Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy

Abstract

Background:Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS.Methods:Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects.Results:Significant reductions in N-acetylaspartate (NAA) and choline-containingCompound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group.Conclusions:Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS.

Accelerated TMS for Depression: A systematic review and meta-analysis

“…Clinical improvement has been associated with GABA concentration increases in the DLPFC, which was previously also shown in standard rTMS trials with healthy individuals and MDD patients (Vidal-Piñeiro et al, 2015). Baseline tNAA/tCr ratios, a measure of neural integrity, were not indicative of clinical response, nor were these concentrations affected by aTMS, in contrast to the findings of Zheng et al (2015) with standard rTMS.…”

Intermittent theta-burst stimulation moderates interaction between increment of N-Acetyl-Aspartate in anterior cingulate and improvement of unipolar depression

“…These results implicate NAA as a putative marker of both neuronal function in MDD as well as a marker of changes associated with (successful) clinical intervention. In addition, one group reported a significant increase of NAA (reduced at baseline) in the left ACC, to be associated with favorable performance in the Wisconsin card sorting test after successful HF-rTMS [38]. In our cohort, we found an association between NAA increment and clinical improvement of MDD, which was statistically significant in the iTBS group only.…”

“…Recent imaging studies on functional connectivity demonstrate the involvement of the ACC during antidepressant treatment with rTMS [36,37]. Also, a significant increase of at baseline reduced NAA was found in the left ACC after successful HF-rTMS, whereas its enhancement was associated with a favorable performance in the Wisconsin card sorting test [38].…”

Executive Dysfunction in Obsessive-Compulsive Disorder and Anterior Cingulate-Based Resting State Functional Connectivity

“…The goal of present study was to illustrate the differential impact of ACC-based inter-modular communication between the DMN, 36 SN, 33 executive control network (ECN) 37 or dorsal attention network (DAN) 38 based on executive functioning performance when comparing OCD with HC. Specifically, between-group comparisons of ACC-based rs-FCN between OCD and HC groups using five ACC sub-regions were examined based on the following brain-cognition relationships: caudal ACC (hub region of somatomotor network)-based rs-FCN vs. set-shifting with visuomotor sequencing (TMT-B), 39 dorsal ACC (hub region of SN)-based rs-FCN vs. visuospatial organization (RCFT organization score), 40 41 42 supragenual ACC (hub region of ECN)-based rs-FCN vs. setshifting with strategic planning (WCST perseverative error), 43 44 45 and rostral ACC (hub region of DMN)-based rs-FCN vs. response inhibition (SCWT incongruent trial reaction time). 5 46 47 …”