The role of polygenic risk in Alzheimer's disease prediction for African Americans.

Auditory-evoked electro- and magnetoencephalographic (EEG/MEG) responses, hereafter referred to as auditory-evoked responses or AERs, represent a direct measure of auditory neural activity and can be recorded with essentially unlimited temporal resolution. Particularly when measured with EEG, AERs enable tracking of neural activity across the entire auditory processing hierarchy—from the auditory nerve to cortex (e.g., ). AERs thus hold considerable promise for revealing how auditory information is propagated and transformed across processing levels, and how these transformations may be altered by experience, hearing loss, or aging (; ; ). Quantitative interpretation of AERs, however, remains limited by poor understanding of their relationship to underlying neuroelectric sources. The scalp characteristics of AERs—such as spatial distribution and amplitude—are determined not only by the strengths of these sources but also by their geometric configurations. Cortical AERs reflect the aggregate activity of thousands, or even millions, of microscopic electrical currents, each oriented perpendicular to the local cortical surface (). Depending on the morphology (shape and orientation) of the response-generating surface patch(es), these currents can either reinforce or cancel one another, creating scalp responses with widely varying amplitudes and scalp distributions (or “scalp topographies”), even when underlying sources are equally strong and originate from the same functional area(s) (). A particularly striking example of the effect of surface morphology can be seen in the visual domain: EEG responses from the primary visual area, V1, can exhibit opposite scalp polarities for stimuli in the upper versus lower visual hemifields, because, in the V1 retinotopic map, these hemifields are represented on opposite banks of the calcarine fissure (). The auditory-responsive supratemporal region is the principal contributor to the common obligatory (or “exogenous”; ) components of cortical AERs, as measured with either MEG or with the vertical montage in EEG (between the vertex and mastoid channels; , ). Much, if not all, of this region is tonotopically organized (e.g., ; ). By analogy to the effect of retinotopy on visual-evoked responses, morphology-related variation in obligatory cortical AERs should therefore be primarily dictated by the supratemporal tonotopic layout. Although the supratemporal auditory surface is comparatively flatter than the visual cortical surface, and so, morphology-related variation in AERs should be more modest, the transverse gyrification of the supratemporal plane (STP) through Heschl's gyrus (HG), which, in individual subjects or hemispheres, can be partially or fully duplicated, or—in rare cases—even triplicated (), could exert substantial impact on frequency-related and inter-individual variation in AER characteristics (amplitude and scalp topography). Understanding morphology-related effects on cortical AERs may thus help to account for a substantial proportion of their inter-individual variation and establish a more direct quantitative relationship between measured AER amplitudes and underlying source strengths.