THE CEREBRAL CORTEX

The cerebral cortex in humans occupies a volume of about 600 cm³ and has a surface area of 2500 cm². The surface of the cortex is highly convoluted and folded into ridges known as gyri. Gyri are separated by grooves called sulci (if shallow) or fissures (if deep). This folding greatly increases the surface area of cortex that can be fit into the limited and fixed volume that exists within the skull. Indeed, most of the cortex cannot be seen from the brain surface because of this folding.

The cerebral cortex can be divided into the left and right hemispheres and subdivided into a number of lobes (Fig. 10-1), including the frontal, parietal, temporal, and occipital lobes. These lobes are named for the overlying bones of the skull. The frontal and parietal lobes are separated by the central sulcus; they are separated from the temporal lobe by the lateral fissure. The occipital and parietal lobes are separated (on the medial surface of the hemisphere) by the parietooccipital fissure (Fig. 10-1). Buried within the lateral fissure is another lobe, the insula (Fig. 4-7A). The limbic lobe is formed by the cortex on the medial aspect of the hemisphere that borders on the brainstem. Part of the limbic lobe, the hippocampal formation, is folded into the parahippocampal gyrus of the temporal lobe and cannot be seen from the surface of the brain.

Figure 10-1 Lateral and medial views of the left hemisphere of the human cerebrum with the major features labeled and the lobes indicated by color. R, G, B, and S indicate, respectively, the rostrum, genu, body, and splenium of the corpus callosum.

(From Haines DE [ed]: Fundamental Neuroscience for Basic and Clinical Applications, 3rd ed. Philadelphia, Churchill Livingstone, 2006.)

Activity in the two hemispheres of the cerebral cortex is coordinated by interconnections through the cerebral commissures. The bulk of the neocortex on the two sides is connected through the massive corpus callosum (Fig. 10-1). Parts of the temporal lobes connect through the anterior commissure, and the hippocampal formations on the two sides communicate through the hippocampal commissure (which is formed between the fornices on the two sides as they approximate each other at the back of the septum pellucidum and pass under the corpus callosum).

Functions of the Lobes of the Cerebral Cortex

Some specific functions of the cerebral cortex can be associated with different lobes of the cerebral hemispheres.

Frontal Lobe

One of the main functions of the frontal lobe is motor behavior. As discussed in Chapter 9, the motor, premotor, cingulate motor, and supplementary motor areas are located in the frontal lobe, as is the frontal eye field. These areas are crucial for planning and executing motor behavior. Broca’s area, essential for the generation of speech, is located in the inferior frontal gyrus of the dominant hemisphere for human language (almost always the left hemisphere, as explained later). In addition, the prefrontal cortex in the rostral part of the frontal lobe plays a major role in personality and emotional behavior.

Bilateral lesions of the prefrontal cortex may be produced either by disease or by surgically induced frontal lobotomy. Such lesions produce deficits in attention, difficulty in planning and problem solving, and inappropriate social behavior. Aggressive behavior is also reduced, and the motivational-affective component of pain is lost, although pain sensation remains. Frontal lobotomies are rarely performed today because improved drug therapies have become available for mental illness and chronic pain.

Parietal Lobe

The parietal lobe contains the somatosensory cortex and the adjacent parietal association cortex (see Chapter 7). This lobe is involved in the processing and perception of sensory information. Connections with the frontal lobe allow somatosensory information to affect voluntary motor activity. Visual information from the occipital lobe reaches the parietal association cortex and the frontal lobe, where it also helps guide voluntary movements. Somatosensory information can also be transferred to language centers, such as Wernicke’s area, in the dominant hemisphere, as described later. The parietal lobe in the nondominant hemisphere is involved in determining spatial context, as shown by the effects of specific lesions (see Chapters 7 and 9).

Occipital Lobe

The primary function of the occipital lobe is visual processing and perception (see Chapter 8). Connections to the frontal eye fields affect eye movements, and a projection to the midbrain assists in the control of convergent eye movements, pupillary constriction, and accommodation, all of which occur when the eyes adjust for near vision.

Temporal Lobe

The temporal lobe has many different functions. One of these functions is hearing, which depends on processing and perception of information related to sounds (see Chapter 8). Another function is processing of vestibular information. Several visual areas have been discovered in the temporal lobe; hence, this lobe is also involved in higher-order visual processing (see Chapter 8). For example, the infratemporal cortex, on its inferior surface, is involved in the recognition of faces. In addition, Meyer’s loop, which forms part of the optic pathway, passes through the temporal lobe. Therefore, temporal lobe lesions can damage vision in part of the visual fields. Similarly, some of Wernicke’s area, essential for the understanding of language, lies in the posterior region of the temporal lobe.

The medial temporal lobe belongs to the limbic system, which participates in emotional behavior and regulates the autonomic nervous system (see Chapter 11). The hippocampal formation is involved in learning and memory (see later).

Neocortical Layering and Subdivisions

The cerebral cortex can be subdivided phylogenetically into the archicortex, paleocortex, and neocortex. In humans, 90% of the cortex is neocortex.

The different phylogenetic subdivisions of the cerebral cortex can be recognized on the basis of their layering pattern. The neocortex is generally characterized by the presence of six cortical layers (Fig. 10-2). In contrast, the archicortex has only three layers and the paleocortex has four to five layers.

Figure 10-2 A small area of neocortex stained by three different methods. The Nissl stain (center) shows the cell bodies of all neurons and reveals how different types are distributed among the six layers. The Golgi stain (left) shows only a sample of the neuronal population but reveals details of their dendrites. The Weigert stain for myelin (right) demonstrates vertically oriented bundles of axons entering and leaving the cortex and horizontally coursing fibers that interconnect neurons within a layer.

(From Brodmann K: Vergleichende Lokalisation lehre der Grosshirnrinde in ihren prinzipien Dargestellt auf Grund des Zellenbaues. Leipzig, Germany, JA Barth, 1909.)

IN THE CLINIC

The functions of the different lobes of the cerebral cortex have been defined both from the effects of lesions produced by disease or by surgical interventions to treat disease in humans and from experiments on animals. In another approach, the physical manifestations of epileptic seizures have been correlated with the brain locations that give rise to seizures (epileptic seizure foci). For example, epileptic foci in the motor cortex cause movements on the contralateral side; the exact movements relate to the somatotopic location of the seizure focus. Seizures that originate in the somatosensory cortex cause an epileptic aura in which a touch sensation is perceived. Similarly, seizures that start in the visual cortex cause a visual aura (scintillations, colors), those in the auditory cortex cause an auditory aura (humming, buzzing, ringing), and those in the vestibular cortex cause a feeling of spinning. Complex behavior results from seizures that originate in the temporal lobe association areas; in addition, a malodorous aura may be perceived if the olfactory cortex is involved (uncinate fit).

Cell Types in the Neocortex

A number of different cell types have been described in the neocortex (Fig. 10-2). Pyramidal cells are the most abundant cell type and account for approximately 75% of neocortical neurons. Stellate cells and various other types of nonpyramidal cells make up the balance. Pyramidal cells have a large triangular cell body, a long apical dendrite directed toward the cortical surface, and several basal dendrites. The axon emerges from the cell body opposite the apical dendrite, and those from the larger pyramidal cells project into the subcortical white matter. The axon may give off collaterals as it descends through the cortex. Pyramidal cells use an excitatory amino acid (glutamate or aspartate) as their neurotransmitter. Stellate cells, often called granule cells, are interneurons. They have a small soma and numerous branched dendrites, although many will have an apical dendrite and thus look like small pyramidal cells. Some are excitatory interneurons; these cells are abundant in layer IV of the cortex (see below). Their axons remain in the same cortical region and frequently ascend into the upper cortical layers. Other stellate cells are inhibitory interneurons that use γ-aminobutyric acid (GABA) as their neurotransmitter.

Cytoarchitecture of Cortical Layers

Each of the six layers of the neocortex has a characteristic cellular content (Fig. 10-2). Layer I (molecular layer) has few neuronal cell bodies; instead, it contains mostly axon terminals and synapses on dendrites. Layer II (external granular layer) contains mostly stellate cells. Layer III (external pyramidal layer) consists mostly of small pyramidal cells. Layer IV (internal granular layer) contains mostly stellate cells, including the excitatory type. Layer V (internal pyramidal layer) is dominated by large pyramidal cells. These cells are the main source of cortical efferents to most subcortical regions. Layer VI (multiform layer) contains pyramidal, fusiform, and other types of cells. This layer is also an important origin of cortical efferents, those that target thalamic nuclei.

Cortical Afferent and Efferent Fibers

Thalamocortical afferent fibers from thalamic nuclei that have specific (topographically mapped) cortical projections end chiefly in layers III, IV, and VI. Neurons in other thalamic nuclei (particularly those relaying input from the reticular formation) project diffusely and terminate in layers I and VI.

Several nonthalamic, diffusely projecting nuclei (including the basal nucleus of Meynert, the locus coeruleus, and the dorsal raphe nucleus) project to all cortical layers. These projections, along with those projecting from the thalamus to layers I and VI, modulate cortical activity globally, perhaps in conjunction with changes in state (e.g., sleep or waking).

The cortical efferent axons originate from pyramidal cells. The pyramidal cells of layers II and III project to other cortical areas, either ipsilaterally or contralaterally, via the corpus callosum. The pyramidal cells of layer V project in many descending pathways and have synaptic targets in the spinal cord, brainstem, striatum, and thalamus. The pyramidal cells of layer VI form corticothalamic projections to the thalamic nuclei with specific cortical projections. Reciprocal thalamocortical and corticothalamic interconnections are likely to make important contributions to the electroencephalogram (EEG) (see later).

Regional Variations in Neocortical Structure

On the basis of differences in cytoarchitecture, a number of subdivisions of the neocortex can be recognized. Most of the cortex is composed of six readily distinguishable layers. The primary and premotor areas are sometimes said to be agranular cortex. This is a misnomer because all cortical areas, including these motor areas, have similar percentages of pyramidal and nonpyramidal cells (≈75% versus 25%). However, in the frontal motor areas, the nonpyramidal cell bodies do not group in a manner that leads to the formation of distinct “granular” layers. Moreover, local inhibitory interneurons play an important role in somatotopic organization of the primary motor cortex (see Chapter 9).

The primary motor cortex, in fact, is characterized by the presence of the largest pyramidal neurons in the cortex, called Betz cells. These enormous cells have axons that contribute to the corticospinal tracts and whose soma size (diameter >150 μm) is necessary for the metabolic maintenance of so much axoplasm. (Note that most corticospinal axons are from other pyramidal cells because Betz cell axons account for less than 5% of all corticospinal fibers.)

Another type of cortex has a very prominent layer IV and thus is called granular cortex. Dominated as it is by the stellate cells seen in layer IV of Figure 10-2, it is specialized for processing afferent input. Therefore, this kind of cortex is found in the primary sensory receiving areas: the somatosensory cortex (S-I), the primary auditory cortex, and the primary visual (striate) cortex. The striate cortex is given its name because of a particularly prominent horizontal sheet of axons in layer IV known as the stripe of Gennari.

Most of the other regions of cortex show less dramatic variations and often seem to grade from one type of layer morphology to the next as one looks at adjacent areas of cortex. On the basis of such an extensive cytoarchitectural analysis, Brodmann divided the cortex into 52 discrete areas (Fig. 10-3). Commonly referred to areas include Brodmann’s areas 3, 1, and 2 (the S-I cortex of the postcentral gyrus); area 4 (the primary motor cortex of the precentral gyrus); area 6 (the premotor and supplementary motor cortex); areas 41 and 42 (the primary auditory cortex on the superior temporal gyrus); and area 17 (the primary visual cortex mostly on the medial surface of the occipital lobe). Detailed studies have confirmed that the Brodmann areas are, in fact, distinctly different, both with respect to their interconnections and with respect to their functions, but more recent work has shown that there is some plasticity, both in the size of the areas and in their internal organization (see later).