Numerous studies have demonstrated functional magnetic resonance imaging (fMRI)-based resting-state functional connectivity (RSFC) between cortical areas. Recent evidence suggests that synchronous fluctuations in blood oxygenation level-dependent fMRI reflect functional organization at a scale finer than that of visual areas. In this study, we investigated whether RSFCs within and between lower visual areas are retinotopically organized and whether retinotopically organized RSFC merely reflects cortical distance. Subjects underwent retinotopic mapping and separately resting-state fMRI. Visual areas V1, V2, and V3, were subdivided into regions of interest (ROIs) according to quadrants and visual field eccentricity. Functional connectivity (FC) was computed based on Pearson's linear correlation (correlation), and Pearson's linear partial correlation (correlation between two time courses after the time courses from all other regions in the network are regressed out). Within a quadrant, within visual areas, all correlation and nearly all partial correlation FC measures showed statistical significance. Consistently in V1, V2, and to a lesser extent in V3, correlation decreased with increasing eccentricity separation. Consistent with previously reported monkey anatomical connectivity, correlation/partial correlation values between regions from adjacent areas (V1-V2 and V2-V3) were higher than those between nonadjacent areas (V1-V3). Within a quadrant, partial correlation showed consistent significance between regions from two different areas with the same or adjacent eccentricities. Pairs of ROIs with similar eccentricity showed higher correlation/partial correlation than pairs distant in eccentricity. Between dorsal and ventral quadrants, partial correlation between common and adjacent eccentricity regions within a visual area showed statistical significance; this extended to more distant eccentricity regions in V1. Within and between quadrants, correlation decreased approximately linearly with increasing distances separating the tested ROIs. Partial correlation showed a more complex dependence on cortical distance: it decreased exponentially with increasing distance within a quadrant, but was best fit by a quadratic function between quadrants. We conclude that RSFCs within and between lower visual areas are retinotopically organized. Correlation-based FC is nonselectively high across lower visual areas, even between regions that do not share direct anatomical connections. The mechanisms likely involve network effects caused by the dense anatomical connectivity within this network and projections from higher visual areas. FC based on partial correlation, which minimizes network effects, follows expectations based on direct anatomical connections in the monkey visual cortex better than correlation. Last, partial correlation-based retinotopically organized RSFC reflects more than cortical distance effects.

Objective: Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor type 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [ 11 C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site. Methods: Thirty-one unilateral MTLE patients and 30 healthy controls underwent [ 11 C]ABP688 PET. We compared partial volume corrected [ 11 C]ABP688 nondisplaceable binding potentials (BP ND ) between groups using region-of-interest and whole-brain voxelwise analyses. [ 18 F]Fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [ 11 C]ABP688 BP ND and [ 18 F]FDG uptake to compare lateralization and localization differences. Results: [ 11 C]ABP688 BP ND was focally reduced in the epileptogenic hippocampal head and amygdala (p < 0.001). Patients with hippocampal atrophy showed more extensive abnormalities, including the ipsilateral temporal neocortex (p = 0.006). [ 11 C]ABP688 BP ND showed interhemispheric differences of higher magnitude and discriminated the epileptogenic structures more accurately when compared to [ 18 F]FDG uptake, which showed more widespread hypometabolism. Among 23 of 25 operated patients with >1 year of follow-up, 13 were seizure-free (Engel Ia) and showed significantly lower [ 11 C]ABP688 BP ND in the ipsilateral entorhinal cortex. Interpretation: [ 11 C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [ 18 F]FDG PET. Focally reduced mGluR5 availability in the EZ might reflect receptor internalization or conformational changes in response to excessive extracellular glutamate, supporting a potential role for mGluR5 as therapeutic target in human MTLE. ANN NEUROL 2019;85:218-228 M etabotropic glutamate receptor type 5 (mGluR5) is a subtype of glutamate receptor that has garnered much interest as to its role in epilepsy. 1 mGluR5 is a postsynaptic G-protein-coupled receptor expressed mostly on the periphery of postsynaptic densities of neurons and astrocytes. It is widely distributed throughout the brain, particularly in limbic regions. 2,3 Group I mGluRs (including mGluR1 and mGluR5) are involved in the postsynaptic modulation of glutamatergic neurotransmission, being able to induce either long-term depression or potentiation. 4,5 View this article online at wileyonlinelibrary.com.

Amblyopia is a prevalent developmental visual disorder of childhood that typically persists in adults. Due to altered visual experience during critical periods of youth, the structure and function of adult visual cortex is abnormal. In addition to substantial deficits shown with task-based fMRI, previous studies have used resting state measures to demonstrate altered long-range connectivity in amblyopia. This is the first study in amblyopia to analyze connectivity between regions of interest that are smaller than a single cortical area and to apply partial correlation analysis to reduce network effects. We specifically assess short-range connectivity between retinotopically defined regions of interest within the occipital lobe of 8 subjects with amblyopia and 7 subjects with normal vision (aged 19–45). The representations of visual areas V1, V2, and V3 within each of the four quadrants of visual space were further subdivided into three regions based on maps of visual field eccentricity. Connectivity between pairs of all nine regions of interest in each quadrant was tested via correlation and partial correlation for both groups. Only the tests of partial correlation, i.e., correlation between time courses of two regions following the regression of time courses from all other regions, yielded significant differences between resting state functional connectivity in amblyopic and normal subjects. Subjects with amblyopia showed significantly higher partial correlation between para-foveal and more eccentric representations within V1, and this effect associated with poor acuity of the worse eye. In addition, we observed reduced correlation in amblyopic subjects between isoeccentricity regions in V1 and V2, and separately, between such regions in V2 and V3. We conclude that partial correlation-based connectivity is altered in an eccentricity-dependent pattern in visual field maps of amblyopic patients. Moreover, results are consistent with known clinical and psychophysical vision loss. More broadly, this provides evidence that abnormal cortical adaptations to disease may be better isolated with tests of partial correlation connectivity than with the regular correlation techniques that are currently widely used.