Neurochemical Dysregulation in Compulsive Behavior: Insights from 7-Tesla 1H-MRS Study

Abstract: Compulsivity is a psychiatric trait characterized by persistent and maladaptive behaviors. Understanding the neurochemical basis of compulsive behavior is essential for developing effective treatments. This study utilized high-resolution 7-Tesla proton magnetic resonance spectroscopy (1H-MRS) to investigate the neurochemical properties of two key fronto-striatal regions, the anterior cingulate cortex (ACC) and the supplementary motor area (SMA), in individuals with and without obsessive-compulsive disorder (OCD).

The study aimed to explore the relationship between neurochemical imbalances, compulsivity, and habitual tendencies.

Introduction

Compulsivity is a transdiagnostic trait that exists on a spectrum without clear boundaries between healthy and pathological manifestations. Previous research has linked individual differences in compulsive behavior to the functioning of fronto-striatal loops. Neurochemical dysregulation within cortical networks, particularly involving glutamate (Glu) and γ-amino butyric acid (GABA) neurotransmission, is believed to underlie these changes. However, inconsistent findings from proton magnetic resonance spectroscopy (1H-MRS) studies have hindered a comprehensive understanding of the neurochemical alterations in compulsive behavior. This study aimed to overcome these limitations by utilizing 7-Tesla 1H-MRS to quantify Glu, its metabolite glutamine (Gln), and GABA with higher resolution.

Methods

Participants included 30 healthy individuals and 31 individuals diagnosed with OCD. The ACC and SMA were targeted as regions of interest, given their associations with compulsivity and their involvement in the pathophysiology of OCD. The occipital cortex (OCC) served as a posterior cortical comparison region. Neurochemical levels were quantified using the semi-LASER MRS sequence, allowing for accurate measurement of Glu, Gln, and GABA. Clinical and demographic measures were collected for both groups.

Results

The study findings indicated that changes in the neurochemical properties of the ACC and SMA were more pronounced in individuals with OCD. Additionally, these changes were suggested to exist in the general population along the transdiagnostic dimension of compulsivity. The balance between Glu and GABA function in these regions was found to be related to compulsive and habitual tendencies, as well as clinical symptoms associated with compulsive behavior.

Discussion

The ACC and SMA play crucial roles in error monitoring, reward prediction, and habit learning processes, which are all relevant to compulsive behavior. Enhanced prediction errors and aberrant activity in these regions have been observed in individuals with OCD.

Neurochemical dysregulation, particularly involving Glu and GABA, may contribute to the imbalanced cortico-striatal circuitry favoring the habit system in OCD. The present study provides novel insights into the neurochemical basis of compulsivity, shedding light on the potential therapeutic targets for OCD and related disorders.

Conclusion

This study highlights the importance of neurochemical dysregulation in compulsive behavior. By utilizing advanced 7-Tesla 1H-MRS techniques, the research identified specific neurochemical imbalances in the ACC and SMA that are associated with compulsive and habitual tendencies. These findings contribute to our understanding of the pathophysiology of OCD and have implications for the development of targeted treatments for compulsive disorders. Further research is warranted to explore the precise mechanisms underlying these neurochemical alterations and their potential as therapeutic targets.

reference link: https://www.nature.com/articles/s41467-023-38695-z#Sec7