As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12–71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.

HIV-1 infection can be associated with neuropsychological (NP) deficits ranging from subtle to severe. The purpose of this study was to evaluate the functional, or "real-world" impact of HIV-associated NP impairment in a group of 267 HIV-infected participants. All participants received comprehensive NP, neuromedical, and standardized functional evaluations that included laboratory measures of shopping, cooking, financial management, medication management and vocational abilities. Compared to NP-normal participants, those with NP impairment performed significantly worse on all laboratory measures of everyday functioning. Multivariate analyses revealed that the NP ability domains of Abstraction0Executive Function, Learning, Attention0Working Memory and Verbal abilities most strongly and consistently predicted failures on the functional battery. Both NP impairment and impairment on the functional battery were significantly associated with subjective experiences of cognitive difficulties, as well as unemployment and increased dependence in activities of daily living; multivariate prediction models that also considered depressed mood and biological measures of disease progression revealed that impairment on the functional battery and depression were the only unique predictors of all three indicators of "real-world" functioning. The current results add to growing evidence concerning the clinical significance of HIV-associated NP impairment. Objective, laboratory based functional measures, such as those used here, may compliment NP testing in future studies directed at understanding the impact on life quality of central nervous system disorders and their treatments. Finally, there is a need for additional research investigating the apparently independent effect of depression on level of everyday functioning in HIV infected persons. (JINS, 2004, 10, 317-331.)

The California Verbal Learning Test was used to characterize the learning and memory impairment in schizophrenia (SC) and to evaluate potential clinical and demographic factors associated with this impairment. SC patients (n= 175) performed worse than normal comparison (NC) subjects (n= 229) on all learning, recall, and recognition memory measures. The most important clinical correlates of these impairments were earlier age of onset, more negative symptoms, and greater anticholinergic medication dosage. SC patients showed a prominent retrieval deficit as indicated by disproportionate improvement when tested in a recognition, rather than a free recall, format. A residual impairment seen with recognition testing suggests a mild encoding deficit as well. In contrast, the relative absence of a storage deficit is suggested by the lack of rapid forgetting. Using a discriminant function analysis that differentiates cortical dementia [i.e., Alzheimer's disease (AD)], subcortical dementia [i.e., Huntington's disease (HD)], and normals, it was found that 5070 of the SC patients were classified as having a subcortical memory profile and 35% were classified as having a normal profile, whereas only 15% were classified as having a cortical memory profile. Although these findings reflect the clinical heterogeneity often found in SC, results suggest that most SC patients demonstrate a pattern of learning and memory impairments that resembles the pattern seen in patients with primary subcortical (specifically striatal) pathology. (JINS, 1995,I, 88–99.)

fMRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During fMRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation of words given a rhyming word, generation of words given a semantic category at a fast rate (matched to the rate of nonsense syllable generation), and generation of words given a semantic category at a slow rate (matched to the rate of generating of rhyming words). Components of a left pre-SMA-dorsal caudate nucleus-ventral anterior thalamic loop were active during word generation from rhyming or category cues but not during nonsense syllable generation. Findings indicate that this loop is involved in retrieving words from pre-existing lexical stores. Relatively diffuse activity in the right basal ganglia (caudate nucleus and putamen) also was found during word-generation tasks but not during nonsense syllable generation. Given the relative absence of right frontal activity during the word generation tasks, we suggest that the right basal ganglia activity serves to suppress right frontal activity, preventing right frontal structures from interfering with language production. Current findings establish roles for the left and the right basal ganglia in word generation. Hypotheses are discussed for future research to help refine our understanding of basal ganglia functions in language generation.

Goldberg (1985) hypothesized that as language output changes from internally to externally guided production, activity shifts from supplementary motor area (SMA) to lateral premotor areas, including Broca's area. To test this hypothesis, 15 right-handed native English speakers performed three word generation tasks varying in the amount of internal guidance and a repetition task during functional magnetic resonance imaging (fMRI). Volumes of significant activity for each task versus a resting state were derived using voxel-by-voxel repeated-measures t tests (p <.001) across subjects. Changes in the size of activity volumes for left medial frontal regions (SMA and pre-SMA/BA 32) versus left lateral frontal regions (Broca's area, inferior frontal sulcus) were assessed as internal guidance of word generation decreased and external guidance increased. Comparing SMA to Broca's area, Goldberg's hypothesis was not verified. However, pre-SMA/BA 32 activity volumes decreased significantly and inferior frontal sulcus activity volumes increased significantly as word generation tasks moved from internally to externally guided.

People with mental illness in Nova Scotia have increased mortality from cancer, which cannot always be explained by increased incidence. Possible explanations for further study include delays in detection or initial presentation leading to more advanced staging at diagnosis, and difficulties in communication or access to health care.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.

Background and Purpose-Despite strong evidence for hand preference and its impact on motor performance, its influence on stroke rehabilitation has not been routinely considered. Previous research demonstrates that patients with hemiparetic stroke use their ipsilesional, nonparetic arm 5 to 6 times more frequently than their paretic arm, but it is unknown if such use varies with laterality of hemiparesis. The purpose of our study was to determine if the right arm is used more frequently in right-handed patients with stroke. Methods-We assessed relative use of the right, left, and both arms with wrist accelerometers on patients with unilateral, paretic stroke matched for degree of paresis (12 with right hemisphere damage, 17 with left hemisphere damage) and 25 neurologically intact control participants as they performed the Arm Motor Ability Test. Results-We showed: (1) ipsilesional arm use was greater after right hemisphere damage than left hemisphere damage; (2) the left hemisphere damage group used both arms together more often than the right hemisphere damage group but less often than the control group; and (3) both stroke groups used their contralesional, paretic arm to the same degree. Conclusions-These findings emphasize the influence of hand preference on arm use after stroke for the ipsilesional but not the contralesional arm. Although both stroke groups used their ipsilesional more than their contralesional arm, the difference was greater for the right hemisphere damage group who used their ipsilesional arm 4 times more frequently than their contralesional arm, whereas the left hemisphere damage group used their ipsilesional arm 2 times more frequently than their contralesional arm.