Chapter 2 - Hemispheric function
The cerebral hemispheres, particularly in the large and redundant cerebral cortical mantle, are the anatomical substrates of the uniqueness of Man. The cortex of the cerebral hemispheres embodies the higher integrative or intellectual capacities of man and its expanse in area and neuronal numbers far outstrips the same parameters of our nearest phylogenetic cousin, the chimpanzee. The complexity of neuronal ramification and interconnection is fantastic! It is estimated that there are nine billion neurons in each cerebral hemisphere and each neuron has between five and ten thousand interconnections with other neurons neighboring and distant. The mathematical dimensions are staggering, little short of infinite. The latest generation of man-made brains, in all their circuit complexity cannot compare.
The higher integrative functions can be divided into those functions having diffuse representation in the cortex and those with more focal representation. Some functions are in both hemispheres and some are unilaterally represented. Obviously, all of this affects the symptoms produced by damage to the brain.
According to Harold Wolff, diffuse bilateral functions include: "(a) the capacity to express appropriate feelings, appetites and drives; (b) the capacity to employ effectively the mechanisms of goal achievement (learning, memory, logic, etc.); (c) the capacity to maintain appropriate thresholds and tolerance for frustration and failure, and to recover promptly from their effects; (d) the capacity to maintain effective and well-modulated defense reactions (i.e., repression, denying, pretending, rationalization, blaming, withdrawal, fantasy, depersonalization, obsessive compulsive behavior and bodily reaction patterns involving alimentation, respiration, metabolism, etc.)." These are the kind of functions that are lost only after diffuse and bilateral injuries to the brain, such as occur in the dementing disorders. Dementia is defined as a progressive loss of intellectual and higher emotional capacities. Many of the early changes in rational and emotional behavior are nonspecific for cerebral dysfunction; that is, they can be the reflection of severe psychological stress and disorder, not of clear-cut organic origin but of the psychiatric sphere (which have been termed "pseudodementia").
Condensing the above further, one can see that man's major intellectual achievement has been the rational control, by inhibitory modulation, of the basic drives of self and species preservation common to all animals: feeding, fighting, fleeing, and procreation. The complexity and variability of these rational and emotional drives and behavior becomes greater and greater as one ascends the phylogenetic scale, culminating with man. The manifestations of functional loss, reversible or irreversible, therefore become more complex and subtle as the functional anatomy of the nervous system ascends through phylogeny.
As neuronal diffuse dysfunction becomes more advanced, obvious and unmistakable changes occur. There are deficits in emotional response, often with a tendency toward apathy and flatness of affect, alternating with wide and inappropriate swings of emotional behavior. The latter reflects a loss of rational inhibitory control of the basic emotional drives mediated by the limbic system. Defects in learning and memory, particularly the former, abstract thinking, general information and capabilities, and in judgment are easily detectible in patients with diffuse bilateral involvement.
It may be difficult to distinguish patients with certain psychiatric disorders from those with early diffuse cortical degeneration. It may be impossible to test cognitive functions in patients who are psychotically depressed or catatonic due to schizophrenia. Fortunately, organic cerebral hemispheric deterioration frequently uncovers primitive reflexes that can be elicited without cooperation from the patient. Most of these complex reflexes occur in infants and are suppressed during normal cortical development. These reflexes reappear with dementia (that is, they become disinhibited). There is a long list of regressive reflexes that has evolved. The most commonly sought and elicited are the feeding or mouthing phenomena including involuntary snouting, sucking, rooting, and biting in response to tactile or visual stimuli, forced grasping with the hands and the feet, and extension of the great toe on plantar stimulation (Babinski response).
Patients with dementia often show motor perseveration, inappropriately repeating the same movement due to loss of ability to inhibit ongoing activity. This may be observed with repetition of words or ideas (this can occasionally be seen in normal individuals when fatigued or under emotional strain). Another manifestation of this perseveration can be seen when testing resting muscle tone. The patient appears to have an inability to relax, termed "paratonia," when the examiner is attempting to passively move a body part. This can be quite frustrating to the examiner, since it appears that the patient is willfully resisting passive movement. This perseveration of tone can meld into a perseveration of movement as the patient overcomes initial inertia and gets into rhythm with the examiners testing movements. The examiner becomes aware of this when releasing the patient's arm or leg and instead of dropping relaxed to the bed, it continues the supposed passive movements. Paratonia (or gegenhalten), can be seen in infants and young children and accordingly may also represent a regression of function. It can be seen in normal individuals, but is much more common in patients with dementia, and therefore has been included with other things as a "soft sign" of dementia.
Historically, diffuse hemispheric disease (i.e., dementia) has been considered to be a progressive and hopeless condition of old age. Twenty years ago, current knowledge and therapeutics accepted just that attitude with few fortunate exceptions. Today the number of treatable and potentially reversible disorders of the cerebral hemispheres is growing although the majority of cases of dementia are not reversible. Additionally, some of the previously untreatable dementias are yielding partially to new therapies. New diseases are not appearing; old entities are being recognized as treatable with the expansion of etiologically and therapeutically oriented research in dementia. Obviously, the treatable causes of dementia must take diagnostic priority though they may be statistically unlikely.
Some brain functions are localized to specific hemispheric regions. For example, there are areas of primary motor and sensory function that are highly localized. On the motor side, skilled movements (particularly of the distal upper limbs) of the contralateral side of the body are initiated by the primary motor cortex in the precentral gyrus. There are areas of highly localized sensory function, including the somatosensory cortex in the postcentral gyrus and the visual cortex of the occipital lobe. Damage to these areas can affect the ability to feel things or see things on the contralateral side of the body. The ability to hear and smell are bilaterally represented, and therefore are generally unaffected by unilateral brain injury. There are several more complex functions that lateralize. Included among these functions are language, handedness and visuospatial orientation and, as already alluded to above, learning, emotionality, and behavioral inhibitory control.
In 97% of the population language is represented in the left hemisphere, with little if any contribution from the right hemisphere. Only three in one hundred people will have significant right hemispheric representation of speech functions; of those three, two will have significant bilateral representation of speech, with only one individual having right hemisphere dominance. It is known that early brain injury (the earlier the better, but generally before the age of about 4), is associated with transference of language function to the spared hemisphere. With increasing age and gradual lateralization and anatomical fixation of speech functions to the left hemisphere, less and less flexibility remains.
The areas involved in the central organization of language, which is man's most advanced capability, are appropriately the most advanced and latest developed neocortical zones. It is not too surprising that this highest function would localize in the most advanced regions and further still that this function would tend to utilize the greatest expanse of advanced cortex, which happens to be, in most, localized on the left. The above is interesting but grossly speculative.
"Why are some functions only represented on one side of the brain?" might be the next question. No one has proposed a fully satisfactory answer to this teleological question. It is possible that this is for efficiency, such that language function does not have to occupy similarly large areas on both sides of the brain (leaving more cortex for other functions). However, this is speculative. Man appears to be, with rare exception, the only animal with significant lateralization of such an important function (some birds apparently have lateralization of their singing capabilities).
Handedness correlates fairly closely with language dominance. Ninety percent of the population is right-handed; of 1,000 right-handed people only one will be right hemisphere dominant for speech; overwhelmingly, to be right-handed is to be left brained for language. Ten percent of the population is left-handed; 7 of 10 left-handed individuals are left-brain dominant for speech, essentially breaking down the nice speech-handedness correlations seen in right-handed individuals. The remaining 3 left-handers will be those with either bilateral representation of speech (2) or with right hemisphere dominance (1). Functional Magnetic Resonance Imaging (fMRI) has added the capability to study regional metabolic activities in the brain, which is adding to and corroborating past findings determined by traditional methods (see Chap. 11 ).
We have learned most of what we know about speech functions and localization from disease processes involving the brain. Some minor contribution has come from stimulation studies and observations of the effects of drugs. Table 2-1 summarizes the effects of destructive lesions of the classic anatomical speech areas of Broca and Wernicke. Dysfunctions of language are called dysphasias, complete loss of some component of language function is called aphasia.
Testing of the patient with a suspected language disorder requires several steps. These include: observation of the characteristics of spontaneous production; response to variably complex commands; the ability to repeat complex phrases; the ability to name objects and parts of objects; and the ability to read and write. Testing of these functions will usually quite accurately localize the area of involvement. The finding of other areas of cortical damage can also help localize the process, since some functions are located close to the language areas of the cortex. For example, a patient with verbal language dysfunction, homonymous hemianopsia and little motor deficit, will more than likely have a receptive (Wernicke) dysphasia. A patient with a verbal language dysfunction, marked hemimotor and hemisensory deficit and no visual abnormality will probably have an expressive (Broca) dysphasia.
For practical purposes it is worth noting that the majority of patients with dysphasia will have a combination of both expressive and receptive dysfunctions (called global dysphasia). This is because the majority of patients who are dysphasic are so because of cerebral infarction and the infarction, usually patchy, involves the middle cerebral artery territory, which encompasses both language areas as well as the pathway connecting them, the arcuate fasciculus (see Fig. 2-1). Damage to the arcuate fasciculus can disconnect the area of the brain that comprehends language (Wernicke area) from the area that is generating language (Broca area). This would abolish the ability to repeat a complex phrase, since the comprehension of the phrase could not be transmitted to the area generating the words.
An even more unusual "disconnection syndrome" occurs when the areas around the primary language areas are damaged, leaving the primary language areas intact (Fig. 2-2). This "disconnects" the language areas from the rest of the cortex, which is contributing to the thought processes that are then being expressed through the primary language areas. Such individuals would be able to repeat, but would have problem spontaneously generating meaningful language.
Damage to the entire corpus callosum can cause a very striking disconnection syndrome (sometimes termed "split brain"), although it may not be observed unless the proper functions are tested. One of the most striking features of the fully expressed "split brain" is the inability to verbally tell you what an article is, if it is placed in the left hand (assuming left hemisphere dominance and that the patient is prevented from looking at it). Additionally, this individual will be unable to understand written language if the writing is presented only to the left visual field. This material reaches only the right hemisphere and cannot be transferred to the left or verbal hemisphere, for interpretation.
A rather striking and frequently-quoted example is that of the woman with corpus callosum transection who snickered when a risqué picture was presented to her left field. When asked why she laughed her left hemisphere answered, "It's a funny test." When the picture was flashed into the right visual field, and therefore seen by the left hemisphere, the patient quipped "You didn't tell me I was going to have to see this kind of a picture." During the first presentation of the picture, the right hemisphere saw the picture and laughed. The left hemisphere rationalized that the laugh must have been because the test was funny. From the above it is obvious that the right and left cerebral hemispheres, to some degree, are able to function as two separate individuals if disconnected.
In addition to having visual transfer problems, transection of the corpus callosum will prevent transfer of auditory verbal commands from the left hemisphere to the right. Commands to do chores with the left hand will therefore be carried out imperfectly or not at all.
These examples and the observation of the patient with a split brain pulling the pant leg up with the right hand and down with the left (as if the right and left hemispheres were in competition) reinforce the assumption of a partial schizo cerebration which comes to light only when the major connection, the corpus callosum, is destroyed. It is noteworthy that there may be other connections between the left and right hemisphere, especially if damage to the corpus callosum occurs early in life (such as agenesis).
The right hemisphere must be considered functionally inferior to the left since it lacks significant speech representation. Therefore it has been termed the "non-dominant" hemisphere. However, certain functions do tend to localize to the right hemisphere. For example, the ability to recognize loss of function, visuospatially oriented perception and behavior, and musicality all appear to be predominantly functions of the right cerebral hemisphere. Also, the ability to generate verbal inflections and to detect tone of voice appears to be localized to the right hemisphere.
The patient with severe right hemispheric dysfunction (e.g., subsequent to infarction, trauma, hemorrhage, or tumor) will manifest rather obvious deficits in elementary hemispheric functions: s/he will have a hemiweakness, hemisensory depression, and various abnormalities of cranial nerve function. These deficits are not at all surprising based on cortical localization. However, particularly if the non-dominant parietal lobe is involved, the capacity to acknowledge or recognize loss is severely impaired; for example, the patient may not know that there is anything wrong and therefore will deny the allegation that there is a deficit. When asked to move the left arm they may say that they have done so even though no visible movement has occurred. More bizarrely they may reach for the left arm and grasp the examiner's, which has been slipped in the path, and claim that it is their own. Also they may deny that their arm actually belongs to them; this abnormality probably depends to some degree upon the amount of sensory depression on the left. Some time ago, a patient with severe right hemisphere dysfunction due to a stroke was examined at the VA hospital. When turned onto his right side for the purpose of carrying out a lumbar puncture he vociferously objected to the presence of another person who was lying on top of him; the other person was his own left side! The term applied to the lack of appreciation (or neglect) of deficits is "anosognosia" is the term applied to this deficit. In time, anosognosia fades, compensated by recovery of right cerebral function or some transfer of this function to the left hemisphere. However, there are usually some remnants of neglect unless the pathology completely reverses (e.g., the patient, when asked what is wrong, might answer, "The doctors tell me I am weak on the left," etc.). These patients, as you may surmise, tend to be poor rehabilitation candidates because their neglect decreases their motivation for improvement. The patient with a similar motor disorder in the right limbs from left hemispheric damage, despite the fact that they may have severe language deficits, is quite conscious of the motor loss and quite willing, even insisting, to rehabilitate him- or herself.
Lesions of the right hemisphere, particularly when they involve the confluence of the parietal, occipital and temporal lobes are frequently associated with visuospatial disorientation of a disabling degree. This can be tested at the bedside by having the patient fill in well-known cities such as San Francisco, New York and Washington on a map of the United States or by having the patient copy a two dimensional rendition of a cube. At a practical level, visuospatial disorientation creates problems with following directions, reading maps and when an unfamiliar place is encountered navigation may become grossly disordered. Penfield described a patient, who after right temporal lobectomy became disoriented as soon as he lost sight of home. He was forced to take a job in the post office across the street from home in order to avoid daily confusion (Fig. 2-3).
Musicality is also a predominance of the right hemisphere. Lesions, particularly of the temporal-occipital-parietal confluence on the right, cause variable deficits in tune learning and reproduction. Left-sided destruction can leave the patient without speech but musical ability will frequently remain intact with the patient readily and correctly reproducing tunes if s/he is cued by the examiner.
The frontal lobes include the areas of the motor cortex and the premotor cortex posteriorly, and the prefrontal cortex anteriorly. The motor and premotor cortices are involved in the planning and initiating of movements. Damage to medial areas of the premotor cortex (supplementary motor area) can prevent the ability to initiate voluntary actions (abulia) that can be so severe as to prevent any movement (akinesia). Additionally, Broca's area is part of the premotor cortex in the dominant hemisphere.
The prefrontal cortex has more complex functions. Broadly, we divide this part of the cortex into dorsolateral prefrontal cortex and the orbitomedial prefrontal cortex. The dorsolateral prefrontal cortex is involved in what has been called executive functions. Osborn described these functions as: "The ability to organize thoughts and work, to create plans and successfully execute them, to manage the administrative functions of one's life. Individuals with impaired executive function may appear to live moment-to-moment, fail to monitor their activities or social interactions to make sure plans are carried out (or even made). With diminished ability to create strategies, to handle more than one task at a time, to be effective, reliable, and productive, the simplest job may be too challenging." Damage to this area also can affect "working memory" which is the ability to hold something in the mind while manipulating it (such as repeating a string of numbers backward) and also inhibits the ability to perform several tasks simultaneously.
The orbitomedial prefrontal cortex is involved in control of impulses and behavior. Damage to this area severely affects personality. Patients display poor judgment, inadequate planning, and little motivation. With more advanced disease, they may become inappropriately jocular ("Witzelsucht") and irritable and lose their social graces. It has been proposed that the orbitomedial prefrontal cortex is anatomically situated (in terms of their connections) between the perceptual motor systems of the hemispheres and the limbic system. Lesions in this area might then divorce perception and action from motivation. A classic example of this was described by Harlow after prolonged observation of a patient, Phineas Gage, who had sustained severe damage to the orbitomedial prefrontal cortex. “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 his friends and acquaintances said that he was ‘no longer Gage.’”
There are a variety of physical findings that are common, but not specific, for prefrontal cortex lesions. Grasp, sucking and snout reflexes are common. Paratonia (gegenhalten) and perseveration of actions or speech are often seen. As described above, paratonia (gegenhalten) refers to an increase in tone; instead of relaxing, the patient either resists or tries to help when the examiner attempts to move the limbs passively. Perseveration refers to the repetition of a response when it is no longer appropriate. A person may raise their hand on command, for example, and then continue to raise their hand when asked to point to the floor or touch the nose. Verbal responses can similarly demonstrate perseveration.
Perseveration may occur for a variety of reasons: inability to make the correct response, failure to check the response against the question, or lack of attention to the task. However, it may also be an inability to terminate or change ongoing motor activity or postures. This has been considered more likely to occur with loss of the inhibitory influences of the frontal lobes.
A number of tests have proved sensitive to the akinesia of patients with frontal lobe disease, and to their tendency to persist in incorrect behavior even when they know they are wrong. A test of word fluency can easily be given at the bedside. The patient is asked to produce as many words as they can that begin with a given letter (excluding proper nouns) in a one minute period. Normal individuals can produce 14 +/- 5, words using the letters A, F, or S. Patients with left frontal lobe lesions produce fewer words, and often repeat words or persist in using proper nouns.
The limbic system, in addition to subserving higher emotional functions, appropriately subserves a major component of the memory system, declarative memory (memory for facts or relationships that can be expressed verbally or symbolically). The ability to imprint new material (short term memory) is lost with bilateral destruction of most of the major paired structures of the limbic system including the cingulate gyri, hippocampi (and adjacent medial temporal lobes), fornices, mammillary bodies and anterior and medialis dorsalis nuclei of the thalamus. The patient with these lesions will be able to retain material as long as they are concentrating on it; this attentive or immediate memory probably depends upon the integrity of the major sensory pathways, the reticular activating system of the upper brainstem and the dorsolateral prefrontal neocortex. If, however, attention is distracted, s/he will have difficulty or be unable to recall the presented material. In fact, the patient may ask, "What three words?" when asked to reproduce three unrelated words such as table, red, 23 Broadway after a period of distraction.
There are several conditions that can produce isolated bilateral depression or destruction of limbic structures involved in short term memory. For example, it can occur as the result of herpes simplex encephalitis, bilateral posterior cerebral artery occlusive disease or may be the result of unilateral temporal lobectomy if the patient has a previously damaged (e.g., from birth trauma) contralateral temporal lobe. Bilateral temporal lobe involvement may be an early and prominent sign of Alzheimer's disease. The limbic system is also much more susceptible to metabolic insults such as hypoxia and thiamin deficiency, the latter being most often seen in malnourished alcoholics. In the case of alcoholic effects on the brain, which probably result from bilateral damage to the dorsomedial nucleus of the thalamus, the memory deficit may be accompanied by confabulation (a tendency to respond to memory tasks by "making up" plausible answers).
Of course, if things cannot be remembered over minutes to hours, they can not be remembered long-term. However, well-learned material is probably represented diffusely and is very resistant to focal destruction. Indeed, well-established memories are lost very late into the course of diffuse bilateral hemispheric dysfunction (dementia). Animal experiments suggest that intermediary or less well-established material is first stored in the temporal lobes and becomes more widespread or redundant in localization with reinforcement. Some clinical corroboration of this is seen in patients with bilateral temporal lobe lesions who have variable and patchy retrograde amnesia.
When testing a patient for problems with learning and memory, it suffices to ask for:
- reproduction of three unrelated words immediately and then after a period of distraction;
- a description of recent past events, for example front page news items, the contents of breakfast (if not stereotyped fare) and what they have been doing recently (assuming that the examiner knows the answers to these questions); and;
- a description of some well learned past material such as the past 4 or 5 presidents, birth dates of patients and family, anniversaries, number and location of children and grandchildren, etc.
- Benson, DF. Aphasia, Alexia, and Agraphia. New York, Churchill Livingstone, 1979.
- Geschwind, N. Selected papers on Language and the Brain. Boston, Reidel, 1974
- Vinken PJ and Bruyn, F.W. (eds). Disorders of speech perception and symbolic behavior, in: Handbook of Clinical Neurology, Vol. 4. New York, John Wiley & Sons, 1969.
Define the following terms:agnosia, agnosagnosia, apraxia, receptive aphasia, expressive aphasia, global aphasia, alexia, agraphia, dysinhibition, dysnomia, paraphasic, paratonia, perseveration.
2-1. Name some cerebral cortical functions that are well localized and unilateral.
2-2. Name some cerebral cortical functions that are well localized and represented bilaterally.
2-3. Name some cerebral cortical functions that are diffusely represented in the cerebral cortex.
2-4. Damage to which cerebral cortex produces aphasia?
2-5. What can you say about the ability to write in patients with aphasia?
2-6. What can you say about the ability of a patient with expressive, receptive, or global aphasia to repeat complex phrases?
2-7. What can you say about the ability of a patient with transcortical aphasia to repeat complex phrases?
2-8. What problems will a patient with a transcortical aphasia have?
2-9. What are the characteristics of the patient with an expressive aphasia (Broca's)?
2-10. What are the characteristics of the patient with a receptive aphasia (Wernicke's)?
2-11. What is the most common lesion to produce alexia without agraphia (can write but can't read)?
2-12. What area is involved in immediate recall (for example of a phone number)?
2-13. What area is involved in short-term memory?
2-14. Where is long-term memory stored?
2-15. What are "executive functions" and where are they primarily located?
2-16. Where are the areas involved in most of emotional control and "personality"?
2-17. Damage to which hemisphere is more likely to produce depression? Which will more likely produce mania?
2-18. Neglect of one side of the world is most commonly due to damage to what area?
2-19. Agnosagnosia most often results from damage to what area?
2-20. What "primitive responses" would be expected to be uncovered by damage to the frontal lobes?
2-21. Paratonia is a sign of what?
2-22. What would you expect to see in the patient with a split corpus callosum?
2-23. The neocortex provides inhibitory modulation of what four basic drives?
2-24. What is the clinical term used to describe diffuse hemispheric disease (one word)?
2-25. What are the clinical signs of advanced dementia?
2-26. What regressive reflexes emerge with loss of cortical inhibition?
2-27. What are the functions of the limbic areas of the brain?
2-28. Of 100 people, how many will have significant R hemispheric representation of speech functions? Of these, how many will have bilateral speech representation?
2-29. What percentage of R-handed people are L-hemisphere dominant for speech?
2-30. What percentage of L-handed people are L-hemisphere dominant for speech?
2-31. Below what age can speech function be recovered if the dominant hemisphere is damaged?
2-32. What are dysfunctions of speech called? What is a complete loss of speech called?
2-33. A patient with verbal language dysfunction, homonymous hemianopsia, right visual field deficit and little motor deficit most likely has what type of dysphasia?
2-34. A patient with verbal language dysfunction, marked hemimotor and hemisensory deficit, and no visual abnormality most likely has what type of dysphasia?
2-35. Where is Broca's area located? Where is Wernicke's area located? Name the fasciculus that links the two of them.
2-36. What gyrus is important in language, especially in word retrieval?
2-37. Do most patients with dysphasia have Broca's, Wernicke's, or a combination of both? Why is this so?
2-38. What language abnormalities are manifested with a lesion to Broca's area? Wernicke's area? Angular gyrus? Arcuate (superior longitudinal) fasciculus?
2-39. What part of the corpus callosum transfers COMPLEX [i.e., verbal] visual info between the two hemispheres?
2-40. What are the predominant functions of the R cerebral hemisphere?
2-41. Which patient will be more motivated to recover from a hemispheric lesion, one with damage on the L or the R?
2-42. Where is the location of a lesion that causes visuospatial disorientation? How does this manifest itself?
2-43. What type of lesion will result in the loss of the ability to imprint new information?
2-44. Can well-learned material be easily destroyed by a focal lesion? Why or why not?
2-45. What three categories of questions need to be asked when testing a patient for problems with learning and memory?
2-46. What evidence would lead to the conclusions that a demented patient has disease localized primarily in the frontal lobes (i.e., what are the manifestations of lesions to the frontal lobes)?
2-47. What is the effect of lesions localized to the medial aspect of the frontal lobes (parasagittal frontal cortex - supplementary motor area)?