In search of multimodal brain alterations in Alzheimer's and Binswanger's disease.

Structural and functional brain abnormalities have been widely identified in dementia, but with variable replicability and significant overlap. Alzheimer's disease (AD) and Binswanger's disease (BD) share similar symptoms and common brain changes that can confound diagnosis. In this study, we aimed to investigate correlated structural and functional brain changes in AD and BD by combining resting-state functional magnetic resonance imaging (fMRI) and diffusion MRI. A group independent component analysis was first performed on the fMRI data to extract 49 intrinsic connectivity networks (ICNs). Then we conducted a multi-set canonical correlation analysis on three features, functional network connectivity (FNC) between ICNs, fractional anisotropy (FA) and mean diffusivity (MD). Two inter-correlated components show significant group differences. The first component demonstrates distinct brain changes between AD and BD. AD shows increased cerebellar FNC but decreased thalamic and hippocampal FNC. Such FNC alterations are linked to the decreased corpus callosum FA. AD also has increased MD in the frontal and temporal cortex, but BD shows opposite alterations. The second component demonstrates specific brain changes in BD. Increased FNC is mainly between default mode and sensory regions, while decreased FNC is mainly within the default mode domain and related to auditory regions. The FNC changes are associated with FA changes in posterior/middle cingulum cortex and visual cortex and increased MD in thalamus and hippocampus. Our findings provide evidence of linked functional and structural deficits in dementia and suggest that AD and BD have both common and distinct changes in white matter integrity and functional connectivity.

MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating.

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages. Hum Brain Mapp 38:5180-5194, 2017. © 2017 Wiley Periodicals, Inc.

Modulatory role of the prefrontal generator within the auditory M50 network.

The amplitude variability of the M50 component of neuromagnetic responses is commonly used to explore the brain's ability to modulate its response to incoming repetitive or novel auditory stimuli, a process conceptualized as a gating mechanism. The goal of this study was to identify the spatial and temporal characteristics of the cortical sources underlying the M50 network evoked by tones in a passive oddball paradigm. Twenty elderly subjects [10 patients diagnosed with mild cognitive impairment (MCI) or probable Alzheimer disease (AD) and 10 age-matched controls] were examined using magnetoencephalographic (MEG) recordings and the multi-dipole Calibrated Start Spatio-Temporal (CSST) source localization method. We identified three cortical regions underlying the M50 network: prefrontal cortex (PF) in addition to bilateral activation of the superior temporal gyrus (STG). The cortical dynamics of the PF source within the 30-100 ms post-stimulus interval was characterized and was found to be comprised of two subcomponents, Mb1c and Mb2c. The PF source was localized for 10/10 healthy subjects, whereas 9/10 MCI/AD patients were lacking the PF source for both tone conditions. The selective activation of the PF source in healthy controls along with the inactivation of the PF region for MCI/AD patients, enabled us to examine the dynamics of this network of activity when it was functional and dysfunctional, respectively. We found significantly enhanced activity of the STG sources in response to both tone conditions for all subjects who lacked a PF source. The reported results provide novel insights into the topology and neurodynamics of the M50 auditory network, which suggest an inhibitory role of the PF source that normally suppresses activity of the STG sources.

Amnesic syndrome in a mammillothalamic tract infarction.

It is controversial whether isolated lesions of mammillothalamic tract (MTT) produce significant amnesia. Since the MTT is small and adjacent to several important structures for memory, amnesia associated with isolated MTT infarction has been rarely reported. We report a patient who developed amnesia following an infarction of the left MTT that spared adjacent memory-related structures including the anterior thalamic nucleus. The patient s memory deficit was characterized by a severe anterograde encoding deficit and retrograde amnesia with a temporal gradient. In contrast, he did not show either frontal executive dysfunction or personality change that is frequently recognized in the anterior or medial thalamic lesion. We postulate that an amnesic syndrome can develop following discrete lesions of the MTT.

An event-related fMRI Study of exogenous facilitation and inhibition of return in the auditory modality.

The orienting of attention to different locations in space is fundamental to most organisms and occurs in all sensory modalities. Orienting has been extensively studied in vision, but to date, few studies have investigated neuronal networks underlying automatic orienting of attention and inhibition of return to auditory signals. In the current experiment, functional magnetic resonance imaging and behavioral data were collected while healthy volunteers performed an auditory orienting task in which a monaurally presented tone pip (cue) correctly or incorrectly cued the location of a target tone pip. The stimulus onset asynchrony (SOA) between the cue and target was 100 or 800 msec. Behavioral results were consistent with previous studies showing that valid auditory cues produced facilitation at the short SOA and inhibition of return at the long SOA. Functional results indicated that the reorienting of attention (100 msec SOA) and inhibition of return (800 msec SOA) were mediated by both common and distinct neuronal structures. Both attention mechanisms commonly activated a network consisting of fronto-oculomotor areas, the left postcentral gyrus, right premotor area, and bilateral tonsil of the cerebellum. Several distinct areas of frontal and parietal activation were identified for the reorienting condition, whereas the right inferior parietal lobule was the only structure uniquely associated with inhibition of return.