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.

Unisensory processing and multisensory integration in schizophrenia: a high-density electrical mapping study.

In real-world settings, information from multiple sensory modalities is combined to form a complete, behaviorally salient percept - a process known as multisensory integration. While deficits in auditory and visual processing are often observed in schizophrenia, little is known about how multisensory integration is affected by the disorder. The present study examined auditory, visual, and combined audio-visual processing in schizophrenia patients using high-density electrical mapping. An ecologically relevant task was used to compare unisensory and multisensory evoked potentials from schizophrenia patients to potentials from healthy normal volunteers. Analysis of unisensory responses revealed a large decrease in the N100 component of the auditory-evoked potential, as well as early differences in the visual-evoked components in the schizophrenia group. Differences in early evoked responses to multisensory stimuli were also detected. Multisensory facilitation was assessed by comparing the sum of auditory and visual evoked responses to the audio-visual evoked response. Schizophrenia patients showed a significantly greater absolute magnitude response to audio-visual stimuli than to summed unisensory stimuli when compared to healthy volunteers, indicating significantly greater multisensory facilitation in the patient group. Behavioral responses also indicated increased facilitation from multisensory stimuli. The results represent the first report of increased multisensory facilitation in schizophrenia and suggest that, although unisensory deficits are present, compensatory mechanisms may exist under certain conditions that permit improved multisensory integration in individuals afflicted with the disorder.

Aging-related changes in auditory and visual integration measured with MEG.

As noted in the aging literature, processing delays often occur in the central nervous system with increasing age, which is often attributable in part to demyelination. In addition, differential slowing between sensory systems has been shown to be most discrepant between visual (up to 20ms) and auditory systems (<5ms). Therefore, we used MEG to measure the multisensory integration response in auditory association cortex in young and elderly participants to better understand the effects of aging on multisensory integration abilities. Results show a main effect for reaction times (RTs); the mean RTs of the elderly were significantly slower than the young. In addition, in the young we found significant facilitation of RTs to the multisensory stimuli relative to both unisensory stimuli, when comparing the cumulative distribution functions, which was not evident for the elderly. We also identified a significant interaction between age and condition in the superior temporal gyrus. In particular, the elderly had larger amplitude responses (∼100ms) to auditory stimuli relative to the young when auditory stimuli alone were presented, whereas the amplitude of responses to the multisensory stimuli was reduced in the elderly, relative to the young. This suppressed cortical multisensory integration response in the elderly, which corresponded with slower RTs and reduced RT facilitation effects, has not been reported previously and may be related to poor cortical integration based on timing changes in unisensory processing in the elderly.