Somatosensory evoked potentials recorded from DBS electrodes: the origin of subcortical N18.

The different peaks of somatosensory-evoked potentials (SEP) originate from a variety of anatomical sites in the central nervous system. The origin of the median nerve subcortical N18 SEP has been studied under various conditions, but the exact site of its generation is still unclear. While it has been claimed to be located in the thalamic region, other studies indicated its possible origin below the pontomedullary junction. Here, we scrutinized and compared SEP recordings from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in various subcortical targets. We studied 24 patients with dystonia, Parkinson's disease, and chronic pain who underwent quadripolar electrode implantation for chronic DBS and recorded median nerve SEPs from globus pallidus internus (GPi), subthalamic nucleus (STN), thalamic ventral intermediate nucleus (Vim), and ventral posterolateral nucleus (VPL) and the centromedian-parafascicular complex (CM-Pf). The largest amplitude of the triphasic potential of the N18 complex was recorded in Vim. Bipolar recordings confirmed the origin to be close to Vim electrodes (and VPL/CM-Pf) and less close to STN electrodes. GPi recorded only far-field potentials in unipolar derivation. Recordings from DBS electrodes located in different subcortical areas allow determining the origin of certain subcortical SEP waves more precisely. The subcortical N18 of the median nerve SEP-to its largest extent-is generated ventral to the Vim in the region of the prelemniscal radiation/ zona incerta.

Disbalanced recruitment of crossed and uncrossed cerebello-thalamic pathways during deep brain stimulation is predictive of delayed therapy escape in essential tremor.

BACKGROUND: Thalamic deep brain stimulation (DBS) is an efficacious treatment for drug-resistant essential tremor (ET) and the dentato-rubro-thalamic tract (DRT) constitutes an important target structure. However, up to 40% of patients habituate and lose treatment efficacy over time, frequently accompanied by a stimulation-induced cerebellar syndrome. The phenomenon termed delayed therapy escape (DTE) is insufficiently understood. Our previous work showed that DTE clinically is pronounced on the non-dominant side and suggested that differential involvement of crossed versus uncrossed DRT (DRTx/DRTu) might play a role in DTE development. METHODS: We retrospectively enrolled right-handed patients under bilateral thalamic DBS >12 months for ET from a cross-sectional study. They were characterized with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) and Scale for the Assessment and Rating of Ataxia (SARA) scores at different timepoints. Normative fiber tractographic evaluations of crossed and uncrossed cerebellothalamic pathways and volume of activated tissue (VAT) studies together with [18F]Fluorodeoxyglucose positron emission tomography were applied. RESULTS: A total of 29 patients met the inclusion criteria. Favoring DRTu over DRTx in the non-dominant VAT was associated with DTE (R2 = 0.4463, p < 0.01) and ataxia (R2 = 0.2319, p < 0.01). Moreover, increasing VAT size on the right (non-dominant) side was associated at trend level with more asymmetric glucose metabolism shifting towards the right (dominant) dentate nucleus. CONCLUSION: Our results suggest that a disbalanced recruitment of DRTu in the non-dominant VAT induces detrimental stimulation effects on the dominant cerebellar outflow (together with contralateral stimulation) leading to DTE and thus hampering the overall treatment efficacy.

Effectiveness and reliability of hypnosis in stereotaxy: a randomized study.

BACKGROUND: Patients suffering from Parkinson's disease (PD) may experience pain during stereotactic frame (SF) fixation in deep brain stimulation (DBS). We assessed the role of hypnosis during the SF fixation in PD patients undergoing awake bilateral subthalamic nucleus (STN) DBS. METHODS: N = 19 patients were included (N = 13 males, mean age 63 years; N = 10 allocated to the hypnosis and N = 9 allocated to the control groups). Patients were randomly assigned to the interventional (hypnosis and local anesthesia) or non-interventional (local anesthesia only) groups. The primary outcome was the pain perceived (the visual analogue scale (VAS)). Secondary outcomes were stress, anxiety, and depression, as measured by the perceived stress scale (PSS) and hospital anxiety and depression scale (HADS). Procedural distress was measured using the peritraumatic distress inventory (PDI-13). RESULTS: In the hypnosis group, VASmean was 5.6 ± 2.1, versus 6.4 ± 1.2 in the control group (p = 0.31). Intervention and control groups reported similar VASmax scores (7.6 ± 2.1 versus 8.6 ± 1.6 (p = 0.28), respectively). Both groups had similar HADS scores (6.2 ± 4.3 versus 6.7 ± 1.92, p = 0.72 (HADSa) and 6.7 ± 4.2 versus 7.7 ± 3, p = 0.58 (HADSd)), so were the PSS scores (26.1 ± 6.3 versus 25.1 ± 7, p = 0.75). Evolutions of VASmean (R2 = 0.93, 95% CI [0.2245, 1.825], p = 0.03) and PDI-13 scores (R2 = 0.94, 95% CI [1.006, 6.279], p = 0.02) significantly differ over follow-up with patients in the hypnosis groups showing lower scores. CONCLUSION: In this unblinded, randomized study, hypnosis does not influence pain, anxiety, and distress during awake SF fixation but modulates pain memory over time and may prevent the integration of awake painful procedures as a bad experience into the autobiographical memory of patients suffering from PD. A randomized controlled study with more data is necessary to confirm our findings.

Overlapping stimulation of subthalamic nucleus and dentato-rubro-thalamic tract in Parkinson's disease after deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor, rigidity, and akinesia. According to the literature, the dentato-rubro-thalamic tract (DRTt) is verified target for DBS in essential tremor; however, its role in the treatment of Parkinson's disease is only vaguely described. The aim of our study was to identify the relationship between symptom alleviation in PD patients and the distance of the DBS electrode electric field (EF) to the DRTt. METHODS: A single-center retrospective analysis of patients (N = 30) with idiopathic Parkinson's disease (PD) who underwent DBS between November 2018 and January 2020 was performed. DRTt and STN were visualized using diffusion-weighted imaging (DWI) and tractography protocol of magnetic resonance (MR). The EF was calculated and compared with STN and course of DRTt. Evaluation of patients before and after surgery was performed with use of UPDRS-III scale. The association between distance from EF to DRTt and clinical outcomes was examined. To confirm the anatomical variation between DRTt and STN observed in tractography, white matter dissection was performed with the Klingler technique on ten human brains. RESULTS: Patients with EF overlapping STN and DRTt benefited from significant motor symptoms improvement. Anatomical findings confirmed the presence of population differences in variability of the DRTt course and were consistent with the DRTt visualized by MR. CONCLUSIONS: DRTt proximity to STN, the main target in PD DBS surgery, confirmed by DWI with tractography protocol of MR combined with proper predefined stimulation parameters may improve efficacy of DBS-STN.

Connectivity-based segmentation of the thalamic motor region for deep brain stimulation in essential tremor: A comparison of deterministic and probabilistic tractography.

OBJECTIVE: Deep brain stimulation (DBS) studies have shown that stimulation of the motor segment of the thalamus based on probabilistic tractography is predictive of improvement in essential tremor (ET). However, probabilistic methods are computationally demanding, requiring the need for alternative tractography methods for use in the clinical setting. The purpose of this study was to compare probabilistic vs deterministic tractography methods for connectivity-based targeting in patients with ET. METHODS: Probabilistic and deterministic tractography methods were retrospectively applied to diffusion-weighted data sets in 36 patients with refractory ET. The thalamus and precentral gyrus were selected as regions of interest and fiber tracking was performed between these regions to produce connectivity-based thalamic segmentations, per prior methods. The resultant deterministic target maps were compared with those of thresholded probabilistic maps. The center of gravity (CG) of each connectivity map was determined and the differences in spatial distribution between the tractography methods were characterized. Furthermore, the intersection between the connectivity maps and CGs with the therapeutic volume of tissue activated (VTA) was calculated. A mixed linear model was then used to assess clinical improvement in tremor with volume of overlap. RESULTS: Both tractography methods delineated the region of the thalamus with connectivity to the precentral gyrus to be within the posterolateral aspect of the thalamus. The average CG of deterministic maps was more medial-posterior in both the left (3.7 ± 1.3 mm3) and the right (3.5 ± 2.2 mm3) hemispheres when compared to 30 %-thresholded probabilistic maps. Mixed linear model showed that the volume of overlap between CGs of deterministic and probabilistic targeting maps and therapeutic VTAs were significant predictors of clinical improvement. CONCLUSIONS: Deterministic tractography can reconstruct DBS thalamic target maps in approximately 5 min comparable to those produced by probabilistic methods that require > 12 h to generate. Despite differences in CG between the methods, both deterministic-based and probabilistic targeting were predictive of clinical improvement in ET.

Neural signal data collection and analysis of Percept™ PC BrainSense recordings for thalamic stimulation in epilepsy.

Deep brain stimulation (DBS) using Medtronic's Percept™ PC implantable pulse generator is FDA-approved for treating Parkinson's disease (PD), essential tremor, dystonia, obsessive compulsive disorder, and epilepsy. Percept™ PC enables simultaneous recording of neural signals from the same lead used for stimulation. Many Percept™ PC sensing features were built with PD patients in mind, but these features are potentially useful to refine therapies for many different disease processes. When starting our ongoing epilepsy research study, we found it difficult to find detailed descriptions about these features and have compiled information from multiple sources to understand it as a tool, particularly for use in patients other than those with PD. Here we provide a tutorial for scientists and physicians interested in using Percept™ PC's features and provide examples of how neural time series data is often represented and saved. We address characteristics of the recorded signals and discuss Percept™ PC hardware and software capabilities in data pre-processing, signal filtering, and DBS lead performance. We explain the power spectrum of the data and how it is shaped by the filter response of Percept™ PC as well as the aliasing of the stimulation due to digitally sampling the data. We present Percept™ PC's ability to extract biomarkers that may be used to optimize stimulation therapy. We show how differences in lead type affects noise characteristics of the implanted leads from seven epilepsy patients enrolled in our clinical trial. Percept™ PC has sufficient signal-to-noise ratio, sampling capabilities, and stimulus artifact rejection for neural activity recording. Limitations in sampling rate, potential artifacts during stimulation, and shortening of battery life when monitoring neural activity at home were observed. Despite these limitations, Percept™ PC demonstrates potential as a useful tool for recording neural activity in order to optimize stimulation therapies to personalize treatment.

Somatotopic organization of the ventral nuclear group of the dorsal thalamus: deep brain stimulation for neuropathic pain reveals new insights into the facial homunculus.

Deep Brain Stimulation (DBS) is an experimental treatment for medication-refractory neuropathic pain. The ventral posteromedial (VPM) and ventral posterolateral (VPL) nuclei of the thalamus are popular targets for the treatment of facial and limb pain, respectively. While intraoperative testing is used to adjust targeting of patient-specific pain locations, a better understanding of thalamic somatotopy may improve targeting of specific body regions including the individual trigeminal territories, face, arm, and leg. To elucidate the somatotopic organization of the ventral nuclear group of the dorsal thalamus using in vivo macrostimulation data from patients undergoing DBS for refractory neuropathic pain. In vivo macrostimulation data was retrospectively collected for 14 patients who underwent DBS implantation for neuropathic pain syndromes at our institution. 56 contacts from 14 electrodes reconstructed with LeadDBS were assigned to macrostimulation-related body regions: tongue, face, arm, or leg. 33 contacts from 9 electrodes were similarly assigned to one of three trigeminal territories: V1, V2, or V3. MNI coordinates in the x, y, and z axes were compared by using MANOVA. Across the horizontal plane of the ventral nuclear group of the dorsal thalamus, the tongue was represented significantly medially, followed by the face, arm, and leg most laterally (p < 0.001). The trigeminal territories displayed significant mediolateral distribution, proceeding from V1 and V2 most medial to V3 most lateral (p < 0.001). Along the y-axis, V2 was also significantly anterior to V3 (p = 0.014). While our results showed that the ventral nuclear group of the dorsal thalamus displayed mediolateral somatotopy of the tongue, face, arm, and leg mirroring the cortical homunculus, the mediolateral distribution of trigeminal territories did not mirror the established cortical homunculus. This finding suggests that the facial homunculus may be inverted in the ventral nuclear group of the dorsal thalamus.

Thalamo-cortical evoked potentials during stimulation of the dentato-rubro-thalamic tract demonstrate synaptic filtering.

Essential tremor DBS targeting the ventral intermediate nucleus (Vim) of the thalamus and its input, the dentato-rubro-thalamic tract (DRTt), has proven to be an effective treatment strategy. We examined thalamo-cortical evoked potentials (TCEPs) and cortical dynamics during stimulation of the DRTt. We recorded TCEPs in primary motor cortex during clinical and supra-clinical stimulation of the DRTt in ten essential tremor patients. Stimulation was varied over pulse amplitude (2-10 â€‹mA) and pulse width (30-250 â€‹µs) to allow for strength-duration testing. Testing at clinical levels (3 â€‹mA, 60 â€‹µs) for stimulation frequencies of 1-160 â€‹Hz was performed and phase amplitude coupling (PAC) of beta phase and gamma power was calculated. Primary motor cortex TCEPs displayed two responses: early and all-or-none (<20 â€‹ms) or delayed and charge-dependent (>50 â€‹ms). Strength-duration curve approximation indicates that the chronaxie of the neural elements related to the TCEPs is <200 â€‹µs. At the range of clinical stimulation (amplitude 2-5 â€‹mA, pulse width 30-60 â€‹µs), TCEPs were not noted over primary motor cortex. Decreased pathophysiological phase-amplitude coupling was seen above 70 â€‹Hz stimulation without changes in power spectra and below the threshold of TCEPs. Our findings demonstrate that DRTt stimulation within normal clinical bounds does not excite fibers directly connected with primary motor cortex but that supra-clinical stimulation can excite a direct axonal tract. Both clinical efficacy and phase-amplitude coupling were frequency-dependent, favoring a synaptic filtering model as a possible mechanism of action.

The promise and challenges of transcranial magnetic stimulation and deep brain stimulation as therapeutic options for obsessive-compulsive disorder.

INTRODUCTION: Obsessive compulsive disorder (OCD) represents a complex and often difficult to treat disorder. Pharmacological and psychotherapeutic interventions are often associated with sub-optimal outcomes, and 40-60% of patients are resistant to first line therapies and thus left with few treatment options. OCD is underpinned by aberrant neurocircuitry within cortical, striatal, and thalamic brain networks. Considering the neurocircuitry impairments that underlie OCD symptomology, neurostimulation therapies provide an opportunity to modulate psychopathology in a personalized manner. Also, by probing pathological neural networks, enhanced understanding of disease states can be obtained. AREAS COVERED: This perspective discusses the clinical efficacy of TMS and DBS therapies, treatment access options, and considerations and challenges in managing patients. Recent scientific progress is discussed, with a focus on neurocircuitry and biopsychosocial aspects. Translational recommendations and suggestions for future research are provided. EXPERT OPINION: There is robust evidence to support TMS and DBS as an efficacious therapy for treatment resistant OCD patients supported by an excellent safety profile and favorable health economic data. Despite a great need for alternative therapies for chronic and severe OCD patients, resistance toward neurostimulation therapies from regulatory bodies and the psychiatric community remains. The authors contend for greater access to TMS and DBS for treatment resistant OCD patients at specialized sites with appropriate clinical resources, particularly considering adjunct and follow-up care. Also, connectome targeting has shown robust predictive ability of symptom improvements and holds potential in advancing personalized neurostimulation therapies.

Mechanical behavior and microstructure of porcine brain tissues under pulsed electric fields.

Pulsed electric fields are extensively utilized in clinical treatments, such as subthalamic deep brain stimulation, where electric field loading is in direct contact with brain tissue. However, the alterations in brain tissue's mechanical properties and microstructure due to changes in electric field parameters have not received adequate attention. In this study, the mechanical properties and microstructure of the brain tissue under pulsed electric fields were focused on. Herein, a custom indentation device was equipped with a module for electric field loading. Parameters such as pulse amplitude and frequency were adjusted. The results demonstrated that following an indentation process lasting 5 s and reaching a depth of 1000 µm, and a relaxation process of 175 s, the average shear modulus of brain tissue was reduced, and viscosity decreased. At the same amplitude, high-frequency pulsed electric fields had a smaller effect on brain tissue than low-frequency ones. Furthermore, pulsed electric fields induced cell polarization and reduced the proteoglycan concentration in brain tissue. As pulse frequency increased, cell polarization diminished, and proteoglycan concentration decreased significantly. High-frequency pulsed electric fields applied to brain tissue were found to reduce impedance fluctuation amplitude. This study revealed the effect of pulsed electric fields on the mechanical properties and microstructure of ex vivo brain tissue, providing essential information to promote the advancement of brain tissue electrotherapy in clinical settings.

Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

Towards an optimised deep brain stimulation using a large-scale computational network and realistic volume conductor model.

Objective. Constructing a theoretical framework to improve deep brain stimulation (DBS) based on the neuronal spatiotemporal patterns of the stimulation-affected areas constitutes a primary target.Approach. We develop a large-scale biophysical network, paired with a realistic volume conductor model, to estimate theoretically efficacious stimulation protocols. Based on previously published anatomically defined structural connectivity, a biophysical basal ganglia-thalamo-cortical neuronal network is constructed using Hodgkin-Huxley dynamics. We define a new biomarker describing the thalamic spatiotemporal activity as a ratio of spiking vs. burst firing. The per cent activation of the different pathways is adapted in the simulation to minimise the differences of the biomarker with respect to its value under healthy conditions.Main results.This neuronal network reproduces spatiotemporal patterns that emerge in Parkinson's disease. Simulations of the fibre per cent activation for the defined biomarker propose desensitisation of pallido-thalamic synaptic efficacy, induced by high-frequency signals, as one possible crucial mechanism for DBS action. Based on this activation, we define both an optimal electrode position and stimulation protocol using pathway activation modelling.Significance. A key advantage of this research is that it combines different approaches, i.e. the spatiotemporal pattern with the electric field and axonal response modelling, to compute the optimal DBS protocol. By correlating the inherent network dynamics with the activation of white matter fibres, we obtain new insights into the DBS therapeutic action.

Electrophysiological characteristics of CM-pf in diagnosis and outcome of patients with disorders of consciousness.

BACKGROUND: Deep brain stimulation (DBS) in the centromedian-parafascicular complex (CM-pf) has been reported as a potential therapeutic option for disorders of consciousness (DoC). However, the lack of understanding of its electrophysiological characteristics limits the improvement of therapeutic effect. OBJECTIVE: To investigate the CM-pf electrophysiological characteristics underlying disorders of consciousness (DoC) and its recovery. METHODS: We collected the CM-pf electrophysiological signals from 23 DoC patients who underwent central thalamus DBS (CT-DBS) surgery. Five typical electrophysiological features were extracted, including neuronal firing properties, multiunit activity (MUA) properties, signal stability, spike-MUA synchronization strength (syncMUA), and the background noise level. Their correlations with the consciousness level, the outcome, and the primary clinical factors of DoC were analyzed. RESULTS: 11 out of 23 patients (0/2 chronic coma, 5/13 unresponsive wakefulness syndrome/vegetative state (UWS/VS), 6/8 minimally conscious state minus (MCS-)) exhibited an improvement in the level of consciousness after CT-DBS. In CM-pf, significantly stronger gamma band syncMUA strength and alpha band normalized MUA power were found in MCS- patients. In addition, higher firing rates, stronger high-gamma band MUA power and alpha band normalized power, and more stable theta oscillation were correlated with better outcomes. Besides, we also identified electrophysiological properties that are correlated with clinical factors, including etiologies, age, and duration of DoC. CONCLUSION: We provide comprehensive analyses of the electrophysiological characteristics of CM-pf in DoC patients. Our results support the 'mesocircuit' hypothesis, one proposed mechanism of DoC recovery, and reveal CM-pf electrophysiological features that are crucial for understanding the pathogenesis of DoC, predicting its recovery, and explaining the effect of clinical factors on DoC.

Comparison of two segmentation software tools for deep brain stimulation of the subthalamic and ventro-intermedius nuclei.

PURPOSE: Deep brain stimulation (DBS) relies on precise targeting of key structures such as the subthalamic nucleus (STN) for Parkinson's disease (PD) and the ventro-intermedius nucleus of the thalamus (Vim) for essential tremor (ET). Segmentation software, such as GuideXT© and Suretune©, are commercially available for atlas-based identification of deep brain structures. However, no study has compared the concordance of the segmentation results between the two software. METHODS: We retrospectively compared the concordance of segmentation of GuideXT© and Suretune© software by comparing the position of the segmented key structures with clinically predicted targets obtained using the newly developed RebrAIn© software as a reference. RESULTS: We targeted the STN in 44 MRI from PD patients (88 hemispheres) and the Vim in 31 MRI from ET patients (62 hemispheres) who were elected for DBS. In 22 STN targeting (25%), the target positioning was not correlating between GuideXT© and Suretune©. Regarding the Vim, targets were located in the segmented Vim in 37%, the posterior subthalamic area (PSA) in 60%, and the STN in 3% of the cases using GuideXT©; the proportions were 34%, 60%, and 6%, respectively, using Suretune©. The mean distance from the centre of the RebrAIn© targeting to the segmented Vim by Suretune© was closer (0.64 mm) than with GuideXT© (0.96 mm; p = 0.0004). CONCLUSION: While there is some level of concordance in the segmentation results of key structures for DBS treatment among software models, differences persist. Therefore, such software should still be considered as tools and should not replace clinician experience in DBS planning.

The Arousal-Related "Central Thalamus" Stimulation Site Simultaneously Innervates Multiple High-Level Frontal and Parietal Areas.

In human and nonhuman primates, deep brain stimulation applied at or near the internal medullary lamina of the thalamus [a region referred to as "central thalamus," (CT)], but not at nearby thalamic sites, elicits major changes in the level of consciousness, even in some minimally conscious brain-damaged patients. The mechanisms behind these effects remain mysterious, as the connections of CT had not been specifically mapped in primates. In marmoset monkeys (Callithrix jacchus) of both sexes, we labeled the axons originating from each of the various CT neuronal populations and analyzed their arborization patterns in the cerebral cortex and striatum. We report that, together, these CT populations innervate an array of high-level frontal, posterior parietal, and cingulate cortical areas. Some populations simultaneously target the frontal, parietal, and cingulate cortices, while others predominantly target the dorsal striatum. Our data indicate that CT stimulation can simultaneously engage a heterogeneous set of projection systems that, together, target the key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.SIGNIFICANCE STATEMENT In human and nonhuman primates, deep brain stimulation at a specific site near the internal medullary lamina of the thalamus ["central thalamus," (CT)] had been shown to restore arousal and awareness in anesthetized animals, as well as in some brain-damaged patients. The mechanisms behind these effects remain mysterious, as CT connections remain poorly defined in primates. In marmoset monkeys, we mapped with sensitive axon-labeling methods the pathways originated from CT. Our data indicate that stimulation applied in CT can simultaneously engage a heterogeneous set of projection systems that, together, target several key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.

Anthropology of Deep Brain Stimulation; the 30th Anniversary of STN DBS in 2023.

Background: The year 2023 marks the 30th anniversary of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD). This procedure prompted a universal interest in DBS for various brain disorders and resulted in a unique expansion of clinical and scientific collaboration between many disciplines, with impact on many aspects of society. Objective: To study the anthropology of DBS, that is, its ethno-geographic origins, its evolution, its impact on clinicians and scientists, and its influence on society at large. Material and Methods: The authors scrutinized the geo-ethnic origins of the pioneers of modern DBS, and they evaluated, based on the literature and on a long-term praxis, the development of DBS and its impact on clinicians, on healthcare, and on society. Results: Scientists and clinicians from various geo-ethnic origins pioneered modern DBS, leading to worldwide spread of this procedure and to the establishment of large multidisciplinary teams in many centers. Neurologists became actively involved in surgery and took on new laborious tasks of programming ever more complicated DBS systems. Publications sky-rocketed and the global spread of DBS impacted positively on several aspects of society, including healthcare, awareness of neurological diseases, interdisciplinary relations, conferences, patient organizations, unemployment, industry, etc. Conclusions: STN DBS has boosted the field of deep brain electrotherapy for many neurological and psychiatric illnesses, and DBS has generated a global benefit on many aspects of society, well beyond its clinical benefits on symptoms of diseases. With the ever-increasing indications for DBS, more positive global impact is expected.

Current Neurostimulation Therapies for Chronic Pain Conditions.

PURPOSE OF REVIEW: Neurostimulation treatment options have become more commonly used for chronic pain conditions refractory to these options. In this review, we characterize current neurostimulation therapies for chronic pain conditions and provide an analysis of their effectiveness and clinical adoption. This manuscript will inform clinicians of treatment options for chronic pain. RECENT FINDINGS: Non-invasive neurostimulation includes transcranial direct current stimulation and repetitive transcranial magnetic stimulation, while more invasive options include spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), dorsal root ganglion stimulation, motor cortex stimulation, and deep brain stimulation. Developments in transcranial direct current stimulation, repetitive transcranial magnetic stimulation, spinal cord stimulation, and peripheral nerve stimulation render these modalities most promising for the alleviating chronic pain. Neurostimulation for chronic pain involves non-invasive and invasive modalities with varying efficacy. Well-designed randomized controlled trials are required to delineate the outcomes of neurostimulatory modalities more precisely.

Impact of 12 Weeks of Vitamin D3 Administration in Parkinson's Patients with Deep Brain Stimulation on Kynurenine Pathway and Inflammatory Status.

The current study aimed to investigate whether a 12-week Body Mass Index (BMI)-based (the higher the BMI, the higher the dosage) vitamin D3 administration may affect both the kynurenine pathway (KP) and the inflammatory state in Parkinson's disease (PD) patients with deep brain stimulation (DBS) and may be useful for developing novel therapeutic targets against PD. Patients were randomly assigned to two groups: supplemented with vitamin D3 (VitD, n = 15) and treated with vegetable oil (PL, n = 21). Administration lasted for 12 weeks. The isotope dilution method by LC-MS/MS was applied to measure KP and vitamin D metabolites. Serum concentrations of cytokines such as IL-6 and TNF-α were measured using ELISA kits. After administration, the serum concentration of TNF-α decreased in PD patients with DBS. Moreover, in KP: 3-hydroksykynurenine (3-HK) was increased in the PL group, picolinic acid was decreased in the PL group, and kynurenic acid tended to be higher after administration. Furthermore, a negative correlation between 3-HK and 25(OH)D3 and 24,25(OH)2D3 was noticed. Our preliminary results provide further evidence regarding a key link between the KP substances, inflammation status, and metabolites of vitamin D in PD patients with DBS. These findings may reflect the neuroprotective abilities of vitamin D3 in PD patients with DBS.

Advancing the frontiers of thalamic neuromodulation: A review of emerging targets and paradigms.

The thalamus is a key structure that plays a crucial role in initiating and propagating seizures. Recent advancements in neuroimaging and neurophysiology have identified the thalamus as a promising target for neuromodulation in drug-resistant epilepsies. This review article presents the latest innovations in thalamic targets and neuromodulation paradigms being explored in pilot or pivotal clinical trials. Multifocal temporal plus or posterior quadrant epilepsies are evaluated with pulvinar thalamus neuromodulation, while centromedian thalamus is explored in generalized epilepsies and Lennox Gastaut syndrome. Multinodal thalamocortical neuromodulation with novel stimulation paradigms such as long bursting or low-frequency stimulation is being investigated to quench the epileptic network excitability. Beyond seizure control, thalamic neuromodulation to restore consciousness is being studied. This review highlights the promising potential of thalamic neuromodulation in epilepsy treatment, offering hope to patients who have not responded to conventional medical therapies. However, it also emphasizes the need for larger randomized controlled trials and personalized stimulation paradigms to improve patient outcomes further.

Functional network dynamics between the anterior thalamus and the cortex in deep brain stimulation for epilepsy.

Owing to its unique connectivity profile with cortical brain regions, and its suggested role in the subcortical propagation of seizures, the anterior nucleus of the thalamus (ANT) has been proposed as a key deep brain stimulation (DBS) target in drug-resistant epilepsy. However, the spatio-temporal interaction dynamics of this brain structure, and the functional mechanisms underlying ANT DBS in epilepsy remain unknown. Here, we study how the ANT interacts with the neocortex in vivo in humans and provide a detailed neurofunctional characterization of mechanisms underlying the effectiveness of ANT DBS, aiming at defining intraoperative neural biomarkers of responsiveness to therapy, assessed at 6 months post-implantation as the reduction in seizure frequency. A cohort of 15 patients with drug-resistant epilepsy (n = 6 males, age = 41.6 ± 13.79 years) underwent bilateral ANT DBS implantation. Using intraoperative cortical and ANT simultaneous electrophysiological recordings, we found that the ANT is characterized by high amplitude θ (4-8 Hz) oscillations, mostly in its superior part. The strongest functional connectivity between the ANT and the scalp EEG was also found in the θ band in ipsilateral centro-frontal regions. Upon intraoperative stimulation in the ANT, we found a decrease in higher EEG frequencies (20-70 Hz) and a generalized increase in scalp-to-scalp connectivity. Crucially, we observed that responders to ANT DBS treatment were characterized by higher EEG θ oscillations, higher θ power in the ANT, and stronger ANT-to-scalp θ connectivity, highlighting the crucial role of θ oscillations in the dynamical network characterization of these structures. Our study provides a comprehensive characterization of the interaction dynamic between the ANT and the cortex, delivering crucial information to optimize and predict clinical DBS response in patients with drug-resistant epilepsy.