Entrainment of gamma oscillations by auditory chirp stimulation in Alzheimer’s disease patients

Abstract

AbstractBackgroundHigh‐level cognitive processes such as binding the processed data from sensory modules with elements stored in the memory involve the activity of long‐range pyramidal cells. These excitatory neuronal populations also provide input to a population of GABAAergic inhibitory interneurons, which in turn recruit feedback links to suppress the activity of the pyramidal cells. Interneuron networks generate rhythmic synchronization in the Gamma band driven by the time constant of the GABA receptors. Disrupted or desynchronized Gamma oscillations have been observed in patients of Alzheimer’s disease (AD). Earlier works have proposed the deficit in coherence between oscillations measured by EEG electrodes across the frontal lobe in the Gamma band in response to olfactory stimulation as a diagnostic marker of AD. This study examines the strength and spatial spread of Gamma band activity induced by auditory chirp stimulation as a marker for AD. The chirp signal is designed to entrain a target frequency of 40Hz at which the populations of inhibitory interneurons are known to operate.MethodA session comprising 11 interleaved periods of 40sec ON and 20sec OFF auditory stimuli of 5kHz tone modulated by a 40Hz chirp at 0.1 duty cycle was administered to mild AD patients and non‐AD elderly participants with memory complaints, and EEG data were collected by a 10/20 system. Magnitude of 40Hz oscillations at different scalp positions during the ON cycles was measured as an indicator of the entrained Gamma oscillations.ResultWhile 40Hz oscillations were recorded across a majority of electrodes in non‐AD demented participants with particular strengths in the temporal and frontal areas, the 40Hz entrainment occurred for a limited number of electrodes in AD patients.ConclusionAuditory chirp stimulation at 40Hz results in spatially distinguishable patterns of entrained Gamma oscillations in AD patients and non‐AD demented participants, and hence suggests a marker for AD. Despite this difference, the fact that 40Hz entrainment still occurs in regions of the brain in AD patients offers a positive indication for the possibility to employ such stimulation to reinvigorate the operation of the involved neural circuitry in therapy campaigns. Further studies are needed to assess such possibility.