The right thalamic glutamate level correlates with functional connectivity with right dorsal anterior cingulate cortex/middle occipital gyrus in unmedicated obsessive–compulsive disorder: A combined fMRI and ¹H-MRS study

Abstract

Objective: The imbalance in neurotransmitter and neuronal metabolite concentration within cortico-striato-thalamocortical (CSTC) circuit contributes to obsessive-compulsive disorder's (OCD) onset. Previous studies showed that glutamate mediated upregulation of resting-state activity in healthy people. However, there have been few studies investigating the correlational features between functional and neurochemical alterations in OCD. Methods: We utilize a combined resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1 H-MRS) approach to investigate the altered functional connectivity (FC) in association with glutamatergic dysfunction in OCD pathophysiology. Three regions of interest are investigated, i.e., medial prefrontal cortex and bilateral thalamus, for seed-based whole-brain FC analysis as well as MRS data acquisition. There are 23 unmedicated adult OCD patients and 23 healthy controls recruited for brain FC analysis. Among them, 12 OCD and 8 controls are performed MRS data acquisition. Results: Besides abnormal FC within CSTC circuit, we also find altered FCs in large-scale networks outside CSTC circuit, including occipital area and limbic and motor systems. The decreased FC between right thalamus and right middle occipital gyrus (MOG) is correlated with glutamatergic signal within right thalamus in OCD patients. Moreover, the FC between right thalamus and right dorsal anterior cingulate cortex (dACC) is associated with glutamate level in right thalamus, specifically in patient's group. Finally, the FC between right thalamus and right MOG is correlated with patient's Yale-Brown Obsessive Compulsive Scale (YBOCS) compulsion and total scores, while the right thalamic glutamatergic signal is associated with YBOCS-compulsion score. Conclusion: Our findings showed that the coupled intrinsic functional-biochemical alterations existed both within CSTC circuit and from CSTC to occipital lobe in OCD pathophysiology.

White matter microstructure and connectivity in patients with obsessive‐compulsive disorder and their unaffected siblings

“…Interestingly, our results were more in line with previous connectivity studies using resting‐state functional imaging in patients with OCD. For example, functional connectivity alterations in OCD have been found between the caudate and temporo‐occipital regions 60‐62 and between the thalamus and occipital cortex 63‐65 . Speculatively, our findings of reduced structural connectivity between occipital and subcortical structures might be associated with visuospatial deficits, which are observed in patients with OCD 66‐70 .…”

Altered Functional Connectivity Strength at Rest in Medication-Free Obsessive-Compulsive Disorder

“…Obsessive-compulsive disorder (OCD) is defined as a combination of intrusive thoughts (obsessions) and repetitive behaviors (compulsions), which affects social and occupational functions and imposes an economic burden on patients and their families [1,2]. Although the pathophysiological mechanism of OCD remains unclear, neuroimaging studies have highlighted abnormalities in the cortical-striatal-thalamic-cortical (CSTC) circuit, including the anterior cingulate cortex, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), thalamus, and striatum [3][4][5][6]. For example, increased and decreased levels of gray matter volumes in the left OFC and striatum and increased regional homogeneity (ReHo) and global brain functional connectivity (FC) in the lateral OFC and DLPFC were discovered at rest in OCD [7,8].…”

Pregabalin augmentation for resistant obsessive–compulsive disorder: a double-blind placebo-controlled clinical trial

“…Several lines of evidence from basic neurobiological studies have indicated the role of glutamatergic abnormalities in the pathogenesis of OCD. [16][17][18]29,30 These studies demonstrated pathologically elevated glutamatergic transmission in the cortical-striatal-thalamic circuitry of the brain in the OCD patients. Following treatment, the decrease in caudate glutamatergic concentration is associated with the decrease in OCD severity.…”

“…First, research has revealed pathologically elevated glutamatergic transmission in cortical-striatal-thalamic circuit of the brain in OCD patients. 16,17 Following treatment with glutamate modulating agents, a decrease in OCD symptoms severity was detected. [18][19][20][21] Further evidence for glutamatergic dysfunction in OCD comes from studies that measured levels of glutamate in cerebrospinal fluid (CSF) of OCD patients and matched psychiatrically normal controls.…”