Alterations in cerebral laterality during acute psychotic illness.

A dichotic listening test was used to assess cerebral laterality in 26 right-handed patients with schizophrenic, schizoaffective, or primary major depressive illness and in 23 controls. Clinical state was assessed by twice-daily nurses' ratings and patient self-ratings. Ratings of psychotic thought and behavior were lower during the week of highest laterality than during the week of lowest laterality (P less than .01). Similarly, when most improved, patients had higher laterality than when most ill (P less than .01). Changes in laterality were not specific to diagnostic group, were not present in control subjects, could not be related to direct drug effects, and were independent of changes in accuracy of performance. There were large, stable, interindividual differences in degree of lateralization, but no differences between patients and controls. These results are consistent with the hypothesis that in acute psychotic illness there is a breakdown in the interhemisphere inhibition that normally mediates cerebral laterality.

Possible subtypes of affective disorder suggested by differences in cerebral laterality and testosterone. A preliminary report.

Two language-related dichotic listening tests of cerebral laterality were used to divide a group of 18 hospitalized patients with affective disorder into two subgroups of nine. The groups proved to differ in serum testosterone levels at the time of admission and in mean serum testosterone levels throughout hospitalization. Moreover, there was a positive correlation between testosterone level and symptom severity in one of the laterality-defined subgroups and a negative correlation in the other. These data (1) provide new evidence of pathophysiological heterogeneity within a single general diagnostic group; (2) suggest that noninvasive, inexpensive, and easily administered dichotic listening tests may be able to define pathophysiologically meaningful subgroups; and (3) suggest a role for testosterone-related alterations in left hemisphere function in the pathogeneses of some affective disorders.

Neurocognitive enhancement therapy with work therapy: effects on neuropsychological test performance.

BACKGROUND: Cognitive deficits are a major determinant of social and occupational dysfunction in schizophrenia. In this study, we determined whether neurocognitive enhancement therapy (NET) in combination with work therapy (WT) would improve performance on neuropsychological tests related to but different from the training tasks. METHODS: Sixty-five patients with schizophrenia or schizoaffective disorder were randomly assigned to NET plus WT or WT alone. Neurocognitive enhancement therapy included computer-based training on attention, memory, and executive function tasks; an information processing group; and feedback on cognitive performance in the workplace. Work therapy included paid work activity in job placements at the medical center (eg, mail room, grounds, library) with accompanying supports. Neuropsychological testing was performed at intake and 5 months later. RESULTS: Prior to enrollment, both groups did poorly on neuropsychological testing. Patients receiving NET + WT showed greater improvements on pretest-posttest variables of executive function, working memory, and affect recognition. As many as 60% in the NET + WT group improved on some measures and were 4 to 5 times more likely to show large effect-size improvements. The number of patients with normal working memory performance increased significantly with NET + WT, from 45% to 77%, compared with a decrease from 56% to 45% for those receiving WT. CONCLUSIONS: Computer training for cognitive dysfunction in patients with schizophrenia can have benefits that generalize to independent outcome measures. Efficacy may result from a synergy between NET, which encourages mental activity, and WT, which allows a natural context for mental activity to be exercised, generalized, and reinforced.

Word and tone working memory deficits in schizophrenia.

BACKGROUND: Verbal memory deficits have been reported in many studies of patients with schizophrenia. We evaluated the specificity of these deficits by comparing patients and control subjects on several verbal and nonverbal auditory memory tests. METHODS: Performance of stable, medicated outpatients with DSM-III-R diagnoses of schizophrenia (N = 38) was compared with that of healthy subjects (N = 39) on a word list immediate recall task, tone delayed discrimination tasks, and word and tone serial position tasks. Before memory testing, patients were divided into 2 groups based on their ability to perform normally on a screening test requiring pitch discrimination and sustained attention. RESULTS: The nonverbal tests were more difficult for control subjects than the verbal tests. Despite this, patients who performed normally on the screening test of perception and attention performed normally on both nonverbal tests but had highly significant deficits on both verbal tests (P<.001 and P = .02). Patients who performed poorly on the screening test had highly significant performance deficits on all the memory tests. CONCLUSIONS: One subgroup of patients with schizophrenia has a selective deficit in verbal memory despite normal motivation, attention, and general perceptual function. Another group has deficits in multiple aspects of cognitive function suggestive of failure in early stages of information processing.

Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging.

BACKGROUND: Verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. We have demonstrated that such deficits do not extend to working memory for tones in a substantial number of patients even when verbal working memory is impaired. In this study we used functional magnetic resonance imaging to study the neural basis of this dissociation of auditory verbal and nonverbal working memory in individuals with schizophrenia. METHODS: While undergoing functional magnetic resonance imaging, 12 schizophrenic patients and 12 matched control subjects performed auditory Word Serial Position Task and Tone Serial Position Task. RESULTS: Both tasks produced activation in frontal cortex and temporal and parietal lobes of the cerebrum in both groups. While robust activation was observed in the left inferior frontal gyrus (areas 6, 44, and 45) in the control group during the Word Serial Position Task, activation in the patient group was much reduced in these areas and failed to show the same task-specific activation as in controls. Reduced activation in patients was not confined to the inferior frontal gyrus, but also extended to a medial area during the Tone Serial Position Task and to premotor and anterior temporal lobe areas during both tasks. CONCLUSIONS: These findings support the hypothesis that abnormalities in cortical hemodynamic response in the inferior frontal gyrus underlie the verbal working memory deficit in schizophrenia. The relationship of verbal working memory deficits to other cognitive functions suggests that abnormal functioning in the speech-related areas may reflect a critical substrate of a broad range of cognitive dysfunctions associated with schizophrenia.

Cerebral laterality, perception of emotion, and treatment response in obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) had lower right-ear advantages than healthy controls on five different language-related dichotic listening tests of cerebral laterality. This abnormality was more pronounced in patients with more severe illness. Stimulus pairs in one test consisted of one word with a positive emotional valence and one emotionally neutral word. Pairs in another test consisted of one negative and one neutral word. Patients with OCD tended to hear fewer emotion-related words than did healthy controls, a finding also noted in depressed patients. Moreover, OCD patients who responded to treatment with serotonin reuptake inhibitors heard fewer emotion-related words than did nonresponders.

Cerebral laterality, symptoms, and diagnosis in psychotic patients.

A dichotic nonsense test and a dichotic word test were used to assess cerebral laterality in 100 acutely symptomatic inpatients. Schizophrenic patients had significantly lower right ear advantages (REAs) than healthy controls, depressed patients, or schizoaffective patients. Manic patients did not differ from any other group, but manics with lower REAs were likely to have more symptoms of thought disorder than of mood disturbance while the reverse was likely to be true for manic patients with higher REAs. A subset of patients tested after symptom remission showed recovery-related increases in REA on the nonsense test and decreases on the word test, replicating previous findings. Those schizophrenics with evidence of greater disease-related decreases in REA on the nonsense than on the word test had predominantly negative symptoms whereas those with similar changes on the two tests had predominantly positive symptoms. These observations suggest the hypothesis that positive symptoms are related to overactivation of a dysfunctional left hemisphere by right hemisphere input while negative symptoms reflect a left hemisphere deficit state.

Affective reactivity of cognitive functioning and family history in schizophrenia.

This article reports the results of two related studies investigating the association between affective reactivity of cognitive functioning in schizophrenia and family psychiatric history. In Study #1, we examined affective reactivity of positive formal thought disorder symptoms in 29 schizophrenic inpatients. We found that thought disorder was greatly exacerbated by negative affect in those patients with a family history of schizophrenia (SFH) (n = 11), and not in those without the family history (SNFH) (n = 18). In Study #2, we replicated this finding with a stable outpatient sample (n = 10). We also administered dichotic listening tests using affectively neutral and affectively negative stimuli, and found that right-ear advantage was more markedly diminished on the affectively negative task than on the neutral task in the SFH (n = 6) but not the SNFH (n = 4) subjects. These findings support our hypothesis that cognitive symptoms in schizophrenia are exacerbated by negative affect, and that this affective reactivity of symptoms is associated with a familial form of the disorder.

Behavioral laterality in individuals with Gilles de la Tourette's syndrome and basal ganglia alterations: a preliminary report.

This study aims to investigate whether abnormalities in structural basal ganglia asymmetries in Tourette's syndrome (GTS) have functional significance. Eleven adult GTS patients and 11 normal controls who had participated in the previous MRI study where GTS patients lacked the normal left-greater-than-right (L > R) lenticular asymmetry were re-recruited. They were administered a battery of lateralizing neuropsychological tasks believed to require intact basal ganglia function. GTS subjects lacked normal functional asymmetries on these measures, as predicted. The neuropsychological measures also accounted for a significant portion of the variance in the severity of tic symptoms. These findings suggest that GTS subjects who lack normal basal ganglia structural asymmetries also lack normal functional asymmetries on related neuropsychological measures.

Cerebral laterality and psychiatry: a review of the literature.

The two sides of the human brain are functionally and anatomically different. Research methods based on this cerebral laterality have been used to investigate regional brain function in psychiatric illness. The author describes the functional and anatomic differences between the two sides of the brain, the research methods based on these differences, and the results of studies that have used these methods to investigate brain dysfunction in psychiatric illness.

Preliminary evidence of improved verbal working memory performance and normalization of task-related frontal lobe activation in schizophrenia following cognitive exercises.

OBJECTIVE: The authors' goal was to evaluate the possibility of treating brain and behavioral aspects of verbal memory dysfunction in patients with schizophrenia through cognitive exercises. METHOD: Eight patients did daily verbal memory exercises that became progressively more difficult over a 10-week training period. Memory performance and regional brain activations during a verbal memory task were assessed before and after these exercises. RESULTS: Verbal but not nonverbal memory performance improved after training; three patients made substantial gains, and five showed little change. Performance gains were correlated with increases in task-related activation of the left inferior frontal cortex. One patient given 5 extra weeks of training 6 weeks after the initial training period showed maintenance of initial performance gains 6 weeks after training, further improvement after the second period of training, and normalization of task-related activation of the left inferior frontal cortex. CONCLUSIONS: Verbal memory deficits can be ameliorated by memory exercises in some patients with schizophrenia. Performance improvements are associated with increased task-related activation of the same brain region that is activated during verbal memory tasks in healthy individuals.

Neuroleptic exposure following inpatient treatment of acute mania with lithium and neuroleptic.

The authors examined continued neuroleptic exposure following inpatient treatment of mania with neuroleptics and lithium through structured chart review of 40 consecutive patients. At discharge, patients were receiving a mean of 793 mg/day (SD = 695) chlorpromazine equivalents; 6 months later they were receiving a mean of 634 mg/day (SD = 684). This decrease was statistically significant, but the patients' ongoing neuroleptic exposure remained substantial.

Functional magnetic resonance imaging of cocaine craving.

OBJECTIVE: Identification of brain activity associated with craving is important for understanding the neurobiology of addiction. METHOD: Brain activity was measured in cocaine addicts and healthy subjects by functional magnetic resonance imaging (fMRI) while the subjects watched videotapes designed to elicit happy feelings, sad feelings, or the desire to use cocaine. The subjects indicated the onset of drug craving or emotional response, allowing comparison of groups before and after such feelings. RESULTS: Robust activation of the anterior cingulate was evident in patients watching cocaine-cue tapes but not in patients watching happy or sad tapes or in healthy subjects under any condition. Anterior cingulate activation preceded the reported onset of craving and was evident in patients who did not report craving. In contrast, patients showed less activation than healthy subjects during the cocaine-cue tapes in areas of the frontal lobes. After the reported onset of craving, cocaine-dependent subjects showed greater activity than healthy subjects in regions that are more active in healthy subjects when they watch sad tapes than when they watch happy tapes, suggesting a physiologic link between cocaine-cue responses and normal dysphoric states. Dynamic aspects of regional brain activations, but not the location of activations, were abnormal in cocaine-dependent subjects watching sad tapes, suggesting more general affective dysregulation. Patients showed low activation of sensory areas during initial viewing of all videotapes, suggesting generalized alteration in neuroresponsiveness. CONCLUSIONS: Cocaine cues lead to abnormally high cingulate and low frontal lobe activation in cocaine addicts. Addicts also show more general abnormalities in affect-related brain activation.

Sex differences in change over time in perceptual asymmetry.

Male (N = 36) and female (N = 43) subjects were given a 120 trial, fused dichotic word test. Males showed higher right ear advantages on the first 60 trials, that then decreased over the next 60 trials. Females showed lower right ear advantages on the first 30 trials, that then increased. The two groups had equal mean asymmetry scores for the last 60 trials. These data suggest that males respond to the novelty of a new task with relative left hemisphere activation while females respond with relative right hemisphere activation. There are no previous reports of sex differences in changes in asymmetry over time.

Dichotic listening tests in studying brain-behavior relationships.

The magnitude of perceptual asymmetry (PA) on a CVC fused dichotic words test and on VCV and CV fused nonsense syllables tests were compared. In each test the set of distinguishing phonemic cues was the same; the six English stop consonants, b,p,d,t,g,k. Although test-retest reliability was very high on all three tests there was no correlation across individuals between the degrees of PA on different tests. Moreover, the magnitude of PA on the VCV nonsense test increased as field dependence (FD) increased on the field dependence index (FDI) of the WAIS while there was no relationship between FD and the magnitude of PA on the CVC words test. In addition, concurrent visual tasks increased PA on the VCV nonsense test and decreased it on the words test. In order to facilitate the use of such data, Kimura's classical model of the physiological basis of PA is modified by including components of primary receptive and secondary and tertiary associative function. Comparison of highly similar PA measures, that differ in specific ways, is discussed as a means of collecting data for mapping cerebral functional space and exploring brain-behavior relationships.

Within-modal and cross-modal consistency in the direction and magnitude of perceptual asymmetry.

Three auditory and three visual tests of PA were administered to 45 healthy dextrals in order to evaluate within-modal and cross-modal consistency in the direction and magnitude of perceptual asymmetry (PA). Thirty-three subjects were retested after a 4-8 week interval to determine reliability of individual measures and stability of inter-test relationships. Pairs of visual and auditory tests consisted of exactly the same stimuli. Within-modal and cross-modal concordance in the direction of PA was high, providing additional empirical support for existing models of the neural basis of PA. Cross-modal correlations in the magnitude of PA were near zero despite highly significant within-modal correlations. Meaningfulness of the stimuli did not affect the magnitude of PA, although the presence of an orienting expression prior to each dichotic pair did. These three observations provide new information about the neural processes that determine the magnitude of PA.

Increasing the power of dichotic methods: the fused rhymed words test.

A dichotic test made up of monosyllabic rhymed CVC words was modified to minimize stimulus dominance and errors and then administered to 194 dextrals and 175 sinistrals in four different laboratories. The proportion of subjects with left ear advantages in both the right and left-handed groups closely approximated that expected from neurologic data. This dichotic test appears to reflect hemispheric specialization for language function more accurately than previously available tests. Further direct validation studies are needed, however, comparing direction of ear asymmetry and other indices of hemispheric specialization for language on a subject by subject basis.

Changes in perceptual asymmetry with the menstrual cycle.

Changes in perceptual asymmetry between the premenstrual and postmenstrual phases of the menstrual cycle were assessed in 39 women. Perceptual asymmetry was measured with fused, single response dichotic listening tests. The usual right ear advantage (REA) for auditory language-related stimuli was significantly greater in the postmenstrual phase of the cycle. Subjects with repressive personality styles were less likely to show a change in REA with the cycle. These neuropsychological findings are related to previously described physiological and psychological features of the menstrual cycle and the repressive personality style.

Effects of emotion on perceptual asymmetry: interactions with personality.

Perceptual asymmetry on a series of four specially constructed dichotic word tests was found to change as a function of the emotional quality of the words in the tests (P = 0.05). This was most pronounced in the case of positively valued words which produced an increase in asymmetry consistent with facilitated left-hemisphere function (P less than 0.004). Changes in asymmetry with emotion differed as a function of personality characteristics of the subjects, with repressors and high anxious subjects showing an increase with emotion while true low anxious subjects showed a decrease (P less than 0.02). Personality groups also differed in asymmetry on an emotionally neutral test (P less than 0.04) and in changes in asymmetry over time independent of emotion (P less than 0.001). These data suggest that emotion mediated activation of the left hemisphere may facilitate information processing within that hemisphere. Moreover, they indicate that dichotic listening tests may provide a non-invasive and inexpensive method for assessing emotion mediated changes in brain state that are clinically relevant.

EEG and EMG responses to emotion-evoking stimuli processed without conscious awareness.

Dichotic stimulus pairs were constructed with one word that was emotionally neutral and another that evoked either negative or positive feelings. Temporal and spectral overlap between the members of each pair was so great that the two words fused into a single auditory percept. Subjects were consciously aware of hearing only one word from most pairs; sometimes the emotion-evoking word was heard consciously, other times the neutral word was heard consciously. Subjects were instructed to let their thoughts wander in response to the word they heard, during which time EEG alpha activity over left and right frontal regions, and muscle activity (EMG) in the corrugator ("frowning") and zygomatic ("smiling") regions were recorded. Both EEG and EMG provided evidence of emotion-specific responses to stimuli that were processed without conscious awareness. Moreover both suggested relatively greater right hemisphere activity with unconscious rather than conscious processing.