Cerebral Cortex and Neurocognitive Disorders

Surfaces of Cerebrum

The cerebrum is divided into right and left hemispheres by a longitudinal fissure. Each hemisphere has three surfaces—superolateral, medial, and inferior—all of which have irregular fissures, or sulci, demarcating convolutions, or gyri. Although there are variations in arrangement between the two hemispheres in the same brain and in those from different persons, a basic similarity in the pattern allows the parts of the brain to be mapped and named.

Cerebral Cortex: Function and Association Pathways

In humans, the cerebral cortex is highly developed, and the complexity of the interhemispheric and intrahemispheric connections parallels this degree of development. The cerebral cortex has definite areas related to specific neurologic functions, either for primary sensory reception or for complex integrated activity.

Association Pathways . When one cortical area is activated by a stimulus, other areas also respond. This is due to the rapid activity along a large number of precisely organized, reciprocally acting association pathways. The pathways may be very short, linking neighboring areas and running only within the gray matter, or they may be longer (arcuate) bundles, passing through the white matter to connect gyrus to gyrus or lobe to lobe within a cerebral hemisphere– intrahemispheric connection . Other commissural bundles conduct interhemispheric activity : the most prominent are the corpus callosum , a large band of fibers, which lies immediately beneath the cingulum; the anterior commissure , which connects both temporal lobes; and the hippocampal commissure (commissure of the fornix) , which connects the right and left hippocampus.

The reciprocal activity of the connections in the cerebral cortex ensures the coordination of sensory input and motor activity, as well as the regulation of higher function. For example, for the appreciation and integration of visual information, the primary visual sensory area of the occipital cortex is linked to the visual association areas. These visual centers are connected by intrahemispheric fibers to the ipsilateral parietal cortex, as well as to other areas, such as the temporal lobe, for further integrated activity. The right and left parietal and posterior temporal areas, in turn, are connected by the corpus callosum.

Prefrontal Cortex. The prefrontal cortex, (which includes the three frontal gyri, the orbital gyri, most of the medial frontal gyrus, and approximately half of the cingulate gyrus) is concerned with higher mental functions , and is involved with many behavioral aspects of man. This area receives numerous connections from the temporal and parietal lobes via pathways in the cingulum, a bundle of long association fibers lying within the cingulate gyrus. Bilateral lesions of the prefrontal area produce a loss of concentration, a decreased intellectual ability, and memory and judgment deficits.

Motor and Sensory Cortices . The somatosensory cortex , which occupies contiguous parts of the frontal and parietal lobes, and the premotor cortex of the frontal lobe are concerned with the initiation, activation and performance of motor activity , and the reception of primary sensation of the body. Lesions of the somatosensory cortex result in contralateral paralysis and loss of somatosensory reception or perception.

Parietal Lobe. The parietal lobe is primarily concerned with the interpretation and integration of information from sensory areas, that is, the visual areas and the somatosensory cortex. Lesions in the parietal lobe result in sensory ataxia, a loss of general awareness, defective recognition of sensory impulses, and a lack of interpretation of spatial relationships.

Occipital Lobe. Lesions of the striate cortex (the primary visual area) on one side result in a contralateral hemianopsia, while lesions of the secondary regions of the visual cortex cause a lack of ability to interpret visual impulses.

Temporal Lobe . The posterior part of the temporal lobe is concerned with the reception and interpretation of auditory information , and with some aspects of pattern recognition and higher visual coordination ; the interconnections of the auditory and visual segments of the occipital, temporal, and parietal lobes make this a highly integrated function. The anterior part of the temporal lobe is concerned with visceral motor activity and certain aspects of behavior . Lesions here may be manifested by psychomotor seizures or, if they occur in the region of the uncus, by uncinate “fits” characterized by alteration of consciousness and hallucinations of taste and odor.

Lesions . In general, lesions of primary receptive areas produce identifiable deficits. A lesion in a specific area of the cerebral cortex may produce a deficit far beyond the functional identity of that particular area because the complex interconnections beneath that cortical region may be damaged.

Major Cortical Association Bundles

Association fibers are predominantly located in the cerebral white matter and connect intrahemispheric cortical regions. There are two main types of association fibers, and they are differentiated by size and function. Short association fibers known as arcuate fibers or “U fibers” connect adjacent gyri, thus allowing for communication between neighboring cortical regions. Long association fibers provide the architectural basis for large-scale neurocognitive networks. These networks connect more widespread cortical regions and are visualized as “bundles of fibers” that allow communication between primary and association cortical regions. For instance, the superior longitudinal fasciculus (SLF) (which has three major bundles, I, II, and III) allows communication between the parietal and frontal lobes. In particular, the SLF I allows information from the superior parietal lobe, or motor cortex, to be relayed to the supplementary motor cortex. SLF II connects the caudal parietal region with the prefrontal lobes, thus allowing an individual to have a visual perception of space. SLF III connects rostral parietal areas with the frontal opercular region (the region that controls facial movements), thus enabling an individual to imitate an action. Other long association fibers include the fronto-occipital fasciculus , which links the posterior and medial parietal and occipital areas; the uncinate fasciculus (or the anterior limbic fiber bundle), which connects the temporal lobe and frontal lobes; the inferior longitudinal fasciculus, which connects the temporal lobe to the occipital and parietal regions, and the cingulum bundle (or the posterior limbic fiber bundle), which stretches from the frontal lobe to the parahippocampal gyrus. The cingulum bundle enables monoamines (dopamine, norepinephrine, and serotonin), along with cholinergic projections, to travel to widespread cortical targets.

Lesions to cortical association bundles can provide clinical relevance to fiber pathway tracts and cortical origins and destinations. For instance, a patient who develops acute damage to the uncinate fasciculus and right anterior frontal cortex (e.g., from a stroke) will have a “disconnection” between the temporal and frontal lobes. This individual may develop amnesia for experiences predating the stroke, along with impairment of self-awareness of personal experiences across time (this clinical finding is also known as a disruption of autonoetic consciousness).

Corticocortical and Subcorticocortical Projection Circuits

The cerebral white matter consists of myelinated axons that link cortical areas with both cortical and subcortical regions. There exist three main categories of efferent fibers from a cortical area: association fibers, striatal fibers, and commissural/subcortical fibers. Corticocortical projections allow both adjacent and distant cortical regions to communicate, whereas corticosubcortical projections allow reciprocal communication between cortical regions and subcortical structures. These subcorticocortical projections connect the cortex to the thalamus, the pontocerebellar system, brainstem, and spinal cord.

Corticocortical Circuits. Local short association fibers, or U fibers, connect adjacent cortical gyri and lie beneath the sixth cortical layer. Neighborhood association fibers traverse longer distances than U fibers, but still connect nearby cortical regions. Long association fibers travel within the same hemisphere and connect more distant cortical regions. These include the superior, middle, and inferior longitudinal fasciculi, arcuate fasciculus, extreme capsule, fronto-occipital fasciculus, uncinate fasciculus, and cingulum bundle (see Plate 2-5 , Major Cortical Association Bundles).

Subcorticocortical Circuits. Striatal fibers describe fiber groups that connect cortical regions to the striatum (the caudate and putamen). For instance, these fibers allow cortical motor control. The commissural bundle is a collection of fibers that travel from a cortical region to the opposite hemisphere via the corpus callosum or anterior commissure. Subcortical fibers travel via the internal capsule to diencephalic structures (e.g., thalamus) and brainstem (e.g., pons). The origins of the subcorticocortical cell bodies are laminae V and VI. Cortical activity is modulated via excitatory and inhibitory projections in subcortical areas. For instance, diffuse cortical cholinergic projections to the cortex rise from the nucleus basalis of Meynert, and norepinephrine projections from the locus ceruleus.

In the case of Alzheimer disease, a loss of corticocortical projection neurons is associated with neurofibrillary tangle formation. This indicates a “disconnection” of adjacent cortex and cortical association areas. The disconnection of subcorticocortical circuits is evident in the reduction of cholinergic projections throughout the cortex, resulting in reduced acetylcholine levels in the cortex. This observation led to the development of the first effective therapies for Alzheimer disease, acetylcholinesterase inhibitors, which boost acetylcholine levels in the brain.

Corpus Callosum

The corpus callosum is the major commissure of the forebrain, connecting homologous cortical regions of the two cerebral hemispheres. The corpus callosum is divided into anterior and posterior parts, known as the genu and splenium, respectively. The genu includes fibers of the frontal forceps (forceps minor) interconnecting frontal areas. Posteriorly, the splenium includes the occipital forceps (forceps major), interconnecting the parietal, occipital, and temporal lobes. A corpus callosotomy, a surgical lesioning of the corpus callosum, has been performed in patients with medication-refractory epilepsy. The goal of this surgery is to prevent seizure spread from one hemisphere to another.

Agenesis of the corpus callosum (ACC) is a congenital birth defect characterized by an absence of a corpus callosum. This condition can occur in isolation (with little to no impact on cognitive performance) or can occur as part of abnormalities such as Dandy-Walker syndrome, Arnold-Chiari malformation, schizencephaly, holoprosencephaly, Andermann syndrome, or Aicardi syndrome (a syndrome more commonly seen in females). Midline facial defects often accompany ACC.

Rhinencephalon and Limbic System

The rhinencephalon is a term that describes quite literally the “nose” or “smell” regions of the brain. The limbic system refers to the structures and tracts involved with emotion, including memory formation, as well as autonomic and endocrine response to emotional stimuli. The terms rhinencephalon and limbic system are sometimes used synonymously, but the rhinencephalon refers to olfactory structures and related pathways. Located in the medial and inferior surface of the forebrain, these parts include the olfactory bulb, tract and striae, the anterior perforated substance, the uncus, the hippocampus, the dentate gyrus, the gyrus fasciolaris, the indusium griseum, the habenular trigone, the subcallosal area, the paraterminal gyrus, the fornix, and the amygdaloid body as direct olfactory afferents project to the amygdala. The olfactory pathway is described and illustrated in Plate 5-8 .

The limbic forebrain refers to the areas that are functionally and anatomically connected structures that relate to emotion, motivation, and self-preservation. The limbic system is thought to be a major substrate for regulation of emotional responsiveness and behavior, for individualized reactivity to sensory stimuli and internal stimuli, and for integrated memory tasks. The main regions of the limbic forebrain include the hypothalamus, amygdala, hippocampus, and limbic cortex (prefrontal cortex and orbital frontal cortex). The hippocampal formation and amygdala send axonal projections through the forebrain, via the fornix and stria terminalis, respectively, to the hypothalamus and septal region. The amygdala also has a more direct pathway to the hypothalamus via the anterior amygdalofugal pathway. The septal nuclei lie rostral to the hypothalamus, and send axons to the habenular nuclei via the stria medullaris thalami.

Piriform Area . The anterior (rostral) perforated substance, the uncus, the anterior end of the dentate gyrus, and the anterior part of the parahippocampal gyrus medial to the rhinal sulcus are often referred to as the piriform area. These regions function to give perception of smell. The anterior perforated substance is continuous with the paraterminal gyrus and separated from the anterior part of the globus pallidus of the lentiform nucleus by the anterior (rostral) commissure, ansa lenticularis, and ansa peduncularis; posteromedially, it blends into the tuber cinereum.

The indusium griseum is a thin layer of gray matter spread over the upper surface of the corpus callosum. Anteriorly, it curves around the genu and rostrum to merge with the paraterminal gyri; laterally, it becomes continuous with the cortex of the cingulate gyrus; and posteriorly, it passes over the splenium to blend with the dentate and parahippocampal gyri through the narrow gyrus fasciolaris. Two slender strands of white fibers, the medial and lateral longitudinal striae , are embedded in the indusium griseum.

Hippocampus

Hippocampal Formation . The hippocampus, the posterior part of the dentate gyrus and the indusium griseum are sometimes grouped together as the hippocampal formation. In humans, the attenuated gray and white structures of this formation are produced by the enormous enlargement of the corpus callosum, which encroaches upon the parahippocampal and dentate gyri and the hippocampi, thus expanding them.

The hippocampus is a part of the marginal cortex of the parahippocampal gyrus that has been invaginated, or rolled, into the floor of the inferior horn of the lateral ventricle by the exuberant growth of the nearby temporal cortex. The curved hippocampal eminence is composed mostly of gray matter, and its anterior end is expanded and grooved like a paw, the pes hippocampi . Axons conveying efferent impulses from the pyramidal cells of the hippocampus form a white layer on its surface, the alveus , and then converge toward its medial edge to form a white strip, the fimbria . The hippocampus is an important part of the olfactory apparatus in lower animals; in humans, few or no secondary olfactory fibers end in it. However, it possesses substantial connections with the hypothalamus, which regulates many visceral activities that influence emotional behavior and with temporal lobe areas reputedly associated with memory.

The dentate gyrus (dentate fascia) is a crenated fringe of cortex occupying the narrow furrow between the fimbria of the hippocampus and the parahippocampal gyrus. Anteriorly, this fringe fades away on the surface of the uncus, and posteriorly, it becomes continuous with the indusium griseum through the gyrus fasciolaris.

The hippocampus contains pyramidal cells in regions CA1 and CA3 that project via the efferent fornix to the septal nuclei and hypothalamus. The subiculum receives input from the hippocampal pyramidal cells and also projects via the fornix to the mammillary nuclei and anterior nucleus of the thalamus. It is connected reciprocally with the amygdala and sends axons to cortical association areas of the temporal lobe. The dentate gyrus contains granule cells that project to the pyramidal cells of the hippocampus and subiculum and receive hippocampal input. The afferent connections to the hippocampal formation include the cerebral association cortices, prefrontal cortex, cingulate cortex, the insular cortex, amygdaloid nuclei, and olfactory bulb via projections to the entorhinal cortex. Afferent cholinergic axons from septal nuclei traverse the fornix to provide the dentate gyrus and hippocampal CA regions.

There exist several clinical conditions where damage unique to the hippocampal formation occurs. CA1 neurons are particularly susceptible to ischemic conditions as seen in cardiorespiratory arrest. Also, patients with temporal lobe epilepsy can suffer CA1 neuronal loss. The most common clinical scenario affecting the hippocampal formation is Alzheimer disease (AD). AD is pathologically associated with neuronal cell loss, neurofibrillary tangles, neuritic amyloid plaques, and granule vacuolar degeneration of the hippocampal region. AD is discussed in more detail in Plates 2-24 to 2-26 .