(OCD) Using Treatment-Induced Neuroimaging Changes
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Neurosurgery J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-324478 on 27 April 2021. Downloaded from Review Defining functional brain networks underlying obsessive–compulsive disorder (OCD) using treatment- induced neuroimaging changes: a systematic review of the literature Kelly R. Bijanki ,1 Yagna J. Pathak,2 Ricardo A. Najera,1 Eric A. Storch,3 Wayne K Goodman,3 H. Blair Simpson,4 Sameer A. Sheth1 ► Additional material is ABSTRACT Aberrant signalling in cortico- striato- thalamo- published online only. To view Approximately 2%–3% of the population suffers from cortical (CSTC) circuits is considered to be an please visit the journal online obsessive–compulsive disorder (OCD). Several brain important pathological mechanism underlying (http:// dx. doi. org/ 10. 1136/ [S1- S3] jnnp- 2020- 324478). regions have been implicated in the pathophysiology OCD. These circuits are composed of glutama- of OCD, but their various contributions remain unclear. tergic and GABAergic projections that connect fron- 1 Department of Neurosurgery, We examined changes in structural and functional tocortical and subcortical brain areas.[S4- S9] Within Baylor College of Medicine, the CSTC loop, the direct pathway from striatum Houston, Texas, USA neuroimaging before and after a variety of therapeutic 2Department of Neurological interventions as an index into identifying the underlying to internal pallidum to thalamus and back to cortex Surgery, Columbia University networks involved. We identified 64 studies from 1990 exerts a net excitatory effect, and the indirect Medical Center, New York, New to 2020 comparing pretreatment and post-treatment pathway, which additionally includes the external York, USA 3 imaging of patients with OCD, including metabolic pallidum and subthalamic nucleus, produces a Menninger Department of net inhibitory effect.[S4] A lack of balance in these Psychiatry and Behavioral and perfusion, neurochemical, structural, functional Sciences, Baylor College of and connectivity-based modalities. Treatment class pathways is hypothesised to lead to a dysregulated Medicine, Houston, TX, USA included pharmacotherapy, cognitive–behavioural thalamo- cortical drive resulting in inappropriate 4Department of Psychiatry, therapy/exposure and response prevention, stereotactic selection of actions and failure to inhibit maladap- Columbia University Medical tive behaviours, both of which are characteristic Center, New York, New York, lesions, deep brain stimulation and transcranial [S4,S10-11] USA magnetic stimulation. Changes in several brain of the OCD phenotype. CSTC regions regions are consistent and correspond with treatment most frequently investigated in OCD are regions Correspondence to response despite the heterogeneity in treatments and of prefrontal cortex (PFC) (including orbitofrontal Dr Sameer A. Sheth, Department neuroimaging modalities. Most notable are decreases cortex (OFC), dorsolateral PFC (DLPFC), ventro- of Neurosurgery, Baylor College medial PFC (VMPFC) and anterior cingulate cortex in metabolism and perfusion of the caudate, anterior of Medicine, Houston, Texas, (ACC)), striatum and mediodorsal thalamus. USA; Sameer. Sheth@ bcm. edu cingulate cortex, thalamus and regions of prefrontal OCD treatment includes pharmacological and cortex (PFC) including the orbitofrontal cortex (OFC), cognitive–behavioural therapies (CBT) as well as http://jnnp.bmj.com/ KRB and YJP contributed dorsolateral PFC (DLPFC), ventromedial PFC (VMPFC) equally. less- common neuromodulatory strategies, which and ventrolateral PFC (VLPFC). Modulating activity may be neurosurgical (eg, stereotactic lesions and KRB and YJP are joint first within regions of the cortico- striato- thalamo- cortical deep brain stimulation (DBS)) or non- invasive (eg, authors. system may be a common therapeutic mechanism [S12- S13] transcranial magnetic stimulation, TMS). across treatments. We identify future needs and current Received 15 July 2020 This review summarises studies that examined the Revised 24 February 2021 knowledge gaps that can be mitigated by implementing brain before and after treatment to discover changes Accepted 24 March 2021 integrative methods. Future studies should incorporate in the brain that were associated with symptom on October 1, 2021 by guest. Protected copyright. a systematic, analytical approach to testing objective improvement, with the hypothesis that common correlates of treatment response to better understand neural mediators may be observed regardless of neurophysiological mechanisms of dysfunction. treatment modality. We also identify knowledge gaps and recommendations for future research. © Author(s) (or their RESULTS employer(s)) 2021. Re- use INTRODUCTION Our results are organised by treatment and subse- permitted under CC BY- NC. No Obsessive–compulsive disorder (OCD) is a chronic, quently by imaging modality. Following literature commercial re- use. See rights disabling disease characterised by recurrent, intru- review as summarised (figure 1), in total, we included and permissions. Published sive thoughts (obsessions) and/or repetitive mental by BMJ. 64 distinct studies which report changes in neuro- or physical actions (compulsions). Typical onset imaging markers following treatment and examine To cite: Bijanki KR, Pathak occurs during the childhood or adolescence and correlation with clinical outcome measured by Yale- YJ, Najera RA, et al. J Neurol often lasts through adulthood; lifetime prevalence Brown Obsessive Compulsive Scale (Y-BOC S), as Neurosurg Psychiatry Epub 1 ahead of print: [please is estimated at 2.3% in the American population. the most standardised and validated instrument to include Day Month Year]. Patients often suffer from impaired interpersonal quantify OCD symptomatology. Of the studies that doi:10.1136/jnnp-2020- relationships as a result of their symptoms, and reported significant correlations with Y-BOC S, 28 324478 unemployment rates are reported as high as 38%.2 focused on an adult cohort, 5 on a paediatric cohort Bijanki KR, et al. J Neurol Neurosurg Psychiatry 2021;0:1–11. doi:10.1136/jnnp-2020-324478 1 Neurosurgery J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-324478 on 27 April 2021. Downloaded from after SRI or TCA intervention; however, these did not correlate with symptom reduction. Three studies reported no significant change in OFC metabolism with SRI or TCA treatment (n=9 adults),3 (n=11 adults),7 (n=7 adults).12 SPECT studies found decrease in OFC perfusion bilater- ally that did not correlate with reduction in Y-BOC S (n=8 adults).22 Others noted no change in OFC metabolism after fluvoxamine (n=15 adults)11 or fluoxetine (n=6 adults).4 ► PFC/ACC: One fluoro- deoxyglucose positron emission tomography (FDG- PET) study noted decreased metabolism in the bilateral ACC that correlated with decreased Y- BOCS (n=11 adults).7 Another study reported decreased metabo- lism in the right ACC that did not, however, correlate with symptom improvement (n=9 adults).3 Several others noted no significant change in ACC metabolism corresponding Figure 1 PRISMA flow chart. OCD, obsessive–compulsive disorder; with SRI or TCA outcomes (n=13 adults),5 (n=20 adults),14 PRISMA, Preferred Reporting Items for Systematic Reviews and Meta- (n=20 adults),16 (n=8 adults).21 Analyses. ► Thalamus: One study noted a decreased metabolism in the left thalamus after fluoxetine administration; however, this finding did not correlate with Y- BOCS reduction and 1 included patients between the ages of 16–29. Within each (n=9 adults).3 Other studies that used SRI or TCA phar- section, we first summarise statistically significant results from macotherapy found no corresponding significant metabolic regions most frequently implicated in the CSTC circuit (OFC, change in the thalamus (n=20 adults),16 (n=8 adults),21 DLPFC, VMPFC, ventrolateral PFC (VLPFC), ACC, caudate (n=11 adults).7 Results from perfusion studies in the thal- and thalamus). All other regions that changed significantly are amus varied depending on treatment class. Two studies also reported. Laterality is indicated if included in table 1. At the showed rCBF decreases in the right thalamus after SRIs end of each section, we summarise the subset of results in which (n=11 adults),18 but only one reported a significant correla- neuroimaging changes correlated significantly with treatment tion with Y-BOC S improvement (n=15 adults).11 response (i.e., decreased Y-BOC S). ► Other Regions: Decreased metabolism in bilateral middle and posterior cingulate cortices correlated with Y-BOC S Pharmacotherapy reduction (n=11 adults).7 Another study found both a Studies evaluated imaging changes after administration of sero- decrease in metabolism in the right putamen, bilateral cere- 3–10 7 11 tonin reuptake inhibitors (SRIs) (fluoxetine ; fluvoxamine ; bella and right hippocampus and an increase in metabolism 8 12–17 8 9 18–20 paroxetine and other SRIs ; tricyclic antidepressants in the right lateral postcentral gyrus, posterior and superior 5 7 21 22 (TCAs) (clomipramine) and after selective SRI (SSRI) parietal lobes, and medial and superior occipital gyri after 23 24 augmentation with the atypical antipsychotic risperidone. SRI treatment (n=10 adults).8 Conversely, others noted 6 13 15 17 Patient populations ranged from treatment-naïve children, an increase in metabolism in the putamen bilaterally (n=8 24 to pharmacotherapy-resistant adults and treatment duration adults).21 These findings from these studies were not corre- 5 23 varied