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

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.

Interhemispheric functional interactions between the subthalamic nuclei of patients with Parkinson's disease.

Parkinson's disease (PD) is characterized by widespread neural interactions in cortico-basal-ganglia networks primarily in beta oscillations (approx. 10-30 Hz), as suggested by previous findings of levodopa-modulated interhemispheric coherence between the bilateral subthalamic nuclei (STN) in local field potential recordings (LFPs). However, due to confounding effects of volume conduction the existence of 'genuine' interhemispheric subcortical coherence remains an open question. To address this issue we utilized the imaginary part of coherency (iCOH) which, in contrast to the standard coherence, is not susceptible to volume conduction. LFPs were recorded from eight patients with PD during wakeful rest before and after levodopa administration. We demonstrated genuine coherence between the bilateral STN in both 10-20 and 21-30 Hz oscillations, as revealed by a non-zero iCOH. Crucially, increased iCOH in 10-20 Hz oscillations positively correlated with the worsening of motor symptoms in the OFF medication condition across patients, which was not the case for standard coherence. Furthermore, across patients iCOH was increased after levodopa administration in 21-30 Hz oscillations. These results suggest a functional distinction between low and high beta oscillations in STN-LFP in line with previous studies. Furthermore, the observed functional coupling between the bilateral STN might contribute to the understanding of bilateral effects of unilateral deep brain stimulation. In conclusion, the present results imply a significant contribution of time-delayed neural interactions to interhemispheric coherence, and the clinical relevance of long-distance neural interactions between bilateral STN for motor symptoms in PD.

Quadruple deep brain stimulation in Huntington's disease, targeting pallidum and subthalamic nucleus: case report and review of the literature.

Deep brain stimulation (DBS) represents an established treatment option in a growing number of movement disorders. Recent case reports suggest beneficial effect of globus pallidus internus (GPi)-DBS in selected patients suffering from Huntington's disease with marked disabling chorea. We present a 41-year-old man with genetically confirmed HD following quadruple GPi- and subthalamic nucleus (STN)-DBS. Motor function was assessed by Abnormal Involuntary Movement Scale (AIMS) and by Unified Huntington Disease Rating Scale (UHDRS) presurgery and postsurgery for up to 4 years. Furthermore, cognitive, neuropsychiatric state and quality of life (QoL) including life satisfaction (QLS) were annually evaluated. Chorea assessed by AIMS and UHDRS subscores improved by 52 and 55 %, 45 and 60 %, 35 and 45 % and 55-66 % at 1-4 years, respectively, compared to presurgical state following GPi-STN-DBS. During these time periods bradykinesia did not increase following separate STN- and combined GPi-STN-DBS compared to presurgical state. Mood, QoL and QLS were ameliorated. However, dysexecutive symptoms increased at 4 years postsurgery. The present case report suggests that bilateral GPi- and STN-DBS may represent a new treatment avenue in selected HD patients. Clinically, GPi-DBS attenuated chorea and was associated with a larger effect-adverse effect window compared to STN-DBS. However, GPi-DBS-induced bradykinesia may emerge as one main limitation of GPi-DBS in HD. Thus, quadruple GPi-STN-DBS may be indicated, if separate GPi-DBS does not result in sufficient control of motor symptoms. Future controlled studies need to confirm if the present anecdotal observation of additive beneficial effects of GPi- and STN-DBS in a HD patient with severe generalized chorea and relatively intact cognitive and affective functions indeed represents a new therapeutic option.

Long-range temporal correlations in the subthalamic nucleus of patients with Parkinson's disease.

Neuronal activity in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD) is characterised by excessive neuronal synchronization, particularly in the beta frequency range. However, less is known about the temporal dynamics of neuronal oscillations in PD. In this respect long-range temporal correlations (LRTC) are of special interest as they quantify the neuronal dynamics on different timescales and have been shown to be relevant for optimal information processing in the brain. While the presence of LRTC has been demonstrated in cortical data, their existence in deep brain structures remains an open question. We investigated (i) whether LRTC are present in local field potentials (LFP) recorded bilaterally from the STN at wakeful rest in ten patients with PD after overnight withdrawal of levodopa (OFF) and (ii) whether LRTC can be modulated by levodopa treatment (ON). Detrended fluctuation analysis was utilised in order to quantify the temporal dynamics in the amplitude fluctuations of LFP oscillations. We demonstrated for the first time the presence of LRTC (extending up to 50 s) in the STN. Importantly, the ON state was characterised by significantly stronger LRTC than the OFF state, both in beta (13-35 Hz) and high-frequency (> 200 Hz) oscillations. The existence of LRTC in subcortical structures such as STN provides further evidence for their ubiquitous nature in the brain. The weaker LRTC in the OFF state might indicate limited information processing in the dopamine-depleted basal ganglia. The present results implicate LRTC as a potential biomarker of pathological neuronal processes in PD.

German registry of paediatric deep brain stimulation in patients with childhood-onset dystonia (GEPESTIM).

BACKGROUND: Data on paediatric deep brain stimulation (DBS) is limited, especially for long-term outcomes, because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We seek to systematically evaluate the clinical outcome of paediatric patients undergoing DBS. METHODS: A German registry on paediatric DBS (GEPESTIM) was created to collect data of patients with dystonia undergoing DBS up to the age of 18 years. Patients were divided into three groups according to etiology (group 1 inherited, group 2 acquired, and group 3 idiopathic dystonia). RESULTS: Data of 44 patients with a mean age of 12.8 years at time of operation provided by 6 German centers could be documented in the registry so far (group 1 n = 18, group 2 n = 16, group 3 n = 10). Average absolute improvement after implantation was 15.5 ± 18.0 for 27 patients with pre- and postoperative Burke-Fahn-Marsden Dystonia Rating scale movement scores available (p < 0.001) (group 1: 19.6 ± 19.7, n = 12; group 2: 7.0 ± 8.9, n = 8; group 3: 19.2 ± 20.7, n = 7). Infection was the main reason for hardware removal (n = 6). 20 IPG replacements due to battery expiry were necessary in 15 patients at 3.7 ± 1.8 years after last implantation. DISCUSSION: Pre- and postoperative data on paediatric DBS are very heterogeneous and incomplete but corroborate the positive effects of DBS on inherited and acquired dystonia. Adverse events including relatively frequent IPG replacements due to battery expiry seem to be a prominent feature of children with dystonia undergoing DBS. The registry enables collaborative research on DBS treatment in the paediatric population and to create standardized management algorithms in the future.

Functional and effective connectivity in subthalamic local field potential recordings of patients with Parkinson's disease.

In Parkinson's disease (PD) levodopa-associated changes in the power and long-range temporal correlations of beta oscillations have been demonstrated, yet the presence and modulation of genuine connectivity in local field potentials (LFP) recorded from the subthalamic nucleus (STN) remains an open question. The present study investigated LFP recorded bilaterally from the STN at wakeful rest in ten patients with PD after overnight withdrawal of levodopa (OFF) and after a single dose levodopa administration (ON). We utilized connectivity measures being insensitive to volume conduction (functional connectivity: non-zero imaginary part of coherency; effective connectivity: phase-slope index). We demonstrated the presence of neuronal interactions in the frequency range of 10-30 Hz in STN-LFP without a preferential directionality of interactions between different contacts along the electrode tracks. While the direction of neuronal interactions per se was preserved after levodopa administration, functional connectivity and the ventral-dorsal information flow were modulated by medication. The OFF-ON differences in functional connectivity were correlated with the levodopa-induced improvement in clinical Unified Parkinson's Disease Rating Scale scores. We hypothesize that regional neuronal interactions, as reflected in STN-LFP connectivity, might represent a basis for the intra-nuclear spatial specificity of deep brain stimulation. Moreover, our results suggest the potential use of volume conduction-insensitive measures of connectivity in STN-LFP as a marker of clinical motor symptoms in PD.