Table 3.

Treatment options for OCD

Treatment	Description	Neurocircuits/clinical profiles affected
Behavioral interventions
Cognitive behavioral therapy (CBT)	CBT is a first-line treatment for children and adults with OCD and comprises two components: exposure and response prevention (ERP) and cognitive reappraisal. ERP involves gradual and prolonged exposure to fear-provoking stimuli combined with instructions to abstain from the compulsive behavior. Cognitive reappraisal involves the patient learning to change their thoughts and emotions concerning symptoms.	The ERP aspect of CBT is likely to be most helpful for individuals with dysregulated fear, targeting over-active fronto-limbic circuitry (amygdala, vmPFC) during the experience of OCD symptoms. The cognitive reappraisal aspect of CBT engages dorsal cognitive circuitry to down-regulate over-active fronto-limbic activity and may be useful for individuals with dysregulated fear (fronto-limbic circuit dysfunction) and impaired emotion regulation (dorsal cognitive circuit dysfunction).
Habit-reversal training	Habit-reversal training is currently used for treatment of tics in Tourette syndrome (TS). Patients are trained to become aware of the sensory sensations that precede tics (premonitory urges) and to make competing, voluntary movements that prevent tic production.	Habit-reversal training could be used to address compulsive habits in OCD, for instance those that are preceded by sensory phenomena (sensorimotor system dysfunction).
Pharmacotherapy
Selective serotonin reuptake inhibitors (SSRIs)	SSRIs are the first-line pharmacological treatment for OCD based on their evidence of efficacy, tolerability, safety and absence of abuse potential. As a rule, higher doses of SSRIs are used for OCD than for other anxiety disorders or major depression.	SSRIs may be particularly appropriate for individuals with dysregulated fear and intolerance of uncertainty symptom expressions (fronto-limbic circuit dysfunction) but may also be helpful for individuals with altered responsiveness to rewards (ventral affective circuit dysfunction).
Pharmacotherapy in treatment-resistant OCD
Antipsychotics and methylphenidate	Antipsychotic agents have shown efficacy as add-ons for patients who do not show symptom improvements with SSRIs (including clomipramine), especially haloperidol, risperidone, aripiprazole, olanzapine and quetiapine [175]. Symptom improvements with augmentation with methylphenidate has also been found in treatment-resistant patients.	Because antipsychotic medications and methylphenidate regulate dopaminergic signalling, the use of such medications may be particularly helpful for individuals with impaired response inhibition (ventral cognitive circuit dysfunction), altered responsiveness to rewards (ventral affective circuit dysfunction) and executive dysfunction (dorsal cognitive circuit dysfunction).
Neuromodulation and neurosurgery
Deep Brain Stimulation (DBS)	Deep brain stimulation is a neurosurgical intervention for OCD patients refractory to multiple conventional treatments. An implantable neurostimulator is connected to electrodes that are inserted in a brain region related to the pathophysiology of OCD. Different targets have been studied so far, such as the anterior limb of the internal capsule (ALIC) and ventral capsule/ventral striatum (VC/VS), white matter bundles immediately above the accumbens, the subthalamic nucleus (STN), the bed nucleus of stria terminalis (BNST), and the inferior thalamic peduncle. The supero-lateral branch of the medial forebrain bundle (slMFB) and the anteromedial globus pallidus internus (GPi) are currently under investigation as targets as well.	DBS has applications for improving dysfunctions in fronto-limbic circuitry (BNST target for intolerance of uncertainty), ventral cognitive circuitry (STN target for response inhibition) and ventral affective circuitry (NAcc target for altered reward responsiveness). Note, however, that stimulation of the STN, the entire ALIC or its most ventral portions (as in NAcc DBS) might act on a common white matter network connecting frontal regions to the STN [70] and further tractography studies are needed to investigate the specificity of these targets to individual neurocircuits. The ALIC may be an effective target for dysfunctions in several of the neurocircuits depending on where it is targeted and the connecting white matter networks affected by stimulation [70–71, 132].
Transcranial Magnetic Stimulation (TMS)	Repetitive TMS (rTMS) can be either excitatory or inhibitory and modulates neuronal activity via electric currents that are induced by a magnetic coil positioned over the head. The excitatory and inhibitory effects of rTMS are hypothesized to be similar to long-term potentiation (LTP) and long-term depression (LTD), respectively. LTP and LTD are two mechanisms of synaptic plasticity that lead to synaptic strengthening (LTP) or weakening (LTD) (i.e. an increase or decrease in synaptic efficiency). rTMS is considered to be excitatory or inhibitory when applying high-frequency (≥ 10Hz) or low-frequency (< 1Hz) protocols, respectively [195]. Widely used targets include the (pre-SMA) and the dlPFC.	rTMS targeting the SMA could be useful for addressing sensorimotor dysfunctions while rTMS targeted at the dlPFC would have applications in improving top-down control of emotional reactions (dysregulated fear symptom expression, fronto-limbic circuit) and planning and working memory problems (dorsal cognitive circuit dysfunctions). Deep TMS targeting the ACC could potentially address problems with reward alterations involved in hyperactive monitoring of errors (ventral affective circuit dysfunction).
Transcranial Direct Current Stimulation (tDCS)	tDCS involves the application of a weak current to the scalp, with only a fraction of the current entering the brain. Anodal tDCS is usually facilitatory whereas cathodal tDCS induces inhibitory effects [195].	tDCS targeted at the SMA could be useful in improving sensorimotor atypicalities caused by disturbances in the sensorimotor circuit (sensory phenomena), while tDCS targeted at the OFC may help to improve fear extinction and hyperactive fear responses involved in the dysregulated fear symptom expression (fronto-limbic circuit).
Neurofeedback	Neurofeedback involves learning to modulate neural activity through real-time monitoring of one’s current brain state (self-regulation of mind-brain). This self-regulatory neuromodulation can be done using EEG, functional near-infrared spectroscopy (fNIRS) and fMRI.	Neurofeedback could be targeted at key regions within any of the five circuits discussed here as implicated in OCD. EEG and fNIRS based neurofeedback would be appropriate only for regions close to the surface of the head (e.g. SMA, dlPFC) due to their inability to measure deep brain structures, while fMRI-based neurofeedback could be used for both surface and deep brain structures.
Executive Function training	Cognitive training programs target specific cognitive functions, such as organization/planning and working memory, with daily training.	Cognitive training could be targeted at a variety of neurocognitive alterations implicated in OCD, including executive dysfunction (dorsal cognitive circuit), dysregulation fear and intolerance of uncertainty (fronto-limbic circuit) and response inhibition (ventral cognitive circuit).