Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world’s population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLAGlu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA–mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.
A large proportion of patients with obsessive-compulsive disorder (OCD) respond unsatisfactorily to pharmacological and psychological treatments. An alternative novel treatment for these patients is repetitive transcranial magnetic stimulation (rTMS). This study aimed to investigate the underlying neural mechanism of rTMS treatment in OCD patients. A total of 37 patients with OCD were randomized to receive real or sham 1-Hz rTMS (14 days, 30 min/day) over the right presupplementary motor area (preSMA). Resting-state functional magnetic resonance imaging data were collected before and after rTMS treatment. The individualized target was defined by a personalized functional connectivity map of the subthalamic nucleus. After treatment, patients in the real group showed a better improvement in the Yale-Brown Obsessive Compulsive Scale than the sham group (F 1,35 = 6.0, p = .019). To show the neural mechanism involved, we identified an "ideal target connectivity" before treatment. Leave-one-out cross-validation indicated that this connectivity pattern can significantly predict patients' symptom improvements (r = .60, Gong-Jun Ji and Wen Xie contributed equally to this work.
Impaired decision-making is well documented in obsessive-compulsive disorder (OCD) and a range of electrophysiological and functional neuroimaging measures have begun to reveal the pathological mechanisms that underlie the decision-making process. Obsessive-compulsive personality disorder (OCPD) has core symptoms that often overlap with OCD, but similarities between these disorders at the behavioral and neurological levels are often unclear, including whether OCPD exhibits similar decisionmaking deficits and shared neurological dysfunction. To address these issues, we examined 24 cases of OCD, 19 cases of OCPD, and 26 matched normal control (NC) subjects during the revised Iowa Gambling Task (IGT) using event-related potentials (ERPs). The net IGT scores were lower for OCD subjects than for OCPD or NC subjects, thus indicating that OCD subjects chose more disadvantageous options and were "short-sighted" with regards to information. The feedback-related negativity (FRN) waveform (lose-win) was larger in both OCD and OCPD subjects, which suggested that obstacles exist in the feedback process. Consequently, these subjects might share similar neural mechanisms under ambiguous decision-making circumstances. Furthermore, IGT net scores were significantly and negatively correlated with Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) scales. This implies that more severe obsessive-compulsive symptoms inspired more negative emotions that led to worse decision-making ability. Therefore, although similar neural mechanisms might exist, this led to different behaviors in which OCPD is associated with better behavioral performance compared to OCD patients.
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