Michael David Horner

The Trail Making Test, Part B: Cognitive Flexibility or Ability to Maintain Set?

The Trail Making Test (TMT) is a well-established test sensitive to impairment in multiple cognitive domains. There has been ambiguity about which cognitive demands are placed on the patient by TMT Part B over and above those required to perform TMT Part A. In particular, cognitive flexibility and ability to maintain a complex response set have been 2 competing hypotheses. This study preliminarily examined which of these 2 abilities primarily contributes to Part B performance. A total of 121 clinically referred Veterans Affairs patients were administered the TMT, as well as other tests of executive and other cognitive functions. Regression analyses were used to examine which tests predicted Part B performance above and beyond Part A performance. The results provide preliminary support for TMT Part B performance being more sensitive to cognitive flexibility (operationalized as Wisconsin Card Sorting Test [WCST], percent perseverative errors) than ability to maintain set (operationalized as WCST, failure to maintain set).

Patterns of alcohol use 1 year after traumatic brain injury: A population-based, epidemiological study

This study delineated patterns of alcohol use 1 year after traumatic brain injury (TBI) in a large, population-based, epidemiological, nonclinical sample, and identified predictors of heavy alcohol use in these individuals. Participants were 1,606 adults identified by review of a South Carolina statewide hospital discharge data set, on the basis of satisfying the Centers for Disease Control case definition of TBI, and were interviewed by telephone 1 year after TBI-related discharge. Alcohol use in the month prior to interview was classified according to categories from the Quantity-Frequency-Variability Index; heavy drinking was defined as nearly daily use with > or = 5 drinks at least occasionally, or at least three occasions with > or = 5 drinks. A polychotomous logistic regression with 3 response levels (heavy, moderate, and abstinent/infrequent/light drinking) was used to identify predictors of heavy drinking. Heavy drinking in the month prior to interview was reported by 15.4% of participants, while 14.3% reported moderate drinking and 70.3% reported abstinence or light/infrequent drinking. Risk factors for heavy drinking included male gender, younger age, history of substance abuse prior to TBI, diagnosis of depression since TBI, fair/moderate mental health, and better physical functioning. There was no association between drinking patterns and TBI severity.

Neurocognitive deficits and prefrontal cortical atrophy in patients with schizophrenia

RATIONALE Cognitive deficits are of particular importance in schizophrenia since they are strongly associated with poor prognosis. We investigated the relationship between prefrontal cortical atrophy as measured by MRI and the neuropsychological performance of participants diagnosed with DSM-IV-TR schizophrenia. METHODS Fourteen unmedicated adult patients and thirteen matched controls were studied. Subjects underwent MRI yielding 1 mm isotropic T1-weighted images. Voxel based morphometry was applied to all images using SPM5. The mean gray level of Brodmann area (BA) 9 was also extracted and evaluated using simple regression along with relative score differences on patients neuropsychological tests compared to controls. RESULTS Patients exhibited a poorer performance on the Controlled Word Association Task (COWAT), Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT). Patients also presented a greater level of apathy as indexed by the Apathy Evaluation Scale (AES). There was a significant decrease in gray matter volume in patients with schizophrenia in left supplementary motor area, bilateral superior frontal gyrus, left middle frontal gyrus, right opercular area, left angular gyrus, left superior temporal gyrus and left cerebellar hemisphere. Within the schizophrenia group, decreased BA9 gray matter volume was correlated with poorer performance on the WCST and TMT-B. CONCLUSION Prefrontal gray matter abnormalities in schizophrenia patients may be associated with some symptoms including difficulties with set-shifting and decreased mental flexibility. Further studies evaluating prefrontal connectivity may clarify if such impairment results from abnormalities of the frontal area alone, or are a result of altered networks involving the frontal and extra-frontal areas.

Neuropsychological Predictors of the Attainment of Treatment Objectives in Substance Abuse Patients

This study examined the contribution of neuropsychological functioning to the attainment of treatment objectives in substance abuse patients. Subjects were 85 patients enrolled in comprehensive, inpatient and outpatient substance abuse treatment at a VA Medical Center. Most subjects were diagnosed with Alcohol Dependence or Abuse, and nearly half were seeking treatment for Cocaine Dependence or Abuse. After acute detoxification, but before beginning individualized treatment, subjects were administered a neuropsychological screening battery to assess cognitive functioning and affective status. They then attended a variety of daily group therapies. Each therapy group had its own set of specific treatment objectives; on each treatment day, group therapists rated each patients attainment of the specific objectives for their group. Groups included Assertiveness Training (Levels I and II), Stress Management (Levels I and II), Social Skills Training, Job Skills, Relapse Prevention (Levels I and II), Leisure Planning, Leisure Skills, Occupational Therapy, and 12-Step Study. Stepwise multiple regression indicated that the best predictors of overall objective attainment were better attention (WMS-R Digits Backwards) and less depressive symptomatology (Beck Depression Inventory). These results suggest that attention and mood have a modest yet significant impact on the success of treatment interventions for substance abuse patients. Thus, evaluation of cognitive as well as affective factors in substance abuse patients might be helpful in designing and implementing specialized interventions to maximize the likelihood of treatment success.

Measures of cognitive functioning as predictors of treatment outcome for cocaine dependence

Amlodipine is a calcium-channel antagonist with neuropharmacological properties believed to be protective against cerebral hypoperfusion, microinfarcts, and excitoxic cell death. Based on its pharmacological properties, we hypothesized that amlodipine would be associated with improved attention, processing speed, memory, and executive functioning at treatment follow-up in 84 cocaine-dependent individuals enrolled in a 12-week, placebo-controlled, double-blind clinical trial of amlodipine. We also hypothesized that better cognitive functioning at baseline would be associated with reduced cocaine use (negative urine drug screens) and longer treatment retention (last session attended). Results indicated that amlodipine produced no measurable benefit in cognitive functioning. Percent perseverative errors on Wisconsin Card Sorting Test was negatively correlated with treatment retention (n = 84, r = -.350, p < .01). No other findings were significant. Thus, cocaine-dependent individuals who repeated mistakes and benefited less from corrective feedback on a problem-solving task discontinued treatment earlier. Notably, no other cognitive measures predicted treatment outcome. The observed relationship implicates the relevance of executive functioning to treatment outcome for cocaine dependence.

Augmenting Atypical Antipsychotics with a Cognitive Enhancer (Donepezil) Improves Regional Brain Activity in Schizophrenia Patients: A Pilot Double-blind Placebo Controlled BOLD fMRI Study

Cognitive impairments are cardinal features of schizophrenia and predictors of poor vocational and social outcome. Imaging studies with verbal fluency tasks (VFT) lead some to suggest that in schizophrenia, the combination of a failure to deactivate the left temporal lobe and a hypoactive frontal lobe reflects a functional disconnectivity between the left prefrontal cortex and temporal lobe. Others have theorized that an abnormal cingulate gyrus modulates such fronto-temporal connectivity. Thus addition of a cognitive enhancing medication to current antipsychotic therapy might improve functionality of networks necessary in working memory and internal concept generation. To test this hypothesis, we serially measured brain activity in 6 subjects on stable atypical antipsychotics performing a VFT, using BOLD fMRI. Measurements were made at baseline and again after groups were randomized to receive 12 weeks of donepezil (an acetylcholinesterase inhibitor) and placebo in a blind cross-over design. Donepezil addition provided a functional normalization with an increase in left frontal lobe and cingulate activity when compared to placebo and from baseline scans. This pilot study supports the cingulate’s role in modulating cognition and neuronal connectivity in schizophrenia.

Attentional functioning in abstinent cocaine abusers

The effect of chronic cocaine use on attention is directly relevant to the treatment of cocaine dependence, since attention underlies most other cognitive processes, and thus the ability to profit from cognitively-based interventions. This paper reviews 17 studies examining attention in patients with cocaine abuse or dependence. Findings have been inconsistent, largely due to various methodological difficulties. There has been some suggestion of reduced cognitive speed, while focused and sustained attention have generally been unimpaired. Divided attention has been largely unexplored. Thus, there is insufficient evidence either to accept or reject the hypothesis of attentional dysfunction associated with chronic cocaine use.

A double-blind placebo-controlled case study of the use of donepezil to improve cognition in a schizoaffective disorder patient: functional MRI correlates.

Cognitive impairment in multiple domains is common in patients with schizophrenia and may be a powerful determinant of poor functional ability and quality of life. We report a double-blind, placebo-controlled, cross-over study of donepezil augmentation in a schizoaffective disorder patient stabilized on olanzapine pharmacotherapy. The patient showed significant improvements in several cognitive measures and increased activation of prefrontal cortex and basal ganglia on functional MRI during the donepezil augmentation. In addition, the donepezil augmentation resulted in a reduction of depressive symptoms and in significant improvements in functional abilities and quality of life. Further studies of donepezil augmentation of neuroleptics in schizophrenia are warranted.

Self-report and objective measures of cognitive deficit in patients entering substance abuse treatment

The relationship between self-reported cognitive deficits and objectively measured cognitive performance was examined in 86 patients entering substance abuse treatment. Self-ratings of cognitive impairment were strongly correlated with indices of depression and vulnerability to stress, but not with objective cognitive performance. Confirming the lack of relationship between self-report and objective cognitive measures, cognitive performance did not differ between patients at the extremes of the cognitive-complaint distribution; and cognitively impaired patients did not differ from cognitively intact patients in their self-ratings of impairment.

Temporal Lobe Epilepsy and Performance on the Wisconsin Card Sorting Test

The replicability of previous evidence for differential performance between left and right temporal lobe epileptic patients on the Wisconsin Card Sorting Test (WCST) was evaluated in a new sample of candidates for focal resection. Many subjects obtained high scores on indices of perseveration, which are commonly thought to reflect frontal dysfunction, but there were no differences in performance between patients with language-dominant and nondominant temporal foci. The findings confirm existing evidence that performance decrements on the WCST can be associated with epileptic foci and focal lesions in nonfrontal brain lesions.