Different patterns of local field potentials from limbic DBS targets in patients with major depressive and obsessive compulsive disorder

Abstract

The role of distinct limbic areas in emotion regulation has been largely inferred from neuroimaging studies. Recently, the opportunity for intracranial recordings from limbic areas has arisen in patients undergoing deep brain stimulation (DBS) for neuropsychiatric disorders including major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Here we test the hypothesis that distinct temporal patterns of local field potential (LFP) activity in the human limbic system reflect disease state and symptom severity in MDD and OCD patients. To this end, we recorded LFPs via implanted DBS electrodes from the bed nucleus of stria terminalis (BNST area) in 12 patients (5 OCD, 7 MDD) and from the subgenual cingulate cortex in 7 MDD patients (CG25 area). We found a distinct pattern of oscillatory activity with significantly higher α-power in MDD compared with OCD in the BNST area (broad α-band 8-14 Hz; P<0.01) and a similar level of α-activity in the CG25 area as in the BNST area in MDD patients. The mean α-power correlated with severity of depressive symptoms as assessed by the Beck depression inventory in MDD (n=14, r=0.55, P=0.042) but not with severity of obsessive compulsive symptoms in OCD. Here we show larger α-band activity in MDD patients compared with OCD recorded from intracranial DBS targets. Our results suggest that α-activity in the limbic system may be a signature of symptom severity in MDD and may serve as a potential state biomarker for closed loop DBS in MDD.

Neuroelectronics and Biooptics

“…18,55 These studies will be critical as closed-loop paradigms are applied to increasingly diverse clinical disorders, including stroke rehabilitation, 56 minimally consciousstate, 57 and a host of psychiatric disorders. 58,59 Effective closed-loop systems for clinical use require advanced understanding of pathophysiological brain signals combined with sophisticated technology for signal processing and subsequent modulation. Only when advancements in basic science, engineering, and materials science are coupled to clinical need will closed-loop technologies translate efficiently to improvements in therapeutic devices for patients with neurological disorders.…”

Multimodal Approaches to Define Network Oscillations in Depression

“…Intracranial recordings from implanted DBS electrodes in TRD patients provide new support for a subcortical role for alpha. Recordings from both the subcallosal cingulate (Brodmann area 25) and the nucleus accumbens acquired in different patients in separate studies report increases in resting alpha rhythm in TRD patients when compared with obsessive-compulsive disorder patients (50). While there are no healthy or nondepressed patient control subjects with comparable recordings in these studies, this is the first direct evidence of striatal and limbic alpha rhythm dysfunction in MDD.…”

“…Such studies have generally been performed in the operating room or in the days thereafter. In separate studies, SCC alpha power was positively correlated with baseline depression severity scores (50); single neurons in the SCC were shown to be preferentially activated by negatively relative to positively valenced emotional images (131); SCC beta coherence changes predicted subsequent decisions in an affective valuation task (134); and the accumbens activity increased in anticipation of an impending reward (118,132). These studies generally confirm previous findings using other imaging modalities.…”

“…In addition, potential behavioral correlates and changes in local activity with and without therapeutic doses of stimulation can be characterized. Until recently, SCC recordings were restricted to intraoperative recordings or those performed in the immediate postoperative period with externalized leads (50,131,133,134). Devices are now available that not only deliver therapeutic stimulation but also record ongoing oscillations directly off the implanted DBS electrodes (135–138).…”

Rats overexpressing the dopamine transporter display behavioral and neurobiological abnormalities with relevance to repetitive disorders

“…Alpha and gamma activity has been associated with spontaneous tic exertion and TS32. In general, alterations in LFP oscillatory activity are proposed as biomarkers of dopamine dysfunction31 and neuro-psychiatric disorders33.…”