Intermuscular coherence as biomarker for pallidal deep brain stimulation efficacy in dystonia

ObjectiveFinding a non-invasive biomarker for Globus Pallidus interna Deep Brain Stimulation (GPi-DBS) efficacy. Dystonia heterogeneity leads to a wide variety of clinical response to GPi-DBS, making it hard to predict GPi-DBS efficacy for individual patients.MethodsEEG-EMG recordings of twelve dystonia patients who received bilateral GPi-DBS took place pre- and 1 year post-surgery ON and OFF stimulation, during a rest, pinch, and flexion task. Dystonia severity was assessed using the BFMDRS and TWSTRS (pre- and post-surgery ON stimulation). Intermuscular coherence (IMC) and motorcortex corticomuscular coherence (CMC) were calculated. Low frequency (4–12 Hz) and beta band (13–30 Hz) peak coherences were studied.ResultsDystonia severity improved after 1 year GPi-DBS therapy (BFMDRS: 30%, median 7.8 (IQR 3–10), TWSTRS: 22%, median 6.8 (IQR 4–9)). 86% of IMC were above the 95% confidence limit. The highest IMC peak decreased significantly with GPi-DBS in the low frequency and beta band. Low frequency and beta band IMC correlated partly with dystonia severity and severity improvement. CMC generally were below the 95% confidence limit.ConclusionsPeak low frequency IMC functioned as biomarker for GPi-DBS efficacy, and partly correlated with dystonia severity.SignificanceIMC can function as biomarker. Confirmation in a larger study is needed for use in clinical practice.     

A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation

BackgroundDeep brain stimulation is an established therapy for several neurological disorders; however, its effects on neuronal activity vary across brain regions and depend on stimulation settings. Understanding these variable responses can aid in the development of physiologically-informed stimulation paradigms in existing or prospective indications.ObjectiveProvide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on neuronal activity.MethodsIn patients with movement disorders, single-neuron recordings were acquired from the subthalamic nucleus, substantia nigra pars reticulata, ventral intermediate nucleus, or reticular thalamus during microstimulation across various frequencies (1–100 Hz) to assess single-pulse and frequency-response functions. Moreover, a biophysically-realistic computational framework was developed which generated postsynaptic responses under the assumption that electrical stimuli simultaneously activated all convergent presynaptic inputs to stimulation target neurons. The framework took into consideration the relative distributions of excitatory/inhibitory afferent inputs to model site-specific responses, which were in turn embedded within a model of short-term synaptic plasticity to account for stimulation frequency-dependence.ResultsWe demonstrated microstimulation-evoked excitatory neuronal responses in thalamic structures (which have predominantly excitatory inputs) and inhibitory responses in basal ganglia structures (predominantly inhibitory inputs); however, higher stimulation frequencies led to a loss of site-specificity and convergence towards neuronal suppression. The model confirmed that site-specific responses could be simulated by accounting for local neuroanatomical/microcircuit properties, while suppression of neuronal activity during high-frequency stimulation was mediated by short-term synaptic depression.ConclusionsBrain-region-specific and frequency-dependant neuronal responses could be simulated by considering neuroanatomical (local microcircuitry) and neurophysiological (short-term plasticity) properties.     

Probabilistic maps for deep brain stimulation – Impact of methodological differences

BackgroundGroup analysis of patients with deep brain stimulation (DBS) has the potential to help understand and optimize the treatment of patients with movement disorders. Probabilistic stimulation maps (PSM) are commonly used to analyze the correlation between tissue stimulation and symptomatic effect but are applied with different methodological variations.ObjectiveTo compute a group-specific MRI template and PSMs for investigating the impact of PSM model parameters.MethodsImprovement and occurrence of dizziness in 68 essential tremor patients implanted in caudal zona incerta were analyzed. The input data includes the best parameters for each electrode contact (screening), and the clinically used settings. Patient-specific electric field simulations (n = 488) were computed for all DBS settings. The electric fields were transformed to a group-specific MRI template for analysis and visualization. The different comparisons were based on PSMs representing occurrence (N-map), mean improvement (M-map), weighted mean improvement (wM-map), and voxel-wise t-statistics (p-map). These maps were used to investigate the impact from input data (clinical/screening settings), clustering methods, sampling resolution, and weighting function.ResultsScreening or clinical settings showed the largest impacts on the PSMs. The average differences of wM-maps were 12.4 and 18.2% points for the left and right sides respectively. Extracting clusters based on wM-map or p-map showed notable variation in volumes, while positioning was similar. The impact on the PSMs was small from weighting functions, except for a clear shift in the positioning of the wM-map clusters.ConclusionThe distribution of the input data and the clustering method are most important to consider when creating PSMs for studying the relationship between anatomy and DBS outcome.     

Neuromodulation effects of deep brain stimulation on beta rhythm: A longitudinal local field potential study

BackgroundDeep brain stimulation (DBS) holds great promise in treating various brain diseases but its chronic therapeutic mechanisms are unclear.ObjectiveTo explore the immediate and chronic effects of DBS on brain oscillations, and understand how different sub-bands of oscillations may be related to symptom improvement in Parkinson's patients.MethodsWe carried out a longitudinal study to examine the effects of DBS on local field potentials recorded by sensing-enabled neurostimulators in the subthalamic nuclei of Parkinson's patients, using a novel block-design stimulation paradigm.ResultsDBS significantly suppressed beta activity (13–35Hz) but the suppression effect appeared to gradually attenuate during a 6-month follow-up period after surgery (p = 0.002). However, beta suppression did not attenuate after repeated stimulation over several minutes (p > 0.110), suggesting that the changes in beta suppression may reflect a slow reconfiguration of neural pathways instead of habituation. Suppression of beta was also associated with clinical symptom improvement across subjects. Importantly, symptom-relevant features fell within the high beta band at month 1 but shifted to the low beta band at month 6, indicating that the high beta and the low beta oscillations may play different functional roles and respond differently to stimulation over the long-term treatment.ConclusionThese data may advance understanding of chronic DBS effects on beta oscillations and their association with clinical improvement, offering novel insights to the therapeutic mechanisms of DBS.     

Inter-ictal network of focal epilepsy and effects of clinical factors on network activity

ObjectiveAim of the study was to explore the inter-ictal, resting-state EEG network in patients with focal epilepsy (FE) and to specify clinical factors that influence network activity.MethodsFunctional EEG connectivity (EEGfC) differences were computed between 232 FE patients (FE group) and 77 healthy controls. EEGfC was computed among 23 cortical regions within each hemisphere, for 25 very narrow bands from 1 to 25 Hz. We computed independent effects for six clinical factors on EEGfC in the FE group, by ANOVA and post-hoc t-statistics, corrected for multiple comparisons by false discovery rate method.ResultsRobust, statistically significant EEGfC differences emerged between the FE and the healthy control groups. Etiology, seizure type, duration of the illness and antiepileptic treatment were independent factors that influenced EEGfC. Statistically significant results occurred selectively in one or a few very narrow bands and outlined networks. Most abnormal EEGfC findings occurred at frequencies that mediate integrative and motor activities.ConclusionsFE patients have abnormal resting-state EEGfC network activity. Clinical factors significantly modify EEGfC.SignificanceDelineation of the FE network and modifying factors can open the way for targeted investigations and introduction of EEGfC into epilepsy research and practice.     

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized,double-blinded sham-controlled periods

BackgroundThere is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome.ObjectivesIn this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation.MethodsWe included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety.ResultsActive stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae.ConclusionOur results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.     

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

High density microelectrode recording predicts span of therapeutic tissue activation volumes in subthalamic deep brain stimulation for Parkinson disease

BackgroundSubthalamic deep brain stimulation alleviates motor symptoms of Parkinson disease by activating precise volumes of neural tissue. While electrophysiological and anatomical correlates of clinically effective electrode sites have been described, therapeutic stimulation likely acts through multiple distinct neural populations, necessitating characterization of the full span of tissue activation. Microelectrode recordings have yet to be mapped to therapeutic tissue activation volumes and surveyed for predictive markers.ObjectiveCombine high-density, broadband microelectrode recordings with detailed computational models of tissue activation to describe and to predict regions of therapeutic tissue activation.MethodsElectrophysiological features were extracted from microelectrode recordings along 23 subthalamic deep brain stimulation implants in 16 Parkinson disease patients. These features were mapped in space against tissue activation volumes of therapeutic stimulation, modeled using clinically-determined stimulation programming parameters and fully individualized, atlas-independent anisotropic tissue properties derived from 3T diffusion tensor magnetic resonance images. Logistic LASSO was applied to a training set of 17 implants out of the 23 implants to identify predictors of therapeutic stimulation sites in the microelectrode recording. A support vector machine using these predictors was used to predict therapeutic activation. Performance was validated with a test set of six implants.ResultsAnalysis revealed wide variations in the distribution of therapeutic tissue activation across the microelectrode recording-defined subthalamic nucleus. Logistic LASSO applied to the training set identified six oscillatory predictors of therapeutic tissue activation: theta, alpha, beta, high gamma, high frequency oscillations (HFO, 200–400 Hz), and high frequency band (HFB, 500–2000 Hz), in addition to interaction terms: theta x HFB, alpha x beta, beta x HFB, and high gamma x HFO. A support vector classifier using these features predicted therapeutic sites of activation with 64% sensitivity and 82% specificity in the test set, outperforming a beta-only classifier. A probabilistic predictor achieved 0.87 area under the receiver-operator curve with test data.ConclusionsTogether, these results demonstrate the importance of personalized targeting and validate a set of microelectrode recording signatures to predict therapeutic activation volumes. These features may be used to improve the efficiency of deep brain stimulation programming and highlight specific neural oscillations of physiological importance.     

Naming impairments evoked by focal cortical electrical stimulation in the ventral temporal cortex correlate with increased functional connectivity

BackgroundHigh-frequency cortical electrical stimulations (HF-CES) are the gold standard for presurgical functional mapping. In the dominant ventral temporal cortex (VTC) HF-CES can elicit transient naming impairment (eloquent sites), defining a basal temporal language area (BTLA).ObjectiveWhether naming impairments induced by HF-CES within the VTC are related to a specific pattern of connectivity of the BTLA within the temporal lobe remains unknown. We addressed this issue by comparing the connectivity of eloquent and non-eloquent sites from the VTC using cortico-cortical evoked potentials (CCEP).MethodsLow frequency cortical electrical stimulations (LF-CES) were used to evoke CCEP in nine individual brains explored with Stereo-Electroencephalography. We compared the connectivity of eloquent versus non eloquent sites within the VTC using Pearson's correlation matrix.ResultsOverall, within the VTC, eloquent sites were associated with increased functional connectivity compared to non-eloquent sites. Among the VTC structures, this pattern holds true for the inferior temporal gyrus and the parahippocampal gyrus while the fusiform gyrus specifically showed a high connectivity in both non eloquent and eloquent sites.ConclusionsOur findings suggest that the cognitive effects of focal HF-CES are related to the functional connectivity properties of the stimulated sites, and therefore to the disturbance of a wide cortical network. They further suggest that functional specialization of a cortical region emerges from its specific pattern of functional connectivity. Cortical electrical stimulation functional mapping protocols including LF coupled to HF-CES could provide valuable data characterizing both local and distant functional architecture.     

A ventromedial prefrontal dysrhythmia in obsessive-compulsive disorder is attenuated by nucleus accumbens deep brain stimulation

BackgroundObsessive-compulsive disorder (OCD) has consistently been linked to abnormal frontostriatal activity. The electrophysiological disruption in this circuit, however, remains to be characterized.Objective/hypothesisThe primary goal of this study was to investigate the neuronal synchronization in OCD patients. We predicted aberrant oscillatory activity in frontal regions compared to healthy control subjects, which would be alleviated by deep brain stimulation (DBS) of the nucleus accumbens (NAc).MethodsWe compared scalp EEG recordings from nine patients with OCD treated with NAc-DBS with recordings from healthy controls, matched for age and gender. Within the patient group, EEG activity was compared with DBS turned off vs. stimulation at typical clinical settings (3.5 V, frequency of stimulation 130 Hz, pulse width 60 μs). In addition, intracranial EEG was recorded directly from depth macroelectrodes in the NAc in four OCD patients.ResultsCross-frequency coupling between the phase of alpha/low beta oscillations and amplitude of high gamma was significantly increased over midline frontal and parietal electrodes in patients when stimulation was turned off, compared to controls. Critically, in patients, beta (16–25 Hz) -gamma (110–166 Hz) phase amplitude coupling source localized to the ventromedial prefrontal cortex, and was reduced when NAc-DBS was active. In contrast, intracranial EEG recordings showed no beta-gamma phase amplitude coupling. The contribution of non-sinusoidal beta waveforms to this coupling are reported.ConclusionWe reveal an increased beta-gamma phase amplitude coupling in fronto-central scalp sensors in patients suffering from OCD, compared to healthy controls, which may derive from ventromedial prefrontal regions implicated in OCD and is normalized by DBS of the nucleus accumbens. This aberrant cross-frequency coupling could represent a biomarker of OCD, as well as a target for novel therapeutic approaches.     

Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS

BackgroundTranscranial direct current stimulation (tDCS) presents small antidepressant efficacy at group level and considerable inter-individual variability of response. Its heterogeneous effects bring the need to investigate whether specific groups of patients submitted to tDCS could present comparable or larger improvement compared to pharmacotherapy. Aggregate measurements might be insufficient to address its effects.Objective/Hypothesis: To determine the efficacy of tDCS, compared to pharmacotherapy and placebo, in depressive symptom clusters.MethodsData from ELECT-TDCS (Escitalopram versus Electrical Direct-Current Therapy for Treating Depression Clinical Study, ClinicalTrials.gov, NCT01894815), in which antidepressant-free, depressed patients were randomized to receive 22 bifrontal tDCS (2 mA, 30 min) sessions (n = 94), escitalopram 20 mg/day (n = 91), or placebo (n = 60) over 10 weeks. Agglomerative hierarchical clustering identified “sleep/insomnia”, “core depressive”, “guilt/anxiety”, and “atypical” clusters that were the dependent measure. Trajectories were estimated using linear mixed regression models. Effect sizes are expressed in raw HAM-D units. P-values were adjusted for multiple comparisons.ResultsFor core depressive symptoms, escitalopram was superior to tDCS (ES = −0.56; CI_95% = -0.94 to −0.17, p = .009), which was superior to placebo (ES = 0.49; CI_95% = 0.06 to 0.92, p = .042). TDCS but not escitalopram was superior to placebo in sleep/insomnia symptoms (ES = 0.87; CI_95% = 0.22 to 1.52, p = .015). Escitalopram but not tDCS was superior to placebo in guilt/anxiety symptoms (ES = 1.66; CI_95% = 0.58 to 2.75, p = .006). No active intervention was superior to placebo for atypical symptoms.ConclusionsPharmacotherapy and non-invasive brain stimulation produce distinct effects in depressive symptoms. TDCS or escitalopram could be chosen according to specific clusters of symptoms for a bigger response.Trial registrationClinicalTrials.gov, NCT01894815     

Decline in drawing ability and cerebral perfusion in Parkinson's disease patients after subthalamic nucleus deep brain stimulation surgery

BackgroundSubthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for alleviating motor symptoms in advanced Parkinson's disease (PD) patients; however, a postoperative decline in cognitive and speech function has become problematic although its mechanism remains unclear. The aim of the present study was to elucidate the properties of language and drawing ability and cerebral perfusion in PD patients after bilateral STN DBS surgery.MethodsWestern aphasia battery, including drawing as a subcategory, and perfusion (N-isopropyl-p-[¹²³I] iodoamphetamine) SPECT scan was conducted in 21 consecutive PD patients, before, and three to six months after, bilateral STN DBS surgery while on stimulation. Perfusion images were compared with those of 17 age- and gender-matched healthy volunteers. In the parametric image analysis, the statistical peak threshold was set at P < 0.001 uncorrected with a cluster threshold set at P < 0.05 uncorrected.ResultsAlthough motor symptoms were improved and general cognition was preserved in the patient group, 11 patients (52.4%) showed a decline in the drawing subcategory after surgery, which showed a reduction in Frontal Assessment Battery score in this group of patients. Statistical parametric analysis of the brain perfusion images showed a decrease of cerebral blood flow in the prefrontal and cingulate cortex after surgery. Patients whose drawing ability declined showed decreased perfusion in the middle cingulate cortex comparing before and after surgery.ConclusionPresent results show that some PD patients show a decline in drawing ability after bilateral STN DBS which may attributable by dysfunction in the cingulate network.     

Training in the practice of noninvasive brain stimulation: Recommendations from an IFCN committee

As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines.     

Exploring and optimizing the neuroplastic effects of anodal transcranial direct current stimulation over the primary motor cortex of older humans

BackgroundtDCS modulates cortical plasticity and has shown potential to improve cognitive/motor functions in healthy young humans. However, age-related alterations of brain structure and functions might require an adaptation of tDCS-parameters to achieve a targeted plasticity effect in older humans and conclusions obtained from young adults might not be directly transferable to older adults. Thus, our study aimed to systematically explore the association between tDCS-parameters and induced aftereffects on motor cortical excitability to determine optimal stimulation protocols for older individuals, as well as to investigate age-related differences of motor cortex plasticity in two different age groups of older adults.Methods32 healthy, volunteers from two different age groups of Young-Old (50–65 years, n = 16) and Old-Old (66–80 years, n = 16) participated in this study. Anodal tDCS was applied over the primary motor cortex, with respective combinations of three intensities (1, 2, and 3 mA) and durations (15, 20, and 30 min), in a sham-controlled cross-over design. Cortical excitability alterations were monitored by single-pulse TMS-induced MEPs until the next day morning after stimulation.ResultsAll active stimulation conditions resulted in a significant enhancement of motor cortical excitability in both age groups. The facilitatory aftereffects of anodal tDCS did not significantly differ between age groups. We observed prolonged plasticity in the late-phase range for two protocols with the highest stimulation intensity (i.e., 3 mA-20 min, 3 mA-30 min).ConclusionsOur study highlights the role of stimulation dosage in tDCS-induced neuroplastic aftereffects in the motor cortex of healthy older adults and delivers crucial information about optimized tDCS protocols in the domain of the primary motor cortex. Our findings might set the grounds for the development of optimal stimulation protocols to reinstate neuroplasticity in different cortical areas and induce long-lasting, functionally relevant plasticity in normal aging and in pathological conditions, which would require however systematic tDCS titration studies over respective target areas.     

Cortical modulation of nociception by galvanic vestibular stimulation: A potential clinical tool?

ObjectiveVestibular afferents converge with nociceptive ones within the posterior insula, and can therefore modulate nociception. Consistent with this hypothesis, caloric vestibular stimulation (CVS) has been shown to reduce experimental and clinical pain. Since CVS can induce undesirable effects in a proportion of patients, here we explored an alternative means to activate non-invasively the vestibular pathways using innocuous bi-mastoid galvanic stimulation (GVS), and assessed its effects on experimental pain.MethodsSixteen healthy volunteers participated in this study. Experimental pain was induced by noxious laser-heat stimuli to the left hand while recording pain ratings and related brain potentials (LEPs). We evaluated changes of these indices during left- or right-anodal GVS (cathode on contralateral mastoid), and contrasted them with those during sham GVS, optokinetic vestibular stimulation (OKS) using virtual reality, and attentional distraction to ascertain the vestibular-specific analgesic effects of GVS.ResultsGVS elicited brief sensations of head/trunk deviation, inoffensive to all participants. Both active GVS conditions showed analgesic effects, greater for the right anodal stimulation. OKS was helpful to attain significant LEP reductions during the left-anodal stimulation. Neither sham-GVS nor the distraction task were able to modulate significantly pain ratings or LEPs.ConclusionsGVS appeared as a well-tolerated and powerful procedure for the relief of experimental pain, probably through physiological interaction within insular nociceptive networks. Either isolated or in combination with other types of vestibular activation (e.g., optokinetic stimuli), GVS deserves being tested in clinical settings.     

Efficacy and quality of life after 6–9 years of deep brain stimulation for depression

BackgroundGiven the invasiveness of deep brain stimulation (DBS), the effect should prove to be stable over the long-term and translate into an improvement of quality of life (QOL).ObjectiveTo study the effectiveness and QOL up to nine years after the DBS surgery.MethodsWe treated 25 adult patients with major depression with DBS of the ventral anterior limb of the internal capsule (vALIC). We followed them up naturalistically for 6–9 years after surgery (mean: 7.7 [SD:1.5] years), including a randomized crossover phase after the first year comparing sham with active DBS. Symptom severity was quantified using the Hamilton Depression Scale with response defined as a ≥50% decrease of the score compared to baseline. Quality of life was measured using the WHOQOL-BREF, assessing 5 domains (general, physical, psychological, social, environmental).ResultsIntention-to-treat response rates remained mostly stable from Year 3 to last follow-up (Year 3, 5 and 6: 40%; Year 4: 36%; Last observation: 44%). General, physical, psychological (all P < 0.001) and the environmental (P = 0.02) domain scores increased during DBS optimization and remained stable over the long term. No statistically significant changes were detected on the social domain. Patients scored significantly higher during active than sham DBS on the psychological, social and environmental domains, and trended towards a higher score on the general and physical domains.ConclusionThis study shows continued efficacy of vALIC DBS in depression, which translates into an improvement of QOL providing further support for DBS as a durable treatment for TRD.     

Abnormal patterns of corticomuscular and intermuscular coherence in childhood dystonia

ObjectiveSensorimotor processing is abnormal in Idiopathic/Genetic dystonias, but poorly studied in Acquired dystonias. Beta-Corticomuscular coherence (CMC) quantifies coupling between oscillatory electroencephalogram (EEG) and electromyogram (EMG) activity and is modulated by sensory stimuli. We test the hypothesis that sensory modulation of CMC and intermuscular coherence (IMC) is abnormal in Idiopathic/Genetic and Acquired dystonias.MethodsParticipants: 11 children with Acquired dystonia, 5 with Idiopathic/Genetic dystonia, 13 controls (12–18 years). CMC and IMC were recorded during a grasp task, with mechanical perturbations provided by an electromechanical tapper. Coherence patterns pre- and post-stimulus were compared across groups.ResultsBeta-CMC increased post-stimulus in Controls and Acquired dystonia (p = 0.001 and p = 0.010, respectively), but not in Idiopathic/Genetic dystonia (p = 0.799). The modulation differed between groups, being larger in both Controls and Acquired dystonia compared with Idiopathic/Genetic dystonia (p = 0.003 and p = 0.022). Beta-IMC increased significantly post-stimulus in Controls (p = 0.004), but not in dystonia. Prominent 4–12 Hz IMC was seen in all dystonia patients and correlated with severity (rho = 0.618).ConclusionIdiopathic/Genetic and Acquired dystonia share an abnormal low-frequency IMC. In contrast, sensory modulation of beta-CMC differed between the two groups.SignificanceThe findings suggest that sensorimotor processing is abnormal in Acquired as well as Idiopathic/Genetic dystonia, but that the nature of the abnormality differs.     

Matching stimulation paradigms resolve apparent differences between optogenetic and electrical VTA stimulation

BackgroundOptogenetic stimulation has grown into a popular brain stimulation method in basic neuroscience while electrical stimulation predominates in clinical applications. In order to explain the effects of electrical stimulation on a cellular level and evaluate potential advantages of optogenetic therapies, comparisons between the two stimulation modalities are necessary. This comparison is hindered, however, by the difficulty of effectively matching the two fundamentally different modalities.ObjectiveComparison of brain-wide activation patterns in response to intensity-matched electrical and optogenetic VTA stimulation.MethodsWe mapped optogenetic and electrical self-stimulation rates in the same mice over stimulation intensity and determined iso-behavioral intensities. Using functional ^99mTc-HMPAO SPECT imaging of cerebral blood flow in awake animals, we obtained brain-wide activation patterns for both modalities at these iso-behavioral intensities. We performed these experiments in two mouse lines commonly used for optogenetic VTA stimulation, DAT::Cre and TH::Cre mice.ResultsWe find iso-behavioral intensity matching of stimulation gives rise to similar brain activation patterns. Differences between mouse lines were more pronounced than differences between modalities.ConclusionsPreviously found large differences of electrical and optogenetic stimulation might be due to unmatched stimulation intensity, particularly relative electrical overstimulation. These findings imply that therapeutic electrical VTA stimulation might be relatively specific if employed with optimized parameters.