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Bruce E Wexler

Publications and source records attributed to Bruce E Wexler.

At least 19 recordsLinked to original sources
PubMed2006

Computer-assisted cognitive remediation in schizophrenia: what is the active ingredient?

An emerging body of research has shown that computer-assisted cognitive remediation, consisting of training in attention, memory, language and/or problem-solving, produces improvement in neurocognitive function that generalizes to untrained neurocognitive tests and may also impact symptoms and work functioning in patients with schizophrenia. The active ingredient of these interventions, however, remains unknown as control groups in these studies have typically included few, if any, of the elements of these complex behavioral treatments. This study compared the effects of an extended (12-month), standardized, computer-assisted cognitive remediation intervention with those of a computer-skills training control condition that consisted of many of the elements of the experimental intervention, including hours spent on a computer, interaction with a clinician and non-specific cognitive stimulation. Forty-two patients with schizophrenia were randomly assigned to one of two conditions and were assessed with a comprehensive neuropsychological test battery before and after treatment. Results revealed that cognitive-remediation training produced a significant improvement in working memory, relative to the computers-skills training control condition, but that there was overall improvement in both groups on measures of working memory, reasoning/executive-function, verbal and spatial episodic memory, and processing speed. Taken together, these findings suggest that specific practice in neurocognitive exercises targeted at attention, memory and language, produce improvements in neurocognitive function that are not solely attributable to non-specific stimulation associated with working with a computer, interacting with a clinician or cognitive challenge, but that non-specific stimulation has a salutary effect on neurocognition as well.

Adult↗
PubMed2006

Neuropsychological deficits in nonsmokers with schizophrenia: effects of a nicotinic antagonist.

BACKGROUND: Biochemical, physiological and genetic evidence suggests dysregulation of central nicotinic acetylcholine receptor (nAChR) systems in schizophrenia, which may contribute to neuropsychological dysfunction and the high rates of smoking in this disorder. To evaluate the effects of nAChR blockade on neuropsychological performance in schizophrenia without the confounding effects of cigarette smoking, we compared neuropsychological performance in schizophrenia and healthy control nonsmokers after pre-treatment with the centrally-acting nAChR antagonist mecamylamine (MEC). METHODS: Using a within-subjects, counterbalanced design, schizophrenia (n = 14) and control (n = 15) nonsmokers were pre-treated for 3 days with MEC (0.0, 5.0, and 10.0 mg/day). Subjects performed repeated neuropsychological assessments including visuospatial working memory (VSWM), Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Word Serial Position Test (WSPT) and Stroop Color Word Test (SCWT) during three sequential test sessions per week over three test weeks. RESULTS: We found significant main effects of schizophrenia diagnosis on: VSWM 30 and 60 delays (p's < 0.01), CPT (% Hit Rate, Reaction Time, Variability Index; p < 0.01 for all outcomes), WCST (p < 0.01 for all outcomes) and Word Serial Position Test (p < 0.01). However, there were no main effects of repeated test administration (Session) or MEC dose on any of these outcomes, and no significant 3-way (DiagnosisxSessionxMEC dose) interactions. CONCLUSIONS: Our results suggest that there are a broad range of neuropsychological deficits in nonsmokers with schizophrenia. Furthermore, pretreatment with a centrally-acting nAChR antagonist did not alter neuropsychological performance in either nonsmoking patients with schizophrenia or controls.

Adult↗
PubMed2006

Cue-induced brain activity changes and relapse in cocaine-dependent patients.

This study used functional magnetic resonance imaging (fMRI) to examine the association between brain activation during exposure to cocaine-related cues and relapse to drug use in cocaine-dependent (CD) patients. We imaged 17 CD subjects during a 2-week in-patient stay. The subjects then entered a 10-week outpatient placebo-controlled, double-blind randomized clinical trial where urine toxicologies were assessed three times weekly to calculate the treatment effectiveness score (TES). Worse TES correlated with BOLD activation in the left precentral, superior temporal, and posterior cingulate cortices (PCC), and right middle temporal and lingual cortices (R>0.65; P<0.005). The left PCC activation also distinguished eight nonrelapsers (TES above mean and completed treatment) from nine relapsers. Cocaine-free urines were significantly greater in the nonrelapsers (92%) than in the relapsers (66%), who also remained in treatment for an average of only 3.2 weeks. Self-reports of craving during fMRI did not differ between nonrelapsers and relapsers and did not correlate with TES. Relapse to cocaine abuse was associated with increased activation in the sensory association cortex, the motor cortex, and PCC while viewing images of cocaine-related cues. These results suggest that relapse to cocaine abuse is associated with increased brain activation to cocaine cues in sensory, motor, and cognitive-emotional processing areas. This physiological activation was a better predictor of relapse than subjective reports of craving, and may be a useful target for treatment development.

Adult↗
PubMed2005

Neural activity associated with stress-induced cocaine craving: a functional magnetic resonance imaging study.

OBJECTIVE: Stress is known to increase cocaine craving and relapse risk in cocaine dependence. Identifying neural activity associated with stress and stress-induced cocaine craving is important in understanding the neurobiology of cocaine craving and relapse. METHOD: Blood oxygenation level dependent (BOLD) signal changes were assessed in a functional magnetic resonance imaging (fMRI) session with healthy controls and treatment-engaged, abstinent, cocaine-dependent individuals (patients) as they participated in brief guided imagery and recall of three personal stress and three personal neutral situations. RESULTS: During stress, patients showed significantly less BOLD activation than controls in specific frontal and para-limbic regions, such as the anterior cingulate (AC) region, left hippocampal/parahippocampal region, right fusiform gyrus, and the right postcentral gyrus. On the other hand, patients had increased activity in the caudate and dorsal striatum region during stress, activation that was significantly associated with stress-induced cocaine craving ratings. CONCLUSIONS: Patients failed to activate AC and related circuits during stress, regions associated with control, and regulation of emotion and distress states. Instead, they exhibited greater craving-related activation in the dorsal striatum, a region related to reward pathways and part of the obsessive-compulsive circuitry. Such functional alterations in stress processing may underlie the stress-related vulnerability to cocaine relapse often observed in cocaine-dependent individuals in early recovery.

Adult↗
PubMed2005

Differences in performance and learning proficiency on the Wisconsin Card Sorting Test in schizophrenia: do they reflect distinct neurocognitive subtypes with distinct functional profiles?

The aim of this study was two-fold: 1) to determine whether a priori subtyping of patients with schizophrenia based on both overall performance on a measure of executive-function, the Wisconsin Card Sorting Test (WCST), and ability to learn the task with expanded instruction, could be confirmed with other, independent measures of executive-function and learning, and, if so, 2) to determine whether these groups have different neurocognitive profiles and show differences in functional capacity. Fifty-four outpatients with schizophrenia were divided by WCST performance into three groups: intact executive-function (n=28), "good learner" (n=13), and "poor learner" (n=13) groups. These groups were then assessed with a comprehensive neurocognitive test battery and a performance-based measure of functional status, the UCSD Performance-based Skills Assessment (UPSA). The WCST-intact subgroup performed significantly better than other groups on a second measure of executive-function and in working memory, and speeded motor sequencing. Impaired WCST patients who benefited from expanded WCST instruction ("good learners") also showed better performance than patients who did not benefit from instruction ("poor-learners") on a second measure of learning, as well as on a measure of auditory divided attention. The intact WCST subgroup had greater functional capacity than either "strong" or "poor" learners. These subtypes may have implications for response to behavioral treatment interventions.

Activities of Daily Living↗
PubMed2005

Cognitive remediation and vocational rehabilitation for schizophrenia.

Cognitive deficits are a central and debilitating aspect of schizophrenia and other major mental illnesses. Although they are largely refractory to pharmacotherapy, multiple studies have now shown that large and lasting improvements in cognition can result from behavioral interventions. We will review our work over the past 10 years demonstrating that cognitive remediation treatment together with work therapy or supported employment can lead to large, lasting, and clinically relevant improvements in cognition and work functioning. While we will make some references to the work of others in these same areas, this is not a general review of these areas of research. Instead, the goal is to provide the rationale for the progression of our studies, describe the methods, and summarize the results, so that readers may understand, critique, and improve upon what we have done.

Cognition Disorders↗
PubMed2005

Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms.

BACKGROUND: Cigarette smoking rates in schizophrenia are higher than in the general population. OBJECTIVES: To determine whether cigarette smoking modifies cognitive deficits in schizophrenia and to establish the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related cognitive enhancement. DESIGN: Neuropsychological assessments were performed at smoking baseline, after overnight abstinence, and after smoking reinstatement across 3 separate test weeks during which subjects were pretreated in a counterbalanced manner with the nonselective nAChR antagonist mecamylamine hydrochloride (0, 5, or 10 mg/d). PARTICIPANTS: Twenty-five smokers with schizophrenia and 25 control smokers. SETTING: Outpatient mental health center. MAIN OUTCOME MEASURES: Visuospatial working memory (VSWM) and Continuous Performance Test (CPT) scores. RESULTS: In smokers with schizophrenia and control smokers, overnight abstinence led to undetectable plasma nicotine levels and an increase in tobacco craving. While abstinence reduced CPT hit rate in both groups, VSWM was only impaired in smokers with schizophrenia. Smoking reinstatement reversed abstinence-induced cognitive impairment. Enhancement of VSWM and CPT performance by smoking reinstatement in smokers with schizophrenia, but not the subjective effects of smoking, was blocked by mecamylamine treatment. CONCLUSIONS: Cigarette smoking may selectively enhance VSWM and attentional deficits in smokers with schizophrenia, which may depend on nAChR stimulation. These findings may have implications for understanding the high rates of smoking in schizophrenia and for developing pharmacotherapies for cognitive deficits and nicotine dependence in schizophrenia.

Adult↗
PubMed2005

Neurocognitive function in schizophrenia at a 10-year follow-up: a preliminary investigation.

INTRODUCTION: A wealth of evidence indicates that neurocognitive deficits are evident in patients with schizophrenia at both illness onset and after many years of treatment. Little is known regarding if or how these deficits change during the lifespan. The goal of the study was to evaluate changes in full-scale intelligence quotient and neurocognitive test performance over a 10-year interval in patients with schizophrenia. METHODS: Twelve patients were administered the Wechsler Adult Intelligence Scale-Revised as a measure of intellectual function and a neuropsychological test battery including measures of attention, verbal and non-verbal memory, language, visuospatial function, problem-solving, and motor function at entry to the study and at a 10-year follow-up. RESULTS: With the exception of performance on a measure of speeded motor sequencing, there was no significant decline in any of the measures at 10-year follow-up. Results from a measure of sustained auditory attention showed improvement at follow-up. DISCUSSION: These data support a neurodevelopmental model of schizophrenia for young adult to middle-age patients by suggesting that neurocognitive deficits that emerge either before disease onset or early in the course of the illness remain stable as the patient ages. CONCLUSION: Overall, measures of intelligence quotient, as well as specific neurocognitive skills, do not decline over a 10-year period in at least a subgroup of patients with schizophrenia.

Adolescent↗
PubMed2004

Functional MRI changes before and after onset of reported emotions.

The social nature of emotion is evident in the importance of facial and vocal displays in emotion-related behavior. This is the first brain-imaging study to use simulated face-to-face social interactions to evoke emotional responses and to compare valence-related activations before and after subjective onset of emotional response. Videotapes were prepared with actresses who described happy or unhappy experiences. Functional magnetic resonance imaging (fMRI) at 1.5 T was used to acquire BOLD images in 21 healthy young adults before, after, and during viewing of the happy and sad tapes. Subjects pushed buttons to indicate the onset of subjective emotional responses. Group data were analyzed by a bootstrap randomization method after anatomical normalization. Significant activation was detected in frontal and sensory regions prior to the reported onset of emotional response, and this activity showed a marked decrease after the report of conscious emotional experience. Significant differences between happy and sad conditions were evident in multiple brain regions both before and after the reported onset of emotional response, including the middle and superior temporal gyri, the middle frontal gyrus, the caudate, and the hippocampus. Socially relevant emotional stimulation is feasible and evokes robust responses. The neural correlates of the evoked emotion are multiple, widely distributed, and inclusive of areas important in many cognitive tasks. Positive and negative emotional responses include activation of common and distinctive brain regions.

Adult↗
PubMed2004

Test-retest stability of neuropsychological testing and individual differences in variability in schizophrenia outpatients.

The accurate measurement of neurocognitive function requires stable and reliable instruments. These assessments are critically important as correlates, predictors, and outcome measures of psychopathology, neuropathology, and treatment. Particularly, in studies that evaluate the impact of treatments on neurocognitive function, it is essential that their reliability as repeated measures be quantified. In an attempt to measure within- and between-subject variance on a battery of neuropsychological tests commonly used in schizophrenia research, baseline measures were administered twice, approximately 10 weeks apart, to 54 stable outpatients with schizophrenia or schizoaffective disorder. Instruments were judged for their stability, and individuals were assessed for individual differences in test-retest variability. The majority of the instruments administered were highly stable. Group means for several tests showed improvement on retest, which may indicate a practice effect, although many tests did not reach our criteria for "change." Of 962 test scores, 21 (2%) showed significant change. Most subjects were stable, with only 7% of subjects accounting for 38% of significant test-retest changes. Results indicate that the instruments assessed have sufficient reliability and stability to be used as repeated measures in clinical trials and that a small number of patients may have instability of performance as an individual characteristic.

Adult↗
PubMed2004

Neuropsychological deficits are associated with smoking cessation treatment failure in patients with schizophrenia.

Schizophrenics have deficits in neuropsychological performance, some of which are modified by cigarette smoking. These patients also have high rates of smoking and resistance to smoking cessation interventions. We examined whether the presence of neuropsychological deficits prior to smoking cessation treatment was associated with smoking cessation treatment failure in schizophrenic as compared to non-psychiatric control smokers. Neuropsychological assessments were performed prior to treatment with pharmacological agents during the course of placebo-controlled trials in schizophrenic and non-psychiatric control smokers, and included the Wisconsin Card Sorting Test (WCST), a Visuospatial Working Memory (VSWM) task, the Stroop Color Word Test (SCWT) and the Continuous Performance Test (CPT). In schizophrenics (n=32), subjects who had greater deficits in VSWM and WCST performance were significantly less likely to quit smoking, but this association was not observed in controls (n=40). Differences between quitters and non-quitters were not likely related to atypical antipsychotic treatment or differences in depressive symptoms. No associations between baseline performance on CPT or SCWT and quit status were found in either group. These preliminary data suggest that in schizophrenics, neuropsychological deficits are associated with smoking cessation treatment failure.

Cognition Disorders↗
PubMed2004

Verbal memory in schizophrenia: additional evidence of subtypes having different cognitive deficits.

A prior study found a selective deficit in verbal working memory in a subgroup of patients with schizophrenia who performed as well as healthy controls on a screening test of attention and auditory perception [Arch. Gen. Psychiatry 55 (1998) 1093]. Given the importance of defining pathophysiologically distinct subtypes of schizophrenia, the present study aimed to replicate and extend this finding. Patients with schizophrenia who passed the screening test (discriminators or Dsz patients) were compared to those who did not (nondiscriminators, NDsz patients), and healthy controls on a word serial position test (WSPT) and on other tests of verbal and nonverbal cognitive function. Dsz patients performed more poorly than controls on the WSPT and showed serial position effects consistent with a verbal memory deficit. They also showed a deficit in verbal memory but not visual memory on the Wechsler Memory Scale-Revised. In contrast, the NDsz patients showed overall poor performance on both verbal and nonverbal tests, consistent with a generalized deficit. Verbal working memory deficits were not related to education, gender, severity of symptoms, medication status, or hemispheric dominance for perceiving dichotic words. The findings add to growing evidence for the existence of a subgroup of schizophrenia having a specific verbal memory deficit that is not limited to working memory, but extends to learning and recall of verbal material.

Adult↗
PubMed2004

The Penn Conditional Exclusion Test (PCET): relationship to the Wisconsin Card Sorting Test and work function in patients with schizophrenia.

Performance on the Penn Conditional Exclusion Test (PCET), a new computerized measure of executive function with alternate forms, was compared with performance on the Wisconsin Card Sorting Test (WCST) in a sample of 32 patients with schizophrenia. In Analysis 1, the PCET and WCST were administered with several other standard neuropsychological measures to assess convergent and divergent validity. Results revealed that categories achieved and total errors on the PCET were closely related to analogous measures from the WCST. Divergent validity was supported through nonsignificant correlations between the PCET and measures of speeded visual sequencing, verbal learning and psychomotor speed. In Analysis 2, the relationship between the PCET, WCST and a detailed measure of vocational function, the Work Behavior Inventory (WBI), was compared. Results revealed that both executive-function measures were related to specific dimensions of work function as measured in a vocational setting. More specifically, categories achieved and total errors on both the WCST and PCET were related to measures of cooperativeness on the job. Errors on the PCET were also related to measurements of work quality and general impressions of work. These results provide the first evidence of criterion-related validity for the PCET and are part of a growing literature suggesting a relationship between performance on measures of executive function and work skills.

Adult↗
PubMed2004

Durability of cognitive remediation training in schizophrenia: performance on two memory tasks at 6-month and 12-month follow-up.

Patients with schizophrenia have consistently been found to exhibit cognitive deficits, particularly in memory, which have been suggested to mediate functional outcomes. Several recent reviews of cognitive retraining have concluded that these deficits respond to training, although the sustainability of cognitive improvement following completion of training has not been adequately evaluated. Most studies had small samples and very short follow-up periods. As part of a larger study, we examined performance on two memory tasks in two groups of participants: those who received computerized cognitive remediation training in addition to work therapy (n=45), vs. those who only received work therapy (n=49). Computerized cognitive remediation included hierarchical training on a computerized digit span task and a computerized words serial position task. Assessments using the same computerized tasks were made at three time points: baseline, end of active intervention, and 6-month follow-up. Compared to the active control condition (work therapy only), the group receiving computerized cognitive remediation in addition to work therapy showed significantly greater improvements on the trained digit span task following training. These improvements were maintained at the 6-month follow-up. There were no significant group differences on the word serial position task at any time point. Results indicate that computerized training can lead to sustained improvements on some, but not all, training tasks.

Adult↗
PubMed2004

Effects of neurocognitive enhancement therapy in schizophrenia: normalisation of memory performance.

INTRODUCTION: A preponderance of research indicates that cognitive function in schizophrenia can be improved through cognitive remediation. However, few studies have attempted to characterise the extent of improvement relative to nonpsychiatric controls. METHOD: Cognitive performance on reaction time, digit recall, and word recall of 58 schizophrenia patients at baseline and after 6 months of cognitive remediation was compared to the performance on these tasks of 39 community controls. Schizophrenia patients participated in Neurocognitive Enhancement Therapy (NET) and received hierarchical training on the memory tasks, but not on the reaction time task, which was only administered at intake and follow-up. RESULTS: The schizophrenia sample showed significantly poorer performances than the community control sample on all three tasks at baseline. NET led to significant improvements in performance on trained memory tasks, but not the untrained reaction time task. There was a significant increase in the proportion of schizophrenia patients who achieved normal range performance on the memory tasks. CONCLUSIONS: 52% of schizophrenia patients who were impaired on at least one of the memory tasks normalised their performance on at least one of those tasks as a result of cognitive training. Results suggest that clinically meaningful improvement may be possible using cognitive remediation.

Journal Article↗
PubMed2004

Neural circuits underlying emotional distress in humans.

Difficulties in the experiences and regulation of emotional stress have been associated with the development of psychiatric and substance use disorders. This study examined neural circuits underlying emotional distress in healthy volunteers using functional magnetic resonance imaging (fMRI) techniques. Recall of personal nontraumatic, highly stressful life events with script-driven guided imagery was used to induce moderate levels of emotional distress in eight healthy volunteers. Subjects participated in six guided imagery trials (3 separate stress and 3 separate neutral-relaxing scripts each) interspersed by rest periods in a 1.5T scanner. Results indicated significant activation in the medial prefrontal, anterior cingulate, caudate, putamen, thalamus, hippocampus, parahippocampal gyrus, and posterior cingulate regions during emotional distress relative to brain activation during neutral-relaxing imagery. These findings suggest that specific striatal-limbic-prefrontal cortical circuits are involved in the experience and regulation of emotional stress in humans. The study also provides a feasible method to study brain correlates of emotional stress processing in healthy individuals and clinical samples.

Adult↗
PubMed2003

Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation.

BACKGROUND: Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. METHODS: Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. RESULTS: Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS: Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.

Adult↗