Basolateral amygdala–ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive–compulsive disorder

Fullana, Miquel À.; Zhu, Xi; Alonso, Pino; Cardoner, Narcı́s; Real, Eva; López-Solà, Clara; Segalás, Cinto; Subirà, Marta; Galfalvy, Hanga; Menchón, José M.; Simpson, Helen Blair; Marsh, Rachel; Soriano‐Mas, Carles

doi:10.1503/jpn.160215

Cited by 52 publications

(32 citation statements)

References 37 publications

(38 reference statements)

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“…Importantly, although this pathway likely contributes to multiple ongoing behavioral actions such as anxiety, fear acquisition, expression, and extinction (18)(19)(20), we elucidated a functional link between this circuit and the OCD-like checking symptoms. This finding is supported by a previous study showing that cognitive behavioral therapy (CBT) decreases BLA-ventromedial PFC connectivity, which predicts a better CBT outcome in patients with OCD (27). It is reasonable to suppose that certain neurocircuitry in the brain controls multiple behavioral responses, including OCD.…”

Section: Discussionsupporting

confidence: 63%

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Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

Sun

Song

Tian

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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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.

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Section: Discussionsupporting

confidence: 63%

“…S4). To the best of our knowledge, there have been no previous reports in mice describing the BLA-mPFC pathway in the process of OCD checking symptoms (26,27). We next focused on the role of this pathway in OCD-like checking symptoms.…”

Section: Resultsmentioning

confidence: 99%

Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

Sun

Song

Tian

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…The amygdalofugal pathway is an output tract from the basolateral nucleus of the amygdala to the mediodorsal thalamus and OFC. A recent functional MRI study of OCD found specific, abnormal connectivity between the basolateral amygdala and medial OFC in OCD, which was predictive of successful treatment with CBT (35) . The habenulointerpeduncular tract has been implicated in the development of depression via inhibition of brainstem serotonergic raphe nuclei (36) .…”

Section: Discussionmentioning

confidence: 97%

A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects

Tyagi

Apergis-Schoute

Akram

et al. 2019

Biological Psychiatry

183

155

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Background Deep brain stimulation (DBS) is an emerging treatment for severe obsessive-compulsive disorder (OCD). We compared the efficacy of ventral capsule/ventral striatal (VC/VS) and anteromedial subthalamic nucleus (amSTN) DBS in the same patients and tested for mechanistic differences on mood and cognitive flexibility and associated neural circuitry. The possible synergistic benefit of DBS at both sites and cognitive behavioral therapy was explored. Methods Six patients with treatment-refractory OCD (5 men; Yale-Brown Obsessive Compulsive Scale score >32) entered double-blind counterbalanced phases of 12-week amSTN or VC/VS DBS, followed by 12-week open phases when amSTN and VC/VS were stimulated together, in which optimal stimulation parameters were achieved and adjunctive inpatient cognitive behavioral therapy was delivered. OCD and mood were assessed with standardized scales and cognitive flexibility with the Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set-Shift task. Diffusion-weighted and intraoperative magnetic resonance imaging scans were performed for tractography from optimally activated electrode contacts. Results DBS at each site significantly and equivalently reduced OCD symptoms with little additional gain following combined stimulation. amSTN but not VC/VS DBS significantly improved cognitive flexibility, whereas VC/VS DBS had a greater effect on mood. The VC/VS effective site was within the VC. VC DBS connected primarily to the medial orbitofrontal cortex, and amSTN DBS to the lateral orbitofrontal cortex, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex. No further improvement followed cognitive behavioral therapy, reflecting a floor effect of DBS on OCD. Conclusions Both the VC/VS and amSTN are effective targets for severe treatment-refractory OCD. Differential improvements in mood and cognitive flexibility and their associated connectivity suggest that DBS at these sites modulates distinct brain networks.

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“…MRI studies have begun to explore predictors of treatment outcome in OCD. Anterior cingulate thickness (3) and various patterns of resting state connectivity have been shown to predict response to cognitive behavioral therapy, specifically exposure and ritual prevention (EX/RP) (4)(5)(6)(7)(8). Task-based functional MRI (fMRI) can provide insight into specific cognitive processes that might serve as potential targets in augmenting EX/RP efficacy.…”

mentioning

confidence: 99%

Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder

Pagliaccio

Middleton²,

Hezel³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Exposure and ritual prevention (EX/RP) is an effective first-line treatment for obsessive-compulsive disorder (OCD), but only some patients achieve minimal symptoms following EX/RP. Herein, we investigate whether task-based neural activity can predict who responds best to EX/RP. Unmedicated adult patients with OCD (n = 36) and healthy participants (n = 33) completed the Simon Spatial Incompatibility Task during high-resolution, multiband functional MRI (fMRI); patients were then offered twice-weekly EX/RP (17 sessions). Linear mixed-effects models were used to identify brain regions where conflict-related activity moderated the slope of change in Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) scores across treatment. Conflict-related activity in the left pallidum and 35 cortical parcels/regions significantly predicted symptom improvement with EX/RP for patients with OCD (false discovery rate-corrected P < 0.05). Significant parcels/regions included cingulo-opercular and default mode network regions, specifically the anterior insula and anterior and posterior cingulate. Summarizing across these parcels/regions, greater conflict-related activity predicted greater EX/RP response and which patients achieved remission (Y-BOCS score ≤ 12; Cohen’s d = 1.68) with >80% sensitivity and specificity. The association between brain activity and treatment response was partially mediated by patient EX/RP adherence (b = −2.99; 43.61% of total effect; P = 0.02). Brain activity and adherence together were highly predictive of remission. Together, these findings suggest that cingulo-opercular and default mode regions typically implicated in task control and introspective processes, respectively, may be targets for novel treatments that augment the ability of persons with OCD to resolve cognitive conflict and thereby facilitate adherence to EX/RP, increasing the likelihood of remission.

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Basolateral amygdala–ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive–compulsive disorder

Cited by 52 publications

References 37 publications

Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects

Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder

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