Connectivity of the Frontal Cortical Oscillatory Dynamics Underlying Inhibitory Control During a Go/No-Go Task as a Predictive Biomarker in Major Depression

Abstract

Background: Major depressive disorder (MDD) is characterized by core functional deficits in cognitive inhibition, which is crucial for emotion regulation. To assess the response to ruminative and negative mood states, it was hypothesized that MDD patients have prolonged disparities in the oscillatory dynamics of the frontal cortical regions across the life course of the disease.

Method: A "go/no-go" response inhibition paradigm was tested in 31 MDD patients and 19 age-matched healthy controls after magnetoencephalography (MEG) scanning. The use of minimum norm estimates (MNE) examined the changes of inhibitory control network which included the right inferior frontal gyrus (rIFG), pre-supplementary motor area (preSMA), and left primary motor cortex (lM1). The power spectrum (PS) within each node and the functional connectivity (FC) between nodes were compared between two groups. Furthermore, Pearson correlation was calculated to estimate the relationship between altered FC and clinical features.

Result: PS was significantly reduced in left motor and preSMA of MDD patients in both beta (13-30 Hz) and low gamma (30-50 Hz) bands. Compared to the HC group, the MDD group demonstrated higher connectivity between lM1 and preSMA in the beta band (t = 3.214, p = 0.002, FDR corrected) and showed reduced connectivity between preSMA and rIFG in the low gamma band (t = -2.612, p = 0.012, FDR corrected). The FC between lM1 and preSMA in the beta band was positively correlated with illness duration (r = 0.475, p = 0.005, FDR corrected), while the FC between preSMA and rIFG in the low gamma band was negatively correlated with illness duration (r = -0.509, p = 0.002, FDR corrected) and retardation factor scores (r = -0.288, p = 0.022, uncorrected).

Conclusion: In this study, a clinical neurophysiological signature of cognitive inhibition leading to sustained negative affect as well as functional non-recovery in MDD patients is highlighted. Duration of illness (DI) plays a key role in negative emotional processing, heighten rumination, impulsivity, and disinhibition.

Keywords: cognitive inhibition; functional connectivity (FC); go/no-go task; magnetoencephalography (MEG); major depressive disorder (MDD); power spectrum (PS).

Figure 1

Illustration of the experimental background and principal hypothesis. A model of the regions included in the dynamic analysis (rIFG, preSMA, and lM1) and the specified connectivity. Hypothesis: the layerspecific burden of pathology is predicted to disrupt the specific-frequency, attenuate dysfunction in the beta and gamma bands, and consequently impair movement control. Modified from (32).

Figure 2

The procedure of the go/no-go experiment. Go trail (green light): 300 ms/per stimulus, 150 times; No-go trail (green + red light): 150 ms/per stimulus, 50 times; Stimulus Intervals 1,500 ms.

Figure 3

FC among rIFG-preSMA-lM1. Schematic diagram of the FC among the three core brain regions based on response inhibition network; solid lines: the FC in beta band, dotted line: the FC in the low gamma band; red color: MDD's FC > HC's FC, blue color: MDD's FC < HC's FC.

Figure 4

Differences of FC in the beta and low gamma bands at no-go trials. (A): the FC between lM1 and preSMA in the beta band; (B): the FC between lM1 and rIFG in the beta band; (C): the FC between preSMA and rIFG in the low gamma band. *p < 0.05, **p < 0.01.

Figure 5

Correlations between FC and clinical information. (A) The FC between lM1 and preSMA in the beta band positively correlated with illness duration; (B) The FC between preSMA and rIFG in the low gamma band negatively correlated with illness duration; (C) The FC between preSMA and rIFG in the low gamma band negatively correlated with retardation factors.