Marc W. Haut

Adjuvant Chemotherapy for Breast Cancer: Effects on Cerebral White Matter Seen in Diffusion Tensor Imaging

PURPOSE The purpose of this study was to examine the effect of adjuvant chemotherapy on normal-appearing white matter in women with breast cancer. PATIENTS AND METHODS Ten patients with early-stage breast cancer who were treated with adjuvant chemotherapy and 9 age-, education-, and IQ-matched healthy controls were studied with magnetic resonance imaging. Diffusion tensor imaging was used to calculate fractional anisotropy (FA), a measure of white matter integrity. Measurements were made in the genu and splenium of the corpus callosum. Participants also completed measures of processing speed, depression, and anxiety. RESULTS Relative to controls, patients had slower processing speed and lower FA in the genu. Processing speed was positively correlated with FA in the genu. CONCLUSION The results of this pilot study suggest that adjuvant chemotherapy affects normal-appearing white matter in the genu of the corpus callosum and that this is related to the cognitive deficits experienced by patients.

Chronic Pain Is Associated with Brain Volume Loss in Older Adults: Preliminary Evidence

OBJECTIVES The primary aim of this pilot investigation was to identify structural brain differences in older adults with chronic low back pain (CLBP) as compared with pain-free individuals. DESIGN Cross-sectional, case-control. PARTICIPANTS Sixteen cognitively intact older adults, eight with CLBP and eight pain-free; excluded if with psychiatric or neurological disorders, substance abuse, opioid use, diabetes mellitus, and/or hypertension. METHODS Brain magnetic resonance imaging (MRI) and tests of neuropsychological performance (digit span, digit symbol substitution, letter-number sequencing, trail making) were administered to all participants. Gray matter (GM), white matter (WM), cerebrospinal fluid, and corpus callosum (CC) volumes were measured as a percentage of total supratentorial intracranial volume. Voxel-based morphometry analysis of GM and WM assessed regional differences. RESULTS Between-groups analysis revealed a non-significant trend toward decreased middle CC volume in the CLBP group (1.43E-03 +/- 2.67E-04, 1.63E-03 +/- 2.00E-04: P = 0.09). Regional analysis in the CLBP group demonstrated significantly decreased GM volume (P < 0.001) in the posterior parietal cortex and middle cingulate WM volume (P < 0.001) of the left hemisphere. CLBP participants performed significantly worse on digit span forward (P = 0.03). CONCLUSIONS Older adults with CLBP have structural brain changes in the middle CC, middle cingulate WM, and the GM of the posterior parietal cortex as well as impaired attention and mental flexibility. Additional investigation is needed to corroborate and extend these findings and more clearly elucidate their relationship to physical function and the risk of disability.

On the nature of Wisconsin Card Sorting Test performance in schizophrenia

Performance on the Wisconsin Card Sorting Test (WCST) is widely reported to be impaired in patients with schizophrenia. It has been hypothesized that the performance deficit on the WCST in schizophrenia is related to a dysfunction of the frontal lobe, specifically the dorsolateral prefrontal cortex. This hypothesis was tested by comparing a group of patients with schizophrenia to patients with low grade right or left frontal lobe tumors and a group of patients with non-frontal high grade tumors. The results demonstrated a remarkable similarity in performance on the WCST between patients with schizophrenia and patients with right frontal lobe tumors. Patients with left frontal lobe tumors, non-frontal tumors, and normal control subjects did not show the same pattern of performance. This study provides support for frontal lobe dysfunction in the symptomatology of schizophrenia.

Reduced Frontal White Matter Volume in Long-Term Childhood Leukemia Survivors: A Voxel-Based Morphometry Study

BACKGROUND AND PURPOSE: To our knowledge, no published studies have examined whole-brain regional differences to identify more discrete volumetric changes in the brains of childhood leukemia survivors. We used voxel-based morphometry (VBM) to examine regional gray and white matter differences in a group of long-term survivors of acute lymphoblastic leukemia (ALL) compared with a group of healthy controls. Differences in regional white matter volume were expected, given previous reports of white matter changes during treatment for ALL and reduced brain white matter volumes in long-term survivors. Follow-up analyses examined the relationship of regional brain volumes to cognitive function. MATERIALS AND METHODS: We compared 9 long-term survivors of ALL with 14 healthy controls. Survivors of ALL were treated with systemic and intrathecal chemotherapy only. T1-weighted axial 3D spoiled gradient high-resolution images collected on a 1.5T MR imaging scanner were used for the VBM analysis. Neuropsychological evaluations were conducted within 2 months of the MR imaging to assess cognitive function. RESULTS: VBM analysis revealed 2 specific regions of reduced white matter in the right frontal lobes of survivors of ALL compared with healthy controls. Survivors of ALL had lower performances on tests of attention, visual-constructional skills, mental flexibility, and math achievement compared with healthy individuals. Decreased performance on neuropsychological measures was associated with decreased regional white matter volumes. No differences were found between the groups with respect to gray matter regions. CONCLUSION: These findings are consistent with previous literature describing the long-term cognitive, academic, and imaging findings of survivors of ALL and suggest that right frontal white matter is particularly vulnerable to disruption following intensive chemotherapy for ALL. Future studies should focus on further clarifying the white matter changes observed.

Amnesia due to Fornix Infarction

Background and Purpose-The fornix connects various structures involved in memory. We report a patient with anterograde amnesia after an acute ischemic infarct in the anterior fornix. Case Description-A 71-year-old female with acute-onset amnesia had neuroimaging studies showing ischemic infarction of both columns and the body of the fornix and the genu of the corpus callosum. Neuropsychological evaluation revealed anterograde amnesia without evidence of callosal disconnection. The patient showed marked improvement in her memory function on the follow-up visit. Conclusions-Amnesia in this case is likely due to infarction of the anterior fornix structures.

Neural activation during performance of number-letter sequencing.

Recent advances in neuroimaging have enabled researchers to establish relatively specific areas of the brain that are involved in working memory. In this positron emission tomography study we examined the pattern of neural activation associated with performance on number-letter sequencing, a purported measure of working memory included in the new Wechsler scales for memory and intelligence. After controlling for basic audition, verbalization, and attention, areas of activation were observed in the orbital frontal lobe, dorsolateral prefrontal cortex, and posterior parietal cortex. This is highly consistent with reports from the literature on activation patterns associated with working memory. More activation peaks were observed in the right hemisphere, suggesting the participants utilized visualization of the verbal information. Consistent with task conceptualization, this study provides support for number-letter sequencing as a task involving working memory.

Current marital functioning as a mediating factor in depression among spouse caregivers in dementia

Abstract A model of spousal caregiving was constructed in which current marital functioning was hypothesized to predict caregiver depression independent of the patients clinical status and caregiver characteristics including burden. The sample was comprised of 96 consecutive marital dyads seeking evaluation at a university-based cognitive disorders program. The results of path analysis supported a model in which current marital functioning was significantly and independently associated with the caregivers mental health. Specifically, spouse caregivers reporting low marital cohesion and satisfaction endorsed significantly more depressive symptoms. These findings supported the models central premise that relational losses are discretely related to the mental health of spouse caregivers and warrant consideration in the assessment and care of spouse caregivers.

The psychological treatment of memory impairment: a review of empirical studies.

Memory impairment is a frequent effect of many different forms of brain dysfunction. Memory impairment is also a frequent focus of treatment interventions, and there have been many different treatment methods suggested. The suggested methods include direct retraining, the use of spared skills in compensating for the impairment (alternate functional systems), and the use of behavioral strategies to circumvent the manifest memory dysfunction (behavioral prosthetics). Unfortunately, there are very few studies comparing the various suggested treatment methods. The present paper evaluates the empirical evidence related to the treatment of memory dysfunction and suggests directions for future investigations. Although the evidence is not conclusive, it appears that some forms of treatment may be helpful in remediating certain types of memory impairment. An approach likely to be productive would include some consideration of the impaired neurological and psychological mechanisms responsible for the manifest memory deficit as well as a consideration of the etiology of the injury thought to be causally related to the memory deficit. As yet, there have been no rigorous empirical evaluations of these considerations.

Differences in brain structure and function in older adults with self-reported disabling and nondisabling chronic low back pain.

OBJECTIVE The primary aim of this pilot study was to identify structural and functional brain differences in older adults with self-reported disabling chronic low back pain (CLBP) compared with those who reported nondisabling CLBP. DESIGN Cross-sectional. PARTICIPANTS Sixteen cognitively intact older adults, eight with disabling CLBP and eight with nondisabling CLBP. Exclusions were psychiatric or neurological disorders, substance abuse, opioid use, or diabetes mellitus. METHODS Participants underwent: structural and functional brain MRI; neuropsychological assessment using the Repeatable Battery for the Assessment of Neuropsychological Status, Trail Making Tests A and B; and physical performance assessment using the Short Physical Performance Battery. RESULTS In the disabled group, there was significantly lower white matter (WM) integrity (P < 0.05) of the splenium of the corpus callosum. This group also demonstrated activation of the right medial prefrontal cortex at rest whereas the nondisabled demonstrated activation of the left lateral prefrontal cortex. Combined groups analysis revealed a strong positive correlation (r(s) = 0.80, P < 0.0002) between WM integrity of the left centrum semiovale with gait-speed. Secondary analysis revealed a strong negative correlation between total months of CLBP and WM integrity of the SCC (r(s) = -0.59, P < 0.02). CONCLUSIONS Brain structure and function is different in older adults with disabling CLBP compared with those with nondisabling CLBP. Deficits in brain morphology combining groups are associated with pain duration and poor physical function. Our findings suggest brain structure and function may play a key role in chronic pain related disability and may be important treatment targets.

Empirical comparison of alternate forms of the Boston Naming Test

Abstract Various short forms of the Boston Naming Test (BNT) are compared including an empirically derived 30-item form, odd and even items split-half forms, four 15-item forms, and a rationally derived 15-item form used in conjunction with the Consortium to Establish a Registry in Alzheimers Disease (CERAD). The present analysis was conducted using a sample of 320 individuals with diagnoses including dementia (n = 194), thought disorder (n = 46), depression (n = 16), general neuropsychiatric disorders (n = 12), and cerebral tumors (n = 52). Results indicated that all forms possess adequate, although variable internal consistency, and correlations between forms were reasonable. Average item difficulty indices also differed with the CERAD version being least desirable. Finally, classification rates were different by forms, indicating limitations on the extent to which the forms may be used interchangeably.