A Possible Common Neurophysiologic Basis for MDD, Bipolar Disorder, and Schizophrenia: Lessons from Electrophysiology

Abstract

There is ample electrophysiological evidence of attention dysfunction in the EEG/ERP signal of major depressive disorder (MDD), bipolar disorder, and schizophrenia. The reduced attention-related ERP waves show much similarity between MDD, bipolar disorder, and schizophrenia, raising the question whether there are similarities in the neurophysiologic process that underlies attention dysfunction in these pathologies. The present work suggests that there is such a unified underlying neurophysiologic process, which results in reduced attention in the three pathologies. Naturally, as these pathologies involve different clinical manifestations, we expect differences in their underlying neurophysiology. These differences and their subtle manifestation in the ERP marker for attention are also discussed. MDD, bipolar disorder, and schizophrenia are just three of multiple neuropsychiatric disorders, which involve changes in the EEG/ERP manifestations of attention. Further work should expand the basic model presented here to offer comprehensive modeling of these multiple disorders and to emphasize similarities and dissimilarities of the underlying neurophysiologic processes.

Keywords: EEG; ERP; MDD; bipolar disorder; drive reduction; schizophrenia.

Figures

Figure 1

Results of simulation of the prefrontal cortex activation in the control (A) and MDD (B) conditions. Note the greater activation of VMPFC, which results from an increase of ~33% in the strength of input from the amygdala, without any other change. The increased activation results in reduced DLPFC activation. (C) If the increased activation of the VMPFC continues for a sufficiently long duration, it enters periods of inactivation. In these periods, lateral prefrontal cortex activation is increased. (D) Further increase of ~33% (beyond that in Figures 1 and 2) in the association strength of the input to the VMPFC from the amygdala reduces its periodic inactivation (and the periodic activation of the lateral prefrontal cortex).

Figure 2

(A) Percentage of activation of perception representations by stimuli normalized to the control condition. (B) Percentage in which a given stimulus evoked representations of other (wrong) stimuli in the simulated secondary perception region. Note that the only difference between the three simulated conditions is in the excitatory effect of the amygdala upon the VMPFC. This effect is 33% larger in MDD/bipolar disorder than in the control condition, and 66% larger in schizophrenia than in the control condition. The presented effect on the perception region is the result of reciprocal inhibition of the VMPFC on the relevant amygdalar complex, which in turn reduces excitation of the perception region.

Figure 3

Model of activation of secondary perception representation. A specific stimulus evokes near-threshold (broken line) activation of its related representation in the secondary perception region. It also activates simultaneously the amygdala, evoking a top-down activation of the secondary perception representation, which is weaker and not specific (gray broken line). The two activations overlap sufficiently in time to enable threshold crossing of the specific activation in the secondary perception region. This activation inhibits the possibility of competitive activations in this region (through lateral inhibition). But if the top-down amygdalar activation is disabled (owing to its inhibition in the schizophrenia condition), the specific representation in the secondary perception region is activated less and, therefore, there is less lateral inhibition and greater likelihood of erroneous activation, which might originate, for example, from the VMPFC, and could activate other representations.