Chapter 11 - The Cerebral Cortex

General Organization

The cerebral cortex is the outer covering of gray matter over the hemispheres. This is typically 2- 3 mm thick, covering the gyri and sulci. Certain cortical regions have somewhat simpler functions, termed the primary cortices. These include areas directly receiving sensory input (vision, hearing, somatic sensation) or directly involved in production of limb or eye movements. The association cortices subserve more complex functions. Regions of association cortex are adjacent to the primary cortices and include much of the rostral part of the frontal lobes also regions encompassing areas of the posterior parietal lobe, the temporal lobe and the anterior part of the occipital lobes. These areas are important in more complex cortical functions including memory, language, abstraction, creativity, judgment, emotion and attention. They are also involved in the synthesis of movements.

The Neocortex

Most of the cerebral cortex is neocortex. However, there are phylogenetically older areas of cortex termed the allocortex. These more primitive areas are located in the medial temporal lobes and are involved with olfaction and survival functions such as visceral and emotional reactions. In turn, the allocortex has two components: the paleocortex and archicortex. The paleocortex includes the piriform lobe, specialized for olfaction, and the entorhinal cortex. The archicortex consists of the hippocampus, which is a three-layered cortex dealing with encoding declarative memory and spatial functions.

The neocortex represents the great majority of the cerebral cortex. It has six layers and contains between 10 and 14 billion neurons. The six layers of this part of the cortex are numbered with Roman numerals from superficial to deep. Layer I is the molecular layer, which contains very few neurons; layer II the external granular layer; layer III the external pyramidal layer; layer IV the internal granular layer; layer V the internal pyramidal layer; and layer VI the multiform, or fusiform layer. Each cortical layer contains different neuronal shapes, sizes and density as well as different organizations of nerve fibers.

Functionally, the layers of the cerebral cortex can be divided into three parts. The supragranular layers consist of layers I to III. The supragranular layers are the primary origin and termination of intracortical connections, which are either associational (i.e., with other areas of the same hemisphere), or commissural (i.e., connections to the opposite hemisphere, primarily through the corpus callosum). The supragranular portion of the cortex is highly developed in humans and permits communication between one portion of the cortex and other regions.

The internal granular layer, layer IV, receives thalamocortical connections, especially from the specific thalamic nuclei. This is most prominent in the primary sensory cortices.

The infragranular layers, layers V and VI, primarily connect the cerebral cortex with subcortical regions. These layers are most developed in motor cortical areas. The motor areas have extremely small or non-existent granular layers and are often called "agranular cortex". Layer V gives rise to all of the principal cortical efferent projections to basal ganglia, brain stem and spinal cord. Layer VI, the multiform or fusiform layer, projects primarily to the thalamus.

There are several identifiable cell types in the cerebral cortex. The pyramidal cells are the main cell type within layers III and V. These cells can be extremely large in layer V of the motor cortex, giving rise to most corticobulbar and corticospinal fibers. The largest of these neurons are called "Betz cells". These cells are pyramidal in shape, with an apical dendrite that extends all the way to layer I of the cortex. There are also several basal dendrites projecting laterally from the base of these neurons. Dendrites of cortical neurons have many spines that are sites of synapse. The thin axon that arises from the base of the pyramidal cell has collaterals and a long process that leaves the cortex. This is the process that connects with other brain regions by extending through the white matter deep to the cortex.

Stellate or granule cells are most prominent in layer IV. Their axons remain in the cortex. There are several less common cell types including horizontal cells, fusiform cells and the cells of Martinotti. It's not important that you know about these minor cell types, however is important to note that pyramidal and granule cells are not the only cell types in the cortex.

Cerebral cortical cytoarchitecture was described by Brodmann in 1908 and 1909 (Figure 34). While this study was done purely on the basis of cellular composition of the cortex (and the cortical layers), the map that he created corresponds very well with functional mapping of the cortex. We will employ this numbering scheme in the following discussion.

Sensory Cortices

Somatosensory Cortex

Primary somatosensory cortex (SI; areas 3,1,2) is located in the post central gyrus. This receives somatotopic input from the VPL and VPM of the thalamus. Histologically, this area would consist of granular cortex. The sensory homunculus includes cortical representation of the body based on the degree of sensory innervation. There are actually four submaps, one each in area 3a, 3b, 1 and 2. Very sensitive areas such as the lips and the fingertips have a huge representation. Neurons within each cortical site (particularly layer IV) are arranged in columns representing specific body regions. If a region is amputated (such as a finger) there is reorganization with neurons responding to stimulation of adjacent body parts. This can also happen as the result of increased use of a body part. Damage to the sensory cortex results in decreased sensory thresholds, an inability to discriminate the properties of tactile stimuli or to identify objects by touch.

The secondary somatosensory cortex (SII; area 40) is in the lower parietal lobe. This receives connections from the primary sensory cortex and also less specific thalamic nuclei. This responds to sensory stimuli bilaterally, although with much less precision than the primary cortex. Nonetheless, lesions to this area may impair some elements of sensory discrimination.

The somatosensory association cortex (areas 5 and 7) is directly posterior to the sensory cortex in the superior parietal lobes. This receives synthesized connections from the primary and secondary sensory cortices. These neurons respond to several types of inputs and are involved in complex associations. Damage can affect the ability to recognize objects even though the objects can be felt (tactile agnosia). Cortical damage, particularly in the area of cortex where the posterior parietal lobe meets the anterior occipital and the posterior, superior temporal lobe, can cause neglect of the contralateral side of the world. This typically happens with nondominant hemisphere lesions since this hemisphere appears necessary to distribute attention to both sides of the body. The dominant hemisphere appears to only “pay attention” to the associated (usually right) side of the world. Therefore, neglect usually involves the left side and can be so severe that the individual even denies that their left side belongs to them.

Visual cortex

The primary visual cortex (VI; area 17) also called the striate cortex, surrounds the calcarine sulcus. This area has a large granular layer with dense columns of neurons, called ocular dominance columns. Adjacent columns come from the same homonomous portions of the left and right eyes (i.e., portions that detect images from corresponding portions of the visual world). The macula, the most sensitive portion of the center of the retina, is represented at the posterior tip of the occipital lobe. The upper part of the world projects to the lower part of the striate cortex. Lesions of the occipital lobe would cause cortical blindness and difficulty tracking objects.

The primary visual cortex projects to cortical areas surrounding it, called the visual association areas (V2, V3; areas 18 and 19), where signals are interpreted and form is recognized. In addition to connections from the visual cortex, there are also inputs to visual association areas directly from the lateral geniculate. Selective lesions of these association areas will produce an inability to recognize objects even when they may be seen. There are additional aspects of visual function that are represented in other regions of adjacent cortex. V4 is necessary for color recognition and V5 (which resides in the posterior part of the middle temporal gyrus - also called MT) is responsible for recognizing movement.

Auditory Cortex

The primary auditory cortices (AI; area 41) are on the transverse temporal gyri, extending into the lateral fissures. These gyri are situated on the upper part of the superior temporal gyri. There are tonotopic maps for different tones. Unilateral cortical lesions do not effect hearing because of completely bilateral sound representation.

There are auditory association areas surrounding the primary auditory cortex (AII; area 42). These areas are involved in the interpretation of sound. In the dominant hemisphere the cortex surrounding the auditory cortex (area 22) is required for understanding language. This is called Wernicke's area. Damage to this area can produce inability to understand language, including written language. In the nondominant hemisphere this may be involved in understanding the tone of voice.

Taste is detected in the inferior part of the post central gyrus, bilaterally, extending into the lateral fissure, including the insula. Vestibular afferent sensations are processed in the superior temporal or inferior parietal gyri.

Motor Cortex

Primary and Secondary Motor Cortices

The primary motor cortex (MI; area 4) is in the precentral gyrus. This is the origin of most of the corticospinal tract and a large number of cortical bulbar fibers, particularly those controlling motor cranial nerves. This also has projections to the thalamus and basal ganglion. The VL of the thalamus makes significant input to this nucleus and the precentral gyrus also receives significant input from sensory cortical areas as well as from the premotor portions of the cerebral cortex. There is a very well-defined somatotopic organization of the motor cortex and this is the region of cortex from which movements can be generated by the lowest intensity of electrical stimulation. Specific movements tend to be represented (such as elbow flexion) rather than specific muscles. Lesions produce spastic contralateral weakness, which is most prominent in the distal extremities.

The premotor cortex (area 6) is immediately anterior to the motor cortex and has many of the same connections as the motor cortex. However, most of its output is to the motor cortex, with a smaller output to the brain stem and the spinal cord. This region receives input from the sensory association cortex as well as feedback from the basal ganglia via the VA and VL of the thalamus. Electrical stimulation of this area tends to produce more complex movements and at a higher stimulus intensity than the simple movements from MI. Lesions produce less severe weakness but greater spasticity than patients with isolated precentral gyrus lesions.

The supplementary motor area (MII, superiomedial part of area 6) is a part of the premotor cortex that extends onto the medial side of hemisphere. This projects to the primary motor cortex, basal ganglia, thalamus and brain stem and also has connections with the contralateral supplementary motor area. This area becomes active before movement and is felt to be involved in initiation of motion. Lesions of this area can cause inability to initiate motions, called abulia.

Eye Fields

The frontal eye fields (inferior area 8) are located just inferior and rostral to the premotor cortex. Activity in this region results in conjugate horizontal eye movement of the eyes away from the stimulus. This receives input from the medial dorsal nucleus of the thalamus as well as other areas of the cerebral cortex. It makes output to the superior colliculus and the PPRF. Lesions of this area initially block voluntary movement away from the side of lesions, although patients will slowly compensate for this deficit.

The occipital eye fields are located in the visual association cortex. This projects to the frontal eye fields as well as to the pontine nuclei to generate smooth pursuit eye movements. Lesions will produce difficulty in fixing on a target and also will produce abnormalities in optokinetic responses.

Language Cortex

There are areas of particular importance of the cerebral cortex. The receptive language area, Wernicke's (area 22) area is in the upper temporal lobe, extending back to the supramarginal (area 40) and angular (area 39) gyri. Lesions produce receptive aphasia with problems understanding spoken and written language.

Lesions of the opercular and triangular portions of the inferior frontal gyrus (areas 44 and 45), called Broca's area in the dominant hemisphere, produce expressive or motor aphasia. These patients have difficulty in generating spoken or written language.

In the nondominant hemisphere, lesions of the regions of the brain that are analogous to Wernicke's and Broca's areas affect the ability to understand or to generate inflections of voice, respectively.

Prefrontal Cortex

The prefrontal cortex is extremely well developed in humans. It also undergoes the greatest amount of postnatal development. There are two main portions of this cortex, the dorsolateral prefrontal cortex (DLPC; mostly areas 9 and 10) and the orbitomedial prefrontal cortex (especially areas 11 and 12). The DLPC is primarily involved in executive functions. These include working memory, judgment, planning, sequencing of activity, abstract reasoning and dividing attention. The orbitomedial prefrontal cortex is involved in impulse control, personality, reactivity to the surroundings and mood. A particular area, the anterior cingulate gyrus (areas 24 and 25; subcallosal and subgenual regions) appears to be most associated with mood (particularly depression and mania). While laterality is not as well recognized in the prefrontal cortex as it is in language, there does appear to be some laterality, with lesions of the dominant cortex tending to produce depression and, of the nondominant hemisphere tending to produce mania.

The first and most striking example of frontal lobe functions came from description of the results of lesion of the orbital and medial prefrontal cortex in a railway construction supervisor, Phineas Gage whose frontal lobes were destroyed by a tamping rod that passed vertically through his skull primarily damaging the orbitomedial frontal regions bilaterally. The description of his subsequent behavior by Harlow in 1868 remains a classic:

"The equilibrium or balance, so to speak, between his intellectual faculties and animal propensities, seems to have been destroyed. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom) manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operation, which no sooner arranged than they are abandoned... in this regard his mind was radically changed, so decidedly that is friends and acquaintances said that he was 'no longer Gage.'"

The frontal lobes connect to all other cortical regions through association fibers. It receives particularly strong input from limbic cortex, amygdala and septal nuclei, areas involved in emotional responses. Patients with lesions in this area are often referred to as having a changed personality.

Association and Commissural Fibers

Finally, regions of the cerebral cortex are tied together by bundles of white matter fibers. There are association bundles that connect one part of the cortex to another. These association fibers typically arise from layer III and terminate in layers I and II. These may be short and connect adjacent gyri or may connect one lobe to another. Common pathways include the superior longitudinal (arcuate) fasciculus, the superior occipital frontal fasciculus, the inferior occipital frontal fasciculus, the uncinate fasciculus and the cingulum.

Commissural fibers connect one hemisphere with the other. The largest commissural connection is the corpus callosum, which consists of about 300,000 fibers. Damage to this pathway can produce a "split brain "in some individuals, where an individual may literally appear to have two minds. The anterior commissure represents a smaller connection between the hemispheres that links anterior temporal lobe structures including the amygdala and other olfactory lobe structures.