Thalamocortical changes in major depression probed by deconvolution and physiology-based modeling

Abstract

Auditory event-related potentials (ERPs) have been extensively studied in patients with depression, but most studies have focused on purely phenomenological analysis methods, such as component scoring. In contrast, this study applies two recently developed physiology-based methods-fitting using a thalamocortical model of neuronal activity and waveform deconvolution — to data from a selective-attention task in four subject groups (49 patients with melancholic depression, 34 patients with non-melancholic depression, 111 participants with subclinical depressed mood, and 98 healthy controls), to yield insight into physiological differences in attentional processing between participants with major depression and controls. This approach found evidence that: participants with depressed mood, regardless of clinical status, shift from excitation in the thalamocortical system towards inhibition; that clinically depressed participants have decreased relative response amplitude between target and standard waveforms; and that patients with melancholic depression also have increased thalamocortical delays. These findings suggest possible physiological mechanisms underlying different depression subtypes, and may eventually prove useful in motivating new physiology-based diagnostic methods.