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ispartof: Brain Stimulation vol:13 issue:6 pages:1639-1641 ispartof: location:United States status: published

BACKGROUND: Some patients suffer from persistent and severely disabling Obsessive-Compulsive Disorder (OCD) symptoms that cannot be alleviated by conventional treatments or neuroablative interventions targeting cortico-striatal loop circuits. Currently, it is unclear how to manage the clinical symptoms of these unique patients. We reasoned that deep brain stimulation (DBS) of the habenula (HB) could be a valuable subsequent treatment option for these otherwise medically intractable cases of severe OCD. The HB is an epithalamic structure critically involved in the encoding and responding to aversive stimulus events, cognitive and brain processes known to be impaired in many patients with OCD. Similarly, HB DBS can alleviate depression and anxiety, which often co-occur with OCD. Here, we explore the clinical benefits and risks of HB DBS treatment in a patient with severe and refractory OCD. CASE PRESENTATION: A 30-year-old male patient presented with persistent and severely disabling OCD symptoms that were refractory to previous psychological and pharmacological treatments as well as to neuroablative surgical interventions involving both capsulotomy and cingulotomy. After HB DBS, however, the severity of the patient's OCD symptoms was markedly reduced at 1-month follow-up, which was sustained until the final (at 12-month) follow-up. The patient also reported enduring improvements in depression, anxiety, and health-related quality of life after several months of HB DBS treatment. CONCLUSIONS: This case report provides the first clinical evidence suggesting that HB DBS could serve as a safe and effective alternative neurosurgical intervention for severe and refractory OCD. The present findings are promising and warrant further research into the role of the HB in pathophysiology and treatment of OCD. ispartof: FRONTIERS IN PSYCHIATRY vol:11 ispartof: location:Switzerland status: published

We studied the feasibility, safety, tolerability and pharmacokinetics of intracerebroventricular delivery of recombinant human vascular endothelial growth factor in patients with amyotrophic lateral sclerosis. In this phase I study in patients with amyotrophic lateral sclerosis, the study drug was delivered using an implantable programmable pump connected to a catheter inserted in the frontal horn of the lateral cerebral ventricle. A first cohort received open label vascular endothelial growth factor (0.2, 0.8 and 2 µg/day), a second cohort received placebo, 0.8 or 2 µg/day of study dug. After the 3-month study period, all patients could participate in an open label extension study. In total, 18 patients with amyotrophic lateral sclerosis, seen at the University Hospitals in Leuven were included. The surgical procedure was well tolerated in most patients. One patient had transient postoperative seizures, due to an ischemic lesion along the catheter tract. The first 3-month study period was completed by 15/18 patients. Administration of 2 µg/day vascular endothelial growth factor resulted in sustained detectable levels in cerebrospinal fluid. A pulmonary embolus occurred in 3 patients, in 1 patient in the first 3-month study, and in 2 patients during the open label extension study. The study drug was well tolerated in the other patients, for up to 6 years in the open label extension study. Our study shows that intracerebroventricular administration of 2 µg/day of vascular endothelial growth factor to patients with amyotrophic lateral sclerosis is feasible, results in detectable cerebrospinal fluid levels and is well tolerated in most patients. The most common serious adverse event was a pulmonary embolus., Vascular endothelial growth factor has been implicated in the pathogenesis of amyotrophic lateral sclerosis. In this phase I study, we investigated the feasibility, safety, tolerability and pharmacokinetics of intracerebroventricular delivery of recombinant human vascular endothelial growth factor in patients with amyotrophic lateral sclerosis., Graphical Abstract Graphical Abstract

Despite the current success of neuromodulation, standard biphasic, rectangular pulse shapes may not be optimal to achieve symptom alleviation. Here, we compared stimulation efficiency (in terms of charge) between complex and standard pulses in two areas of the rat brain. In motor cortex, Gaussian and interphase gap stimulation (IPG) increased stimulation efficiency in terms of charge per phase compared with a standard pulse. Moreover, IPG stimulation of the deep mesencephalic reticular formation in freely moving rats was more efficient compared to a standard pulse. We therefore conclude that complex pulses are superior to standard stimulation, as less charge is required to achieve the same behavioral effects in a motor paradigm. These results have important implications for the understanding of electrical stimulation of the nervous system and open new perspectives for the design of the next generation of safe and efficient neural implants. ispartof: Scientific Reports vol:8 issue:1 pages:1-18 ispartof: location:England status: published

Silicon neuroprobes hold great potential for studies of large-scale neural activity and brain computer interfaces, but data on brain response in chronic implants is limited. Here we explored with in vivo cellular imaging the response to multisite silicon probes for neural recordings. We tested a chronic implant for mice consisting of a CMOS-compatible silicon probe rigidly implanted in the cortex under a cranial imaging window. Multiunit recordings of cortical neurons with the implant showed no degradation of electrophysiological signals weeks after implantation (mean spike and noise amplitudes of 186 ± 42 µVpp and 16 ± 3.2 µVrms, respectively, n = 5 mice). Two-photon imaging through the cranial window allowed longitudinal monitoring of fluorescently-labeled astrocytes from the second week post implantation for 8 weeks (n = 3 mice). The imaging showed a local increase in astrocyte-related fluorescence that remained stable from the second to the tenth week post implantation. These results demonstrate that, in a standard electrophysiology protocol in mice, rigidly implanted silicon probes can provide good short to medium term chronic recording performance with a limited astrocyte inflammatory response. The precise factors influencing the response to silicon probe implants remain to be elucidated.

As part of the efforts of a multi-disciplinary, international working group focused on ethical issues in neuromodulation for neuro-psychiatric disorders, we propose a novel; strategy for study design which iteratively applies new knowledge to on-going and future trials. Under current practice, device studies may be closed or categorized as “failures” before knowledge embedded in them can be fully mined. We propose the use of an iterative process to gain knowledge from subjects who have responded to those who have not. This approach can help maximize outcomes in non-responders and inform the design of future studies. This more agile yet rigorous methodology leverages information at all stages of investigation and promotes both scientific discovery and; stewardship.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS. ispartof: Molecular Psychiatry vol:26 issue:4 pages:1-14 ispartof: location:England status: Published online

OBJECTIVE: This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. APPROACH: A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. MAIN RESULTS: Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. SIGNIFICANCE: The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain. ispartof: JOURNAL OF NEURAL ENGINEERING vol:15 issue:3 ispartof: location:England status: published

Background From 1999 onwards, deep brain stimulation (DBS) has been proposed as an alternative to capsulotomy in refractory cases of obsessive-compulsive disorder (OCD). Although rechargeable implantable pulse generators (rIPGs) have been used extensively in DBS for movement disorders, there are no reports on rIPGs in patients with a psychiatric DBS indication, and even possible objections to their use. Objective We aim to evaluate rIPGs in OCD in terms of effectiveness, applicability, safety, and need for IPG replacement. Methods In this prospective before-after study recruiting from 2007 until 2012, OCD patients requiring at least one IPG replacement per 18 months were proposed to have a rIPG implanted at the next IPG depletion. OCD severity was the primary outcome. Ten patients were analyzed. Results Psychiatric symptoms and global functioning remained stable in the two years after as compared to the two years before rIPG implantation. Over the same period, the prescribed OCD medication doses did not increase and the DBS stimulation parameters were largely unaltered. Until the end of the follow-up (mean 4¾ years; maximum seven years), the DBS-related surgery frequency decreased and there were no rIPG replacements. During the first few weeks after implantation, two patients obsessively checked the rIPG, but afterwards there were no signs of compulsively checking or recharging the rIPG. Two patients experienced rIPG overdischarges (five occurrences in total). Conclusions This is the first report on rIPGs in DBS for OCD patients. The use of rIPGs in this population appears to be effective, applicable, and safe and diminishes the need for IPG replacements.

Exaggerated activity in the beta band (13-35 Hz) is a hallmark of basal ganglia signals in patients with Parkinson's disease (PD). Beta activity however is not constantly elevated, but comes in bursts. In previous work we showed that the longer beta bursts are maintained, the more the oscillatory synchronisation within the subthalamic nucleus (STN) increases, which is posited to limit the information coding capacity of local circuits. Accordingly, a higher incidence of longer bursts correlates positively with clinical impairment, while the opposite is true for short, more physiological bursts. Here, we test the hypothesis that beta bursts not only indicate local synchronisation within the STN, but also phasic coupling across the motor network and hence entail an even greater restriction of information coding capacity in patients with PD. Local field potentials from the subthalamic nucleus and EEG over the motor cortex area were recorded in nine PD patients after temporary lead externalization after surgery for deep brain stimulation and overnight withdrawal of levodopa. Beta bursts were defined as periods exceeding the 75th percentile of signal amplitude and the coupling between bursts was considered using two distinct measurements, first the % overlapping (%OVL) as a feature of the amplitude coupling and secondly the phase synchrony index (PSI) to measure the phase coupling between regions. %OVL between STN and cortex and between the left and the right STN was higher than expected between the regions than if they had been independent. Similarly, PSI was higher during bursts as opposed to non-bursts periods. In addition, %OVL was greater for long compared to short bursts. Our results support the hypothesis that beta bursts involve long-range coupling between structures in the basal ganglia-cortical network. The impact of this is greater during long as opposed to short duration beta bursts. Accordingly, we posit that episodes of simultaneously elevated coupling across multiple structures in the basal ganglia-cortical circuit further limit information coding capacity and may have further impact upon motor impairment. ispartof: NEUROBIOLOGY OF DISEASE vol:117 pages:217-225 ispartof: location:United States status: published

We previously found that electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) alleviates depressive symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we tested the hypothesis that electrical stimulation in either IC/BST or in the inferior thalamic peduncle (ITP) effectively reduces depressive symptoms in treatment-resistant major depressive disorder (TRD). In a double-blind crossover design, the effects of electrical stimulation at both targets were compared in TRD patients. The 17-item Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. During the first crossover, patients received IC/BST stimulation versus no stimulation in random order (2 × 1 weeks). During the second crossover (3 × 2 months), patients received IC/BST versus ITP versus no stimulation. Patients and evaluators were blinded for stimulation conditions. All patients (n=7) were followed up for at least 3 years (3-8 years) after implantation. Six patients completed the first crossover and five patients completed the second. During the first crossover, mean (s.d.) HAM-D scores were 21.5 (2.7) for no stimulation and 11.5 (8.8) for IC/BST stimulation. During the second crossover, HAM-D scores were 15.4 (7.5) for no stimulation, 7.6 (3.8) for IC/BST stimulation and 11.2 (7.5) for ITP stimulation. The final sample size was too small to statistically analyze this second crossover. At last follow-up, only one patient preferred ITP over IC/BST stimulation. Two patients, with a history of suicide attempts before implantation, committed suicide during the follow-up phases of this study. Our data indicate that, in the long term, both ITP and IC/BST stimulation may alleviate depressive symptoms in patients suffering from TRD. ispartof: Translational Psychiatry vol:7 issue:10 ispartof: location:United States status: Published online

In this work a new type of foldable neural electrode is presented. The microfabricated electrode is specifically designed for Deep Brain Stimulation of the cavity wall of thalamic lesions resulting from brain infarcts. On implantation, the electrode is introduced through a cannula, after which the flower-like structure unfolds, contacting the cavity walls and allowing stimulation at different anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching (RIE) is presented. In-Vivo experiments have also been performed in which the implantation procedure and the unfolding of the electrode are tested and visualized. publisher: Elsevier articletitle: A Foldable Neural Electrode for 3D Stimulation of Deep Brain Cavities journaltitle: Procedia Engineering articlelink: http://dx.doi.org/10.1016/j.proeng.2016.11.177 content_type: article copyright: © 2016 The Author(s). Published by Elsevier Ltd. ispartof: pages:137-142 ispartof: Procedia Engineering vol:168 pages:137-142 ispartof: Eurosensors location:Budapest date:4 Sep - 7 Sep 2016 status: published

Stereotactic neurosurgery is used in pre-clinical research of neurological and psychiatric disorders in experimental rat and mouse models to engraft a needle or electrode at a pre-defined location in the brain. However, inaccurate targeting may confound the results of such experiments. In contrast to the clinical practice, inaccurate targeting in rodents remains usually unnoticed until assessed by ex vivo end-point histology. We here propose a workflow for in vivo assessment of stereotactic targeting accuracy in small animal studies based on multi-modal post-operative imaging. The surgical trajectory in each individual animal is reconstructed in 3D from the physical implant imaged in post-operative CT and/or its trace as visible in post-operative MRI. By co-registering post-operative images of individual animals to a common stereotaxic template, targeting accuracy is quantified. Two commonly used neuromodulation regions were used as targets. Target localization errors showed not only variability, but also inaccuracy in targeting. Only about 30% of electrodes were within the subnucleus structure that was targeted and a-specific adverse effects were also noted. Shifting from invasive/subjective 2D histology towards objective in vivo 3D imaging-based assessment of targeting accuracy may benefit a more effective use of the experimental data by excluding off-target cases early in the study. Rangarajan J.R., Vande Velde G., van Gent F., De Vloo P., Dresselaers T., Depypere M., Van Kuyck K., Nuttin B., Himmelreich U., Maes F., ''Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models'', Scientific reports, vol. 6, no. article 38058, 17 pp., 2016. ispartof: Scientific Reports vol:6 issue:1 ispartof: location:England status: published

Summary It is axiomatic that motivation improves learning, a principle repeatedly stressed both in the classroom and on the sports field. Motivation's influence over learning can be considered twofold: a general arousing or energising effect, and a more goal-specific component [1]. Recent developments in reward theory suggest that the latter may be achieved through the increased weighting of ‘teaching signals' computed from feedback related to the success of a given course of action, so that the respective action may be re-inforced. This view has received experimental support in the context of explicit choices between actions [2], but whether it is relevant to the trial-to-trial learning of a single action, such as a tennis return, remains unclear. We previously showed the existence of an evoked activity in the basal ganglia that correlates with accuracy of performance in a simple task and is associated with reiteration of successful motor parameters in subsequent movements [3]. Here we establish that motivation increases the amplitude of this evoked activity for a given trial accuracy, thus promoting trial-to-trial learning.

Practice makes perfect, but the neural substrates of trial-to-trial learning in motor tasks remain unclear. There is some evidence that the basal ganglia process feedback-related information to modify learning in essentially cognitive tasks 1, 2, 3 and 4, but the evidence that these key motor structures are involved in offline feedback-related improvement of performance in motor tasks is paradoxically limited. Lesion studies in adult zebra finches suggest that the avian basal ganglia are involved in the transmission or production of an error signal during song 5, 6 and 7. However, patients with Huntington's disease, in which there is prominent basal ganglia dysfunction, are not impaired in error-dependent modulation of future trial performance [8]. By directly recording from the subthalamic nucleus in patients with Parkinson's disease, we demonstrate that this nucleus processes error in trial performance at short latency. Local evoked activity is greatest in response to smallest errors and influences the programming of subsequent movements. Accordingly, motor parameters are least likely to change after the greatest evoked responses so that accurately performed trials tend to precede other accurate trials. This relationship is disrupted by electrical stimulation of the nucleus at high frequency. Thus, the human subthalamic nucleus is involved in feedback-based learning.

Oscillatory neural activity was reported to have various physiological roles in information processing of brain functions. It is now established that extracellular activity in the motor cortex encodes aspects of movement, involving planning and motor control. Oscillatory patterns have also been hypothesized to play a role in brain recovery and functional remapping. In this study, we measured neural activity from within the cavity wall of a motor cortex lesion, in a rat model, while the animals performed a skilled walking task. We aim at providing a possible framework of analysis, focused on revealing oscillatory patterns in the cavity wall and their correlation with motor deficits, by using a combination of spectral features, involving power spectra and coherence estimates in the beta and gamma frequency bands. ispartof: pages:289-294 ispartof: BIOSIGNALS 2015 pages:289-294 ispartof: Biostec 2015 location:Lisbon date:12 Jan - 15 Jan 2015 status: published

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation. ispartof: Scientific Reports vol:4 issue:1 ispartof: location:England status: published

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

We recently showed that deep brain stimulation (DBS) in the bed nucleus of the stria terminalis (BST) reduces obsessions, compulsions and associated anxiety in patients suffering from severe, treatment-refractory obsessive-compulsive disorder. Here, we investigated the anxiolytic effects of electrical BST stimulation in a rat model of conditioned anxiety, unrelated to obsessions or compulsions. Two sets of stimulation parameters were evaluated. Using fixed settings at 100 Hz, 40 µs and 300 µA (Set A), we observed elevated freezing and startle levels, whereas stimulation at 130 Hz, 220 µs and individually tailored amplitudes (Set B) appeared to reduce freezing. In a follow-up experiment, we evaluated the anxiolytic potential of Set B more extensively, by adding a lesion group and an additional day of stimulation. We found that electrical stimulation significantly reduced freezing, but not to the same extent as lesions. Neither lesions nor stimulation of the BST affected motor behavior or unconditioned anxiety in an open field test. In summary, electrical stimulation of the BST was successful in reducing contextual anxiety in a rat model, without eliciting unwanted motor effects. Our findings underline the therapeutic potential of DBS in the BST for disorders which are hallmarked by pathological anxiety. Further research will be necessary to assess the translatability of these findings to the clinic. Luyck K., Tambuyzer T., Deprez M., Rangarajan J.R., Nuttin B., Luyten L., ''Electrical stimulation of the bed nucleus of the stria terminalis reduces anxiety in a rat model'', Translational psychiatry, vol. 7, article e1033, 8 pp., February 14, 2017. ispartof: Translational Psychiatry vol:7 issue:2 ispartof: location:United States status: published

When a rat is on a limited fixed-time food schedule with full access to a running wheel (activity-based anorexia model, ABA), its activity level will increase hours prior to the feeding period. This activity, called food-anticipatory activity (FAA), is a hypothesized parallel to the hyperactivity symptom in human anorexia nervosa. To investigate in depth the characteristics of FAA, we retrospectively analyzed the level of FAA and activities during other periods in ABA rats. To our surprise, rats with the most body weight loss have the lowest level of FAA, which contradicts the previously established link between FAA and the severity of ABA symptoms. On the contrary, our study shows that postprandial activities are more directly related to weight loss. We conclude that FAA alone may not be sufficient to reflect model severity, and activities during other periods may be of potential value in studies using ABA model. ispartof: Scientific Reports vol:4 issue:1 ispartof: location:England status: published

Background For patients with psychiatric illnesses remaining refractory to ‘standard’ therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. Methods To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. Findings The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered ‘established’ in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient’s capacity and autonomy, multifaceted preoperative as well as postoperative long-term followup evaluation, and reporting of effects and side effects for all patients. Interpretation This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety.

INTRODUCTION: Although spinal cord stimulation (SCS) is a widely used treatment for chronic neuropathic pain secondary to spinal surgery, little is known about the underlying physiological mechanisms. METHODS: The primary aim of this study is to investigate the neural substrate underlying short-term SCS by means of (1)H MR spectroscopy with short echo time, in 20 patients with failed back surgery syndrome. RESULTS: Marked increase of γ-aminobutyric acid (GABA) and decrease in glucose in the ipsilateral thalamus were found between baseline situation without SCS and after 9' of SCS, indicating the key role of the ipsilateral thalamus as a mediator of chronic neuropathic pain. In addition, this study also showed a progressive decrease in glucose in the ipsilateral thalamus over time, which is in line with the findings of previous studies reporting deactivation in the ipsilateral thalamic region. CONCLUSIONS: The observation of GABA increase and glucose decrease over time in the ipsilateral thalamus may be thecausal mechanism of the pain relief due to SCS or an epiphenomenon.

Using (18)F-fluorodeoxyglucose microPET imaging, we investigated the neurocircuitry of contextual anxiety versus control in awake, conditioned rats (n = 7-10 per group). In addition, we imaged a group expressing cued fear. Simultaneous measurements of startle amplitude and freezing time were used to assess conditioning. To the best of our knowledge, no neuroimaging studies in conditioned rats have been conducted thus far, although visualizing and quantifying the metabolism of the intact brain in behaving animals is clearly of interest. In addition, more insight into the neurocircuitry involved in contextual anxiety may stimulate the development of new treatments for anxiety disorders. Our main finding was hypermetabolism in a cluster comprising the bed nucleus of the stria terminalis (BST) in rats expressing contextual anxiety compared with controls. Analysis of a subset of rats showing the best behavioral results (n = 5 per subgroup) confirmed this finding. We also observed hypermetabolism in the same cluster in rats expressing contextual anxiety compared with rats expressing cued fear. Our results provide novel evidence for a role of the BST in the expression of contextual anxiety. ispartof: Journal of Neuroscience vol:32 issue:1 pages:254-263 ispartof: location:United States status: published

ispartof: Neuroscience Letters vol:500 status: published

It is unclear how motivation leads to improved motor performance. Here we test the hypothesis that motivation interacts with behavioural performance in the basal ganglia. We recorded trial-to-trial performance in a bimanual motor task in 10 patients with Parkinson's disease with electrodes chronically implanted in the subthalamic nucleus for deep brain stimulation. Motivation-associated improvements in trial-to-trial performance were contrasted with and without stimulation at high frequency. Motivation and stimulation improved trial-to-trial performance, but the effect of motivation was halved during stimulation. We conclude that the subthalamic area is mechanistically important in those processes linking motivation to improvement in motor performance. This finding may be relevant to some of the cognitive and emotional changes associated with bilateral subthalamic stimulation.