A comparison of occipital and temporal lobe epilepsies.

PURPOSE: Differentiating between occipital lobe epilepsy (OLE) and temporal lobe epilepsy (TLE) is often challenging. This retrospective case-control study compares OLE to TLE and explores markers that suggest the diagnosis of OLE. METHODS: We queried the Jefferson Epilepsy Center surgery database for patients who underwent a resection that involved the occipital lobe. For each patient with OLE, three sequential case-control patients with TLE were matched. Demographic characteristics, symptoms, electrophysiological findings, imaging findings, and surgical outcome were compared. RESULTS: Nineteen patients with OLE and 57 patients with TLE were included in the study. Visual symptoms were unique to patients with OLE (8/19) and were not reported by patients with TLE (P < 0.0001). Occipital interictal spikes (IIS) were found only in one-third of the patients with OLE (6/19) and in no patients with TLE (P < 0.0001). IIS in the posterior temporal lobe were found in five of 19 patients with OLE vs one of 57 patients with TLE (P = 0.003). IIS involved more than one lobe of the brain in most patients with OLE (11/19) but only in nine of 57 the TLE group. (P = 0.0003) Multilobar resection was needed in most patients with OLE (15/19), typically including the temporal lobe, but in only one of the patients with TLE (P < 0.0001). CONCLUSION: Occipital lobe epilepsy is difficult to identify and may masquerade as temporal lobe epilepsy. Visual symptoms and occipital findings in the EEG suggest the diagnosis of OLE, but absence of these features, does not exclude the diagnosis. When posterior temporal EEG findings or multilobar involvement occurs, the diagnosis of OLE should be considered.

The association of mood with quality of life ratings in epilepsy.

OBJECTIVE: To determine the relative contributions of psychological (mood and anxiety), social, and seizure-related variables to quality of life (QOL) scores in epilepsy. METHODS: Outpatients (n = 435) with epilepsy completed the Quality of Life in Epilepsy 31 Inventory (QOLIE-31), Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory, and a social survey. Stepwise linear regression and general linear model analyses determined the set of best predictors and the most unique predictors of composite QOLIE-31 score and subscale scores. RESULTS: A three-variable model accounted for 56% of the variance for the composite QOLIE-31 score. The BDI-II was the strongest (often by several multiples in terms of variance explained) and most consistent predictor of the composite and QOLIE subscales in both types of analytic approaches. In no case did BDI-II significantly interact with the other variables, suggesting that its effect on QOL was direct and not mediated by other factors. Throughout the results, depression had an inverse relation to scores, i.e., lower levels of depression correlated with high QOL scores. Separate correlational analyses showed that poor seizure control was associated with increased numbers of depressive symptoms. DISCUSSION: Quality of Life in Epilepsy (QOLIE) scores, reflecting both general and specific aspects of quality of life, are strongly influenced by mood state, such as depression. Factors such as seizure control exert a more limited effect on the QOLIE. Health-related quality of life measures are needed in which mood does not play such a dominant role.

Differential brain responses when applying criterion attribute versus family resemblance rule learning.

Subsystems of category learning have been identified on the basis of general domains of content (e.g., tools, faces). The present study examined categories from the standpoint of internal structure and determined brain topography associated with expressing two fundamentally different category rule structures (criterion attribute, CA, and family resemblance, FR). CA category learning involves processing stimuli by isolated features and classifying by properties held by all members. FR learning involves processing stimuli by integral wholes and classifying on overall similarity among members without sharing identical features. fMRI BOLD response to CA and FR categorization was measured with pseudowords as stimuli. Category knowledge for both tasks was mastered prior to brain imaging. Areas of activation emerged unique to the structure of each category and followed from the nature of the rule abstraction procedure. CA categorization was implemented by strong target monitoring and expectation (medial parietal), rule maintenance in working memory, feature selection processes (inferior frontal), and a sensitivity to high frequency components of the stimulus such as isolated features (anterior temporal). FR categorization, consistent with its multi-featural nature, involved word-level processing (left extrastriate) that evoked articulatory rehearsal (medial cerebellar). The data suggest category structure is an important determinant of brain response during categorization. For instance, anterior temporal structures may help attune visual processing systems to high frequency components to support the learning of criterial, highly predictive rules.

Cerebellar mediation of the complexity of bimanual compared to unimanual movements.

OBJECTIVE: To study rapidly alternating movements under fMRI in order to identify the brain regions that mediate increased complexity in bimanual vs unimanual movements and to verify the localization of a clinical test of limb ataxia (diadochokinesis). METHODS: Unimanual and bimanual movements, that is, palm(s) pronated then supinated, served as stimulation in a block design fMRI investigation at 1.5 T. Analyses compared bimanual movements and rest for each hand separately and the unimanual conditions combined. A pronation/supination task was chosen as it provides the same objective motor output during unimanual and bimanual formats. The increased coordination demand of the bimanual format (phase/antiphase movements) was expected to result in distinct activation in supplementary motor, primary motor, prefrontal, and cerebellar regions. RESULTS: The bimanual task uniquely elicited responses in specific anterior medial and posterior (vermal) cerebellar regions. CONCLUSIONS: The study corroborated clinical use of diadochokinesis tasks to test for aspects of cerebellar integrity. The data do not support the literature emphasizing basal ganglia mediation of this type of coordinated movement. Cerebellar medial and vermal regions (in connection with central nuclei) are proposed as the locus within the cerebellum for mediating complexity, that is, the effective integration of separate limb movements that proceed in an asynchronous but systematic fashion.

Test of a potential link between analytic and nonanalytic category learning and automatic, effortful processing.

The link between automatic and effortful processing and nonanalytic and analytic category learning was evaluated in a sample of 29 college undergraduates using declarative memory, semantic category search, and pseudoword categorization tasks. Automatic and effortful processing measures were hypothesized to be associated with nonanalytic and analytic categorization, respectively. Results suggested that contrary to prediction strong criterion-attribute (analytic) responding on the pseudoword categorization task was associated with strong automatic, implicit memory encoding of frequency-of-occurrence information. Data are discussed in terms of the possibility that criterion-attribute category knowledge, once established, may be expressed with few attentional resources. The data indicate that attention resource requirements, even for the same stimuli and task, vary depending on the category rule system utilized. Also, the automaticity emerging from familiarity with analytic category exemplars is very different from the automaticity arising from extensive practice on a semantic category search task. The data do not support any simple mapping of analytic and nonanalytic forms of category learning onto the automatic and effortful processing dichotomy and challenge simple models of brain asymmetries for such procedures.

A comparison of memory for verbal and non-verbal material in schizophrenia.

Verbal memory impairment has been well explored in schizophrenia, but it is unclear whether findings relate to the type of material to be learned or the component process required by the memory task. Also, sparse data on non-verbal memory also open the question of how well schizophrenia patients encode this material. We tested whether episodic memory performance in schizophrenia varies as a function of stimulus material (verbal/non-verbal) and determined the integrity of various component memory processes. Memory tests that differ in stimulus material (words, California Verbal Learning Test, CVLT; designs, Biber Figure Learning Test-Extended, BFLT-E) yet produce similar memory component measures were used. Subjects were 28 neuroleptic-medicated inpatients with a diagnosis of chronic schizophrenia. Results showed that both verbal and non-verbal memory performance was impaired relative to age-matched controls. Learning and recall measures were most severely impaired, with memory storage problems and impairment in recognition memory evident. On the verbal task, the relative sparing of recognition memory suggested retrieval processes, in addition to encoding processes, were disrupted. On the non-verbal task, the deficits appeared more limited to encoding. Therefore, while the operational integrity of components such as encoding were compromised regardless of material, retrieval processes showed material-specific effects. To the degree verbal and non-verbal memory functions can be lateralized in the brain, these data support the possibility of deficits in both right and left hemisphere declarative memory systems in schizophrenia.

Anticholinergicity and cognitive processing in chronic schizophrenia.

Patients with chronic schizophrenia suffer from alterations in cholinergic functioning due to several factors, including the disease diathesis and pharmacologic treatments. Acetylcholine-cognition relationships are well explored in normals but are unclear in schizophrenia. Prior work indicated serum anticholinergicity does not cause global cognitive impairment in this group (Tracy et al., 1998a), raising the possibility that anticholinergicity normalizes an abnormal hyperactive cholinergic state. Serum anticholinergic levels were determined in 38 chronic schizophrenia patients using an established radioreceptor assay method. Six cognitive functions associated with cholinergic tone in normals were tested. The potential role of autonomic arousal and cigarette smoking were also assessed as both have been linked to cholinergic functioning. Regression analyses showed measures of inhibitory executive control and effortful memory accounted for a greater proportion of the variance in the anticholinergicity measure compared to the other variables. The data demonstrate a relationship between high anticholinergicity and worse performance on two types of attention-resource demanding cognitive processes and do not support the notion that reduced cholinergic tone normalizes a hyperactive cortical acetylcholine substrate. Relevant neuroanatomic structures and implications for models of cognitive deficits in schizophrenia are discussed.

A comparison of 'Early' and 'Late' stage brain activation during brief practice of a simple motor task.

This research study addresses the question: does the neural circuit implementing a motor task undergo change as a function of even limited practice? To detect potential neural changes associated with limited practice we compared brain activation at the early and late stages of motor performance on a simple task over one relatively brief session. Single-finger opposition served as cognitive stimulation during collection of BOLD fMRI signal. We predicted prefrontal cortex activation would be prominent early, with basal ganglia activation becoming prominent during late stage performance. Results revealed that both early and late performance involve areas in the cerebellum, prefrontal, mid-temporal, extrastriate, and parietal cortices, but that the particular regions within these broad areas differed for the two points of performance. The strongest dissociation between early and late performance involved the corpus striatum, thalamus, and cingulate gyrus. The findings suggested the neural circuit implementing this simple task varied over a relatively brief window of practice. Implications for defining the neurocognitive function of the structures involved, particularly the cerebellum, are discussed.

Investigation of alternating and continuous experimental task designs during single finger opposition fMRI: a comparative study.

The purpose of this study was to empirically investigate and compare the effects of alternating and continuous experimental task designs on blood oxygenation level dependent (BOLD) signal contrast. Six healthy volunteers underwent single-finger opposition functional magnetic resonance imaging (fMRI) using T2*-weighted echo planar imaging technique on a 1.5 T MR scanner. Two different acquisition patterns were tested: alternating (ABABAB) and continuous (AAABBB), rest: A, activation: B. The BOLD signal contrast within a primary motor cortex region of interest (ROI) was evaluated using normalized t-values (z-scores) and mean region of interest (ROI) intensity for the two patterns. Analysis of variance (ANOVA) on ROI mean z-score and signal intensities demonstrate that the alternating pattern of administering rest and activation epochs produced a more robust statistical difference than a continuous pattern. The results showed that different patterns of acquisition yield differences in the BOLD signal at field strength of 1.5 T, and that an alternating task design can be considered more optimal than a continuous task design.

Functional localization of a "Time Keeper" function separate from attentional resources and task strategy.

The functional neuroanatomy of time estimation has not been well-documented. This research investigated the fMRI measured brain response to an explicit, prospective time interval production (TIP) task. The study tested for the presence of brain activity reflecting a primary time keeper function, distinct from the brain systems involved either in conscious strategies to monitor time or attentional resource and other cognitive processes to accomplish the task. In the TIP task participants were given a time interval and asked to indicate when it elapsed. Two control tasks (counting forwards, backwards) were administered, in addition to a dual task format of the TIP task. Whole brain images were collected at 1.5 Tesla. Analyses (n = 6) yielded a statistical parametric map (SPM ¿z¿) reflecting time keeping and not strategy (counting, number manipulation) or attention resource utilization. Additional SPM ¿z¿s involving activation associated with the accuracy and magnitude the of time estimation response are presented. Results revealed lateral cerebellar and inferior temporal lobe activation were associated with primary time keeping. Behavioral data provided evidence that the procedures for the explicit time judgements did not occur automatically and utilized controlled processes. Activation sites associated with accuracy, magnitude, and the dual task provided indications of the other structures involved in time estimation that implemented task components related to controlled processing. The data are consistent with prior proposals that the cerebellum is a repository of codes for time processing, but also implicate temporal lobe structures for this type of time estimation task.

The effect of autonomic arousal on attentional focus.

This study investigates the effect of arousal on visual selection processes. Arousal is predicted to narrow the window of attention surrounding a point of focus. BOLD response to a letter discrimination task was measured under aroused (aversive noise) and non-aroused conditions (n = 8). Results revealed spatially distinct responses for trials invoking a narrow versus wide attentional focus. Under arousal a wide focus showed posterior thalamic activation similar to that associated with the narrowed attentional focus. This reflects altered stimulus filtering and supported the hypothesis. Relevant neuroanatomy involving the locus coeruleus and a triangular circuit of selective attention is discussed. The data demonstrates the intersection of arousal and visual stimulus selection systems, identifies a cognitive consequence of arousal, and provides the first fMRI evidence for brain stem autonomic arousal.

Does akathisia influence psychopathology in psychotic patients treated with clozapine?

BACKGROUND: Akathisia has been reported to predict more severe symptoms and poorer treatment response to typical neuroleptics among patients with schizophrenia. Akathisia has also been associated with symptom exacerbation. This study addressed four questions: 1) Does akathisia predict greater severity in global psychopathology? 2) Is this effect global or specific? 3) Does clozapine treatment alter this relationship? 4) Does severity of psychopathology covary with the level of akathisia? METHODS: Akathisia and clinical symptoms were examined in 33 "treatment refractory" schizophrenic patients treated with clozapine across 16 weeks. Weekly ratings were Barnes Akathisia Rating Scale, Abbreviated Dyskinesia Rating Scale, and Brief Psychiatric Rating Scale (BPRS). Patients were classified as "with" (n = 15) or "without" (n = 18) akathisia. Data analyses involved independent t-test comparisons of selected variables, between-group multivariate analyses of variance across time for BPRS Total scores and Guy's five factors, and partial correlations to assess covariation between BPRS scores and level of akathisia. RESULTS: Akathisia predicted more severe global psychopathology, specific to the Activation (AC) and Thought Disturbance (TH) factors. These relationships did not change with clozapine treatment even when akathisia declined. Interestingly, level of akathisia did not covary with severity of psychopathology. CONCLUSIONS: In this sample, akathisia predicted more severe psychopathology, specific to AC and TH BPRS factor scores. Clozapine treatment did not alter this relationship. Although the presence of akathisia predicted more severe symptoms, the level of akathisia did not covary across time with severity of psychopathology, suggesting an "uncoupling" of these symptom domains.

The selective effects of alcohol on automatic and effortful memory processes.

Automatic and effortful memory processes were evaluated in a 2-session, within-subjects design involving an alcohol challenge and a no-alcohol condition. Free recall of a 90-word list measured effortful processing. Estimation of word frequency from the same list measured automatic processing. Acute intoxication was hypothesized to diminish effortful but not automatic memory processes. Healthy, male volunteers (n = 36) completed the 2 conditions 1 week apart. Presentation frequency influenced both free recall and frequency estimation, with both measures increasing as presentation frequency increased. Free recall was significantly lower in the alcohol than in the no-alcohol condition, but frequency estimation was not differentially affected. The data showed that an alcohol challenge dissociated automatic and effortful memory processes in volunteers. The authors discuss potential neurobiological substrates that may account for alcohol's selective disruption of effortful, verbal, episodic memory processing.

Information-processing characteristics of explicit time estimation by patients with schizophrenia and normal controls.

The information-processing characteristics of time estimation have not been well-documented. This research investigated explicit time estimation to test whether (1) it can occur "automatically" and (2) the cognitive function generally known as "working memory" predicts accuracy of time estimation. Data on two tasks requiring explicit time judgement (time interval estimation and production) are reported for a sample of 43 normal, healthy controls and 19 inpatients with chronic schizophrenia. Each task was given in a standard (passing time interval is unfilled) and dual-task format (interval is filled by oral reading). Multivariate analysis of variance suggested that for both patients' and the normal controls' time estimation accuracy was (1) highly sensitive to whether a passing interval was filled with a concurrent activity such as reading and (2) predictable on the basis of age, education, and working memory skills. Also, the effect of the dual-task manipulation did vary as a function of psychosis for the Time Interval Production task. The data suggest that procedures for explicit time judgements do not occur automatically and utilize controlled processes such as working memory.

Relation of serum anticholinergicity to cognitive status in schizophrenia patients taking clozapine or risperidone.

BACKGROUND: A potential beneficial outcome of treatment with certain of the atypical neuroleptics is the reduced risk of cognitive impairment, stemming from purported low affinity for cholinergic receptors. In vitro experiments have shown that clozapine is highly anticholinergic and risperidone is minimally so. In vivo tests of the anticholinergic burden imposed by these medications and its potential cognitive consequences are needed. This study examines anticholinergic burden in schizophrenia patients taking clozapine and risperidone and tests whether this burden is associated with cognitive deficits. METHOD: Serum anticholinergic levels were determined in a sample of 22 chronic schizophrenia patients using the radioreceptor assay method of Tune and Coyle (1980). Fifteen patients received clozapine; 7 received risperidone. Mean +/- SD age of the sample, comprising 12 men and 10 women (68% white), was 44.7 +/- 8.4 years. Mean +/- SD age at onset of schizophrenia illness was 23.5 +/- 7.4 years. Two anticholinergic assays based on blood samples collected 1 week apart were available on each patient. RESULTS: Data indicated that clozapine patients had significantly (p < .001) higher anticholinergic levels at both collection points, and levels for both drugs remained stable over time. The clozapine and risperidone patients had essentially equivalent scores on the cognitive measure. CONCLUSION: These data suggest that anticholinergicity distinguishes clozapine and risperidone in vivo but that this effect is not associated with differences in global cognitive functioning. Results suggest that clozapine, despite producing moderately high in vivo serum anticholinergic levels, still holds clinical advantage over standard neuroleptics in terms of cognitive side effects. Reasons for this lowered risk of cognitive impairment are discussed.

The effects of clozapine on symptom clusters in treatment-refractory patients.

Preliminary results of a double-blind clozapine study in a population of chronic psychotic patients at a state psychiatric facility are reported. Thirty "treatment-refractory" schizophrenic patients given a diagnosis according to DSM-III-R criteria (mean age of 44 +/- 9.1 years and a duration of illness of 24.9 +/- 8.8 years) who received 300 mg or 600 mg of clozapine and randomized in a double-blind fashion were analyzed. Subjects were evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale on a weekly basis for 16 weeks. Based on the changes in their CGI scores at week 16 of clozapine treatment, subjects were retrospectively categorized as "improvers" (N = 12) and "nonimprovers" (N = 18). The two groups were compared for changes in total BPRS and BPRS factor scores. In terms of total BPRS scores, we expected a difference between the two groups because they were categorized based on changes in their CGI scores. However, the total BPRS scores in improvers showed a significant decrease by week 6 of clozapine treatment. On analyzing the four BPRS factors, the improvers showed improvement in the thinking disturbance factor by week 1 that remained steady from week 7. On the hostility-suspiciousness factor, the improvers showed an improvement across time when compared with nonimprovers. The withdrawal-retardation factor showed improvement in both groups across time, whereas the anxiety-depression factor was least influenced by clozapine. These observations suggested that all BPRS symptom factors did not uniformly contribute to improvement in overall psychopathology, which was observed as a decrease in total BPRS scores.

The serotonin hypothesis of aggression revisited.

Many contemporary theorists believe serotonin (5-HT) neurotransmitter functioning plays a role in the regulation of human aggressive behavior. We argue that the evidence supporting this 5-HT hypothesis of human aggression is less compelling than commonly assumed, due to (a) conflicting study results, and (b) significant methodological limitations of existing studies. Recent models that integrate the role of psychological and contextual variables in 5-HT--associated aggression are reviewed. The need to incorporate psychometrically sound measures of aggression in 5-HT studies, to use experimental and longitudinal designs, and to test hypotheses drawn from multifactorial models in future research is advocated.

A comparison of polydipsia prevalence among chronic psychiatric patients using three measurement approaches.

Many previous prevalence studies of polydipsia (PD) have utilized single and often non-biologic measures. In this study we estimated prevalence using specific gravity of urine (SPGU), normalized diurnal weight gain (NDWG), and staff identification (staff ID). Agreement between these two biologic and one behavioral measure was assessed. A total of 572 psychiatric inpatients were assessed for SPGU and NDWG. Unit staff were asked to identify PD patients. Positive and negative PD groups were formed separately based on the SPGU, NDWG, and staff ID data. All three measures were collected on the same day. Prevalence data for the biologic measures varied. The estimate for PD by SPGU (< 1.009 cutoff) was higher (43.4% of sample) than that of NDWG (> 2.5%; 25.4%) or staff ID (21.4%). These prevalence rates did not change substantially after exclusion of medical causes of polyuria. Agreement, assessed by the kappa statistic, was uniformly low among the measures. Weak association between the measures reflects their multidetermined, nonspecific nature, and highlights the lack of a diagnostic standard in the field. The observed prevalence rates must be considered rough approximations. Associations between the measures and certain subject characteristics suggest the measures may identify different types of potential PD patients. These different types of patients are discussed, as are other issues in the measurement of PD. The data suggest estimates of PD are a function of the type of measure used as even biologic measures vary greatly.

Clock drawing in schizophrenia.

The Clock Drawing Test, a task sensitive to cognitive decline in neurological groups, was administered to 27 patients with schizophrenia. Clock drawings were scored for over-all global performance and the frequency of specific qualitative errors. Mean global performance scores indicated a small proportion of the sample was below the threshold typically used to identify dementia, and the patients displayed qualitative Clock Drawing deficits not fully represented in the global performance measure. Qualitative analyses indicated that size errors, graphic difficulty, and spatial planning problems were most common. Lastly, duration of illness was not related to global performance, suggesting that the latter might not reflect deterioration but the stable trajectory of impairment that may be constant through the schizophrenia illness.

A comparison of reading and demographic-based estimates of premorbid intelligence in schizophrenia.

Estimating premorbid intelligence in schizophrenia is difficult because the illness affects aspects of premorbid and postmorbid functioning. We evaluated two qualitatively different estimates of premorbid intelligence in a sample of schizophrenia patients and tested whether: (1) the two indices were related and produced similar IQ estimates, and (2) either index was related to a measure of cognitive deterioration. The Barona Index (BI, a demographically-based instrument) and the National Adult Reading Test (NART, a reading test of irregularly-spelled words) were utilized. Subjects (n = 40) were adult neuroleptic-medicated inpatients with a DSM-III-R diagnosis of chronic schizophrenia (n = 35) or schizoaffective disorder (n = 5). Paired t-tests revealed statistically equivalent BI and NART estimates for Full Scale and Verbal IQs, but significantly higher NART Performance IQs (t[35] = -3.34, p < 0.01). Correlational analyses suggested the two indices were associated but shared modest variance. BI correlations revealed expected associations with education and social position. NART IQs were related to education and a measure of cognitive status. Regression analyses supported the association between NART estimates and cognitive deterioration. Results suggest BI may be a better estimate of premorbid intelligence in schizophrenia as it is less influenced by potential consequences of the disease.