This study tested the hypothesis that diffusion tensor imaging (DTI) can detect alteration in microscopic integrity of white matter (WM) and basal ganglia (BG) regions known to be involved in Parkinson's disease (PD) pathology. It was also hypothesized that there is an association between the DTI abnormality and PD severity and subtype. DTI at 4 Tesla was obtained in 12 PD and 20 control subjects. The DTI measures of fractional anisotropy (FA) and mean diffusivity (MD) were evaluated using both region of interest (ROI) and voxel-based methods. Movement deficits in PD subjects were assessed using Motor Subscale (Part III) of the Unified Parkinson's Disease Rating Scale (UPDRS). Subtype determination of movement deficits was derived based upon results of subjects’ UPDRS ratings. Reduced FA (p<0.05, corrected) was found in PD subjects in a number of regions, including the precentral gyrus, substantia nigra, putamen, posterior striatum, frontal WM, and in regions related to the supplementary motor areas. Reduced FA in the substantia nigra correlated (p<0.05, corrected) with increased UPDRS motor scores. Significant spatial correlations between FA alterations in putamen and other PD-affected regions were also found in the context of PD subtypes index analysis. Our data suggest that microstructural alterations detected with DTI might serve as a potential biomarker for PD.

Efficient neural processing depends on regulating responses through suppression and facilitation of neural activity. Utilizing a well-known visual motion paradigm that evokes behavioral suppression and facilitation, and combining 5 different methodologies (behavioral psychophysics, computational modeling, functional MRI, pharmacology, and magnetic resonance spectroscopy), we provide evidence that challenges commonly held assumptions about the neural processes underlying suppression and facilitation. We show that: 1) both suppression and facilitation can emerge from a single, computational principle -divisive normalization; there is no need to invoke separate neural mechanisms, 2) neural suppression and facilitation in the motion-selective area MT mirror perception, but strong suppression also occurs in earlier visual areas, and 3) suppression is not driven by GABA-mediated inhibition. Thus, while commonly used spatial suppression paradigms may provide insight into neural response magnitudes in visual areas, they cannot be used to infer neural inhibition.

In peripheral vision, objects in clutter are difficult to identify. The exact cause of this "crowding" effect is unclear. To perceive coherent shapes in clutter, the visual system must integrate certain local features across receptive fields while preventing others from being combined. It is believed that this selective feature integration-segmentation process is impaired in peripheral vision, leading to crowding. We used functional magnetic resonance imaging (fMRI) to investigate the neural origin of crowding. We found that crowding was associated with suppressed fMRI signal as early as V1, regardless of whether attention was directed toward or away from a target stimulus. This suppression in early visual cortex was greatest for stimuli that produced the strongest crowding. In contrast, the pattern of activity was mixed in higher level visual areas, such as the lateral occipital cortex. These results support the view that the deficiency in feature integration and segmentation in peripheral vision is present at the earliest stages of cortical processing.

Efficient neural processing depends on regulating responses through suppression and facilitation of neural activity. Utilizing a well-known visual motion paradigm that evokes behavioral suppression and facilitation, and combining five different methodologies (behavioral psychophysics, computational modeling, functional MRI, pharmacology, and magnetic resonance spectroscopy), we provide evidence that challenges commonly held assumptions about the neural processes underlying suppression and facilitation. We show that: (1) both suppression and facilitation can emerge from a single, computational principle – divisive normalization; there is no need to invoke separate neural mechanisms, (2) neural suppression and facilitation in the motion-selective area MT mirror perception, but strong suppression also occurs in earlier visual areas, and (3) suppression is not primarily driven by GABA-mediated inhibition. Thus, while commonly used spatial suppression paradigms may provide insight into neural response magnitudes in visual areas, they should not be used to infer neural inhibition.

Recent studies associated excess body weight with brain structural alterations, poorer cognitive function, and lower prefrontal glucose metabolism. We found that higher BMI was related to lower concentrations of N‐acetyl‐aspartate (NAA, a marker of neuronal integrity) in a healthy middle‐aged cohort, especially in frontal lobe. Here, we evaluated whether NAA was also associated with BMI in a healthy elderly cohort. We used 4 Tesla proton magnetic resonance spectroscopy (1H MRS) data from 23 healthy, cognitively normal elderly participants (69.4 ± 6.9 years; 12 females) and measured concentrations of NAA, glutamate (Glu, involved in cellular metabolism), choline‐containing compounds (Cho, involved in membrane metabolism), and creatine (Cr, involved in high‐energy metabolism) in anterior (ACC) and posterior cingulate cortices (PCC). After adjustment for age, greater BMI was related to lower NAA/Cr and NAA/Cho ratios (β < −0.56, P < 0.008) and lower Glu/Cr and Glu/Cho ratios (β < −0.46, P < 0.02) in ACC. These associations were not significant in PCC (β > −0.36, P > 0.09). The existence of an association between NAA and BMI in ACC but not in PCC is consistent with our previous study in healthy middle‐aged individuals and with reports of lower frontal glucose metabolism in young healthy individuals with elevated BMI. Taken together, these results provide evidence that elevated BMI is associated with neuronal abnormalities mostly in frontal brain regions that subserve higher cognitive functions and impulse control. Future studies need to evaluate whether these metabolite abnormalities are involved in the development and maintenance of weight problems.

Adaptation is a fundamental property of cortical neurons and has been suggested to be altered in individuals with autism spectrum disorder (ASD). We used fMRI to measure adaptation induced by repeated audio-visual stimulation in early sensory cortical areas in individuals with ASD and neurotypical (NT) controls. The initial transient responses were equivalent between groups in both visual and auditory cortices and when stimulation occurred with fixed-interval and randomized-interval timing. However, in auditory but not visual cortex, the post-transient sustained response was greater in individuals with ASD than NT controls in the fixed-interval timing condition, reflecting reduced adaptation. Further, individual differences in the sustained response in auditory cortex correlated with ASD symptom severity. These findings are consistent with hypotheses that ASD is associated with increased neural responsiveness but that responsiveness differences only manifest after repeated stimulation, are specific to the temporal pattern of stimulation, and are confined to specific cortical regions.

Crowding, the inability to recognize an individual object in clutter (Bouma H. Nature 226: 177-178, 1970), is considered a major impediment to object recognition in peripheral vision. Despite its significance, the cortical loci of crowding are not well understood. In particular, the role of the primary visual cortex (V1) remains unclear. Here we utilize a diagnostic feature of crowding to identify the earliest cortical locus of crowding. Controlling for other factors, radially arranged flankers induce more crowding than tangentially arranged ones (Toet A, Levi DM. Vision Res 32: 1349-1357, 1992). We used functional magnetic resonance imaging (fMRI) to measure the change in mean blood oxygenation level-dependent (BOLD) response due to the addition of a middle letter between a pair of radially or tangentially arranged flankers. Consistent with the previous finding that crowding is associated with a reduced BOLD response [Millin R, Arman AC, Chung ST, Tjan BS. Cereb Cortex (July 5, 2013). doi:10.1093/cercor/bht159], we found that the BOLD signal evoked by the middle letter depended on the arrangement of the flankers: less BOLD response was associated with adding the middle letter between radially arranged flankers compared with adding it between tangentially arranged flankers. This anisotropy in BOLD response was present as early as V1 and remained significant in downstream areas. The effect was observed while subjects' attention was diverted away from the testing stimuli. Contrast detection threshold for the middle letter was unaffected by flanker arrangement, ruling out surround suppression of contrast response as a major factor in the observed BOLD anisotropy. Our findings support the view that V1 contributes to crowding.

DNA looping occurs in many important protein-DNA interactions, including those regulating replication, transcription, and recombination. Recent theoretical studies predict that tension of only a few piconewtons acting on DNA would almost completely inhibit DNA looping. Here, we study restriction endonucleases that require interaction at two separated sites for efficient cleavage. Using optical tweezers we measured the dependence of cleavage activity on DNA tension with 15 known or suspected two-site enzymes (BfiI, BpmI, BsgI, BspMI, Cfr9I, Cfr10I, Eco57I, EcoRII, FokI, HpaII, MboII, NarI, SacII, Sau3AI, and SgrAI) and six one-site enzymes (BamHI, EcoRI, EcoRV, HaeIII, HindIII, and DNaseI). All of the one-site enzymes were virtually unaffected by 5 pN of tension, whereas all of the two-site enzymes were completely inhibited. These enzymes thus constitute a remarkable example of a tension sensing ''molecular switch.'' A detailed study of one enzyme, Sau3AI, indicated that the activity decreased exponentially with tension and the decrease was Ϸ10-fold at 0.7 pN. At higher forces (Ϸ20 -40 pN) cleavage by the one-site enzymes EcoRV and HaeIII was partly inhibited and cleavage by HindIII was enhanced, whereas BamHI, EcoRI, and DNaseI were largely unaffected. These findings correlate with structural data showing that EcoRV bends DNA sharply, whereas BamHI, EcoRI, and DNaseI do not. Thus, DNA-directed enzyme activity involving either DNA looping or bending can be modulated by tension, a mechanism that could facilitate mechanosensory transduction in vivo.DNA looping ͉ protein-DNA interactions ͉ single-molecule manipulation R estriction endonucleases (REases) are prokaryotic enzymes that act to ''restrict'' invasion of foreign DNA by cleaving phosphodiester bonds (1). These enzymes also serve as indispensable tools in molecular biology research and are used in procedures such as DNA cloning, fingerprinting, mapping, and sequencing (2). From the perspective of molecular biophysics, these enzymes are excellent model systems for studying basic principles of protein-DNA interactions (3, 4).The most commonly studied REases are of the type II variety, which cleave within or near specific recognition sites, usually require Mg 2ϩ ions as a cofactor, and do not hydrolyze ATP. More than 3,500 different type II REases having Ͼ200 different binding specificities have been identified (5). Of particular interest in our present study are the many unorthodox type II REases that do not cleave DNA efficiently if the template contains only one recognition site (6, 7). Efficient cleavage is only observed with templates containing two or more sites, suggesting that the active complex binds at two sites and the intervening DNA is looped out (7). This phenomenon of DNA looping is of broad importance in molecular biology and plays a role in many key processes including DNA transcription, replication, recombination, and repair (8-13). Looping of DNA by the Lac and Gal repressor proteins in Escherichia coli, for example, is well demonstrated and h...