An Examination of Rostral Anterior Cingulate Cortex Function and Neurochemistry in Obsessive–Compulsive Disorder

Abstract

The anterior cingulate cortex is implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, few studies have examined functional and neurochemical abnormalities specifically in the rostral subdivision of the ACC (rACC) in OCD patients. We used functional magnetic resonance imaging (fMRI) during an emotional counting Stroop task and single-voxel J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) in the rACC to examine the function and neurochemistry of the rACC in individuals with OCD and comparison individuals without OCD. Between-group differences in rACC activation and glutamine/glutamate ratio (Gln/Glu), Glu, and Gln levels, as well as associations between rACC activation, Gln/Glu, Glu, Gln, behavioral, and clinical measures were examined using linear regression. In a sample of 30 participants with OCD and 29 age- and sex-matched participants without OCD, participants with OCD displayed significantly reduced rACC deactivation compared with those without OCD in response to OCD-specific words versus neutral words on the emotional counting Stroop task. However, Gln/Glu, Glu, and Gln in the rACC did not differ between groups nor was there an association between reduced rACC deactivation and Gln/Glu, Glu, or Gln in the OCD group. Taken together, these findings strengthen the evidence for rACC dysfunction in OCD, but weigh against an underlying association with abnormal rACC glutamatergic neurotransmission.

Striatal Magnetic Resonance Spectroscopy Abnormalities in Young Adult Sapap3 Knockout Mice

“…However, our finding is consistent with a recent human study in people with OCD conducted by our group reporting no glutamate or other MRS metabolite abnormalities in rostral anterior cingulate cortex (62). Collectively, the results in mouse models could suggest that functional deficits in frontal cortex and/or striatum may be sufficient to alter CSTC circuitry and enable compulsive behaviors.…”

Cingulate and thalamic metabolites in obsessive-compulsive disorder

“…Thus, notable elevation of Glu may have been present in pACC in patients but variability in fitting may have rendered it difficult to prove statistically. An alternative mentioned by Brennan et al (2015) is that the Gln subcomponent of Glx may be above-normal in OCD. Their 2D-MRS measurements of Gln argue against this possibility, although even with 2D techniques Gln is challenging to assay in vivo.…”

Acute change in anterior cingulate cortex GABA, but not glutamine/glutamate, mediates antidepressant response to citalopram

“…1 H-MRS acquisition used a modified protocol similar to that described in our previous studies (Brennan et al, 2010; Brennan et al, 2016; Brennan et al, 2015; Jensen et al, 2009). Briefly, a 2×2×2 cm voxel was placed on the pgACC midsagittally, anterior to the genu of the corpus callosum (Figure 1).…”

“…Every J -resolved spectral extraction within a bandwidth of 67Hz was fit with the spectral-fitting package LCModel (Provencher, 1993) and its theoretically-correct template. The integrated area under the entire 2D surface for each metabolite was calculated by summing the raw peak areas across all 64 J -resolved extractions for each metabolite as in our prior publications (Brennan et al, 2010; Brennan et al, 2016; Brennan et al, 2015; Jensen et al, 2009). Our primary 1 H-MRS measure, glutamine/glutamate, is expressed as a ratio, while glutamate, glutamine, and GABA levels are expressed as a ratio to total creatine (tCr) – a widely used approach to reduce subject-specific variance intrinsic to 1 H-MRS data (Ongur et al, 2009).…”