Proactive inhibition is not modified by deep brain stimulation for Parkinson's disease: An electrical neuroimaging study.

In predictable contexts, motor inhibitory control can be deployed before the actual need for response suppression. The brain functional underpinnings of proactive inhibition, and notably the role of basal ganglia, are not entirely identified. We investigated the effects of deep brain stimulation of the subthalamic nucleus or internal globus pallidus on proactive inhibition in patients with Parkinson's disease. They completed a cued go/no-go proactive inhibition task ON and (unilateral) OFF stimulation while EEG was recorded. We found no behavioural effect of either subthalamic nucleus or internal globus pallidus deep brain stimulation on proactive inhibition, despite a general improvement of motor performance with subthalamic nucleus stimulation. In the non-operated and subthalamic nucleus group, we identified periods of topographic EEG modulation by the level of proactive inhibition. In the subthalamic nucleus group, source estimation analysis suggested the initial involvement of bilateral frontal and occipital areas, followed by a right lateralized fronto-basal network, and finally of right premotor and left parietal regions. Our results confirm the overall preservation of proactive inhibition capacities in both subthalamic nucleus and internal globus pallidus deep brain stimulation, and suggest a partly segregated network for proactive inhibition, with a preferential recruitment of the indirect pathway.

Brain networks modulated by subthalamic nucleus deep brain stimulation.

Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour.

Brain tissue properties differentiate between motor and limbic basal ganglia circuits.

Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome.

Compulsions without obsession following stroke.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by intrusive and irrational thoughts as well as repetitive behaviours. OCD-like behaviours have been described in a wide range of neurological disorders. In cerebrovascular accidents, the semiology arises mostly from lesions to the basal ganglia - though cortical regions may also be involved. In the past few years, the mechanisms underlying OCD in psychiatric patients have been re-examined, in particular the functional relationship between anxiety, obsessions and compulsions. Traditionally, obsessions are viewed as a trigger for compulsive behaviour that represents an attempt to reduce anxiety. By contrast, other models place compulsions - as a manifestation of an imbalance between goal-directed action and automatic habits that leads to maladaptive habit learning - at the core of OCD. CASE: We show neurological evidence of pure compulsions without obsession in a patient following stroke in the left subcortical regions. Furthermore, we present comprehensive neuropsychological findings that identify specific alterations across executive and emotional domains. Finally, MRI analyses reveal that the subcortical stroke had resulted in a strong decrease of connectivity suggestive of large network alterations. CONCLUSIONS: Our case provides direct information on how brain structure and function relate in an OCD patient, highlighting the central role of compulsions in the pathology.

Consensus Statement on High-Intensity Focused Ultrasound for Functional Neurosurgery in Switzerland.

Background: Magnetic resonance-guided high-intensity focused ultrasound (MRgHiFUS) has evolved into a viable ablative treatment option for functional neurosurgery. However, it is not clear yet, how this new technology should be integrated into current and established clinical practice and a consensus should be found about recommended indications, stereotactic targets, patient selection, and outcome measurements. Objective: To sum up and unify current knowledge and clinical experience of Swiss neurological and neurosurgical communities regarding MRgHiFUS interventions for brain disorders to be published as a national consensus paper. Methods: Eighteen experienced neurosurgeons and neurologists practicing in Switzerland in the field of movement disorders and one health physicist representing 15 departments of 12 Swiss clinical centers and 5 medical societies participated in the workshop and contributed to the consensus paper. All experts have experience with current treatment modalities or with MRgHiFUS. They were invited to participate in two workshops and consensus meetings and one online meeting. As part of workshop preparations, a thorough literature review was undertaken and distributed among participants together with a list of relevant discussion topics. Special emphasis was put on current experience and practice, and areas of controversy regarding clinical application of MRgHiFUS for functional neurosurgery. Results: The recommendations addressed lesioning for treatment of brain disorders in general, and with respect to MRgHiFUS indications, stereotactic targets, treatment alternatives, patient selection and management, standardization of reporting and follow-up, and initialization of a national registry for interventional therapies of movement disorders. Good clinical evidence is presently only available for unilateral thalamic lesioning in treating essential tremor or tremor-dominant Parkinson's disease and, to a minor extent, for unilateral subthalamotomy for Parkinson's disease motor features. However, the workgroup unequivocally recommends further exploration and adaptation of MRgHiFUS-based functional lesioning interventions and confirms the need for outcome-based evaluation of these approaches based on a unified registry. MRgHiFUS and DBS should be evaluated by experts familiar with both methods, as they are mutually complementing therapy options to be appreciated for their distinct advantages and potential. Conclusion: This multidisciplinary consensus paper is a representative current recommendation for safe implementation and standardized practice of MRgHiFUS treatments for functional neurosurgery in Switzerland.

Mood Effects After Deep Brain Stimulation for Parkinson's Disease: An Update.

Depression in Parkinson's Disease (PD) is a prevalent and invalidating symptom. Deep brain stimulation (DBS) allows for an improvement of PD motor features, but its effects on mood are difficult to predict. Here, we review the evidence regarding mood effects after DBS of either subthalamic nucleus (STN) or globus pallidus pars interna (GPi). Different influences of multiple factors contribute to impact the neuropsychiatric outcome after surgery. Psychosocial presurgical situation, postsurgical coping mechanisms, dopaminergic treatment modifications, and direct effects of the stimulation of either target are all playing a distinct role on the psychological well-being of patients undergoing DBS. No clear advantage of either target (STN vs. GPi) has been consistently found, both being effective and with a favorable profile on depression symptoms. However, specific patients' characteristics or anatomical considerations can guide the neurosurgeon in the target choice. Further research together with technological advances are expected to confine the stimulation area within dysfunctional circuits causing motor symptoms of PD.

Deep brain stimulation of the posterior gyrus rectus region for treatment resistant depression.

BACKGROUND: Deep brain stimulation (DBS) represents an alternative symptomatic treatment for major depressive disorder in case of failure of pharmacotherapy. The sub-genual cingulate-Brodmann area 25 (CG-25), is one of the most widely used targets for electrode implantation. Given the diverging clinical outcome after DBS, there is a pressing need for in-depth study of brain anatomy and function allowing accurate and reliable prognosis before surgery. METHODS: We studied five treatment-resistant major depressive disorder patients planned to undergo DBS targeting the CG-25. Before surgery, we acquired high-resolution magnetic resonance (MR) diffusion-weighted images for each patient followed by post-surgery MRI for electrode localization. To estimate individual anatomical connectivity pattern of the active contact location we performed probabilistic diffusion tractography intra-individually. We then correlated connectivity patterns with outcome assessed with standardized clinical tests. Connectivity results were compared between DBS responders and non-responders. RESULTS: We observed in one patient an excellent clinical response after DBS of the bilateral posterior gyrus rectus rather than the initially targeted CG-25. The remaining four patients with DBS of the CG-25 were considered as non-responders. In the case patient, we demonstrate a strong connectivity of the stimulated regions to the medial prefrontal cortex (mPFC), which contrasted to the lower mPFC connectivity in non-responders. LIMITATIONS: Confirmation in larger cohorts is needed. CONCLUSIONS: We propose the posterior gyrus rectus as viable alternative new target for DBS in major depressive disorder. High connectivity between target and mPFC supports the pivotal role of this region in brain networks involved in mood processing.

Clinical correlates of frontal intermittent rhythmic delta activity (FIRDA).

OBJECTIVES: To investigate the clinical correlates of frontal intermittent rhythmic delta activity (FIRDA). METHODS: we prospectively assessed all EEG studies recorded in our center over 3 months for the presence of frontal intermittent rhythmic delta activity (FIRDA). The FIRDA group was compared with a randomly selected control group from among EEGs recorded during the same period. Comparisons among FIRDA and non-FIRDA groups were performed using uni- and multi-variate analyses. RESULTS: We found 36 patients with FIRDA among 559 EEG recordings (6%); the control group consisted of 80 subjects. While epilepsy was more frequent in the control group, structural brain lesions and encephalopathy were independently associated with the occurrence of FIRDA, but we could not identify any specific etiology. Asymmetric FIRDA was associated with an underlying brain lesion. Occasionally, FIRDA was recorded in otherwise healthy subjects during hyperventilation. CONCLUSION: FIRDA appears more common than previously reported, and is associated with a wide range of lesions and encephalopathic conditions. SIGNIFICANCE: FIRDA occurrence should prompt investigations for toxic-metabolic disturbances and for structural lesions (particularly if asymmetric), but does not suggest an epileptic predilection.