Modulatory role of the prefrontal generator within the auditory M50 network

Abstract

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 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.

Attention modulates topology and dynamics of auditory sensory gating

“…The present results suggest the neural architecture of early top‐down control of information processing, once again affirming the existence of a fast sensory gating loop (Josef Golubic et al, ) that links the prefrontal cortex to primary sensory areas. Here, we show that the sensory gating loop could operate as a dynamic mechanism that monitors and modulates neural adaptation to environmental demands including selective attention to a simple sensory input.…”

“…Oranje and colleagues reported activation of the bilateral STG and medial frontal areas in the P50 gating formation (Oranje, Geyer, Bocker, Leon, & Verbaten, ), still, modeling an interval that covered both the P50 event‐related potential and the peak of the N100, in addition to usual methodological constraints associated with EEG spatial localization, yielded to reduced reliability of reported results. However, recent studies using data of modern whole‐head MEG systems and advanced spatiotemporal source localization techniques (Josef Golubic et al, ; Weiland et al, ), provide strong evidence that the generators underlying auditory sensory gating consisted of a prefrontal (PFC) generator in addition to the anticipated generators in bilateral STG. In addition, Josef Golubic and colleagues, using an auditory oddball‐paradigm that evoked both gating mechanisms, habituation to redundant information (standard stimuli) and preattentive memory‐based comparison processes (deviant stimuli), provided evidence of a modulatory function of the medial PFC generator on bilateral auditory cortices that was activated during both gating‐in and gating‐out responses (Josef Golubic et al, ).…”

P50: A candidate ERP biomarker of prodromal Alzheimer׳s disease

“…Evidence from animal models and human fMRI studies suggests that the PFC may influence the activity of auditory cortex directly or via projections through the thalamus (Mayer et al, 2009; Yingling and Skinner, 1976). Recent M50 localization findings support this hypothesis; healthy elderly showed both prefrontal and superior temporal sources modulating M50 amplitude whereas cognitively impaired elderly showed a temporal but not prefrontal source, which was associated with larger amplitudes in the absence of PFC contributions (Golubic et al, 2014). Unrestrained P50 amplitude may therefore represent a functional disconnection of the prefrontal cortex in modulating the auditory cortical response.…”

“…Findings from EEG, MEG, and fMRI cross-modal sensory gating studies, frontal lesion studies, and from auditory brain stem responses implicate prefrontal cortex (PFC) in the top-down inhibition of the auditory cortical response (Golubic et al, 2014; Irimajiri et al, 2005; Knight et al, 1989; Mayer et al, 2009; Oranje et al, 2006; Tregellas et al, 2007; Weiland et al, 2008). Evidence from animal models and human fMRI studies suggests that the PFC may influence the activity of auditory cortex directly or via projections through the thalamus (Mayer et al, 2009; Yingling and Skinner, 1976).…”

“…Overall, the literature suggests that P50 amplitude first increases during early stage AD and then decreases back to relatively normal levels with disease progression, possibly because the disease first attacks inhibitory mechanisms that restrain the P50 and only later does it impair the sensory cortical areas primarily responsible for generating the P50, consistent with the progression of underlying AD neuropathology (Arnold et al, 1991; Golubic et al, 2014). While this relationship between P50 and disease severity would be problematic for using P50 in differential diagnosis, when amplitudes may be going up or coming down and indistinguishable from controls, it may have utility as a pre-screening tool during prodromal and asymptomatic stages, when inhibitory mechanisms, but not the neural generators of P50, are compromised.…”