It is well established that the cortico-striato-thalamo-cortical (CSTC) circuit is implicated in the pathophysiology of obsessive- compulsive disorder (OCD). However, reports on corticostriatal functional connectivity (FC) in OCD have been inconsistent due to the structural and functional heterogeneity of the striatum. Therefore, in the present study, we investigated corticostriatal FC using a fine 12-seed striatal parcellation to overcome this heterogeneity and discover the neural correlates of symptoms in OCD patients.
We recruited 23 OCD patients and 23 healthy controls (HCs). Whole-brain FC based on striatal seeds was examined using resting-state functional magnetic resonance imaging data and compared across OCD patients and HCs. We conducted correlation analysis between FCs of striatal subregions with significant group differences and symptom severity scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Rating Scale for Depression, and Hamilton Rating Scale for Anxiety (HAM-A).
Compared to HCs, patients demonstrated increased FC of the dorsal caudal putamen and ventral rostral putamen (VRP) with several cortical regions, such as the intracalcarine cortex, inferior frontal gyrus, supramarginal/angular gyrus (SMG/AG), and postcentral gyrus (PCG). Furthermore, FC between the VRP and SMG/AG and between the VRP and PCG was negatively correlated with scores on the Y-BOCS compulsive subscale and the HAM-A, respectively.
These findings suggest that striatal subregions have strengthened FC with extensive cortical regions, which may reflect neural correlates of compulsive and anxious symptoms in OCD patients. These results contribute to an improved understanding of OCD pathophysiology by complementing the current evidence regarding striatal FC.
Obsessive-compulsive disorder (OCD) is a relatively frequent mental disorder, with a lifetime prevalence of approximately 2–3% [
The striatum is one of the most important components of the CSTC circuit. This structure receives and coordinates multiple inputs from the cortical areas and delivers them to the thalamus [
Following studies on structural change, functional aspects have also been identified using resting-state functional magnetic resonance imaging (rs-fMRI). A number of studies have examined striatal functional connectivity (FC) in patients with OCD using the striatum as a seed region of interest (ROI). Many such studies have reported stronger FC between the ventral caudate and the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (DMPFC), and dorsolateral prefrontal cortex (DLPFC) in OCD patients than in HCs [
The results of studies on striatal FC in patients with OCD are still inconsistent. We speculated that the different striatal seeds used in each study might have contributed to this issue. The striatum is a heterogeneous structure that consists of several subregions, each of which is involved in different neurocognitive functions in connections with corresponding cortical areas [
In the present study, we aimed to identify corticostriatal dysfunction and its role as a neural correlate of psychiatric symptoms in patients with OCD using a fine 12-seed striatal parcellation [
A total of 23 OCD patients and 23 HCs who were matched for age, gender, and handedness participated in this study. All patients with OCD were recruited from the outpatient clinic at Seoul National University Hospital (SNUH) and fulfilled the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for OCD. The severity of clinical symptoms was evaluated by the Y-BOCS, Hamilton Rating Scale for Depression (HAM-D), and Hamilton Rating Scale for Anxiety (HAM-A) [
This study was conducted according to the Declaration of Helsinki and was approved by the Institutional Review Board of SNUH (H-1902-142-101). Each subject received a complete description of the study and provided written informed consent before participation. For the minors who participated in this study, informed consent was obtained from both the participants themselves and their parents.
Functional and structural images were obtained with a 3.0-tesla Trio MRI scanner (Siemens Magnetom Trio, Erlangen, Germany) with a 12-channel head coil. T1-weighted structural images were acquired with the following parameters: echo time (TE)=1.89 ms; repetition time (TR)=1670 ms; field of view (FOV)=250 mm; flip angle=9°; matrix=256×256; voxel size=1.0×0.98×0.98 mm3; and 208 slices. Resting-state fMRI images were acquired with the following parameters: TE=30 ms; TR=3,500 ms; FOV=240 mm; flip angle=90°; matrix=128×128; voxel size=1.9×1.9×3.5 mm3; and 35 slices. During the functional imaging session, subjects were instructed to relax and keep their eyes closed but not to fall asleep. A questionnaire was administered to the participants after the scan to ensure that they had not fallen asleep. We used head cushions and asked subjects to move as little as possible during image acquisition to minimize motion artifacts.
We preprocessed the brain images using the CONN toolbox version 18b (CONN18b;
We created 3-mm spherical striatal seeds in the dorsal caudate (DC), ventral caudate (VC), nucleus accumbens (NAc), dorsal rostral putamen (DRP), dorsal caudal putamen (DCP), and ventral rostral putamen (VRP) bilaterally, referring to the coordinate information from previous studies (
Fisher’s exact or the independent t-test was used to compare demographic characteristics between OCD patients and HCs. We conducted Pearson’s correlation analysis between striatal FC values, which were found to be altered in OCD patients compared to HCs, and measures of symptom severity, such as Y-BOCS, HAM-D, and HAM-A scores, within OCD patients. Statistical significance was defined for each test as a p<0.05. All statistical analyses except the group comparisons of FC were conducted using IBM SPSS Statistics 23 (IBM Corp., Armonk, NY, USA).
There was no significant demographic difference between OCD patients and HCs. The clinical characteristics of the patients, including duration of illness and Y-BOCS, HAM-D, and HAM-A scores, were measured to facilitate interpretation of our results. We summarize the subjects’ demographic and clinical characteristics in
FC between the left DCP and the right intracalcarine cortex (ICC) was stronger in OCD patients than in HCs, while FC between the left DCP and the left putamen was weaker in patients than in HCs. FCs between the right VRP and the right inferior frontal gyrus (IFG), left supramarginal gyrus (SMG), right postcentral gyrus (PCG) and right SMG/angular gyrus (AG) were stronger in patients than in controls. The details of the significant regions are summarized in
We found a negative correlation between the FC of the right VRP with the right SMG/AG and Y-BOCS compulsion scores (r=-0.420, p=0.046) (
In the current study, we examined resting-state corticostriatal FC alterations and their relationship with symptom severity using a fine 12-seed striatal parcellation in OCD patients. We found that the FC values of the left DCP and right VRP with extensive cortical regions including the ICC, IFG, SMG/AG, and PCG were significantly stronger in patients than in HCs. Moreover, the FC values between the right VRP and right SMG/AG and between the right VRP and right PCG were negatively correlated with scores on the compulsive subscale of the Y-BOCS and on the HAM-A, respectively.
Strengthened FC between the right VRP and right SMG/AG and right PCG in OCD patients was a notable finding of the present study. The SMG/AG is responsible for a number of cognitive functions that are impaired in OCD patients, including visuospatial cognition, attention, awareness, and conflict resolution [
Compared with HCs, patients with OCD exhibited strengthened FC between the right VRP and the right IFG in the present study. The IFG, especially the right IFG, is already known to be an important region for response inhibition [
We also revealed that patients with OCD show stronger FC between the DCP and ICC than HCs do. In recent studies, the role of the parieto-occipital regions in OCD pathophysiology has received much attention. Such studies have claimed that the occipital regions are associated with deficits in visuospatial processing, which are consistently shown in OCD patients [
One of the most unexpected findings of the current study was the lack of significant alterations in areas where such changes were previously reported, such as the OFC, ACC, and PFC. This discrepancy may be attributed to our patients’ clinical characteristics, which are significantly different from those of subjects in previous studies. In most preceding studies, the mean duration of illness was more than 10 years (
When interpreting the results of the present study, one must further consider several issues. First, 3 out of 23 patients were taking selective serotonin reuptake inhibitors (SSRIs). It is well known that psychotropic drugs, including SSRIs, can affect the FC pattern of the brain [
In conclusion, although we could not replicate the reported results of Posner et al. [
The online-only Data Supplement is available with this article at
Funding was provided by the Basic Science Research Program and the Basic Research Laboratory Program through the National Research Foundation of Korea (NRF) (Grant no. 2019R1A2B5B03100844 and 2018R1A4A1025891).
The authors have no potential conflicts of interest to disclose.
Conceptualization: Minah Kim, Junha Park, Jun Soo Kwon. Data curation: Taekwan Kim, Tae Young Lee. Formal analysis: Junha Park, Taekwan Kim, Minah Kim. Funding acquisition: Jun Soo Kwon. Investigation: Junha Park, Taekwan Kim, Tae Young Lee, Minah Kim, Jun Soo Kwon. Methodology: Junha Park, Taekwan Kim. Project administration: Minah Kim. Resources: Jun Soo Kwon. Software: Junha Park. Supervision: Minah Kim. Validation: Minah Kim, Tae Young Lee, Jun Soo Kwon. Visualization: Junha Park. Writing—original draft: Junha Park. Writing—review & editing: Minah Kim.
t-statistic maps of the significant FC of the left DCP (A) and right VRP (B) in patients with OCD compared to healthy controls. The FC between the left DCP and the right intracalcarine cortex was stronger in patients with OCD than in healthy controls (red through yellow; A-1), whereas the opposite was true of the FC between the left DCP and the left putamen (shades of blue; A-2). The FC values between the right VRP and the right inferior frontal gyrus (B-1), left supramarginal gyrus (B-2), right postcentral gyrus (B-3) and right supramarginal/angular gyrus (B-4) were stronger in patients with OCD (red through yellow). All clusters survived false discovery rate and Bonferroni correction, with p-values<0.05/12. FC: functional connectivity, DCP: dorsal caudal putamen, VRP: ventral rostral putamen, OCD: obsessivecompulsive disorder.
Correlation analysis between the FC of the significant brain regions and clinical variables in patients with OCD. (A) The FC from the right VRP to the right supramarginal/angular gyrus (SMG/AG) was negatively correlated with scores on the compulsive subscale of the Y-BOCS in patients with OCD. (B) The FC from the right VRP to the right PCG was negatively correlated with scores on the HAM-A in patients with OCD. FC: functional connectivity, OCD: obsessive-compulsive disorder, VRP: ventral rostral putamen, Y-BOCS: Yale-Brown Obsessive Compulsive Scale, PCG: postcentral gyrus, HAM-A: Hamilton Rating Scale for Anxiety.
MNI coordinates of 12 striatal subregion seeds
Seed name | MNI coordinates (mm) |
||
---|---|---|---|
x | y | z | |
Dorsal caudate | ±13 | 15 | 9 |
Ventral caudate | ±10 | 15 | 0 |
Nucleus accumbens | ±9 | 9 | 8 |
Dorsal rostral putamen | ±25 | 8 | 6 |
Dorsal caudal putamen | ±28 | 1 | 3 |
Ventral rostral putamen | ±20 | 12 | -3 |
MNI: Montreal Neurological Institute
Demographic and clinical characteristics of subjects
OCD (N=23) | HCs (N=23) | Statistics |
p-value | |
---|---|---|---|---|
Age (years) | 24.74±5.42 | 22.57±3.48 | -1.62 | 0.113 |
Gender (male/female) | 19/4 | 19/4 | 0.00 | 1.000 |
Handedness (left/right) | 1/22 | 1/22 | 0.00 | 1.000 |
IQ | 110.39±15.61 | 109.87±16.53 | -0.11 | 0.913 |
Education years (years) | 13.70±1.96 | 13.22±3.46 | 0.58 | 0.568 |
Onset age (years) | 18.05±6.33 | - | - | - |
Duration of illness (years) | 6.68±4.89 | - | - | - |
Y-BOCS score | ||||
Total | 23.43±6.79 | - | - | - |
Obsession | 12.00±4.00 | - | - | - |
Compulsion | 11.43±3.42 | - | - | - |
HAM-D | 12.61±6.89 | - | - | - |
HAM-A | 13.00±7.08 | - | - | - |
numerical data were assessed by an independent t-test if the variances were equal or by Welch’s t-test otherwise; Fisher’s exact test was used for categorical data.
OCD: obsessive-compulsive disorder, HCs: healthy controls, IQ: intelligence quotient, Y-BOCS: Yale-Brown Obsessive Compulsive Scale, HAM-D: Hamilton Rating Scale for Depression, HAM-A: Hamilton Rating Scale for Anxiety
Group comparisons of striatal functional connectivity between OCD patients and HCs
Seed | Brain region | Cluster size (voxels) | Connectivity strength |
FDR-and Bonferroni-corrected p | MNI coordinates (mm) |
|||
---|---|---|---|---|---|---|---|---|
HC | OCD | x | y | z | ||||
Dorsal caudal putamen (left) | OCD>HC | |||||||
Right intracalcarine cortex | 341 | -0.10 | 0.04 | 0.001 | 2 | -76 | 4 | |
HC>OCD | ||||||||
Left putamen | 192 | 0.26 | 0.11 | 0.043 | -28 | 4 | 4 | |
Ventral rostral putamen (right) | OCD>HC | |||||||
Right inferior frontal gyrus | 231 | -0.02 | 0.11 | 0.025 | 56 | 18 | -6 | |
Left supramarginal gyrus | 220 | -0.05 | 0.08 | 0.025 | -52 | -42 | 32 | |
Right postcentral gyrus | 187 | -0.02 | 0.12 | 0.049 | 60 | -14 | 22 | |
Right supramarginal/angular gyrus | 160 | -0.05 | 0.09 | 0.049 | 68 | -40 | 28 |
FDR: false discovery rate, MNI: Montreal Neurological Institute, OCD: obsessive-compulsive disorder, HCs: healthy controls