We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.

Background: Previous cross-sectional fMRI studies in subjects with prodromal Alzheimer disease

Purpose: To present comprehensive examinations of the assumptions made in functional diffusion map (fDM) analyses and provide a biological basis for fDM classification. Materials and Methods:Sixty-nine patients with gliomas were enrolled in this study. To determine the sensitivity of apparent diffusion coefficients (ADCs) to cellularity, cell density from stereotactic biopsy specimens was correlated with preoperative ADC maps. For definition of ADC thresholds used for fDMs, the 95% confidence intervals (CI) for changes in voxel-wise ADC measurements in normal appearing tissue was analyzed. The sensitivity and specificity to progressing disease was examined using both radiographic and neurological criteria. /s. Application of these measurements as ADC thresholds produce varying levels of sensitivity and specificity to disease progression, which were all significantly better than chance.Conclusion: This study suggests fDMs are valid biomarkers for brain tumor cellularity.

Anti-angiogenic agents targeting brain tumor neovasculature may increase progression-free survival in patients with recurrent malignant gliomas. However, when these patients do recur it is not always apparent as an increase in enhancing tumor volume on MRI, which has been the standard of practice for following patients with brain tumors. Therefore alternative methods are needed to evaluate patients treated with these novel therapies. Furthermore, a method that can also provide useful information for the evaluation of conventional therapies would provide an important advantage for general applicability. Diffusion-weighted magnetic resonance imaging (DWI) has the potential to serve as a valuable biomarker for these purposes. In the current study, we explore the prognostic ability of functional diffusion maps (fDMs), which examine voxel-wise NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript changes in the apparent diffusion coefficient (ADC) over time, applied to regions of fluidattenuated inversion recovery (FLAIR) abnormalities in patients with malignant glioma, treated with either anti-angiogenic or cytotoxic therapies. Results indicate that the rate of change in fDMs is an early predictor of tumor progression, time to progression and overall survival for both treatments, suggesting the application of fDMs in FLAIR abnormal regions may be a significant advance in brain tumor biomarker technology.

Functional MRI holds significant potential to aid in the development of early interventions to improve memory function, and to assess longitudinal change in memory systems in aging and early Alzheimer's disease. However, the test-retest reliability of hippocampal activation and of “beneficial” deactivation in the precuneus has yet to be fully established during memory encoding tasks in older subjects. Using a mixed block and event-related face-name associative encoding paradigm, the reliability of hippocampal activation and default network deactivation was assessed over a four-to-six week inter-scan interval in 27 older individuals who were cognitively normal (Clinical Dementia Rating Scale= 0; n=18) or very mildly impaired (CDR=0.5; n=9). Reliability was assessed in whole brain maps and regions-of-interest using both a full task paradigm of six functional runs as well as an abbreviated paradigm of the first two functional runs, which would be advantageous for use in clinical trials. We found reliable hippocampal signal response across both block and event-related designs in the right hippocampus. Comparable reliability in hippocampal activation was found in the full and the abbreviated paradigm. Similar reliability in hippocampal activation was observed across both CDR groups overall, but the CDR 0.5 group was more variable in left hippocampal activity. Task-related deactivation in the precuneus demonstrated much greater variability than hippocampal activation in all analyses. Overall, these results are encouraging for the utility of fMRI in “Proof of Concept” clinical trials investigating the efficacy of potentially therapeutic agents for treatment of age-related memory changes, cognitive impairment, and early Alzheimer's disease.

By age 2, children attribute referential mental states such as perceptions and emotions to themselves and others, yet it is not until age 4 that they attribute representational mental states such as beliefs. This raises an interesting question: Is attribution of beliefs different from attribution of perceptions and emotions in terms of its neural substrate? To address this question with a high degree of anatomic specificity, we partitioned the TPJ, a broad area often found to be recruited in theory of mind tasks, into 2 neuroanatomically specific regions of interest: Superior Temporal Sulcus (STS) and Inferior Parietal Lobule (IPL). To maximize behavioral specificity, we designed a tightly controlled verbal task comprised of sets of single sentences - sentences identical except for the type of mental state specified in the verb (belief, emotion, perception, syntax control). Results indicated that attribution of beliefs more strongly recruited both regions of interest than did emotions or perceptions. This is especially surprising with respect to STS, since it is widely reported in the literature to mediate the detection of referential states - among them emotions and perceptions - rather than the inference of beliefs. An explanation is offered that focuses on the differences between verbal stimuli and visual stimuli, and between a process of sentence comprehension and a process of visual detection.

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