++
Many of the foregoing ideas about the role of the limbic system have come from experimentation in laboratory animals. Only in relatively recent years have neurologists, primed with the knowledge of these studies, begun to relate emotional disturbances in patients with disease of limbic structures. These clinical observations, summarized in the following pages, form an interesting chapter in neurology. Table 25-1 lists the most readily recognized disturbances of emotion. The list is tentative, as our understanding of many of these states, particularly their pathologic basis, is incomplete. Only a small number of these derangements can be used as indicators of lesions and diseases in particular parts of the human brain. Taken in context, however, these disturbances are useful diagnostically. As knowledge of emotional disorders increases, an understanding of the functioning of limbic structures will undoubtedly bring together large segments of psychiatry and neurology.
+++
Emotional Disturbances in Hallucinatory and Pain States
++
These are portrayed by the patient with a florid delirium. Threatened by imaginary figures and voices that seem real and inescapable, the patient trembles, struggles to escape, and displays the full picture of terror. The patient's affect, emotional reaction, and visceral and somatic motor responses are altogether appropriate to the content of hallucinations. We have seen a patient slash his wrists and another try to drown himself in response to hallucinatory voices that admonished them for their worthlessness and the shame they had brought on their families. But the abnormality in these circumstances is one of disordered perception and thinking, and we have no reason to believe that there is a fundamental derangement of the mechanisms for emotional expression.
++
There also occurs a state, difficult to classify, of overwhelming emotionality in patients who are in severe, acute pain. The patient's attention can be captured only briefly, but within moments, there is a return to an extreme state of angst, groaning, and anger. We have encountered this with spinal subdural hemorrhage, subarachnoid hemorrhage, explosive migraine, trauma with multiple fractures, and intense pelvic, renal, or abdominal pain, all understandable as responses to extralimbic stimuli.
+++
Disinhibition of Emotional Expression
++
It is a commonplace clinical experience that cerebral diseases of many types, seemingly without respect to location, weaken the mechanism of control of emotional expression. A patient whose cerebrum has been damaged, for example, by a series of vascular lesions, may suffer the humiliation of crying in public upon meeting an old friend or hearing the national anthem, or of displaying uncontrollable laughter in response to a mildly amusing remark or an attempt to tell a funny story. There may also be easy vacillation from one state to another, an emotional lability that has for more than a century been accepted as a sign of "organic brain disease." In this type of emotional disturbance, the response, while excessive, does not quite reach the degree of forced emotionality of the special form of lability described as pseudobulbar (see below); furthermore, it is appropriate to the stimulus and the affect is congruent with the visceral and motor components of the expression. The anatomic substrate is obscure. Perhaps lesions of the frontal lobes more than of other parts of the brain are conducive to this state, but the authors are unaware of a critical clinicoanatomic study that substantiates this impression. Emotional lability is a frequent accompaniment of diffuse cerebral diseases, such as Alzheimer disease, but these diseases involve the limbic cortex as well. Also under this heading might be included the tearfulness and facile mood that so often accompany chronic diseases of the nervous system, and the shallow facetiousness (witzelsucht) and behavioral disinhibition of the patient with frontal lobe disease.
+++
Pseudobulbar (Spasmodic) Laughing and Crying
++
This form of disordered emotional expression, characterized by outbursts of involuntary, uncontrollable, and stereotyped laughing or crying, has been recognized since the late nineteenth century. Numerous references to these conditions (the Zwangslachen and Zwangsweinen noted by German neurologists and the rire et pleurer spasmodiques described by the French) can be found in the writings of Oppenheim, von Monakow, and Wilson (see Wilson for historical references). The term emotional incontinence applied by psychiatrists may be accurate but is a bit pejorative. Forced laughing or crying always has a pathologic basis in the brain, either diffuse or focal; hence, this stands as a syndrome of multiple causes. It may occur with degenerative and vascular diseases of the brain (Table 25-2) and no doubt is the direct result of them, but often the diffuse nature of the underlying disease precludes useful topographic analysis and clinicoanatomic correlation.
++
++
The best examples of pathologic laughing and crying are provided by multiple lacunar vascular disease and by amyotrophic lateral sclerosis, multiple sclerosis, and progressive supranuclear palsy, in each case the lesions being distributed bilaterally and generally involving the motor tracts, specifically, the corticobulbar motor system as discussed further on. They may also be part of the residue of the more widespread lesions of hypoxic–ischemic encephalopathy, Binswanger ischemic encephalopathy, cerebral trauma, infiltrative gliomas of the frontal lobe or pons, and infectious and noninfectious encephalitides. Typical in our experience is a sudden hemiplegia from a stroke that is engrafted upon a preexistent (and often clinically silent) lesion in the opposite hemisphere; this sets the stage for the pathologic displays of emotionality.
++
In this state, there is sometimes a striking incongruity between the loss of voluntary movements of muscles innervated by the motor nuclei of the lower pons and medulla (inability to forcefully close the eyes, elevate and retract the corners of the mouth, open and close the mouth, chew, swallow, phonate, articulate, and move the tongue) and the preservation of movement of the same muscles in yawning, coughing, throat clearing, and spasmodic laughing or crying (i.e., in reflexive pontomedullary activities). This is the motor syndrome of pseudobulbar palsy for which reason the term pseudobulbar affective state has been applied to the emotional disorder.
++
On the slightest provocation and sometimes for no apparent reason, the patient is thrown into a stereotyped spasm of laughter that may last for moments or up to many minutes, to the point of exhaustion. Or, far more often, the opposite happens—the mere mention of the patient's family or the sight of the doctor provokes an uncontrollable spasm of crying or, more accurately stated, a caricature of crying. The severity of the emotional display and the ease with which it is provoked does not correspond with the severity of the pseudobulbar paralysis or with an exaggeration of the facial and masseter ("jaw jerk") tendon reflexes. In some patients with forced crying and laughing, there is little or no detectable weakness of facial and bulbar muscles; in others, forced laughing and crying are lacking despite a severe upper motor neuron weakness of these muscles. In certain diseases, such as progressive supranuclear palsy and central pontine myelinolysis, of which pseudobulbar palsy is a frequent manifestation, forced laughing and crying are less dramatic or absent. Consequently, the pathologic emotional state cannot be equated with pseudobulbar palsy even though the two usually occur together.
++
Is this state, whether one of involuntary laughing or of crying, activated by an appropriate stimulus? In other words, does the emotional response accurately reflect the patient's affect or feeling? There are no simple answers to these questions. One problem is to determine what constitutes an appropriate stimulus for the patient in question. Virtually always, the emotional response is set off by some stimulus or thought; but usually, it is trifling, or at least it appears so to the physician. Merely addressing the patient or making some casual remark in his presence may suffice. Oppenheim and others stated that these patients need not feel sad when crying or mirthful when laughing, and at least in some cases, this is in agreement with our experience. Other patients, however, do report a general congruence of affect and emotional experience (mood), but the amplitude of the response is nonetheless excessive.
++
Noteworthy are the stereotyped nature of the initial motor facial response, and the relatively undifferentiated nature of the emotional reaction. Laughter or crying may merge, one with the other. Poeck (1985) puts great emphasis on the latter point, but it does not seem surprising when one considers the closeness of these two forms of emotional expression, a phenomenon that is particularly evident in young children. More impressive to us is the fact that in some patients with pseudobulbar palsy, laughing and crying, or caricatures thereof, are the only available forms of emotional expression; intermediate phenomena, such as smiling and frowning, are lost. In other patients with pseudobulbar palsy, there are lesser degrees of forced laughing and crying, perhaps bridging the gap between this phenomenon, and the type of emotional lability discussed earlier.
++
Wilson, in his discussion of the anatomic basis and mechanism of forced laughing and crying, pointed out that both involve the same facial, vocal, and respiratory musculature and have similar visceral accompaniments (dilatation of facial vessels, secretion of tears, etc). Two major supranuclear pathways control the pontomedullary mechanisms of facial and other movements required in laughing and crying. One is the familiar corticobulbar pathway that runs from the motor cortex through the posterior limb of the internal capsule and controls volitional movements; the other is a more anterior pathway that descends just rostral to the genu of the internal capsule, and contains facilitatory and inhibitory fibers. Unilateral involvement of the anterior pathway leaves the opposite side of the face under volitional control but paretic during laughing, smiling, and crying (emotional facial paralysis); the opposite is observed with a unilateral lesion of the posterior pathway. Wilson's argument, based to some extent on clinicopathologic evidence, was that in pseudobulbar palsy, it was the descending motor pathways, which naturally inhibit the expression of the emotions, that were interrupted although he was uncertain of the exact level. Almost 40 years later, Poeck (1985), after reviewing all the published pathologic anatomy in 30 verified cases, was able to do no more than conclude that supranuclear motor pathways are always involved, with loss of a control mechanism somewhere in the brainstem between thalamus and medulla. However, this clinical state is observed in amyotrophic lateral sclerosis, where the corticobulbar tracts may be involved at a cortical and subcortical level. As mentioned earlier, the lesions are bilateral in practically all instances (Poeck, 1985). There have been reports of spasmodic laughter following unilateral striatocapsular infarction (Ceccaldi et al) and occasional cases after unilateral pontine infarction or arteriovenous malformation, but these were not verified pathologically.
++
Of interest is the beneficial effect on distressing pseudobulbar displays of drugs such as imipramine and fluoxetine (Schiffer et al). A study has also shown benefit from dextromethorphan combined with quinidine in the pseudobulbar state of amyotrophic lateral sclerosis (Brooks et al). In a few personally observed cases, both the emotional lability and pathologic laughter and crying were partially suppressed by these drugs; but in most others, there was no effect.
++
A rare but probably related syndrome is le fou rire prodromique (prodromal laughing madness) of Féré, in which uncontrollable laughter begins abruptly and is followed after several hours by hemiplegia. We have seen two such cases in which basilar artery occlusion evolved after a brief bout of such forced laughter. Martin cites examples where patients laughed themselves to death. Again, the pathologic anatomy is unsettled. Protracted laughing and (less often) crying may occur rarely as a manifestation of epileptic seizures, usually of focal temporal lobe type. Ictal laughter is usually without affect (mirthless laughter); Daly and Mulder referred to these as "gelastic" seizures. The concurrence of gelastic seizures and precocious puberty is characteristic of an underlying hamartoma (or other lesion) of the hypothalamus (see Chaps. 16 and 27).
+++
Aggressiveness, Anger, Rage, and Violence
++
Aggressiveness is an integral part of social behavior. The emergence of this trait early in life enables the individual to secure a position in the family and later in an ever-widening social circle. Individual differences are noteworthy. Timidity, for example, is a persistent trait recognized in infancy (Kagan). Males tend to be more aggressive than females. The degree to which excessively aggressive behavior is tolerated varies in different cultures. In most civilized societies, tantrums, rage reactions, and outbursts of violence and destructiveness are not condoned and one of the principal objectives of child rearing and education is the suppression and sublimation of such behavior. The rate at which this developmental process proceeds varies from one individual to another. In some males and the cognitively impaired, it is not complete until 25 to 30 years of age; the deviant behavior results in sociopathy (see Chap. 28). Undoubtedly, from our own casual and others' more systematic observations, aggressiveness is an inherited tendency.
++
That seemingly groundless outbreaks of unbridled and disorganized rage may rarely represent the initial or main manifestation of disease is not fully appreciated. A patient with these symptoms may, with little provocation, change from a reasonable state to one of the wildest rage, with a blindly furious impulse to violence and destruction. In such states, the patient appears out of contact with reality and is impervious to all argument or pleading. There are examples also of a dissociation of affect and behavior in which the patient may spit, cry out, attack, or bite without seeming to be angry. This is especially true of the developmentally delayed.
++
All the human and animal data point to an origin of aggressiveness, anger, and rage in the temporal lobes and particularly in the amygdala. In humans, stimulation of the medial amygdaloid nuclei, through depth electrodes, evokes a display of anger, whereas stimulation of the lateral nuclei does not; destruction of the amygdaloid complex bilaterally reportedly reduces aggressiveness (Kiloh; Narabayashi et al). Lesions in the mediodorsal thalamic nuclei, which receive projections from the amygdaloid nuclei, render humans more placid and docile. In an unintended experiment in a patient with Parkinson disease, Bejjani and colleagues found that aggressive behavior could be induced by stimulation of the posteromedial hypothalamus. As with the comparable elicitation of depression from an aberrant electrode in the substantia nigra that was reported by the same group, it is not clear whether the effect was because of changes induced in adjacent neuronal pathways or if the physiologic response was the result of excitatory or inhibitory neuronal activity in the hypothalamus.
++
Sex hormones influence the activity of these temporal lobe circuits; testosterone promotes aggressiveness and estradiol suppresses it, suggesting an explanation for sex differences in the disposition to anger. Surprisingly, propranolol and lithium have benefited such patients more than haloperidol, other neuroleptics, or sedatives.
++
Animal studies have corroborated observations in humans. As mentioned in the introductory section, bilateral removal of the amygdaloid nuclei in the macaque greatly reduces the expressions of both fear and anger. Electrical stimulation in or near the amygdala of the unanesthetized cat yields a variety of motor and vegetative responses. One of these has been referred to as the fear or flight response, in which the animal appears frightened, and runs away and hides; another is the anger or defense reaction, characterized by growling, hissing, and piloerection. However, structures other than the amygdaloid nuclei are also involved in these reactions. Lesions in the ventromedial nuclei of the hypothalamus (which receive abundant input from the amygdaloid nuclei) have been shown to cause aggressive behavior, and bilateral ablation of Brodmann area 24 (rostral cingulate gyrus) has produced the opposite state—tameness and reduced aggressiveness—at least in some species.
++
Rage reactions of the intensity described above may be encountered in the following medical settings: (1) rarely as part of a temporal lobe seizure; (2) as an episodic reaction without recognizable seizures or other neurologic abnormality, as in certain sociopaths; (3) in the course of a recognizable acute neurologic disease; and (4) with the clouding of consciousness that accompanies a metabolic or toxic encephalopathy; (5) as a reaction to designed psychogenic drugs (dragonfly, K4, and others).
+++
Rage in Temporal Lobe Seizures
++
(See also "Focal Seizures" in Chap. 16)
++
According to Gastaut and colleagues, a directed attack of uncontrollable rage may occur either as part of a seizure or as an interictal phenomenon. Some patients describe a gradual heightening of excitability for 2 to 3 days, either before or after a seizure, before bursting into a rage. Certainly, such attacks have been observed, but they are rare. A lesser degree of aggressive behavior as part of a temporal lobe seizure is not uncommon; it is usually part of the ictal or postictal behavioral automatism and tends to be brief in duration and poorly directed. Usually, the lesion is in the temporal lobe of the dominant hemisphere. Similarly, a feeling of rage or severe anger occurs but is relatively infrequent as an ictal emotion, much less common than feelings of fear, sadness, or pleasure (Williams reported only 17 cases of anger among 165 patients with ictal emotion). Geschwind emphasized the frequency of a profound deepening of all of the patient's emotional experiences in temporal lobe epilepsy.
+++
Rage Attacks Without Seizure Activity
++
In some instances of this type, the patient had from early life been hot-headed, intolerant of frustration, and impulsive, exhibiting behavior that would be classified as sociopathic (Chap. 51). There are others, however, who, at certain periods of life, usually adolescence or early adulthood, begin to have episodes of wild, aggressive behavior. Alcohol or some other drug may trigger episodes. One suspects epilepsy, but there is no history of a recognizable seizure and no interruption of consciousness, which are so typical of focal temporal lobe epilepsy. We have been consulted from time to time on patients who report a proclivity to anger, cursing, and momentary unreasonableness in behavior that is acquired in adulthood. Most such individuals are remorseful afterwards and otherwise function at a high cognitive level. Each of these patients described a first-order relative with the same traits. In a very few such cases, in which aggression has resulted in serious injury to others (or homicide), depth electrodes placed in the amygdaloid nuclear complex have recorded what could be construed as seizure discharges. Attacks of excitement and various autonomic accompaniments have been aroused by stimulation of the same region, and the abnormal behavior has in some instances been relieved by ablation of the abnormally discharging structures. Mark and Ervin have documented a number of examples of this "dyscontrol syndrome," but we are doubtful that they are truly epileptic.
+++
Violent Behavior in Acute or Chronic Neurologic Disease
++
One encounters patients in whom intense excitement, rage, and aggressiveness begin abruptly in association with an acute neurologic disease or in a phase of partial recovery. In most cases, the medial and anterior temporal lobes have been damaged. Serious head injury with protracted coma may be followed by personality changes consisting of aggressive outbursts, suspiciousness, poor judgment, indifference to the feelings of family, and variable degrees of cognitive impairment. Hemorrhagic leukoencephalitis, lobar hemorrhage, infarction, traumatic contusion, and herpes simplex encephalitis affecting the medial and orbital portions of the frontal lobes and anterior portions of the temporal lobes may have the same effect (Fig. 25-3). Fisher noted the occurrence of intense rage reactions as an aftermath of a dominant temporal lobe lesion that had caused a Wernicke type of aphasia. Cases of this type have also been reported with ruptured aneurysm of the circle of Willis and extension of a pituitary adenoma; references to these reports can be found in the articles of Poeck (1969) and of Pillieri.
++
++
Also of interest are the effects of slow-growing tumors of the temporal lobe. Malamud described outbursts of rage in association with temporal lobe gliomas. Other of his patients harboring such tumors had no rage reactions but exhibited a clinical picture superficially resembling schizophrenia. It is noteworthy that 8 of the 9 patients with temporal lobe glioma described by Malamud also had seizures. The anteromedial part of the left temporal lobe has been the site of the tumor in the majority of cases. Falconer and Serafetinides have described patients with rage reactions in whom there was a hamartoma or sclerotic focus in this region.
++
A special form of violent outburst during REM sleep is detailed in Chap. 19, on Sleep. This, REM sleep behavior disorder, is associated with certain degenerative brain diseases.
+++
Aggressive Behavior in Acute Toxic–Metabolic Encephalopathies and Drug Intoxications
++
Here the patient is not in a clear-headed state and rage or aggression is superimposed on an encephalopathy of toxic or metabolic origin. The most dramatic examples in our experience have been during hypoglycemic reactions. When the patient is left alone, the aggressive behavior is undirected and disorganized, but anyone in the immediate neighborhood may be struck by the agitated individual. Attempts at physical restraint provoke an even more violent reaction.
++
A similar state may occur with phencyclidine and cocaine intoxication, and with other hallucinogens, accompanied by agitation and, usually, by hallucinosis. Perhaps the most berserk episodes we have encountered have been after ingestion of large amounts of designed street drugs such as the hallucinogen dragonfly and with cannabis derivatives such as K4 (Spice). These furious behaviors may last for hours or days and are resistant to large doses of haloperidol and benzodiazepines. We have found alpha-2 agonists such as dexmedetomidine to be effective. Outbursts of rage and violence with alcohol intoxication are somewhat different in nature: some instances represent a rare paradoxical or idiosyncratic reaction to alcohol (see Chap. 42); more typically alcohol appears to disinhibit an underlying sociopathic behavior pattern.
++
Animals normally indulge in and display highly energized, exploratory activity of their environment. Some of this activity is motivated by the drive for sexual satisfaction and procurement of food; in humans, it may be a matter of curiosity. These activities are governed by "expectancy circuits," involving nuclear groups in mesolimbic and mesocortical dopaminergic circuits connected with the diencephalon and mesencephalon via the medial forebrain bundles; lesions that interrupt these connections are said to abolish the expectancy reactions. Positron emission tomography (PET) studies correlate functional difficulty in the initiation of movements with impaired activation of the anterior cingulum, putamen, prefrontal cortex, and supplementary motor area (Playford et al).
++
A quantitative reduction in all activity is probably the most frequent of all psychobehavioral alterations in patients with cerebral disease, particularly in those with involvement of the anterior parts of the frontal lobes. There are fewer thoughts, fewer words uttered, and fewer movements per unit of time. That this is not a purely motor phenomenon is disclosed in conversation with the patient, who seems to perceive and think more slowly, to make fewer associations with a given idea, to initiate speech less frequently, and to exhibit less inquisitiveness and interest. This reduction in psychomotor activity is recognized as a striking personality change by the family.
++
Depending on how this state is viewed, it may be interpreted as a heightened threshold to stimulation, inattentiveness or inability to maintain an attentive attitude, impaired thinking, apathy, or lack of impulse (abulia). In a sense, all are correct, for each represents a different aspect of the reduced mental activity. Clinicoanatomic correlates are inexact, but bilateral lesions deep in the septal region (basal frontal, as sometimes occur with bleeding from an anterior communicating aneurysm) have resulted in the most striking lack of impulse, spontaneity, and conation (drive) (see Fig. 25-3). Impairment of learning and memory functions may be added. Typically, the patient is fully attentive, wide awake, and looks around. Upon recovery, memory is retained for all that happened. In this respect, abulia differs from stupor and hypersomnolence.
++
Patients who exhibit abulia are difficult to test because they respond slowly or not at all to every type of test. Yet on rare occasions, when intensely stimulated, they may speak and act normally. It is as though some energizing mechanism (possibly striatocortical), different from the reticular activating system of the upper brainstem, were impaired. Often, patients with severe abulia perform better with automatic or overlearned behaviors, such as talking on the telephone.
++
Quite apart from this abulic syndrome, which has already been discussed in relation to coma and to extensive lesions of the frontal lobes (Chaps. 17 and 22), there are lesser degrees in which a lively, sometimes volatile person has been rendered placid (hypobulic) by a disease of the nervous system.
++
Most often, the frontal lobe damage is bilateral, but sometimes on the left only, as discussed in Chap. 22. Diseases as diverse as hydrocephalus, glioma, strokes, trauma, and encephalitis may be causative. Formerly, changes of this type were observed following bilateral prefrontal leukotomy. Barris and Schuman, and many others have documented states of extreme placidity with lesions of the anterior cingulate gyri. Unlike the case in depression, the mood is neutral; the patient is apathetic rather than depressed.
++
The subdued emotional behavior described earlier differs from that observed in the Klüver-Bucy syndrome, which results from total bilateral temporal lobectomy in adult rhesus monkeys (see also Chap. 22). While these animals were made rather placid and lacked the ability to recognize objects visually (they could not distinguish edible from inedible objects), they had a striking tendency to examine everything orally, were unusually alert and responsive to visual stimuli (they touched or mouthed every object within their visual fields), became hypersexual, and increased their food intake. This constellation of behavioral changes has been sought in human beings, for example, after removal of the temporal lobes but the complete picture has occurred only infrequently (Marlowe et al; Terzian and Dalle). Pillieri, and Poeck (1969) have collected cases that have come closest to reproducing the syndrome (see Fig. 25-3). Many human examples have occurred in conjunction with diffuse diseases (Alzheimer and Pick cerebral atrophies, meningoencephalitis because of toxoplasmosis, herpes simplex, and AIDS) and hence are of limited value for anatomic analysis. With bitemporal surgical ablations, placidity and enhanced oral behavior were the most frequent consequences; altered sexual behavior and visual agnosia were less frequent. In all patients who showed placidity and an amnesic state, the hippocampi and medial parts of the temporal lobe had been destroyed, but not the amygdaloid nuclei.
++
Reduced emotionality in humans, albeit one that is very restricted in scope, is associated with acute lesions in the right, or nondominant, parietal lobe. Not only is the patient indifferent to the paralysis but, as Bear points out, he is unconcerned about his other diseases as well as personal and family problems, is less able to interpret the emotional facial expressions of others, and is inattentive in general. There may be a lack of emotional inflection to speech (aprosodia) and an inability to interpret the emotional state of other individuals, as discussed in Chap. 23. Dimond and coworkers interpret this to mean that the right hemisphere is more involved in affective-emotional experience than the left, which is committed to language. Observations derived from the study of split-brain patients and from selective anesthetization of the cerebral hemispheres by intracarotid injection of amobarbital (Wada test) lend some support to this probably oversimplified view. Rarely, lesions of the left (dominant) hemisphere appear to induce the opposite effect, a frenzied excitement lasting for days or weeks.
++
The normal pattern of sexual behavior in both males and females may be altered by cerebral disease quite apart from impairment due to obvious physical disability or to diseases that destroy or isolate the segmental reflex mechanisms (see Chap. 26).
++
Hypersexuality in men or women is a rare but well-documented complication of neurologic disease. It has long been believed that lesions of the orbital frontal lobes may remove moral-ethical restraints and lead to indiscriminate sexual behavior, and that superior frontal lesions may be associated with a general loss of initiative that reduces all, including sexual, impulsivity. In rare cases, extreme hypersexuality marks the onset of encephalitis or develops gradually with tumors of the temporal region. Possibly the limbic parts of the brain are disinhibited, the ones from which MacLean and Ploog could evoke penile erection and orgasm by electrical stimulation (medial dorsal thalamus, medial forebrain bundle, and septal preoptic region).
++
In humans, Heath has observed that stimulation of the ventroseptal area (through depth electrodes) evokes feelings of pleasure and lust. Also, Gorman and Cummings have described two patients who became sexually disinhibited after a shunt catheter had perforated the dorsal septal region. This is in keeping with the experience of Heath and Fitzjarrell, who found that infusion of acetylcholine into the septal region (as an experimental treatment for Parkinson disease) produced euphoria and orgasm, and with Heath's recordings from the septum of patients during sexual intercourse, showing greatly increased activity with spikes and slow waves. Perhaps these are examples of a true overdrive of libido, as contrasted with simple disinhibition of sexual behavior. However, we know of no case in which a stable lesion that caused abnormal sexual behavior has been studied carefully by sections of the critical parts of the brain.
++
In clinical practice, the most common cause of disinhibited sexual behavior, next to the aftermaths of head injury and cerebral hemorrhage, is the use of dopaminergic drugs in Parkinson disease. An intriguing effect of the administration of L-dopa in a few patients has been excessive or perverse sexual behavior, as in the cases described by Quinn and colleagues. Usually there are other manifestations of manic behavior. Primary mania may do the same.
++
Hyposexuality, meaning loss of libido, is most often the result of a depressive illness. However, certain medications, notably antihypertensive, antiepileptic, serotonergic antidepressant, and neuroleptic drugs may be responsible in individual patients. A variety of cerebral diseases may also have this effect, in parallel with a loss of interest and drive in a number of spheres.
++
Lesions that involve the tuberoinfundibular region of the hypothalamus are known to cause specific disturbances in sexual function. If such lesions are acquired early in life, pubertal changes are prevented from occurring; or, hamartomas of the hypothalamus, as in von Recklinghausen neurofibromatosis and tuberous sclerosis, may cause sexual precocity. Autonomic neuropathies and lesions involving the sacral parts of the parasympathetic system, the most common being prostatectomy, may abolish normal sexual performance but do not alter libido or orgasm.
++
Blumer and Walker have reviewed the literature on the association of epilepsy and abnormal sexual behavior. They note that sexual arousal, as an ictal phenomenon, is apt to occur in relation to temporal lobe seizures, particularly when the discharging focus is in the mediotemporal region. However, these authors also emphasize the high incidence of global hyposexuality in patients with temporal lobe epilepsy. Temporal lobectomy in such patients has sometimes been followed by a period of hypersexuality.
+++
Acute Fear, Anxiety, Elation, and Euphoria
++
The phenomenon of acute fear and anxiety occurring as a prelude to or part of a seizure is familiar to every neurologist. Williams's study, already mentioned, is of particular interest; from a series of about 2,000 epileptics, he was able to cull 100 patients in whom an emotional experience was part of the seizure. Of the latter, 61 experienced feelings of fear and anxiety, and 21 experienced depression. Daly has made similar observations. These clinical data call to mind the effects that had been noted by Penfield and Jasper when they stimulated the upper, anterior, and inferior parts of the temporal lobe and cingulate gyrus during surgical procedures; frequently, the patient described feelings of strangeness, uneasiness, and fear. In most instances, consciousness was variably impaired at the same time, and some patients had hallucinatory experiences as well.
++
In these cortical stimulations, neuronal circuits subserving fear are coextensive with those of anger; both are thought to lie in the medial part of the temporal lobe and amygdala, as discussed earlier. Both in animals and in humans, electrical stimulation in this region can arouse each emotion, but the circuitry subserving fear appears to be located lateral to that of anger and rage. Destruction of the central part of the amygdaloid nuclear complex abolishes fear reactions. These nuclei are connected to the lateral hypothalamus and midbrain tegmentum, regions from which Monroe and Heath, as well as Nashold and associates, have been able to evoke feelings of fear and anxiety by electrical stimulation.
++
Depression is less frequent as an ictal emotion, although it occurs often enough as an interictal phenomenon (Benson et al). Of interest is the observation that lesions of the dominant hemisphere are more likely than nondominant ones to be attended by an immediate pervasive depression of mood, disproportionate to the degree of severity of physical disability (Robinson et al). We are inclined to the view that the onset of depression after a stroke is a reaction to disability, i.e., a reactive depression, akin to that which follows myocardial infarction (Chap. 52).
++
Odd mixtures of depression and anxiety are often associated with temporal lobe tumors and less often with tumors of the hypothalamus and third ventricle (see review by Alpers), and they sometimes occur at the onset of a degenerative disease, such as multiple system atrophy.
++
Elation and euphoria are less well documented as limbic phenomena, nor has this elevation in mood in some patients with multiple sclerosis ever been adequately explained. Feelings of pleasure and satisfaction as well as "stirring sensations" are unusual, but well-described emotional experiences in patients with temporal lobe seizures, and this type of affective response, like that of fear, has been elicited by stimulating several different parts of the temporal lobe (Penfield and Jasper). In states of hypomania and mania, every experience may be colored by feelings of delight and pleasure, and a sense of power, and the patient may remember these experiences after he has recovered.
+++
Differential Diagnosis of Perturbations in Emotion and Affect
++
Aside from clinical observation, there are no reliable means of evaluating or quantifying the emotional disorders described earlier. Although neurologic medicine has done little more than describe and classify some of the clinical states dominated by emotional derangements, knowledge of this type is nonetheless of both theoretical and practical importance. In theory, it prepares one for the next step, of passing from a superficial to a deeper order of inquiry, where questions of pathogenesis and etiology can be broached. Practically, it provides certain clues that are useful in differential diagnosis. A number of particular neurologic possibilities must always be considered when one is confronted with one of the following clinical states.
+++
Uninhibited Laughter and Crying and Emotional Lability
++
As indicated earlier, one may confidently assume that the syndrome of forced or spasmodic laughing and crying signifies cerebral disease, and, more specifically, bilateral disease of the corticobulbar tracts (see Table 25-2). Usually the motor and reflex changes of spastic bulbar (pseudobulbar) palsy (described in the discussion of "Spastic [Pseudobulbar] Dysarthria" in Chap. 23) are associated usually, but not always, with heightened facial and mandibular reflexes ("jaw jerk"), and often corticospinal tract signs in the limbs as well. Extreme emotional lability also indicates bilateral cerebral disease, although only the signs of unilateral disease may be apparent clinically. The most common pathologic bases for these clinical states are lacunar infarction or other cerebrovascular lesions, diffuse hypoxic-hypotensive encephalopathy, amyotrophic lateral sclerosis, and multiple sclerosis, as already indicated; but in a number of less-common processes, such as progressive supranuclear palsy and Wilson disease, it may be quite a prominent feature. Abrupt onset, of course, points to vascular disease.
++
These may be the earliest and most important signs of cerebral disease. Clinically, placidity and apathy must be distinguished from the akinesia or bradykinesia of Parkinson disease and the reduced mental activity of depressive illness. Here, Alzheimer disease, normal-pressure hydrocephalus, and frontal-corpus callosum tumors are the most common pathologic states underlying apathy and placidity, but these disturbances may complicate a variety of other frontal and temporal lesions, such as those occurring with demyelinating disease or as an aftermath of ruptured anterior communicating aneurysm.
+++
Outbursts of Rage and Violence
++
Most often such an outburst is but another episode in a lifelong sequence of sociopathic behaviors (see Chap. 51). More significance attaches to its abrupt appearance as a sudden departure from an individual's normal personality. If an outburst of rage accompanies a seizure, the rage should be viewed as the consequence of the disruptive effect of seizure activity on temporal lobe function; however, as indicated earlier, an outburst of uncontrolled rage and violence is only rarely a manifestation of temporal lobe epilepsy. Lesser degrees of poorly directed combative behavior as part of ictal or postictal automatism are more common. Rarely, rage and aggressivity are expressive of an acute neurologic disease that involves the mediotemporal and orbitofrontal regions, such as a glioma. We have several times observed such states in the course of a dementing disease and in a stable individual as a transient expression of an obscure encephalopathy.
++
Rage reactions with continuous violent activity must be distinguished from mania, in which there is flight of ideation to the point of incoherence, euphoric or irritable mood, and incessant psychomotor activity; from organic drivenness, in which continuous motor activity, accompanied by no clear ideation occurs, usually in a child, as an aftermath of encephalitis; and from extreme instances of akathisia, where incessant restless movements and pacing may occur in conjunction with extrapyramidal symptoms.
+++
Extreme Fright and Agitation
++
Here the central problem must be clarified by determining whether the patient is delirious (clouding of consciousness, psychomotor overactivity, and hallucinations), deluded (schizophrenia), manic (overactive, flight of ideas), or experiencing an isolated panic attack (palpitation, trembling, feeling of suffocation). Rarely does panic prove to be an expression of temporal lobe epilepsy. In an adult without a characterologic trait of anxiety, an acute panic attack may signify the onset of a depressive illness or schizophrenia.
+++
Bizarre Ideation Developing over Weeks or Months
++
Although these symptoms are usually caused by a psychosis (schizophrenia or bipolar disease), one should consider a tumor, immune or paraneoplastic encephalitis, or other lesion of the temporal lobe, particularly when accompanied by temporal lobe seizures, aphasic symptoms, rotatory vertigo (rare), and quadrantic visual field defects. Such states have also been described in hypothalamic disease, suggested by somnolence, diabetes insipidus, visual field defects, and in hydrocephalus (see Chap. 27).