The effect of time since stroke, gender, age, and lesion size on thalamus volume in chronic stroke: a pilot study.

Recent stroke studies have shown that the ipsi-lesional thalamus longitudinally and significantly decreases after stroke in the acute and subacute stages. However, additional considerations in the chronic stages of stroke require exploration including time since stroke, gender, intracortical volume, aging, and lesion volume to better characterize thalamic differences after cortical infarct. This cross-sectional retrospective study quantified the ipsilesional and contralesional thalamus volume from 69 chronic stroke subjects' anatomical MRI data (age 35-92) and related the thalamus volume to time since stroke, gender, intracortical volume, age, and lesion volume. The ipsi-lesional thalamus volume was significantly smaller than the contra-lesional thalamus volume (t(68) = 13.89, p < 0.0001). In the ipsilesional thalamus, significant effect for intracortical volume (t(68) = 2.76, p = 0.008), age (t(68) = 2.47, p = 0.02), lesion volume (t(68) = - 3.54, p = 0.0008), and age*time since stroke (t(68) = 2.46, p = 0.02) were identified. In the contralesional thalamus, significant effect for intracortical volume (t(68) = 3.2, p = 0.002) and age (t = - 3.17, p = 0.002) were identified. Clinical factors age and intracortical volume influence both ipsi- and contralesional thalamus volume and lesion volume influences the ipsilesional thalamus. Due to the cross-sectional nature of this study, additional research is warranted to understand differences in the neural circuitry and subsequent influence on volumetrics after stroke.

Neural substrates of object identification: Functional magnetic resonance imaging evidence that category and visual attribute contribute to semantic knowledge.

Recent findings suggest that neural representations of semantic knowledge contain information about category, modality, and attributes. Although an object's category is defined according to shared attributes that uniquely distinguish it from other category members, a clear dissociation between visual attribute and category representation has not yet been reported. We investigated the contribution of category (living and nonliving) and visual attribute (global form and local details) to semantic representation in the fusiform gyrus. During functional magnetic resonance imaging (fMRI), 40 adults named pictures of animals, tools, and vehicles. In a preliminary study, identification of objects in these categories was differentially dependent on global versus local visual feature processing. fMRI findings indicate that activation in the lateral and medial regions of the fusiform gyrus distinguished stimuli according to category, that is, living versus nonliving, respectively. In contrast, visual attributes of global form (animals) were associated with higher activity in the right fusiform gyrus, while local details (tools) were associated with higher activity in the left fusiform gyrus. When both global and local attributes were relevant to processing (vehicles), cortex in both left and right medial fusiform gyri was more active than for other categories. Taken together, results support distinctions in the role of visual attributes and category in semantic representation.

Informed consent in medication-free schizophrenia research.

OBJECTIVE: The authors' goal was to determine whether people with schizophrenia experience changes in decisional capacity when their antipsychotic regimens are discontinued for research purposes. METHOD: Capacity for informed consent for research, neuropsychological performance, and psychiatric symptoms were assessed before and after discontinuation of antipsychotic medication in 10 individuals with schizophrenia. RESULTS: Overall, participants showed minimal change on most measures during the medication-free interval, although their reasoning ability declined significantly. All participants who demonstrated adequate understanding of study procedures at enrollment retained this capacity throughout the study. CONCLUSIONS: Participants in medication-free schizophrenia research do not show a major decline in decisional capacity. However, the apparent decline in reasoning ability found in this study is of concern and underscores the need for both additional research on this topic and the development of remediational interventions aimed at enhancing this aspect of decisional capacity.

Blood vessel function and cognition in elderly patients with atherosclerosis.

BACKGROUND AND PURPOSE: Although a strong relationship has been established between vascular disease and cognitive decline, the current challenge is to identify vascular risk factors and mechanisms that are associated with cognitive function before the development of severe dysfunction (eg, vascular dementia). This study was conducted to determine the relationship between blood vessel function and cognition in elderly patients with atherosclerosis. METHODS: Participants were 14 elderly individuals with atherosclerotic vascular disease, who had no history of stroke, cardiac surgery, or dementia diagnosis. Forearm blood flow was measured before and after brachial artery infusion of 3 vasoactive agents (verapamil, acetylcholine, nitroprusside), and these measures of vessel function were then correlated with neuropsychological performance (total scale score on the Repeatable Battery for the Assessment of Neuropsychological Status). RESULTS: Positive correlations were found between neuropsychological performance and vasodilation in response to all 3 agents, with 2 reaching statistical significance (verapamil: rho=0.78, P=0.001; nitroprusside: rho=0.56, P=0.038) and the third showing a strong trend toward significance (acetylcholine: rho=0.49, P=0.076). Correlations between neuropsychological performance and more conventional vascular-related variables were much weaker. CONCLUSIONS: These data provide preliminary evidence of a relationship between resistance vessel function and neuropsychological performance. With further research, measures of vessel dysfunction may be useful in identifying individuals at risk for cognitive decline and vascular dementia.

Capacity to provide informed consent for participation in schizophrenia and HIV research.

OBJECTIVE: The degree to which people with psychiatric symptoms and cognitive dysfunction can provide informed consent to participate in research is a controversial issue. This study was designed to examine the capacity of subjects with schizophrenia and subjects with HIV to provide informed consent for research participation and to determine the relationships among cognitive dysfunction, psychiatric symptoms, and decisional capacity. METHOD: Twenty-five men and women with a DSM-IV diagnosis of schizophrenia and 25 men and women with HIV were recruited. The groups were compared in terms of neuropsychological functioning, psychiatric symptoms, and ability to provide informed consent to a hypothetical drug trial. RESULTS: Eighty percent of the subjects with schizophrenia and 96% of the HIV-positive subjects demonstrated adequate capacity to consent to the hypothetical drug trial, but subjects in the schizophrenia group had significantly lower scores on two of the four aspects of decisional capacity. For the subjects with schizophrenia, neuropsychological functioning and psychiatric symptoms (e.g., apathy and avolition), but not psychotic symptoms (e.g., hallucinations and delusions), were significantly associated with decisional capacity. CONCLUSIONS: The majority of subjects who are recruited and willing to participate in schizophrenia or HIV research will have adequate capacity to provide consent. Cognitive dysfunction and the symptoms shown to be associated with impaired decisional capacity are not unique to schizophrenia and may occur with many other forms of illness. These findings underscore the importance of considering how decisional capacity will be assessed in all types of research, regardless of the specific condition being studied.

fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's Disease.

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) has been used to probe basal ganglia function in people with presymptomatic Huntington's disease (pre-HD). A previous fMRI study in healthy individuals demonstrated activation of the basal ganglia during a time-discrimination task. The current study was designed to examine the relative sensitivity of fMRI compared with that of behavioral testing and morphometric measurements in detecting early neurodegenerative changes related to Huntington's disease (HD). METHODS: Pre-HD participants were assigned to two groups based on estimated years to diagnosis of manifest disease: close <12 years and far >or=12 years. Age at disease onset was estimated using a regression equation based on the number of trinucleotide CAG repeats. The time-discrimination task required participants to determine whether a specified interval was shorter or longer than a standard interval of 1200 milliseconds. RESULTS: Participants in the close group performed more poorly on the time-task discrimination than did control subjects; however, no differences were observed between far participants and control subjects. Similarly, close participants had reduced bilateral caudate volume relative to that of control subjects, whereas far participants did not. On functional imaging, close participants had significantly less activation in subcortical regions (caudate, thalamus) than control subjects; far participants had an intermediate degree of activation. In contrast, far participants had hyperactivation in medial hemispheric structures (anterior cingulate, pre-supplementary motor area) relative to close and control subjects. CONCLUSION: Hyperactivation of medial prefrontal regions compensated for reduced subcortical participation during time discrimination in pre-HD. This pattern of brain activation may represent an early neurobiologic marker of neuronal dysfunction.

Dosing of a cued picture-naming treatment for anomia.

PURPOSE: Recent investigations into effects of intensity or distribution of aphasia therapy have provided moderate evidence supporting intensive therapy schedules on aphasia treatment response. The purpose of the present study was to investigate the feasibility of creating an intensive therapy session without extending the amount of daily time a person spends in treatment. METHOD: Individuals who presented with chronic anomia poststroke (N = 8) participated in 2 weeks of a computerized, therapist-delivered, cued, picture-naming treatment. Dosing parameters for each session were 8 presentations of 50 pictures, totaling 400 teaching episodes per session. RESULTS: Of the 8 participants, 6 achieved significant increases from baseline on trained items after 400 teaching episodes (i.e., 1 treatment hr), and the remaining 2 participants achieved significant increases from baseline after 1200 teaching episodes (i.e., 3 treatment hr). Maintenance data from 7 of the participants indicated that 6 participants maintained significant improvement from baseline on trained items. CONCLUSIONS: Given an intensive and saturated context, anomic individuals were surprisingly quick at relearning to produce problematic words successfully. Most participants demonstrated retention of the gains 2 months after treatment ended. The high density of teaching episodes within the treatment session (i.e., the intensive treatment schedule) may have contributed to the behavioral gains.

Delayed Stimulus-Specific Improvements in Discourse Following Anomia Treatment Using an Intentional Gesture.

Purpose: In this study, the authors assessed how the addition of intentional left-hand gestures to an intensive treatment for anomia affects 2 types of discourse: picture description and responses to open-ended questions.Method: Fourteen people with aphasia completed treatment for anomia comprising 30 treatment sessions over 3 weeks.Seven subjects also incorporated intentional left-hand gestures into each treatment trial.Results: Both groups demonstrated significant changes in trained items and improved naming of untrained items but no change in Western Aphasia Battery­Aphasia Quotient(WAB­AQ; Kertesz, 1982) scores. Changes in discourse were limited to the 3-month follow-up assessment. Several discourse measures showed significant improvements in the picture description task and declines during question responses. Additionally, the gesture group produced more words at each assessment, whereas the no gesture group produced fewer words at each assessment. These patterns led to improvements in picture descriptions and minimal declines in question responses in the gesture group. In contrast, the no gesture group showed minimal improvements in picture descriptions and production declines in question responses relative to pretreatment levels.Conclusion: The intensive treatment protocol is a successful method for improving picture naming even of untrained items.Further, the authors conclude that the intentional left-hand gesture contributed significantly to the generalization of treatment to discourse.

A Behavioral Manipulation Engages Right Frontal Cortex During Aphasia Therapy.

Background An aphasia treatment was designed to shift laterality from the left to right lateral frontal lobe during word production by initiating word-finding trials with complex left-hand movements. Previous findings indicated successful relateralization. Objective The current study was designed to ascertain whether the shift was attributable to the left-hand movement. Methods Using stratified random sampling, 14 subjects were equally divided between Intention (IT) and Control (CT) treatments. CT was identical to IT, except with no left-hand movements. Both treatments trained picture naming (phases 1 and 2) and category-member generation (phase 3), each phase lasting 10 sessions. Functional magnetic resonance imaging of category member generation occurred at pretreatment, posttreatment, and 3-month follow-up. Results IT shifted lateral frontal activity rightward compared with pretreatment both at posttreatment (t = -2.602, df = 6, P < .05) and 3-month follow-up (t = -2.332, df = 5, P < .05), but CT did not. IT and CT yielded similar changes for all picture-naming and category probes. However, IT patients showed gains for untrained category (t = 3.33, df = 6, P < .01) and picture-naming probes (t = 3.77, df = 5, P < .01), but CT patients did not. Conclusions The rightward shift in lateral frontal activity for IT was because of the left-hand movements. IT evoked greater generalization than CT.

A qualitative analysis of beginning mindfulness experiences for women with post-traumatic stress disorder and a history of intimate partner violence.

This article presents the beginning mindfulness experiences of low income, minority women with a history of intimate partner violence. Ten women participated in a Mindfulness-Based Stress Reduction group, three interviews and a focus group over 15 months. Using an interpretive phenomenological analysis approach, we derived the following themes: struggles to practice meditation; a vision of growing and helping; personal improvements, and interpersonal improvements. We share recommendations for clinical practice.

Impact of changed positive and negative task-related brain activity on word-retrieval in aging.

Previous functional imaging studies that compared activity patterns in older and younger adults during nonlinguistic tasks found evidence for 2 phenomena: older participants usually show more pronounced task-related positive activity in the brain hemisphere that is not dominant for the task and less pronounced negative task-related activity in temporo-parietal and midline brain regions. The combined effects of these phenomena and the impact on word retrieval, however, have not yet been assessed. We used functional magnetic resonance imaging to explore task-related positive (active task > baseline) and negative activity (baseline > active task) during semantic and phonemic verbal fluency tasks. Increased right frontal positive activity during the semantic task and reduced negative activity in the right hemisphere during both tasks was associated with reduced performance in older subjects. No substantial relationship between changes in positive and negative activity was observed in the older participants, pointing toward 2 partially independent but potentially co-occurring processes. Underlying causes of the observed functional network inefficiency during word retrieval in older adults need to be determined in the future.

Perceptual cues used by listeners to discriminate fluent from nonfluent narrative discourse.

BACKGROUND: Language fluency is a common diagnostic marker for discriminating among aphasia subtypes and improving clinical inference about site of lesion. Nevertheless, fluency remains a subjective construct that is vulnerable to a number of potential sources of variability, both between and within raters. Moreover, this variability is compounded by distinct neurological aetiologies that shape the characteristics of a narrative speech sample. Previous research on fluency has focused on characteristics of a particular patient population. Less is known about the ways that raters spontaneously weigh different perceptual cues when listening to narrative speech samples derived from a heterogeneous sample of brain-damaged adults. AIM: We examined the weighted contribution of a series of perceptual predictors that influence listeners' judgements of language fluency among a diverse sample of speakers. Our goal was to sample a range of narrative speech representing most fluent (i.e., healthy controls) to potentially least nonfluent (i.e., left inferior frontal lobe stroke). METHODS #ENTITYSTARTX00026; PROCEDURES: Three raters blind to patient diagnosis made forced choice judgements of fluency (i.e., fluent or nonfluent) for 61 pseudorandomly presented narrative speech samples elicited by the BDAE Cookie Theft picture. Samples were collected from a range of clinical populations, including patients with frontal and temporal lobe pathologies and non-brain-damaged speakers. We conducted a logistic regression analysis in which the dependent measure was the majority judgement of fluency for each speech sample (i.e., fluent or non-fluent). The statistical model contained five predictors: speech rate, syllable type token ratio, speech productivity, audible struggle, and filler ratio. OUTCOMES #ENTITYSTARTX00026; RESULTS: This statistical model fit the data well, discriminating group membership (i.e., fluent or nonfluent) with 95.1% accuracy. The best step of the regression model included the following predictors: speech rate, speech productivity, and audible struggle. Listeners were sensitive to different weightings of these predictors. CONCLUSIONS: A small combination of perceptual variables can strongly discriminate whether a listener will assign a judgement of fluent versus nonfluent. We discuss implications for these findings and identify areas of potential future research towards further specifying the construct of fluency among adults with acquired speech and language disorders.

An fMRI study of the differences in brain activity during active ankle dorsiflexion and plantarflexion.

Little is known regarding the differences in active cortical and subcortical systems during opposing movements of an agonist-antagonist muscle group. The objective of this study was to characterize the differences in cortical activation during active ankle dorsiflexion and plantarflexion using functional MRI (fMRI). Eight right-handed healthy adults performed auditorily cued right ankle dorsiflexions and plantarflexions during fMRI. Differences in activity patterns between dorsiflexion and plantarflexion during fMRI were assessed using between- and within-subject voxel-wise t-tests. Results indicated that ankle dorsiflexion recruited significantly more regions in left M1, the supplementary motor area (SMA) bilaterally, and right cerebellum. Both movements activated similar left hemisphere regions in the putamen and thalamus. Dorsiflexion activated additional areas in the right putamen. Results suggest that ankle dorsiflexion and plantarflexion may be controlled by both shared and independent neural circuitry. This has important implications for functional investigations of gait pathology and how rehabilitation may differentially affect each movement.

Regional changes in word-production laterality after a naming treatment designed to produce a rightward shift in frontal activity.

Five nonfluent aphasia patients participated in a picture-naming treatment that used an intention manipulation (opening a box and pressing a button on a device in the box with the left hand) to initiate naming trials and was designed to re-lateralize word production mechanisms from the left to the right frontal lobe. To test the underlying assumption regarding re-lateralization, patients participated in fMRI of category-member generation before and after treatment. Generally, the four patients who improved during treatment showed reduced frontal activity from pre- to post-treatment fMRI with increasing concentration of activity in the right posterior frontal lobe (motor/premotor cortex, pars opercularis), demonstrating a significant shift in lateraliity toward the right lateral frontal lobe, as predicted. Three of these four patients showed no left frontal activity by completion of treatment, indicating that right posterior lateral frontal activity supported category-member generation. Patients who improved in treatment showed no difference in lateralization of lateral frontal activity from normal controls pre-treatment, but post-treatment, their lateral frontal activity during category-member generation was significantly more right lateralized than that of controls. Patterns of activity pre- and post-treatment suggested increasing efficiency of cortical processing as a result of treatment in the four patients who improved. The one patient who did not improve during treatment showed a leftward shift in lateral frontal lateralization that was significantly different from the four patients who did improve. Neither medial frontal nor posterior perisylvian re-lateralization from immediately pre- to immediately post-treatment images was a necessary condition for significant treatment gains or shift in lateral frontal lateralization. Of the three patients who improved and in whom posterior perisylvian activity could be measured at post-treatment fMRI, all maintained equal or greater amounts of left-hemisphere perisylvian activity as compared to right. This finding is consistent with reviews suggesting both hemispheres are involved in recovery of language in aphasia patients.

Age-related changes in word retrieval: role of bilateral frontal and subcortical networks.

Healthy older adults frequently report word-finding difficulties, yet the underlying cause of these problems is not well understood. This study examined whether age-related changes in word retrieval are related to changes in areas of the frontal lobes thought to subserve word retrieval or changes in areas of the inferior temporal lobes thought to be involved in semantic knowledge. Twenty younger and 20 older healthy adults named aloud photographs during event-related fMRI. Results showed that in the face of equivalent naming accuracy, older adults activated a larger frontal network than younger adults during word retrieval, but there were no activity differences between groups in the fusiform gyrus, suggesting that the substrates for word retrieval but not for semantic knowledge change with aging. Additionally, correlations between BOLD response and naming accuracy and response latency were found in several frontal and subcortical regions in older adults. Findings are discussed in the context of possible compensatory mechanisms invoked to maintain performance in healthy aging, and suggest that increased involvement of the right hemisphere is not universally beneficial to performance.

Functional MRI of language in aphasia: a review of the literature and the methodological challenges.

Animal analogue studies show that damaged adult brains reorganize to accommodate compromised functions. In the human arena, functional magnetic resonance imaging (fMRI) and other functional neuroimaging techniques have been used to study reorganization of language substrates in aphasia. The resulting controversy regarding whether the right or the left hemisphere supports language recovery and treatment progress must be reframed. A more appropriate question is when left-hemisphere mechanisms and when right-hemisphere mechanisms support recovery of language functions. Small lesions generally lead to good recoveries supported by left-hemisphere mechanisms. However, when too much language eloquent cortex is damaged, right-hemisphere structures may provide the better substrate for recovery of language. Some studies suggest that recovery is particularly supported by homologues of damaged left-hemisphere structures. Evidence also suggests that under some circumstances, activity in both the left and right hemispheres can interfere with recovery of function. Further research will be needed to address these issues. However, daunting methodological problems must be managed to maximize the yield of future fMRI research in aphasia, especially in the area of language production. In this review, we cover six challenges for imaging language functions in aphasia with fMRI, with an emphasis on language production: (1) selection of a baseline task, (2) structure of language production trials, (3) mitigation of motion-related artifacts, (4) the use of stimulus onset versus response onset in fMRI analyses, (5) use of trials with correct responses and errors in analyses, and (6) reliability and stability of fMRI images across sessions. However, this list of methodological challenges is not exhaustive. Once methodology is advanced, knowledge from conceptually driven fMRI studies can be used to develop theoretically driven, mechanism-based treatments that will result in more effective therapy and to identify the best patient candidates for specific treatments. While the promise of fMRI in the study of aphasia is great, there is much work to be done before this technique will be a useful clinical tool.

Depression and stages of Huntington's disease.

Individuals with manifest Huntington's disease (HD) were interviewed with regard to the presence, frequency, and severity of depression symptoms to better characterize depressed mood across the disease course in HD. Rates of depression were more than twice that found in the general population. One-half reported that they had sought treatment for depression, and more than 10% reported having at least one suicide attempt. The proportion of HD patients endorsing significant depression diminished with disease progression. Despite the public health impact of depression, available treatments are underutilized in HD, and research is needed to document the efficacy and effectiveness of standard depression treatments in this population.

Coercion and informed consent in research involving prisoners.

Prison-based research has been limited due to concern that prisoners may represent a vulnerable population secondary to possible coercion and limited capacity for voluntary informed consent. This study was designed to assess decisional capacity and susceptibility to coercion in prison research subjects. Subjects were 30 mentally ill prisoners and 30 healthy controls. The groups were compared on ability to provide informed consent to a hypothetical drug trial, susceptibility to possible coercion, neuropsychological functioning, and psychiatric symptoms. Results indicated that all controls and all but one of the prisoners demonstrated adequate capacity to consent to the hypothetical drug trial. However, when decisional capacity was measured quantitatively, prisoners performed significantly worse regarding two aspects of this ability. Regarding possible coercion, prisoners' main reasons for participating in research included avoiding boredom, meeting someone new, appearing cooperative in hopes of being treated better, and helping society. Neuropsychological functioning was strongly positively correlated with decisional capacity and negatively correlated with susceptibility to possible coercion, whereas psychiatric symptoms were only weakly correlated with these variables. In conclusion, a very high percentage of particularly vulnerable, mentally ill prisoners demonstrated adequate capacity to consent to research. Lower scores on a quantitative measure of decisional capacity suggest that extra care should be taken during the consent process when working with these subjects. The reasons prisoners gave for participating in our research indicated that the prison setting may have influenced their decision to participate, but that they were not actually coerced into doing so. Despite serious past incidents, ethicists will need to consider the possibility that prisoners have become an overprotected population.

Neuropsychological functioning pretreatment and posttreatment in an inpatient eating disorders program.

OBJECTIVE: This study was conducted to determine whether neuropsychological dysfunction associated with anorexia nervosa resolves with inpatient treatment. METHOD: Subjects were 28 women being treated for anorexia nervosa. Main study variables included body mass index (BMI), Beck Depression Inventory-II, and neuropsychological test scores. Subjects were tested at admission and discharge. RESULTS: Neuropsychological functioning improved across the course of treatment, with significant changes on tests of memory and psychomotor speed. This improvement was not significantly associated with change in BMI or with the other variables that were studied. DISCUSSION: Patients with anorexia nervosa exhibit subtle neuropsychological dysfunction, which resolves at least partially during treatment. This improvement does not appear to be associated with an increase in BMI. However, it is possible that BMI is not a sufficiently sensitive indicator of nutritional status or that longer-term follow-up is necessary to reveal the nutrition-cognition relationship that we were seeking.