Electrophysiological differences between upper and lower limb movements in the human subthalamic nucleus

ObjectiveFunctional processes in the brain are segregated in both the spatial and spectral domain. Motivated by findings reported at the cortical level in healthy participants we test the hypothesis in the basal ganglia of Parkinson’s disease patients that lower frequency beta band activity relates to motor circuits associated with the upper limb and higher beta frequencies with lower limb movements.MethodsWe recorded local field potentials (LFPs) from the subthalamic nucleus using segmented “directional” DBS leads, during which patients performed repetitive upper and lower limb movements. Movement-related spectral changes in the beta and gamma frequency-ranges and their spatial distributions were compared between limbs.ResultsWe found that the beta desynchronization during leg movements is characterised by a strikingly greater involvement of higher beta frequencies (24–31 Hz), regardless of whether this was contralateral or ipsilateral to the limb moved. The spatial distribution of limb-specific movement-related changes was evident at higher gamma frequencies.ConclusionLimb processing in the basal ganglia is differentially organised in the spectral and spatial domain and can be captured by directional DBS leads.SignificanceThese findings may help to refine the use of the subthalamic LFPs as a control signal for adaptive DBS and neuroprosthetic devices.     

Directional stimulation of subthalamic nucleus sweet spot predicts clinical efficacy: Proof of concept

BackgroundDirectional deep brain stimulation (dDBS) of the subthalamic nucleus for Parkinson's disease (PD) increases the therapeutic window. However, empirical programming of the neurostimulator becomes more complex given the increasing number of stimulation parameters. A better understanding of dDBS is needed to improve therapy and help guide postoperative programming.ObjectiveTo determine whether clinical effects of dDBS can be predicted in individual patients based on lead location and volume of tissue activated (VTA) modelling.MethodsWe analysed a prospective series of 28 PD patients. Imaging analysis and systematic clinical testing performed 4–6 months postoperatively yielded location, clinical efficacy and corresponding therapeutic windows for 272 directional contacts. We calculated the corresponding VTAs to build a probabilistic stimulation map using voxel-wise statistical analysis.ResultsWe found a positive and statistically significant correlation between the overlap ratio of a patient's individual stimulation volume and the probabilistic map's sweet spot –defined as the 10% voxels with the highest clinical efficacy values (average Spearman's rho = 0.43, average p ≤ 0.036). Patients who had a larger therapeutic window with directional compared to omnidirectional stimulation had a larger distance between the electrode and the sweet spot centroid (average distances 2.3 vs. 1.5 mm, p = 0.0019).ConclusionOur analysis provides new insights into how the definition of a probabilistic sweet spot based on directional stimulation data and individual VTA modelling can be applied to predict clinically effective directional stimulation and help guide clinicians with the intricate postoperative DBS programming.     

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.     

A new potential specifically marks the sensory thalamus in anaesthetised patients

ObjectiveDuring deep brain stimulation (DBS) surgery, we analysed somatosensory evoked potentials (SSEPs) using microelectrode recordings (MERs) in patients under general anaesthesia.MethodsWe obtained MERs from 5 patients with refractory epilepsy. Off-line analysis isolated local field potentials (LFPs, 2–200 Hz) and high frequency components (HFCs, 0.5–5 kHz). Trajectories were reconstructed off-line.ResultsThe ventral caudate (V.c.) nucleus was most frequently recorded from (171 mm). Very high frequency oscillations (VHFOs) were recorded up to 8 mm in length from all 4 electrodes but were most frequently recorded from the V.c. The properties of VHFOs were similar among all nuclei (frequency >1500 Hz, amplitude ∼3 µV, starting time ∼14 ms, duration 8–9 ms). Consecutive recordings did not show any synchronization or propagation, but a new kind of potential (high frequency oscillation, HFO) appeared abruptly inside the V.c. (frequency = 848 ± 66 Hz, amplitude = 5.2 ± 1.8 µV starting at 17.7 ± 0.5 ms, spanning 3.4 ± 0.3 ms).ConclusionsVHFOs are widely extending and cannot be ascribed to the V.c. HFOs in patients under general anaesthesia can serve as a landmark to identify the V.c. in thalamic DBS surgery.SignificanceThalamic processing involves nuclei other than the V.c, and HFO can be used to improve DBS surgery.     

Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

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.     

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.     

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.     

Accumbens coordinated reset stimulation in mice exhibits ameliorating aftereffects on binge alcohol drinking

BackgroundAlcohol use disorder (AUD) affects nearly 5% of the world’s adult population. Despite treatment, AUD often manifests with relapse to binge drinking, which has been associated with corticostriatal hypersynchrony involving the nucleus accumbens (NAc).MethodsA modified “Drinking in the Dark” protocol was used to provoke binge-like alcohol drinking. We implemented Coordinated Reset Stimulation (CRS), a computationally designed, spatio-temporal stimulation algorithm, to desynchronize abnormal neuronal activity via a deep brain stimulation (DBS) electrode in the NAc of mice exhibiting binge-like alcohol drinking. Integral CRS charge injected would be 2.5% of that of conventional high-frequency DBS.ResultsNAc CRS delivery during only the initial phase of exposure to alcohol and prior to the exposure (but not during) significantly reduced binge-like drinking without interfering with social behavior or locomotor activity.ConclusionsNAc CRS ameliorates binge-like alcohol drinking and preliminarily exhibits sustained aftereffects that are suggestive of an unlearning of hypersynchrony.     

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia

BackgroundDeep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms.ObjectivesThe aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome.MethodsThis open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity).ResultsCompared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls.ConclusionsAll in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.     

What do intracerebral electrodes measure?

ObjectiveGain insight and improve our interpretation of measurements from intracerebral electrodes. Determine if interpretation of intracerebral EEG is dependent on electrode characteristics.MethodsWe use intracerebral EEG measurements differing only in the recording electrodes (Dixi or homemade electrodes), and numerical simulations to determine the spatial sensitivity of intracerebral electrodes and its dependence on several parameters.ResultsThere is a difference in the high frequency (>20 Hz) power depending on the electrode type, which cannot be explained by the different contact sizes or distance between contacts. Simulations show that the width of the gap between electrode and brain and the extent of the generators have an effect on sensitivity, while other parameters are less important.ConclusionsThe sensitivity of intracerebral electrodes is not affected in an important way by the dimensions of the contacts, but depends on the extent of generators. The unusual insertion technique of homemade electrodes resulting in a large gap between functional brain and electrodes, explains the observed signal difference.SignificanceNumerical simulation is a useful tool in the choice or design of intracerebral electrodes, and increases our understanding of their measurements. The interpretation of intracerebral EEG is not affected by differences between typical commercially available electrodes.     

Phase-amplitude coupling of ripple activities during seizure evolution with theta phase

ObjectiveHigh-frequency activities (HFAs) and phase-amplitude coupling (PAC) are key neurophysiological biomarkers for studying human epilepsy. We aimed to clarify and visualize how HFAs are modulated by the phase of low-frequency bands during seizures.MethodsWe used intracranial electrodes to record seizures of focal epilepsy (12 focal-to-bilateral tonic-clonic seizures and three focal-aware seizures in seven patients). The synchronization index, representing PAC, was used to analyze the coupling between the amplitude of ripples (80–250 Hz) and the phase of lower frequencies. We created a video in which the intracranial electrode contacts were scaled linearly to the power changes of ripple.ResultsThe main low frequency band modulating ictal-ripple activities was the θ band (4–8 Hz), and after completion of ictal-ripple burst, δ (1–4 Hz)-ripple PAC occurred. The ripple power increased simultaneously with rhythmic fluctuations from the seizure onset zone, and spread to other regions.ConclusionsRipple activities during seizure evolution were modulated by the θ phase. The PAC phenomenon was visualized as rhythmic fluctuations.SignificanceRipple power associated with seizure evolution increased and spread with fluctuations. The θ oscillations related to the fluctuations might represent the common neurophysiological processing involved in seizure generation.     

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.     

High-gamma modulation language mapping with stereo-EEG: A novel analytic approach and diagnostic validation

ObjectiveA novel analytic approach for task-related high-gamma modulation (HGM) in stereo-electroencephalography (SEEG) was developed and evaluated for language mapping.MethodsSEEG signals, acquired from drug-resistant epilepsy patients during a visual naming task, were analyzed to find clusters of 50–150 Hz power modulations in time–frequency domain. Classifier models to identify electrode contacts within the reference neuroanatomy and electrical stimulation mapping (ESM) speech/language sites were developed and validated.ResultsIn 21 patients (9 females), aged 4.8–21.2 years, SEEG HGM model predicted electrode locations within Neurosynth language parcels with high diagnostic odds ratio (DOR 10.9, p < 0.0001), high specificity (0.85), and fair sensitivity (0.66). Another SEEG HGM model classified ESM speech/language sites with significant DOR (5.0, p < 0.0001), high specificity (0.74), but insufficient sensitivity. Time to largest power change reliably localized electrodes within Neurosynth language parcels, while, time to center-of-mass power change identified ESM sites.ConclusionsSEEG HGM mapping can accurately localize neuroanatomic and ESM language sites.SignificancePredictive modelling incorporating time, frequency, and magnitude of power change is a useful methodology for task-related HGM, which offers insights into discrepancies between HGM language maps and neuroanatomy or ESM.     

Neuronal oscillations of the pedunculopontine nucleus in progressive supranuclear palsy: Influence of levodopa and movement

ObjectiveThe pedunculopontine nucleus (PPN) has been proposed as a new deep brain stimulation (DBS) target for the treatment in idiopathic Parkinson’s syndrome (IPS) and progressive supranuclear palsy (PSP). In IPS, levodopa has been shown to induce alpha activity in the PPN, indicating a possible physiological role for these oscillations in movement control. Despite shared clinical features, the PPN is more severely affected in PSP than IPS. Here we investigated neuronal oscillations in the PPN in PSP and the influence of levodopa and movement.MethodsLocal field potentials were recorded bilaterally from the PPN of 4 PSP patients at rest, with levodopa and during self-paced leg movements.ResultsDuring rest, levodopa administration was associated with significantly increased alpha and reduced gamma activity in the PPN. Without levodopa, continuous movements were associated with reduced alpha and beta power. These differences between oscillatory power during movement and resting state were not observed with levodopa administration.ConclusionIn PSP the changes in neuronal oscillations in the PPN region on levodopa administration are similar to those reported in IPS. The enhancement of lower frequency oscillations in the PPN is possibly influenced by a dopaminergic activation of the striatal pathway and a reduced pallidal inhibition.SignificanceLevodopa influences neuronal oscillations at low and high frequencies in the PPN region in Parkinsonian disorders.     

Intraoperative lateral rectus electromyographic recordings optimized by deep intraorbital needle electrodes

ObjectiveWe demonstrate the advantages and safety of long, intraorbitally-placed needle electrodes, compared to standard-length subdermal electrodes, when recording lateral rectus electromyography (EMG) during intracranial surgeries.MethodsInsulated 25 mm and uninsulated 13 mm needle electrodes, aimed at the lateral rectus muscle, were placed in parallel during 10 intracranial surgeries, examining spontaneous and stimulation-induced EMG activities. Postoperative complications in these patients were reviewed, alongside additional patients who underwent long electrode placement in the lateral rectus.ResultsIn 40 stimulation-induced recordings from 10 patients, the 25 mm electrodes recorded 6- to 26-fold greater amplitude EMG waveforms than the 13 mm electrodes. The 13 mm electrodes detected greater unwanted volume conduction upon facial nerve stimulation, typically exceeding the amplitude of abducens nerve stimulation. Except for one case with lateral canthus ecchymosis, no clinical or radiographic complications occurred in 36 patients (41 lateral rectus muscles) following needle placement.ConclusionsIntramuscular recordings from long electrode in the lateral rectus offers more reliable EMG monitoring than 13 mm needles, with excellent discrimination between abducens and facial nerve stimulations, and without significant complications from needle placement.SignificanceLong intramuscular electrode within the orbit for lateral rectus EMG recording is practical and reliable for abducens nerve monitoring.     

Sleep modulates effective connectivity: A study using intracranial stimulation and recording

ObjectiveSleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks’ organization.MethodsWe analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM – N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach.ResultsSleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity.In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep.ConclusionsSleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity.SignificanceWe found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition.     

Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial

ObjectivesLittle evidence is available on the role of transcranial direct current stimulation (tDCS) in patients affected by chronic migraine (CM) and medication overuse headache (MOH). We aim to investigate the effects of tDCS in patients with CM and MOH as well as its role on brain activity.MethodsTwenty patients with CM and MOH were hospitalized for a 7-day detoxification treatment. Upon admission, patients were randomly assigned to anodal tDCS or sham stimulation delivered over the primary motor cortex contralateral to the prevalent migraine pain side every day for 5 days. Clinical data were recorded at baseline (T0), after 1 month (T2) and 6 months (T3). EEG recording was performed at T0, at the end of the tDCS/Sham treatment, and at T2.ResultsAt T2 and T3, we found a significant reduction in monthly migraine days (p = 0.001), which were more pronounced in the tDCS group when compared to the sham group (p = 0.016).At T2, we found a significant increase of alpha rhythm in occipital leads, which was significantly higher in tDCS group when compared to sham group.ConclusionstDCS showed adjuvant effects to detoxification in the management of patients with CM and MOH. The EEG recording showed a significant potentiation of alpha rhythm, which may represent a correlate of the underlying changes in cortico-thalamic connections.SignificanceThis study suggests a possible role for tDCS in the treatment of CM and MOH. The observed clinical improvement is coupled with a potentiation of EEG alpha rhythm.     

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.