In this comprehensive meta-analysis covering the entire brain, we investigated abnormal CTh in OCD compared to HCs. Our results revealed that OCD patients exhibited reduced CTh in the left anterior cingulate/paracingulate gyri and the right insula. Conversely, increased cortical thickness was observed in OCD patients in regions including the left lingual gyrus, left inferior frontal gyrus, orbital part, and left superior frontal gyrus, dorsolateral to the regions of interest. Additionally, through meta-regression analyses, we identified a negative correlation between CTh in the right insula region and the average age of OCD patients, suggesting that as the age increases, the CTh of the OCD patients in the right insula decreases. These findings offered insights into the pathophysiology of OCD.
Compared to HCs, OCD patients showed significantly higher CTh in the lingual gyrus. The lingual gyrus, situated within the visual cortex, is implicated in emotional perception elicited by visual stimuli and subsequent processing of intricate visual information.(de Gelder et al., 2015; Stern et al., 2017)The scenario memory, executive function, potential comorbid anxiety symptoms, and visual processing impairments(Gonçalves et al., 2010) observed in patients with OCD are believed to be potentially associated with structural and functional abnormalities in the lingual gyrus. However, contrary to the conclusions drawn from our findings, several studies have reported alterations in the brain structures of the lingual gyrus, including a thinner cortex and a reduced surface area.(Shin et al., 2007; Venkatasubramanian et al., 2012) Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies have shown decreased centrality degree of the lingual gyrus,(X. Li et al., 2022; Yu et al., 2021) while amplitude of low-frequency fluctuations (ALFF) values were found to be increased in the insular cortex but decreased in the lingual gyrus of OCD patients, which correlated with symptom severity.(Lei et al., 2020; J.-D. Ma et al., 2021)
In addition, we also found that compared to HCs, patients with OCD exhibited increased CTh in the frontal lobe, including the left inferior frontal gyrus, orbital part, and left superior frontal gyrus, dorsolateral. The orbitofrontal cortex (OFC) was defined in some studies as Brodmann Area (BA) 47/45,(Cecconi et al., 2008) in others as BA 10, or as BA 11(Bijanki et al., 2021) ,so we can think that the above-mentioned regions belong to the OFC. Several studies have reported structural and functional alterations at the OFC in OCD patients(Atmaca et al., 2007; Chamberlain et al., 2008) may be related to non-planning impulsivity, which is involved in reward and emotion processing in OCD patients. The abnormalities in the OFC brain region structure in patients with OCD may be associated with the pathophysiology of the disorder, such as response selection and inhibition, goal selection and cognitive flexibility, and performance monitoring. The CTh of the OFC is a strong predictor of treatment response in treatment-naïve OCD patients(Hoexter et al., 2015). Consistent with our meta-analysis findings, a resent research reported increased CTh at the superior frontal gyrus (BA10, which belongs to the OFC) compared with HCs.(Besiroglu et al., 2022) A CBMA reported that the gray matter volume (GMV) of OCD patients was significantly decreased in right inferior frontal gyrus triangular part, right superior temporal gyrus and right hippocampus.(Tao et al., 2023) The divergent conclusions above may be attributed to differences in sample size and analytical methods.
It is worth noting that the elevated brain regions are all located in the left hemisphere, which also suggests the lateralization characteristic of neurobiological alterations in OCD.(Deng et al., 2019)
Our meta-analysis simultaneously found, OCD patients showed significantly lower CTh in the right anterior insula,(Besiroglu et al., 2022) compared to HCs. The insula, a cortical structure with extensive connections to many regions of the cortex and limbic system, relates to disparate high-level cognitive control and attentional processes, emotional responses, and regulatory functions(Augustine, 1996; Menon & Uddin, 2010), as well as including nociception(Guenot et al., 2004), in disgust(Wicker et al., 2003), and so on. Meanwhile insula are part of the fronto-parietal network (FPN)(Yeo et al., 2011) which is involved in goal-oriented/attention external-oriented tasks. The structural abnormalities in the insular cortex may be closely associated with the manifestation of obsessive thoughts and compulsive behaviors in individuals with OCD. Previous studies using surface-based methods (SBM) have reported CTh alterations in the left superior temporal gyrus and posterior insular cortex(Nakamae et al., 2012), anterior cingulate cortex(Venkatasubramanian et al., 2012; Kühn et al., 2013), posterior cingulate cortex(Zhou et al., 2018) and pre-supplementary motor, dorsomedial prefrontal, anterior cingulate cortices and in the right anterior insula(Wagner et al., 2019). The results reported in the aforementioned research literature partially align with the findings obtained from our analysis. A multisite mega-analysis exhibit decreased CTh in a number of frontoparietal regions, which including the superior and inferior frontal gyri findings(Jp et al., 2017) similar to previous VBM meta-analyses and CTh work. In addition to other temporoparietal regions such as the precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also limbic involvement as evidenced by decreased hippocampal volume compared with HCs.
The left anterior cingulate / paracingulate gyri are regions of the brain located in the frontal lobe, specifically in the medial part of the cerebral cortex. Simultaneously, the left anterior cingulate and paracingulate gyri encompass the anterior cingulate cortex (ACC). The caudal or dorsal anterior cingulate gyri (ACG), which is the cognitive sub-division, is critically involved in monitoring conflict and detecting error(Bush et al., 2000). The ACG abnormalities in OCD Neurocognitive models of OCD propose that obsessions are related to the increased evaluation of negative consequences following an action that an individual with OCD misinterprets as erroneous or faulty. The sustained elevation of the "error signal," identified as the central component in the genesis of OCD symptoms, precipitates pathological doubt coupled with heightened anxiety. Subsequently, compulsive behaviors may manifest as responses aimed at alleviating or counteracting the anxiety provoked by the obsessional process. However, this alleviation is transient within the framework of enduring "error signals," resulting in the cyclical perpetuation of these behaviors(Rotge et al., 2008). In a SBM study, researchers observed a significant negative correlation between the severity of compulsions and right caudal ACG volume as well as surface area.(Venkatasubramanian et al., 2012) This is in tune with a quantitative voxel-based meta-analysis of functional neuroimaging studies that implicated cognitive sub-division of ACG in OCD symptom genesis(Rotge et al., 2008).
Furtherly, Neuroanatomical models of OCD assume that pathways consisting of OFC, ACC and basal ganglia, the so-called frontostriatal loops, are implicated in OCD.(Maia et al., 2008; Menzies et al., 2008) It has been suggested that activity in frontostriatal loops may be involved in establishing cognitive habits, in a similar way as they are in the development of motor habits(Graybiel & Rauch, 2000). Therefore, the abnormal cognitive habits observed in individuals with OCD are associated with the activity of frontostriatal loops. In addition, the OFC belongs to the affective circuit of the CSTC, which influences emotion processing and reward, such as reward value evaluation(Gottfried et al., 2003), reversal learning(Chamberlain et al., 2008) and decision-making.
Through our meta-regression analysis, we found a negative correlation between CTh and age in the right insular region, indicating that as age increases, the cortical thickness of the right insula decreases. This finding is consistent with our primary analysis results. In line with an earlier study, age-related effects were observed in striatal and limbic regions, with preservation of putamen volume and more pronounced age-related volume decreases in limbic parts of the middle and inferior temporal cortex with increasing age. Most of these findings were replicated using a different analysis technique focusing on cortical thickness(Jp et al., 2017). Together, these findings suggest that neuroplastic changes occur in patients with OCD, which could occur as a result of disease chronicity and/or long-term effects of medication. This insight suggests that in clinical practice, particularly when analyzing MRI scans, especially for assessing cortical thickness in patients, it's essential to take age into consideration. Only by doing so can we obtain accurate analytical conclusions.