Comparison of the connectivity of the posterior intralaminar thalamic nucleus and peripeduncular nucleus in rats and mice.

The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.

Structural Plasticity of GABAergic Pallidothalamic Terminals in MPTP-Treated Parkinsonian Monkeys: A 3D Electron Microscopic Analysis.

The internal globus pallidus (GPi) is a major source of tonic GABAergic inhibition to the motor thalamus. In parkinsonism, the firing rate of GPi neurons is increased, and their pattern switches from a tonic to a burst mode, two pathophysiological changes associated with increased GABAergic pallidothalamic activity. In this study, we used high-resolution 3D electron microscopy to demonstrate that GPi terminals in the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM), the two main GPi-recipient motor thalamic nuclei in monkeys, undergo significant morphometric changes in parkinsonian monkeys including (1) increased terminal volume in both nuclei; (2) increased surface area of synapses in both nuclei; (3) increased number of synapses/GPi terminals in the CM, but not VApc; and (4) increased total volume, but not number, of mitochondria/terminals in both nuclei. In contrast to GPi terminals, the ultrastructure of putative GABAergic nonpallidal terminals was not affected. Our results also revealed striking morphological differences in terminal volume, number/area of synapses, and volume/number of mitochondria between GPi terminals in VApc and CM of control monkeys. In conclusion, GABAergic pallidothalamic terminals are endowed with a high level of structural plasticity that may contribute to the development and maintenance of the abnormal increase in pallidal GABAergic outflow to the thalamus in the parkinsonian state. Furthermore, the evidence for ultrastructural differences between GPi terminals in VApc and CM suggests that morphologically distinct pallidothalamic terminals from single pallidal neurons may underlie specific physiological properties of pallidal inputs to VApc and CM in normal and diseased states.

Pediatric neuromodulation for drug-resistant epilepsy: Survey of current practices, techniques, and outcomes across US epilepsy centers.

Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug-resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty-two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6-10 new RNS devices per year; all DBS programs implant <5 annually. The youngest RNS patient was 3 years old. Most centers (11/12) utilize MP2RAGE and/or FGATIR sequences for planning. Centromedian thalamic nuclei were the unanimous target for Lennox-Gastaut syndrome. Surgeon exposure to neuromodulation occurred mostly in clinical practice (14/17). Clinically significant hemorrhage (n = 2) or infection (n = 3) were rare. Meaningful seizure reduction (>50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. PLAIN LANGUAGE SUMMARY: We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug-resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research.

Deep Brain Stimulation of Bilateral Centromedian Thalamic Nuclei in Pediatric Patients with Lennox-Gastaut Syndrome: An Institutional Experience.

BACKGROUND: Surgical management of pediatric patients with nonlesional, drug-resistant epilepsy, including patients with Lennox-Gastaut syndrome (LGS), remains a challenge given the lack of resective targets in most patients and shows seizure freedom rates <50% at 5 years. The efficacy of deep brain stimulation (DBS) is less certain in children than in adults. This study examined clinical and seizure outcomes for pediatric patients with LGS undergoing DBS targeting of the centromedian thalamic nuclei (CMTN). METHODS: An institutional review board-approved retrospective analysis was performed of patients aged ≤19 years with clinical diagnosis of LGS undergoing bilateral DBS placement to the CMTN from 2020 to 2021 by a single surgeon. RESULTS: Four females and 2 males aged 6-19 years were identified. Before surgery, each child experienced at least 6 years of refractory seizures; 4 children had experienced seizures since infancy. All took antiseizure medications at the time of surgery. Five children had previous placement of a vagus nerve stimulator and 2 had a previous corpus callosotomy. The mean length of stay after DBS was 2 days. No children experienced adverse neurologic effects from implantation; the mean follow-up time was 16.3 months. Four patients had >60% reduction in seizure frequency after surgery, 1 patient experienced 10% reduction, and 1 patient showed no change. No children reported worsening seizure symptoms after surgery. CONCLUSIONS: Our study contributes to the sparse literature describing CMTN DBS for children with drug-resistant epilepsy from LGS. Our results suggest that CMTN DBS is a safe and effective therapeutic modality that should be considered as an alternative or adjuvant therapy for this challenging patient population. Further studies with larger patient populations are warranted.

Dysconnectivity of the parafascicular nucleus in Parkinson's disease: A dynamic causal modeling analysis.

BACKGROUND: Recent animal model studies have suggested that the parafascicular nucleus has the potential to be an effective deep brain stimulation target for Parkinson's disease. However, our knowledge on the role of the parafascicular nucleus in Parkinson's disease patients remains limited. OBJECTIVE: We aimed to investigate the functional alterations of the parafascicular nucleus projections in Parkinson's disease patients. METHODS: We enrolled 72 Parkinson's disease patients and 60 healthy controls, then utilized resting-state functional MRI and spectral dynamic causal modeling to explore the effective connectivity of the bilateral parafascicular nucleus to the dorsal putamen, nucleus accumbens, and subthalamic nucleus. The associations between the effective connectivity of the parafascicular nucleus projections and clinical features were measured with Pearson partial correlations. RESULTS: Compared with controls, the effective connectivity from the parafascicular nucleus to dorsal putamen was significantly increased, while the connectivity to the nucleus accumbens and subthalamic nucleus was significantly reduced in Parkinson's disease patients. There was a significantly positive correlation between the connectivity of parafascicular nucleus-dorsal putamen projection and motor deficits. The connectivity from the parafascicular nucleus to the subthalamic nucleus was negatively correlated with motor deficits and apathy, while the connectivity from the parafascicular nucleus to the nucleus accumbens was negatively associated with depression. CONCLUSION: The present study demonstrates that the parafascicular nucleus-related projections are damaged and associated with clinical symptoms of Parkinson's disease. Our findings provide new insights into the impaired basal ganglia-thalamocortical circuits and give support for the parafascicular nucleus as a potential effective neuromodulating target of the disease.

Neuroestimulación del nervio vago, hipocampal y de núcleos anteriores y centromedianos del tálamo en epilepsia temporal: revisión de la literatura / Neurostimulation of the vagus nerve, hippocampal and anterior and centromedian nuclei of the thalamus in temporal epilepsy: literature review

Introducción: En pacientes con epilepsia del lóbulo temporal refractarios que no son candidatos a cirugía, se debe considerar la estimulación eléctrica cerebral como una opción. Contenido: La estimulación eléctrica cerebral es la administración directa de pulsos eléctricos al tejido nervioso que permite modular un sustrato patológico, interrumpir la manifestación clínica de las crisis y reducir la gravedad de estas. Así, dada la importancia de estos tratamientos para los pacientes con epilepsia del lóbulo temporal refractaria, se hace una revisión de cuatro tipos de estimulación eléctrica. La primera, la del nervio vago, es una buena opción en crisis focales y crisis generalizadas o multifocales. La segunda, la del hipocampo, es más útil en pacientes no candidatos a lobectomía por riesgo de pérdida de memoria, con resonancia magnética normal o sin esclerosis mesial temporal. La tercera, la del núcleo anterior, es pertinente principalmente en pacientes con crisis focales, pero debe realizarse con precaución en pacientes con alto riesgo de cambios cognitivos, como los ancianos, o en los que presentan alteración del estado de ánimo basal, y, por último, la del núcleo centromediano se recomienda para el tratamiento crisis focales en el síndrome de Rasmussen y crisis tónico-clónicas en el síndrome de Lennox-Gastaut. Conclusiones: El interés por la estimulación eléctrica cerebral ha venido aumentando, al igual que las estructuras diana en las cuales se puede aplicar, debido a que es un tratamiento seguro y eficaz en pacientes con epilepsia del lóbulo temporal para controlar las crisis, pues disminuye la morbimortalidad y aumenta la calidad de vida.

Introduction: In patients with refractory temporal lobe epilepsy who are not candidates for surgery, electrical brain stimulation should be considered as another option. Contents: Electrical brain stimulation is the direct administration of electrical pulses to nerve tissue that modulates a pathological substrate, interrupts the clinical manifestation of seizures, and reduces their severity. Thus, given the importance of these treatments for patients with refractory temporal lobe epilepsy, four types of electrical stimulation are reviewed. The first, vagus nerve stimulation, is a good option in focal seizures and generalized or multifocal seizures. The second, hippocampal stimulation, is more useful in patients who are not candidates for lobectomy due to the risk of memory loss, with normal MRI or without mesial temporal sclerosis. The third, the anterior nucleus, is mainly in patients with focal seizures, but with caution in patients at high risk of cognitive changes such as the elderly, or in those with baseline mood disturbance and, finally, the centromedian nucleus is recommended for the treatment of focal seizures in Rasmussen's syndrome and tonic-clonic seizures in Lennox-Gastaut syndrome. Conclusions: the interest in brain electrical stimulation has been increasing as well as the target structures in which it can be applied because it is a safe and effective treatment in patients with temporal lobe epilepsy to control seizures, decreasing morbidity and mortality and increasing quality of life

Sensing with deep brain stimulation device in epilepsy: Aperiodic changes in thalamic local field potential during seizures.

OBJECTIVE: Thalamic deep brain stimulation (DBS) is an effective therapeutic option in patients with drug-resistant epilepsy. Recent DBS devices with sensing capabilities enable chronic, outpatient local field potential (LFP) recordings. Whereas beta oscillations have been demonstrated to be a useful biomarker in movement disorders, the clinical utility of DBS sensing in epilepsy remains unclear. Our aim was to determine LFP features that distinguish ictal from inter-ictal states, which may aid in tracking seizure outcomes with DBS. METHODS: Electrophysiology data were obtained from DBS devices implanted in the anterior nucleus (N = 12) or centromedian nucleus (N = 2) of the thalamus. Power spectra recorded during patient/caregiver-marked seizure events were analyzed with a method that quantitatively separates the oscillatory and non-oscillatory/aperiodic components of the LFP using non-parametric statistics, without the need for pre-specification of the frequency bands of interest. Features of the LFP parameterized using this algorithm were compared with those from inter-ictal power spectra recorded in clinic. RESULTS: Oscillatory activity in multiple canonical frequency bands was identified from the power spectra in 86.48% of patient-marked seizure events. Delta oscillations were present in all patients, followed by theta (N = 10) and beta (N = 9). Although there were no differences in oscillatory LFP features between the ictal and inter-ictal states, there was a steeper decline in the 1/f slope of the aperiodic component of the LFP during seizures. SIGNIFICANCE: Our work highlights the potential and shortcomings of chronic LFP recordings in thalamic DBS for epilepsy. Findings suggest that no single frequency band in isolation clearly differentiates seizures, and that features of aperiodic LFP activity may be clinically-relevant biomarkers of seizures.

The structural connectivity mapping of the intralaminar thalamic nuclei.

The intralaminar nuclei of the thalamus play a pivotal role in awareness, conscious experience, arousal, sleep, vigilance, as well as in cognitive, sensory, and sexual processing. Nonetheless, in humans, little is known about the direct involvement of these nuclei in such multifaceted functions and their structural connections in the brain. Thus, examining the versatility of structural connectivity of the intralaminar nuclei with the rest of the brain seems reasonable. Herein, we attempt to show the direct structural connectivity of the intralaminar nuclei to diencephalic, mesencephalic, and cortical areas using probabilistic tracking of the diffusion data from the human connectome project. The intralaminar nuclei fiber distributions span a wide range of subcortical and cortical areas. Moreover, the central medial and parafascicular nucleus reveal similar connectivity to the temporal, visual, and frontal cortices with only slight variability. The central lateral nucleus displays a refined projection to the superior colliculus and fornix. The centromedian nucleus seems to be an essential component of the subcortical somatosensory system, as it mainly displays connectivity via the medial and superior cerebellar peduncle to the brainstem and the cerebellar lobules. The subparafascicular nucleus projects to the somatosensory processing areas. It is interesting to note that all intralaminar nuclei have connections to the brainstem. In brief, the structural connectivity of the intralaminar nuclei aligns with the structural core of various functional demands for arousal, emotion, cognition, sensory, vision, and motor processing. This study sheds light on our understanding of the structural connectivity of the intralaminar nuclei with cortical and subcortical structures, which is of great interest to a broader audience in clinical and neuroscience research.

Gamma Knife surgery and deep brain stimulation of the centromedian nucleus for chronic pain: A systematic review.

Chronic pain has been a major problem in personal quality of life and social economy, causing psychological disorders in people and a larger amount of money loss in society. Some targets were adopted for chronic pain, but the efficacy of the CM nucleus for pain was still unclear. A systematic review was performed to summarize GK surgery and DBS of the CM nucleus for chronic pain. PubMed, Embase and Medline were searched to review all studies discussing GK surgery and DBS on the CM nucleus for chronic pain. Studies that were review, meet, conference, not English or not the therapy of pain were excluded. Demographic characteristics, surgery parameters and outcomes of pain relief were selected. In total, 101 patients across 12 studies were included. The median age of most patients ranged from 44.3 to 80 years when the duration of pain ranged from 5 months to 8 years. This review showed varied results of 30%-100% pain reduction across studies. The difference in the effect between GK surgery and DBS cannot be judged. Moreover, three retrospective articles related to GK surgery of the CM nucleus for trigeminal neuralgia presented an average pain relief rate of 34.6-82.5%. Four studies reported adverse effects in a small number of patients. GK surgery and DBS of the CM nucleus might be promising therapeutic approaches for chronic refractory pain. More rigorous studies and larger samples with longer follow-up periods are needed to support the effectiveness and safety.

The role of the parafascicular thalamic nucleus in action initiation and steering.

The parafascicular (Pf) nucleus of the thalamus has been implicated in arousal and attention, but its contributions to behavior remain poorly characterized. Here, using in vivo and in vitro electrophysiology, optogenetics, and 3D motion capture, we studied the role of the Pf nucleus in behavior using a continuous reward-tracking task in freely moving mice. We found that many Pf neurons precisely represent vector components of velocity, with a strong preference for ipsiversive movements. Their activity usually leads velocity, suggesting that Pf output is critical for self-initiated orienting behavior. To test this hypothesis, we expressed excitatory or inhibitory opsins in VGlut2+ Pf neurons to manipulate neural activity bidirectionally. We found that selective optogenetic stimulation of these neurons consistently produced ipsiversive head turning, whereas inhibition stopped turning and produced downward movements. Taken together, our results suggest that the Pf nucleus can send continuous top-down commands that specify detailed action parameters (e.g., direction and speed of the head), thus providing guidance for orienting and steering during behavior.

Ambulatory Local Field Potential Recordings from the Thalamus in Epilepsy: A Feasibility Study.

INTRODUCTION: Stimulation of the thalamus is gaining favor in the treatment of medically refractory multifocal and generalized epilepsy. Implanted brain stimulators capable of recording ambulatory local field potentials (LFPs) have recently been introduced, but there is little information to guide their use in thalamic stimulation for epilepsy. This study sought to assess the feasibility of chronically recording ambulatory interictal LFP from the thalamus in patients with epilepsy. METHODS: In this pilot study, ambulatory LFP was recorded from patients who underwent sensing-enabled deep brain stimulation (DBS, 2 participants) or responsive neurostimulation (RNS, 3 participants) targeting the anterior nucleus of the thalamus (ANT, 2 electrodes), centromedian nucleus (CM, 7 electrodes), or medial pulvinar (PuM, 1 electrode) for multifocal or generalized epilepsy. Time-domain and frequency-domain LFP was investigated for epileptiform discharges, spectral peaks, circadian variation, and peri-ictal patterns. RESULTS: Thalamic interictal discharges were visible on ambulatory recordings from both DBS and RNS. At-home interictal frequency-domain data could be extracted from both devices. Spectral peaks were noted at 10-15 Hz in CM, 6-11 Hz in ANT, and 19-24 Hz in PuM but varied in prominence and were not visible in all electrodes. In CM, 10-15 Hz power exhibited circadian variation and was attenuated by eye opening. CONCLUSION: Chronic ambulatory recording of thalamic LFP is feasible. Common spectral peaks can be observed but vary between electrodes and across neural states. DBS and RNS devices provide a wealth of complementary data that have the potential to better inform thalamic stimulation for epilepsy.

Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice.

Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience.

The rostral intralaminar nuclear complex of the thalamus supports striatally mediated action reinforcement.

The dorsal striatum (DS) mediates the selection of actions for reward acquisition necessary for survival. Striatal pathology contributes to several neuropsychiatric conditions, including aberrant selection of actions for specific rewards in addiction. A major source of glutamate driving striatal activity is the rostral intralaminar nuclei (rILN) of the thalamus. Yet, the information that is relayed to the striatum to support action selection is unknown. Here, we discovered that rILN neurons projecting to the DS are innervated by a range of cortical and subcortical afferents and that rILN→DS neurons stably signaled at two time points in mice performing an action sequence task reinforced by sucrose reward: action initiation and reward acquisition. In vivo activation of this pathway increased the number of successful trials, whereas inhibition decreased the number of successful trials. These findings illuminate a role for the rostral intralaminar nuclear complex in reinforcing actions.

Vestibular modulation of the tail of the rat striatum.

Fragmented and piecemeal evidence from animal and human studies suggests that vestibular information is transmitted to the striatum, a part of the basal ganglia that degenerates in Parkinson's Disease. Nonetheless, surprisingly little is known about the precise effects of activation of the vestibular system on the striatum. Electrophysiological studies have yielded inconsistent results, with many studies reporting only sparse responses to vestibular stimulation in the dorsomedial striatum. In this study, we sought to elucidate the effects of electrical stimulation of the peripheral vestibular system on electrophysiological responses in the tail of the rat striatum, a newly discovered region for sensory input. Rats were anaesthetised with urethane and a bipolar stimulating electrode was placed in the round window in order to activate the peripheral vestibular system. A recording electrode was positioned in the tail of the striatum. Local field potentials (LFPs) were recorded ipsilaterally and contralaterally to the stimulation using a range of current parameters. In order to confirm that the vestibular system was activated, video-oculography was used to monitor vestibular nystagmus. At current amplitudes that evoked vestibular nystagmus, clear triphasic LFPs were evoked in the bilateral tail of the striatum, with the first phase of the waveform exhibiting latencies of less than 22 ms. The LFP amplitude increased with increasing current amplitude (P ≤ 0.0001). In order to exclude the possibility that the LFPs were evoked by the activation of the auditory system, the cochlea was surgically lesioned in some animals. In these animals the LFPs persisted despite the cochlear lesions, which were verified histologically. Overall, the results obtained suggest that there are vestibular projections to the tail of the striatum, which could possibly arise from projections via the vestibular nucleus or cerebellum and the parafasicular nucleus of the thalamus.

Evidence for Thalamic Responsive Neurostimulation in Treatment of Adult and Pediatric Epilepsy.

Responsive neurostimulation (RNS) has well-established efficacy in patients with identifiable seizure foci. Emerging evidence suggests the feasibility of expanding this treatment to patients with nonfocal or multifocal epileptic profiles with thalamic targeting. Our institution performed two successful implantations of thalamic RNS (tRNS) targeting the centromedian nucleus of the thalamus (CMT), and 1-year postoperative outcomes are provided. Additionally, a literature review of all reported tRNS was conducted. Publications were excluded if they did not include demographic data and/or epilepsy outcomes at follow-up. In the literature, 19 adult and 3 pediatric cases were identified. These cases were analyzed for outcome, indications, previous operations, and surgical practice variations. Both of our patients had failed multiple previous pharmacological and neurosurgical interventions for epilepsy. Case #1 underwent tRNS with bilateral CMT stimulation. Case #2 underwent tRNS with simultaneous right CMT and right insular stimulation, although an additional lead was placed in the left CMT and left capped for potential future use. Each has achieved ≥90% reduction in seizure burden and approach seizure freedom. 71% of patients in the literature review had multifocal, bilateral, or cryptogenic seizure onset. Three patients were implanted for Lennox Gastaut (2 of 3 are pediatric). 16 patients underwent an average of 1.6 failed procedures prior to successful tRNS implantation. Taken together, the 21 adult patients reviewed have experienced an average seizure reduction of 77% at the latest follow-up. 95% of the adult patients reported in the literature experienced >50% reduction in seizure activity following tRNS and 52% experienced ≥90% reduction in seizure burden following tRNS. Pediatric patients have experienced 70-100% improvement.

Magnetic resonance-guided focused ultrasound central lateral thalamotomy against chronic and therapy-resistant neuropathic pain: retrospective long-term follow-up analysis of 63 interventions.

OBJECTIVE: Medial thalamotomies were introduced in the late 1940s. Pain relief was shown to be achieved for all body locations. With some exceptions, these early relatively small series showed frequent, more or less complete recurrence of the original pain. The posterior part of the central lateral nucleus in the human medial thalamus was identified in the 1990s using multiarchitectonic studies and intraoperative single-cell recordings and was confirmed as a surgical target. This retrospective patient series extended over 11 years. Its goal was to demonstrate the efficacy and risk profile of the MR-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) against chronic and therapy-resistant neuropathic (i.e., neurogenic) pain. METHODS: In this single-center, nonrandomized retrospective cross-sectional analysis of consecutive patients, 63 consecutive MRgFUS CLT interventions were performed in 55 patients. RESULTS: The mean follow-up duration was 55 months. A total of 112 CLT targets were performed, and the CLT was applied bilaterally in 48 patients and contralateral to their pain in 7 patients. Repeat MRgFUS interventions were performed in 8 patients. One serious adverse event with numbness of the upper lip was recorded. The mean pain relief rated by patients was 42% ± 32% at 3 months, 43% ± 36% at 1 year, and 42% ± 37% at the last follow-up (n = 63). The proportions of cases with ≥ 30% pain relief were 65% at 3 months, 63% at 1 year, and 61% at the last follow-up. Good outcomes (≥ 50% pain relief) were found in 54% of patients at 3 months, 49% at 1 year, and 51% at the last follow-up. The reduction in mean VAS scores showed similar percentage reductions as those for pain relief (-41% for continuous pain and -49% for pain attacks) at the 1-year follow-up. The mean frequency of pain attacks was reduced by 92%. Allodynia was reduced or suppressed in 68% of patients and never appeared de novo after MRgFUS CLT. CONCLUSIONS: These results suggest that MRgFUS CLT against neuropathic pain is a safe approach and its results are stable over time. At a mean follow-up duration of 55 months, the mean pain relief was 42% and more than 50% of patients still reported ≥ 50% pain relief. Patients with classical and idiopathic trigeminal neuralgia reported a higher mean pain relief compared with the whole patient group.

Deep Brain Stimulation of the Centromedian Nucleus of the Thalamus for Lennox-Gastaut Syndrome: A Systematic Review and Individual Patient Data Analysis.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset pharmacoresistant epilepsy. Deep brain stimulation (DBS) of the centromedian nucleus of the thalamus (CMN) has been utilized. OBJECTIVE: To conduct a systematic review and individual patient data (IPD) analysis to characterize outcomes of DBS of CMN in LGS. METHODS: PubMed, Embase, and Scopus were searched per Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles were screened by title/abstract then full text. Included articles were reviewed for bibliographic, demographic, and outcome data. IPD were extracted from studies providing IPD for all patients. RESULTS: Of 72 resultant articles, 10 studies (114 patients) were included. Six of 7 studies reporting the outcome of ≥50% seizure reduction indicated that ≥50% of patients achieved this, with improved functional ability. Seizure freedom rate was generally <10%. Six studies with 47 patients provided IPD. The mean ages at epilepsy onset and CMN DBS were 3.9 ± 4.5 years and 17.4 ± 8.8 years, respectively. Nineteen of 41 (46.3%) patients had positive MRI findings. Seizure types included atypical absence in 39 (83.0%) patients, generalized tonic-clonic in 32 (68.1%), tonic in 22 (46.8%), and atonic in 20 (42.6%). Thirty-eight (80.9%) patients experienced ≥50% reduction in seizure frequency, and only 3 (6.4%) experienced seizure freedom. The mean seizure reduction was 62.9% ± 31.2% overall. Quality of life improved in 30/34 (88.2%) and was unchanged in the remainder (11.8%). The complication rate was 2/41 (4.9%). The mean length of follow-up was 19.8 ± 26.1 months (IQR: 4-18 months). CONCLUSION: Limited data indicate that DBS of the CMN may be effective and safe for people with LGS.

Activating PV-positive neurons in ventral thalamic reticular nucleus reduces pain sensitivity in mice.

Previous studies have demonstrated that thalamic reticular nucleus (TRN) and the sub-nuclei play important roles in pain sensation. Our previous findings showed that activating parvalbumin-positive (PV+) neurons in dorsal sector of TRN (dTRN) could reduce the pain threshold and consequently increase the pain sensitivity of mice. Recent studies have shown that activation of GABAergic projection of TRN to ventrobasal thalamus (VB) alleviated pathological pain. GABAergic neurons in TRN are mainly PV+ neurons. However, the exact roles of ventral TRN (vTRN) PV+ neurons in pain sensation remain unclear. In this study, the designer receptors exclusively activated by designer drugs (DREADD) method was used to activate the PV+ neurons in vTRN of PV-Cre transgenic mice, and the mechanical threshold and thermal latency were measured to investigate the regulatory effects of vTRN on pain sensitivity in mice. Thereafter, PV-Cre transgenic mice, conditional anterograde axonal tract tracing, and immunohistochemistry were used to investigate the distribution of PV+ neurons fibers in vTRN. The results showed that the activation of PV+ neurons in vTRN increased the mechanical threshold and thermal latency, which indicated reduction of pain sensitivity. The fibers of these neurons mainly projected to ventral posterolateral thalamic nucleus (VPL), ventral posteromedial thalamic nucleus (VPM), ventrolateral thalamic nucleus (VL), centrolateral thalamic nucleus (CL) and various other brain regions. These findings indicated that activation of PV+ neurons in the vTRN decreased pain sensitivity in mice, which provided additional evidence on the mechanisms of PV+ neurons of TRN in regulating neuralgia.