Regional Cerebral Dysfunction: Higher Mental Functions

Definition

Higher mental function is at the core of what defines competent, independent individuals. Impairment of higher mental function can be broadly classified into four categories. Intellectual developmental disorder is a form of cognitive impairment that is present from infancy. Acquired forms of cognitive impairment are delirium, dementia, and focal cognitive disorders. Delirium ( Chapter 361 ) is defined by its acute or subacute onset and coexistent alterations in alertness. Dementia ( Chapter 371 ) represents an acquired cognitive impairment that is usually gradual in onset and not associated with alterations in alertness.

The evaluation of higher mental function presupposes that the patient has intact arousal and alertness. Higher mental function is not a unitary entity, and these functions are not homogenously distributed throughout the brain. Human cognitive functioning can be decomposed into several domains (memory, language, visuospatial cognition, and executive cognitive functioning), each with a regional anatomic localization in the brain.

Clinical Manifestations and Diagnosis

In the vast majority of encounters with patients in the practice of adult medicine, the default approach to patients should be that they have no cognitive impairment, defined by the absence of evidence of cognitive dysfunction. No cognitive impairment implies that the clinician believes that the patient possesses sufficient mental capacity to understand the nature of their own health, to acquire and retain new information, to appreciate the consequences of most choices related to their well-being, and to be able to weigh different options on their merits and risks. Thus, a determination of no cognitive impairment means that a patient must be treated as a competent adult and afforded the agency to engage in medical and other decisions. This determination may be based on the clinician’s own observations of the patient, on the patient’s own statements regarding their thinking and memory, or on presumably reliable family members or close companions of the patient.

By comparison, a provisional impression of cognitive impairment cannot be based on an informal conversation. Rather, it requires further attention ( Fig. 371-1 , Chapter 371 ), including a history from the patient, a family member, or companion regarding the patient’s capabilities in instrumental and basic activities of daily living, as well as a more formal examination of cognition. The purpose of the formal cognitive assessment is to gain an objective measure from which the clinician can judge whether the responses meet expectations for cognitive normality.

Bedside evaluations of orientation, memory, language, reasoning, and visuospatial function can be used to derive an impression of cognitive function using relatively brief but validated instruments (see Chapter 361 ). Performance on these brief examinations of cognition must be evaluated in the context of the patient’s alertness, cooperation, education, native language, sensorimotor function, and mood (i.e., in light of the totality of the medical and psychosocial condition of the patient). If uncertainty exists as to whether a patient has cognitive impairment after careful consideration of the findings from the history and examination, more detailed cognitive testing by a neuropsychologist may be indicated.

Definition

Amnestic disorders almost always involve impairment in learning new information and involve dysfunction in the episodic memory system. Episodic memory refers to learning and recall of specific events. Retention of information for more than a few seconds in the face of exposure to additional facts, details, or events requires a person to encode, store, and organize the information suitable for later recall. Anterograde amnesia is the clinical manifestation of disturbances in episodic memory. Anterograde refers to failure to learn, and hence recall, new information on an ongoing basis. Some conditions that cause acute brain injury also lead to retrograde amnesia, a disturbance of the ability to retrieve information that was acquired some time prior to the brain injury.

Immediate recall of information with zero delay and zero intervening information is a very short-term memory function. Immediate memory is capable of storing an image of an auditory message in exact form, but only a small amount and for a short period. The fidelity of immediate memory recall accuracy drops off dramatically over seconds, particularly if intervening sensory stimuli attract attention. A comparable system exists in the visual modality in that the memory acts like a photograph that fades rapidly. From a clinical perspective, immediate memory is separate from episodic memory. Immediate recall is generally used as a marker of attention and alertness and not memory per se.

Pathobiology

The hippocampal formations are the anatomic structures of importance for the declarative episodic memory system. The hippocampal formations are imaged well with magnetic resonance imaging (MRI). The principal input to the hippocampus comes through the entorhinal cortex from multimodal association areas in the frontal, parietal, and temporal neocortices. A second important input is a cholinergic pathway that originates in the septum of the medial-orbital frontal lobe. There are two principal output circuits of the hippocampal formations. One is via the subiculum back to multimodal association areas. The other hippocampal efferent pathway projects via the fornix to the mammillary bodies. The projection from the mammillary bodies passes through the medial thalamus to the ventral anterior nucleus of the thalamus, then to the posterior cingulate, and then back to the entorhinal cortex. The hippocampal circuit is believed to facilitate the formation of memory in association neocortices. The hippocampus does not store a particular learned fact, but rather it enables the appropriate region in a multimodal association cortical region to do so.

Lesions in one hippocampal formation will not generally have as devastating an impact on episodic memory as bilateral lesions will. However, in older persons who may have subclinical bilateral hippocampal pathology, a unilateral lesion, particularly in the dominant hemisphere, may produce dense anterograde amnesia. Lesions in the columns of the fornix, mammillary bodies, and medial thalamus have also been linked to anterograde amnesia.

Clinical Manifestations and Diagnosis

Human memory is a particularly imperfect activity, and many persons with no brain disease may experience forgetfulness on occasion. It is the persistence and pervasiveness of memory loss that distinguishes pathologic amnestic disorders.

The diagnosis of anterograde amnesia begins with a complaint of memory impairment from the patient or someone close to the patient. Patients with anterograde amnesia have poor or no recollection of events, conversations, or observations in a manner that exceeds normal forgetting. Family members report that patients repeat themselves in conversation or re-ask the same questions over the course of a few minutes to hours. Patients will generally forget important events and conversations, even when they were fully engaged in them. They will lose track of the date and time of day. They will forget appointments, even with reminders. The consequences of such memory failure are usually more evident to the family and acquaintances of patients with the disorder than they are to the patients themselves. Anosognosia (lack of awareness) for the deficit of anterograde amnesia is very common, though not universal. In contrast, many patients with milder amnestic disorders can recall information from years or decades earlier, as those memories are more permanently stored.

Objective testing of short-term memory is a critical diagnostic step in the evaluation of persons with memory complaints. Testing of memory can be performed at the bedside in alert patients. The patient is asked to learn three or four words and recall them after 1 or 2 minutes. A patient with severe anterograde amnesia will recall none or, at most, one of the words, whereas individuals with normal memory can recall all of the words or all but one.

In patients with questionable memory difficulties, assessment by an experienced neuropsychologist can be helpful. Standardized tests of memory have greater precision and reliability than bedside tests and involve the use of lengthier material to be remembered and a longer delay between learning and recall.