Hemispheric specialization in emotion: attention, arousal, and EEG activation in unilateral temporal lobe epilepsy.

To investigate the neural processing of emotion in right and left temporal lobe epilepsy (TLE), we monitored EEG during neutral and emotionally positive and negative auditory stimulation. Left TLE patients displayed increased right lateralization and a negative emotional stimulus rating bias, while right TLE patients did not. This EEG arousal and negative affect may reflect deactivated inhibition of the right hemisphere, symptomatically expressed as arousal and anxiety. Failure to increase lateralization to emotional stimuli in right TLE may reflect compromised emotional attention/arousal centers in the right hemisphere. Results support a two-dimensional theory of the neural processing of emotion.

A direct comparison of PET activation and electrocortical stimulation mapping for language localization.

Mapping eloquent language cortex in presurgical patients typically is accomplished using highly invasive direct cortical stimulation techniques. Functional imaging during language activation using positron emission tomography (PET) is a promising, noninvasive alternative that requires validation. In seven patients undergoing surgical evaluation for intractable epilepsy, we performed both direct cortical stimulation and PET activation mapping of language cortex using identical tasks. MRI, PET, and CT scans were coregistered to directly compare the location of language centers determined by cortical stimulation versus activation PET. We found that cortical regions that showed increased cerebral blood flow during both visual and auditory naming tasks were located in the same regions as subdural electrodes which disrupted language during electrical stimulation. Cortical regions underlying electrodes that did not disrupt language also showed no consistent changes in regional cerebral blood flow during PET activation. Used cautiously, PET activation produces language maps similar to those obtained with direct cortical stimulation, with more complete brain coverage and considerably less invasion.

Semantic, phonological, and perceptual changes following left and right intracarotid injection (Wada) with a low amytal dosage.

Intracarotid injection of a low dosage of amobarbital (75 mg, 5% solution) was studied in 30 temporal lobectomy candidates while naming achromatic, incongruously, and congruously colored pictorial objects and reading real, nonsense, and embedded words. Semantic errors and phonological alexia followed the left injection, while the right injection induced visuoperceptual errors. When the contralateral hemisphere was anesthetized, the left brain formulated supraordinate categories for words and objects, while the right brain applied concrete labels. The basic language proficiency of patients influenced recovery and outcome; left temporal patients who were interictally anomic performed especially poorly after both injections. Codifying phonological and perceptual changes during the intracarotid amobarbital procedure can improve interpretations about language laterality and organization.

Emotional arousal in temporal lobectomy: autonomic and performance effects of success and failure feedback.

Both theory and evidence suggest that right temporal lobectomy (RTL) patients show hypoarousal and left temporal lobectomy (LTL) patients show relative hyperarousal (Davidson, Fedio, Smith, Aurielle, & Martin, 1992). However, we hypothesized that these differences occur only under passive, nonevaluative stimulus conditions. The present study employed, instead, conditions of performance evaluation. We recorded the skin conductance responses (SCRs) and reaction times (RTs) of RTLs, LTLs, and normal controls (NCs) during easy and difficult trial blocks on a target-detection task, with auditory success/failure feedback. We found that LTLs exhibited relative hypoarousal and retarded RTs and that RTLs were normally aroused following success feedback. These results demonstrated that the arousal level of LTLs is contingent on stimulus conditions, thus calling into question the theory that this group is generally subject to hyperarousal. The two-dimensional theory of the neural processing of emotional experience partially explains our data.

Memory and intelligence in lateralized temporal lobe epilepsy and schizophrenia.

Recent neuroimaging studies of patients with schizophrenia have suggested structural and functional abnormalities of mesial temporal lobe structures. We compared the intelligence and memory test performance of 70 patients with schizophrenia and 72 patients with focal, lateralized temporal lobe epilepsy (30 left, 42 right temporal lobe) in order to examine the adequacy of a temporal lobe model of schizophrenic cognitive deficits. The groups did not differ in age, education, or Full Scale IQ. The right temporal lobe group had better overall memory performance than either the left temporal or schizophrenic patients. Unlike the schizophrenic patients, the memory impairment of the left temporal group was most evident with verbal materials and was amplified by delayed testing. Both epilepsy groups had better visual memory than the schizophrenic group. The clear differences in performance pattern between groups suggests that lateralized temporal lobe dysfunction does not by itself provide an adequate model of schizophrenic cognitive impairment.

Interictal aggression in epilepsy: the Buss-Durkee Hostility Inventory.

Adult patients with left, right, or bilateral temporal lobe epilepsy or absence epilepsy, and normal controls completed the Buss-Durkee Hostility Inventory (BDHI), a standardized questionnaire of aggressive tendencies. Patients with left temporal lobe seizure foci scores higher on the Suspicion scale than did other patients or controls (p < 0.05). Factor analysis scale scores identified three factors: hostile feelings, covert aggression, and overt aggression. The groups differed on their pattern of factor scores (p < 0.01): patients with left temporal lobe epilepsy scored higher than other groups on hostile feelings, normal controls scored higher on Covert aggression, and bitemporal patients scores higher on Overt aggression. Patients with absence seizures did not differ from controls. Lateralization of the seizure focus in patients with temporal lobe epilepsy may alter expression of aggressive behavior.

Isolated horizontal supranuclear gaze palsy as a marker of severe systemic involvement in Gaucher's disease.

Type 3 neuronopathic Gaucher's disease (GD3) is phenotypically heterogeneous. In many GD3 patients, progressive myoclonus and dementia dominate the illness, with death secondary to progressive CNS disease. We have designated this group as GD3a. We studied 14 children with Gaucher's disease, isolated horizontal supranuclear gaze palsy, and aggressive systemic disease, and designated this group as GD3b. In comparison with 13 children with type 1 non-neuronopathic Gaucher's disease, the GD3b children presented earlier, and were shorter, underweight, and more prone to cardiopulmonary, hepatic, and skeletal complications. One-half of the children died in childhood or adolescence of systemic complications. Patients with at least one copy of the mutation that causes substitution of asparagine for serine at amino acid 370 of glucocerebrosidase did not develop neurologic signs. Patients homoallelic for the mutation causing substitution of leucine for proline at position 444 had severe systemic disease; neurologic signs were frequently, but not invariably, present. Early diagnosis and timely enzyme replacement therapy promise to improve the prognosis in GD3b.

Lateralized mediation of arousal and habituation: differential bilateral electrodermal activity in unilateral temporal lobectomy patients.

The purpose of the present study was to increase our understanding of the differential hemispheric processing of arousal and habituation. Subjects were unilateral temporal lobectomy patients and controls. Each was exposed to an arousal/habituation task consisting of a series of tones and an auditory discrimination paradigm. Electrodermal activity was recorded from the left and right hands throughout. Results provide evidence for a state of hypoarousal in right temporal patients and some support for hyperarousability in lefts. This is consistent with data showing that right hemisphere damage is associated with inattention and denial and left hemisphere damage with hypervigilance and anxiety. The concept of laterally differentiated mediation of arousal and habituation was supported.

Parallel distributed processing and neuropsychology: a neural network model of Wisconsin Card Sorting and verbal fluency.

Neural networks can be used as a tool in the explanation of neuropsychological data. Using the Hebbian Learning Rule and other such principles as competition and modifiable interlevel feedback, researchers have successfully modeled a widely used neuropsychological test, the Wisconsin Card Sorting Test. One of these models is reviewed here and extended to a qualitative analysis of how verbal fluency might be modeled, which demonstrates the importance of accounting for the attentional components of both tests. Difficulties remain in programming sequential cognitive processes within a parallel distributed processing (PDP) framework and integrating exceedingly complex neuropsychological tests such as Proverbs. PDP neural network methodology offers neuropsychologists co-validation procedures within narrowly defined areas of reliability and validity.

Visuospatial cognition in Huntington's disease.

The notion of specificity of visuospatial dysfunction in Huntington's disease (HD) was evaluated in a sample of afflicted patients as a function of symptom duration, age at onset, and overall dementia severity. Factor analytic procedures indicated that overall visuospatial processing capacity (factor 1) as well as the ability for spatial manipulation (factor 3) was markedly affected in HD patients. In contrast, consistency of spatial judgment (factor 2) appeared to remain relatively intact in these patients. Age at onset seemed to have no relationship with any of these variables, whereas dementia severity demonstrated a significant relationship with overall visuospatial processing capacity. Most importantly, duration of symptoms was significantly associated with the declining ability to mentally perform spatial manipulations. The observation of circumscribed visuospatial impairment in HD patients may have important consequences for the further understanding of the neurobehavioral consequences of this disorder.

Selective deficits in Alzheimer and parkinsonian dementia: visuospatial function.

Deficits in visuospatial cognition are frequently cited as an important component of the cognitive changes accompanying Parkinson's disease. To characterize possible differences between Parkinson's (PD) and Alzheimer's (AD) dementia, patients from both groups, matched for overall dementia severity, age and education, were contrasted neuropsychologically. Visuospatial tasks dissociated from memory, were significantly compromised in both patient groups. Differential impairment was evident on visuospatial abstraction and reasoning (Object Assembly), which was most deficient in PD. Visuospatial cognition associated with memory, classified both patient groups as impaired compared to controls, but AD patients demonstrated substantially lower performance levels than those with PD. Parkinsonian dementia thus appears to have some distinct features compared to Alzheimer's disease, which may indicate differences in underlying pathogenic mechanisms.

Selective deficits in cognition and memory in high-functioning parkinsonian patients.

To evaluate the profile and extent of cognitive deficits in Parkinson's disease, afflicted patients of exceptional professional distinction, who continue to function successfully in leadership positions, were compared neuropsychologically to neurologically normal individuals, matched for sex, age, education and professional standing. While patients showed relative preservation of verbal skills and higher executive function, they exhibited a significant reduction in episodic memory and visuospatial function. The observation of circumscribed impairment in this select group of Parkinsonian patients further implicates cognitive and memory deficits as consistent features of Parkinson's disease.

Impairment of central auditory function in Alzheimer's disease.

Accuracy and laterality of ear preference on dichotic listening (DL) takes were compared in patients with Alzheimer's disease (AD) and a group of normal subjects, matched for age and education, using parameters (list length, stimulus matching, and order of recall), previously shown to significantly alter DL performance in normals. Alzheimer patients tended to show qualitatively similar, but significantly worse performance compared to controls as a function of increasing dichotic list length as well as stimulus set content (semantically, v. phonemically and unmatched dichotic items). Furthermore, these patients were unable to attend selectively to either the right- or left-ear and thus could not increase right- or left-ear advantages over the free recall procedure, an order of recall task easily mastered by the normal subjects. These results suggest that Alzheimer's disease is associated with a breakdown of cortical mechanisms involved in the selective allocation of attention.

Short-term memory impairment in cannabis-dependent adolescents.

The concentration of delta-9-tetrahydro-cannabinol in marijuana available in the United States has increased by 250% since investigations of the effects of marijuana on short-term memory first appeared in scientific journals. Moreover, previous investigations of short-term memory in long-term marijuana smokers involved adults only. We evaluated the auditory/verbal and visual/spatial memory of 10 cannabis-dependent adolescents and compared the results with performance of 17 subjects in two control groups. The control groups included 8 adolescent drug abusers who had not been long-term users of cannabis and another 9 adolescents who had never abused any drug. All three groups were matched on age, IQ, and absence of previous learning disabilities. Adolescents with a history of frequent alcohol or phencyclidine abuse were excluded from entering the study. A battery of seven neuropsychological tests was administered initially to all subjects and a parallel test battery was administered 6 weeks thereafter. Significant differences between the cannabis-dependent group and the two control groups were obtained initially on the Benton Visual Retention Test (F[2,24] = 6.07) and the Wechsler Memory Scale Prose Passages (F[2,23] = 7.04). After 6 weeks of supervised abstention from intoxicants, subjects in the cannabis-dependent group showed some significant improvement on the Wechsler Memory Prose Passages score and on the Benton Visual Retention Test; however, the improvement failed to achieve statistical significance. We concluded that cannabis-dependent adolescents have selective short-term memory deficits that continue for at least 6 weeks after the last use of marijuana.

Clonidine treatment of Alzheimer's disease.

A loss of cortical noradrenergic innervation may contribute to the intellectual deterioration in Alzheimer's disease. To test the hypothesis that noradrenergic replacement may confer symptomatic benefit, a double-blind, placebo-controlled therapeutic trial with clonidine hydrochloride (Catapres), a centrally active noradrenergic receptor agonist, was undertaken in eight patients with the clinical diagnosis of Alzheimer's disease. No statistically significant changes in cognitive function were found over a range of doses, including those that produced clinically observable side effects. These preliminary results indicate a need for alternative noradrenergic replacement strategies in Alzheimer's disease.

Dopamine and memory function in Parkinson's disease.

Response fluctuations in motor function, complicating long-term dopaminomimetic therapy of Parkinson's disease, may extend to the cognitive realm. To evaluate the effect of levodopa treatment both on attention as well as acquisition and retrieval of memory tasks, parkinsonian patients were examined neuropsychologically both while medicated with levodopa/carbidopa ("on") and when the medication's antiparkinsonian effect had worn off ("off"). Significant cognitive differences emerged only on the delayed recall of complex verbal materials, where patients when "on" performed better compared with their "off" state. Comparison of change scores across states (administration or withholding of levodopa/carbidopa between acquisition and retrieval, "off" to "on" or "on" to "off"), revealed no substantial differences as a function of dopaminomimetic therapy. These results support the view that slight changes in cognition are associated with dopaminomimetic therapy of Parkinson's disease, but that these changes may be task-specific.

Relation of EEG alpha background to parietal lobe function in Alzheimer's disease as measured by positron emission tomography and psychometry.

Fourteen patients with Alzheimer's disease were evaluated by psychometric testing, fluorodeoxyglucose positron emission tomography (PET), and EEG. They were divided into two groups according to the EEG findings. Group A (seven patients) had normal alpha backgrounds and group B (seven patients) had decreased alpha backgrounds. Group A had significantly higher WAIS Performance IQ scores (p = 0.005) than group B. Group A also had higher Weschler Memory Scale scores (p = 0.047) and parietal glucose metabolic rates (p = 0.038) than group B, but these differences are not statistically significant given the multiple comparisons made between the two groups. Relative intactness of parietal lobe function, as measured by psychometric testing and PET, appears to correlate with preservation of EEG alpha background. The EEG may be useful in assessing regional cortical involvement or the clinical stage in Alzheimer's disease.

Cognitive concomitants of dopamine system stimulation in parkinsonian patients.

Verbal, visuospatial and motor functions were studied in eight Parkinsonian patients both during levodopa stimulated and unstimulated state and in eight matched, untreated, healthy controls. Profound changes in patients' motor status were accompanied by relatively selective effects on delayed verbal memory, a function which was also most impaired compared with controls. With dopaminomimetic therapy, tests of delayed verbal memory consistently improved, but did not reach control performance levels. These results could indicate a functional impairment in the mesocortical dopamine system, which can be attenuated, but not entirely corrected, by dopaminomimetic therapy.

Alzheimer's disease: low cerebral somatostatin levels correlate with impaired cognitive function and cortical metabolism.

Somatostatin-like immunoreactivity in Alzheimer CSF was significantly lower than in that from age-matched controls. The degree of reduction correlated with indices of intellectual impairment and decline in cortical glucose utilization as determined by PET. There was a close association between reduction in CSF somatostatin and glucose hypometabolism in the parietal lobe. In postmortem cortical tissue from Alzheimer patients, somatostatin levels were lower in posterior parietal but not in anterior frontal cortex. Loss of somatostatin-containing neurons, especially in the parietal association cortex, may be a critical determinant for Alzheimer dementia.