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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.

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.

Previous functional imaging studies that compared activity patterns in older and younger adults during non-linguistic tasks found evidence for two 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 towards two 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.

The cognitive effects of active and sham repetitive transcranial magnetic stimulation (rTMS) were examined in 19 middle-aged and elderly patients with refractory depression. Patients received either active (n = 9) or sham (n = 10) rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients in the active rTMS group improved significantly on a test of cognitive flexibility and conceptual tracking (Trail Making Test-B).

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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.

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.