widest variety of functions, and latest part of the brain to devo post-natally -\> integrates info to allow us to _plan and execute behaviors_, and also allows us to choose b/t actions - Important for determining personality, sense of self 1. _Orbitofrontal_: part of limbic system, and assoc w/aggression and emotions 2. _Dorsolateral_: responsible for working memory (i.e., keeping #'s in mind to make phone call), and thought crucial for planning behaviors - **RIO** = restraint (INH inappropriate actions), initiative (motivation to pursue productive, + actions), and order (plan) - DAMAGE to PFC leads to _personality changes_, incl notable loss of INH or restraint; may also lead to _lack of initiative_ and deficits in planning - At present, it is thought that the PFC **puts everything from the cortex together** (motor, sensory, memory) to guide and plan behavior

Question 45

How can thalamic connections be used to define particular areas of cortex?

Answer 45

- Parietal and occipital association cortex receives their specific input from the pulvinar (thalamic nucleus) - Lateral posterior (LP) nucleus (auditory) of thalamus projects to temporal association cortex - Medial dorsal nucleus (DM) projects (limbic) to prefrontal association cortex