Deep Brain Stimulation for Obsessive-Compulsive Disorder: Optimal Stimulation Sites.

BACKGROUND: Deep brain stimulation (DBS) is a promising treatment option for treatment-refractory obsessive-compulsive disorder (OCD). Several stimulation targets have been used, mostly in and around the anterior limb of the internal capsule and ventral striatum. However, the precise target within this region remains a matter of debate. METHODS: Here, we retrospectively studied a multicenter cohort of 82 patients with OCD who underwent DBS of the ventral capsule/ventral striatum and mapped optimal stimulation sites in this region. RESULTS: DBS sweet-spot mapping performed on a discovery set of 58 patients revealed 2 optimal stimulation sites associated with improvements on the Yale-Brown Obsessive Compulsive Scale, one in the anterior limb of the internal capsule that overlapped with a previously identified OCD-DBS response tract and one in the region of the inferior thalamic peduncle and bed nucleus of the stria terminalis. Critically, the nucleus accumbens proper and anterior commissure were associated with beneficial but suboptimal clinical improvements. Moreover, overlap with the resulting sweet- and sour-spots significantly estimated variance in outcomes in an independent cohort of 22 patients from 2 additional DBS centers. Finally, beyond obsessive-compulsive symptoms, stimulation of the anterior site was associated with optimal outcomes for both depression and anxiety, while the posterior site was only associated with improvements in depression. CONCLUSIONS: Our results suggest how to refine targeting of DBS in OCD and may be helpful in guiding DBS programming in existing patients.

Electrophysiological underpinnings of reward processing: Are we exploiting the full potential of EEG?

Understanding how the brain processes reward is an important and complex endeavor, which has involved the use of a range of complementary neuroimaging tools, including electroencephalography (EEG). EEG has been praised for its high temporal resolution but, because the signal recorded at the scalp is a mixture of brain activities, it is often considered to have poor spatial resolution. Besides, EEG data analysis has most often relied on event-related potentials (ERPs) which cancel out non-phase locked oscillatory activity, thus limiting the functional discriminative power of EEG attainable through spectral analyses. Because these three dimensions -temporal, spatial and spectral- have been unequally leveraged in reward studies, we argue that the full potential of EEG has not been exploited. To back up our claim, we first performed a systematic survey of EEG studies assessing reward processing. Specifically, we report on the nature of the cognitive processes investigated (i.e., reward anticipation or reward outcome processing) and the methods used to collect and process the EEG data (i.e., event-related potential, time-frequency or source analyses). A total of 359 studies involving healthy subjects and the delivery of monetary rewards were surveyed. We show that reward anticipation has been overlooked (88% of studies investigated reward outcome processing, while only 24% investigated reward anticipation), and that time-frequency and source analyses (respectively reported by 19% and 12% of the studies) have not been widely adopted by the field yet, with ERPs still being the dominant methodology (92% of the studies). We argue that this focus on feedback-related ERPs provides a biased perspective on reward processing, by ignoring reward anticipation processes as well as a large part of the information contained in the EEG signal. Finally, we illustrate with selected examples how addressing these issues could benefit the field, relying on approaches combining time-frequency analyses, blind source separation and source localization.

Inhibitory control dysfunction in parkinsonian impulse control disorders.

Impulse control disorders (ICDs) in Parkinson's disease have been associated with dysfunctions in the control of value- or reward-based responding (choice impulsivity) and abnormalities in mesocorticolimbic circuits. The hypothesis that dysfunctions in the control of response inhibition (action impulsivity) also play a role in Parkinson's disease ICDs has recently been raised, but the underlying neural mechanisms have not been probed directly. We used high-resolution EEG recordings from 41 patients with Parkinson's disease with and without ICDs to track the spectral and dynamical signatures of different mechanisms involved in inhibitory control in a simple visuomotor task involving no selection between competing responses and no reward to avoid potential confounds with reward-based decision. Behaviourally, patients with Parkinson's disease with ICDs proved to be more impulsive than those without ICDs. This was associated with decreased beta activity in the precuneus and in a region of the medial frontal cortex centred on the supplementary motor area. The underlying dynamical patterns pinpointed dysfunction of proactive inhibitory control, an executive mechanism intended to gate motor responses in anticipation of stimulation in uncertain contexts. The alteration of the cortical drive of proactive response inhibition in Parkinson's disease ICDs pinpoints the neglected role the precuneus might play in higher order executive functions in coordination with the supplementary motor area, specifically for switching between executive settings. Clinical perspectives are discussed in the light of the non-dopaminergic basis of this function.

Functional imaging studies of Impulse Control Disorders in Parkinson's disease need a stronger neurocognitive footing.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated with dopaminergic dysfunction and treatment, but have no satisfactory therapeutic solution. While studies assessing the neurofunctional bases of ICDs are important for advancing our understanding and management of ICDs, they remain sparse and inconsistent. Based on a systematic analysis of the neuroimaging literature, the present review pinpoints various abnormalities beyond the mesocorticolimbic circuit that supports reward processing, suggesting possible dysfunction at the sensorimotor, executive and affective levels. We advocate that: 1) Future studies should use more sophisticated psychological models and behavioral designs that take into account the potentially multifaceted aspect of ICDs; this would allow a more accurate assessment of the underlying neurocognitive processes, which are not all dependent on the dopaminergic system. 2) Future neuroimaging studies should rely more strongly on task-based, event-related analyses to disentangle the various mechanisms that can be dysfunctional in ICDs. We believe these guidelines constitute a prerequisite towards distinguishing causes, correlates and individual susceptibility factors of PD patients with ICDs.