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ABSTRACT: The eating disorder anorexia nervosa (AN) is associated with high anxiety. The brain mechanisms that drive those behaviors are unknown. In this study we wanted to test whether brain white matter (WM) integrity is altered in AN, and related to heightened anxiety. Sixteen adult women with AN (mean age 24 ± 7 years) and 17 healthy control women (CW, mean age 25 ± 4 years) underwent diffusion tensor imaging (DTI) of the brain. The DTI brain images were used to calculate the fractional anisotropy (FA) of WM tracts, which is a measure for WM integrity. AN individuals compared to CW showed clusters of significantly reduced FA (p<0.05, corrected) in the bilateral fimbria-fornix and the fronto-occipital fasciculus, as well as the posterior cingulum WM. In the AN group, Harm Avoidance was predicted by FA in the left and right fimbria-fornix. Those findings were not due to WM volume deficits in AN. This study indicates that WM integrity is abnormal in AN in limbic and association pathways, which could contribute to disturbed feeding, emotion processing and body perception in AN. The prediction of Harm Avoidance in AN by fimbria-fornix WM integrity suggests that this pathway may be mechanistically involved in high anxiety in AN.
Psychiatry Research 05/2011; 192(2):109-16. · 2.52 Impact Factor
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Jason Tregellas
American Journal of Psychiatry 03/2009; 166(2):134-6. · 12.54 Impact Factor
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ABSTRACT: Cortical deficits in schizophrenia have been related to diverse psychophysiological, neurobiological, and genetic deficits.
This chapter reviews specific psychophysiological deficits in sensory and motor gating, their neurobiological substrate in
nicotinic acetylcholine-mediated neurotransmission, and their genetic basis. Detailed correlations between these several levels
of observation are necessary to parse schizophrenia into discrete and hopefully more treatable elements.
09/2007: pages 97-111;
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ABSTRACT: Vision often requires attending to, and integrating information from, distant parts of the visual field. However, the neural basis for such long-range integration is not clearly understood. Here, we demonstrate a specific neural signature of attentional integration between stimuli in different parts of the visual field. Using functional MRI, we found that a task requiring the integration of information between two attended but spatially separated stimuli actively modulated the degree of functional integration (in terms of effective connectivity) between their retinotopic representations in visual cortical areas V1, V2, and V4. Spatial attention enhanced long-distance coupling between distinct neuronal populations that represented the attended visual stimuli, even at the earliest stages of cortical processing. In contrast, unattended stimulus representations were decoupled both from attended representations and particularly strongly from each other. Furthermore, enhanced functional integration between cortical representations was associated with enhanced behavioral performance. Attention may thus serve to "bind" together cortical loci at multiple levels of the visual hierarchy that are commonly involved in processing attended stimuli, promoting integration between otherwise functionally isolated cortical loci.
Proceedings of the National Academy of Sciences 11/2005; 102(41):14925-30. · 9.68 Impact Factor
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Robert Freedman,
Randal Ross,
Sherry Leonard,
Marina Myles-Worsley,
Catherine E Adams,
Merilyne Waldo, Jason Tregellas,
Laura Martin,
Ann Olincy,
Jody Tanabe,
Michael A Kisley,
Sharon Hunter,
Karen E Stevens
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ABSTRACT: Biological traits that are predictive of the later development of psychosis have not yet been identified. The complex, multidetermined nature of schizophrenia and other psychoses makes it unlikely that any single biomarker will be both sensitive and specific enough to unambiguously identify individuals who will later become psychotic. However, current genetic research has begun to identify genes associated with schizophrenia, some of which have phenotypes that appear early in life. While these phenotypes have low predictive power for identifying individuals who will become psychotic, they do serve as biomarkers for pathophysiological processes that can become the targets of prevention strategies. Examples are given from work on the role of the alpha(T)nicotinic receptor and its gene CHRNA7 on chromosome 15 in the neurobiology and genetic transmission of schizophrenia.
Dialogues in clinical neuroscience 02/2005; 7(1):17-29.
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ABSTRACT: Several lines of evidence suggest a pathophysiological role for nicotinic receptors in schizophrenia. Activation by nicotine alters physiological dysfunctions, such as eye movement and sensory gating abnormalities, but effects on neuropsychological performance are just beginning to be investigated. Nicotine-induced desensitization and the well-known tachyphylaxis of nicotinic receptors may confound such efforts. In all, 20 schizophrenics, 10 smokers, and 10 nonsmokers were assessed following the administration of nicotine gum and placebo gum. The Repeatable Battery for the Assessment of Neuropsychological Status was administered. Nicotine affected only the Attention Index; there were no effects on learning and memory, language, or visuospatial/constructional abilities. Attentional function was increased in nonsmokers, but decreased in nicotine-abstinent smokers after nicotine administration. The effects of nicotine in schizophrenia do not extend to all areas of cognition. Effects on attention may be severely limited by tachyphylaxis, such that decremented performance occurs in smokers, while modest effects may be achieved in nonsmokers.
Neuropsychopharmacology 08/2004; 29(7):1378-85. · 7.99 Impact Factor
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ABSTRACT: A potential application of studying eye movements with functional MRI (fMRI) is to examine patient populations with known eye movement dysfunction, but the reliability with which normal subjects demonstrate activity in specific brain regions has not been established. To date, fMRI studies of smooth-pursuit eye movements have used relatively small numbers of subjects and have been restricted to fixed-effects analyses. We extend these studies to whole brain imaging at 1.5 T, properly accounting for intersubject variation using random effects analysis. Smooth-pursuit eye movements elicited activation consistently in dorsal cortical eye fields and cerebellum. Subcortical activation was greatly attenuated, but not eliminated, with the random-effects second-level analysis. In addition, session-dependent changes in activation were greater in some regions than others and may indicate areas of brain, such as the supplementary eye fields, that are sensitive to attentional modulation of eye movements.
NeuroImage 12/2002; 17(3):1315-24. · 5.89 Impact Factor
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ABSTRACT: Because of the inherently low signal to noise ratio (SNR) of fMRI data, removal of low frequency signal intensity drift is an important preprocessing step, particularly in those brain regions that weakly activate. Two known sources of drift are noise from the MR scanner and aliasing of physiological pulsations. However, the amount and direction of drift is difficult to predict, even between neighboring voxels. Further, there is no concensus on an optimal baseline drift removal algorithm. In this paper, five voxel-based detrending techniques were compared to each other and an auto-detrending algorithm, which automatically selected the optimal method for a given voxel time-series. For a significance level of P < 10(-6), linear and quadratic detrending moderately increased the percentage of activated voxels. Cubic detrending decreased activation, while a wavelet approach increased or decreased activation, depending on the dataset. Spline detrending was the best single algorithm. However, auto-detrending (selecting the best algorithm or none, if detrending is not useful) appears to be the most judicious choice, particularly for analyzing fMRI data with weak activations in the presence of baseline drift.
NeuroImage 04/2002; 15(4):902-7. · 5.89 Impact Factor
