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Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface (BCI) to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other BCI studies to ensure the successful placement of stimulation electrodes., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Tactile feedback from brain-controlled bionic hands can be partially restored via intracortical microstimulation (ICMS) of the primary somatosensory cortex. In ICMS, the location of percepts depends on the electrode's location and the percept intensity depends on the stimulation frequency and amplitude. Sensors on a bionic hand can thus be linked to somatotopically appropriate electrodes, and the contact force of each sensor can be used to determine the amplitude of a stimulus. Here we report a systematic investigation of the localization and intensity of ICMS-evoked percepts in three participants with cervical spinal cord injury. A retrospective analysis of projected fields showed that they were typically composed of a focal hotspot with diffuse borders, arrayed somatotopically in keeping with their underlying receptive fields and stable throughout the duration of the study. When testing the participants' ability to rapidly localize a single ICMS presentation, individual electrodes typically evoked only weak sensations, making object localization and discrimination difficult. However, overlapping projected fields from multiple electrodes produced more localizable and intense sensations and allowed for a more precise use of a bionic hand., Competing Interests: Competing interests: N.G.H. and R.A.G. served as consultants for Blackrock Neurotech, Inc. at the time of the study. R.A.G. is also on the scientific advisory board of Neurowired LLC. M.L.B., J.L.C. and R.A.G. received research funding from Blackrock Neurotech, Inc. though that funding did not support the work presented here. A.R.S. serves as a consultant for Google DeepMind. The other authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an increasingly promising treatment option for refractory epilepsy. Optimal therapeutic benefit has been associated with stimulation at the junction of ANT and the mammillothalamic tract (mtt), but electrophysiologic markers of this target are lacking. The present study examined microelectrode recordings (MER) during DBS to identify unique electrophysiologic characteristics of ANT and the ANT-mtt junction., Methods: Ten patients with medically refractory epilepsy underwent MER during ANT-DBS implantation under general anesthesia. MER locations were determined based on coregistration of preoperative MRI, postoperative CT, and a stereotactic atlas of the thalamus (Morel atlas). Several neurophysiological parameters including single unit spiking rate, bursting properties, theta and alpha power and cerebrospinal fluid (CSF)-normalized root mean square (NRMS) of multiunit activity were characterized at recording depths and compared to anatomic boundaries., Results: From sixteen hemispheres, 485 recordings locations were collected from a mean of 30.3 (15.64 ± 5.0 mm) recording spans. Three-hundred and ninety-four of these recording locations were utilized further for analysis of spiking and bursting rates, after excluding recordings that were more than 8 mm above the putative ventral ANT border. The ANT region exhibited discernible features including: (1) mean spiking rate (7.52 Hz ± 6.9 Hz; one-way analysis of variance test, p = 0.014 when compared to mediodorsal nucleus of the thalamus [MD], mtt, and CSF), (2) the presence of bursting activity with 40% of ANT locations (N = 59) exhibited bursting versus 24% the mtt (χ2; p < 0.001), and 32% in the MD (p = 0.38), (3) CSF-NRMS, a proxy for neuronal density, exhibited well demarcated changes near the entry and exit of ANT (linear regression, R = -0.33, p < 0.001). Finally, in the ANT, both theta (4-8 Hz) and alpha band power (9-12 Hz) were negatively correlated with distance to the ventral ANT border (linear regression, p < 0.001 for both). The proportion of recordings with spiking and bursting activity was consistently highest 0-2 mm above the ventral ANT border with the mtt., Conclusion: We observed several electrophysiological markers demarcating the ANT superior and inferior borders including multiple single cell and local field potential features. A local maximum in neural activity just above the ANT-mtt junction was consistent with the previously described optimal target for seizure reduction. These features may be useful for successful targeting of ANT-DBS for epilepsy., (© 2024 S. Karger AG, Basel.)

The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded - in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands - the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger's movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation., (© 2023. The Author(s).)

Background: Medically refractory hemispheric epilepsy is a devastating disease with significant lifetime costs and social burden. Functional hemispherotomy is a highly effective treatment for hemispheric epilepsy but is associated with significant complication rates. Percutaneous hemispherotomy through laser interstitial thermal therapy (LITT) based on morphological MRI has been recently described in a single patient but not replicated in the literature., Objective: To describe the first 2 cases of tractography-guided interstitial laser hemispherotomy and their short-term outcomes., Methods: Two 11-year-old male patients with medically refractory epilepsy secondary to perinatal large vessel infarcts were referred for hemispherotomy. Both patients underwent multitrajectory LITT to disconnect the remaining pathological hemisphere, using tractography to define targets and assess structural outcomes., Results: Both cases had minor complication of small intraventricular/subarachnoid hemorrhage not requiring additional intervention. Both patients remain seizure-free at all follow-up visits., Conclusion: LITT hemispherotomy can produce seizure freedom with short hospitalization and recovery. Tractography allows surgical planning to be tailored according to individual patient anatomy, which often is distorted in perinatal stroke. Minimally invasive procedures offer the greatest potential for seizure freedom without the risks of an open hemispherotomy., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

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., (© 2023 S. Karger AG, Basel.)

Objective: Stereo-electroencephalography (SEEG) is inherently-three-dimensional and can be modeled using source localization. This study aimed to assess the validity of ictal SEEG source localization., Methods: The dominant frequency at ictal onset was used for source localization in the time and frequency domains using rotating dipoles and current density maps. Validity was assessed by concordance with the epileptologist-defined seizure onset zone (conventional SOZ) and the surgical treatment volume (TV) of seizure-free versus non-seizure-free patients., Results: Source localization was performed on 68 seizures from 27 patients. Median distance to nearest contact in the conventional SOZ was 7 (IQR 6-12) mm for time-domain dipoles. Current density predicted ictal activity with up to 86 % (60-87 %) accuracy. Distance from time-domain dipoles to the TV was smaller (P = 0.045) in seizure-free (2 [0-4] mm) versus non-seizure-free (12 [2-17] mm) patients, and predicted surgical outcome with 91 % sensitivity and 63 % specificity. Removing near-field data from contacts within the TV negated outcome prediction (P = 0.51)., Conclusions: Source localization of SEEG accurately mapped ictal onset compared with conventional interpretation. Proximity of dipoles to the TV predicted seizure outcome when near-field recordings were analyzed., Significance: Ictal SEEG source localization is useful in corroborating the epileptogenic zone, assuming near-field recordings are obtained., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Anterior capsulotomy is a well-established treatment for refractory obsessive-compulsive disorder (OCD). MRI-guided laser interstitial thermal therapy (LITT) allows creation of large, sharply demarcated lesions with the safeguard of real-time imaging., Objective: To characterise the outcomes of laser anterior capsulotomy, including radiographical predictors of improvement., Methods: Patients with severe OCD refractory to pharmacotherapy and cognitive-behavioural therapy underwent bilateral anterior capsulotomy via LITT. The primary outcome was per cent reduction in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score over time. Lesion size was measured on postablation MRI. Disconnection of the anterior limb of the internal capsule (ALIC) was assessed via individual and normative tractography., Results: Eighteen patients underwent laser anterior capsulotomy. Median follow-up was 6 months (range 3-51 months). Time occupied by obsessions improved immediately (median Y-BOCS item 1 score 4-1, p=0.002). Mean (±SD) decrease in Y-BOCS score at last follow-up was 46%±32% (16±11 points, p<0.0001). Sixty-one per cent of patients were responders. Seven patients (39%) exhibited transient postoperative apathy. One patient had an asymptomatic intracerebral haemorrhage. Reduction in Y-BOCS score was positively associated with ablation volume (p=0.006). Individual tractography demonstrated durable ALIC disconnection. Normative tractography revealed a dorsal-ventral gradient, with disconnection of orbitofrontal streamlines most strongly associated with a positive response (p<0.0001)., Conclusions: Laser anterior capsulotomy resulted in immediate, marked improvement in OCD symptom severity. Larger lesions permit greater disconnection of prefrontal-subcortical pathways involved in OCD. The importance of greater disconnection is presumably related to variation in ALIC structure and the complex role of the PFC in OCD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Stereo-electroencephalography (SEEG) uses a three-dimensional configuration of depth electrodes to localize epileptiform activity, but traditional analysis of SEEG is spatially restricted to the point locations of the electrode contacts. Interpolation of brain activity between contacts might allow for three-dimensional representation of epileptiform activity and avoid pitfalls of SEEG interpretation., Objective: The goal of this study was to validate SEEG-based interictal source localization and assess the ability of this technique to monitor far-field activity in non-implanted brain regions., Methods: Interictal epileptiform discharges were identified on SEEG in 26 patients who underwent resection, ablation, or disconnection of the suspected epileptogenic zone. Dipoles without (free) and with (scan) gray matter restriction, and current density (sLORETA and SWARM methods), were calculated using a finite element head model. Source localization results were compared to the conventional irritative zone (IZ) and the surgical treatment volumes (TV) of seizure-free vs. non-seizure-free patients., Results: The median distance from dipole solutions to the nearest contact in the conventional IZ was 7 mm (interquartile range 4-15 mm for free dipoles and 4-14 mm for scan dipoles). The IZ modeled with SWARM predicted contacts within the conventional IZ with 83% (75-100%) sensitivity and 94% (88-100%) specificity. The proportion of current within the TV was greater in seizure-free patients ( P = 0.04) and predicted surgical outcome with 45% sensitivity and 93% specificity. Dipole solutions and sLORETA results did not correlate with seizure outcome. Addition of scalp EEG led to more superficial modeled sources ( P = 0.03) and negated the ability to predict seizure outcome ( P = 0.23). Removal of near-field data from contacts within the TV resulted in smearing of the current distribution ( P = 0.007) and precluded prediction of seizure freedom ( P = 0.20)., Conclusions: Source localization accurately represented interictal discharges from SEEG. The proportion of current within the TV distinguished between seizure-free and non-seizure-free patients when near-field recordings were obtained from the surgical target. The high prevalence of deep sources in this cohort likely obscured any benefit of concurrent scalp EEG. SEEG-based interictal source localization is useful in illustrating and corroborating the epileptogenic zone. Additional techniques are needed to localize far-field epileptiform activity from non-implanted brain regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Satzer, Esengul, Warnke, Issa and Nordli.)

Objective: The authors aimed to examine the relationship between mesial temporal subregion ablation volume and seizure outcome in a diverse cohort of patients who underwent stereotactic laser amygdalohippocampotomy (SLAH) for mesial temporal lobe epilepsy (MTLE)., Methods: Seizure outcomes and pre- and postoperative images were retrospectively reviewed in patients with MTLE who underwent SLAH at a single institution. Mesial temporal subregions and the contrast-enhancing ablation volume were manually segmented. Pre- and postoperative MR images were coregistered to assess anatomical ablation. Postoperative MRI and ablation volumes were also spatially normalized, enabling the assessment of seizure outcome with heat maps., Results: Twenty-eight patients with MTLE underwent SLAH, 15 of whom had mesial temporal sclerosis (MTS). The rate of Engel class I outcome at 1 year after SLAH was 39% overall: 47% in patients with MTS and 31% in patients without MTS. The percentage of parahippocampal gyrus (PHG) ablated was higher in patients with an Engel class I outcome (40% vs 25%, p = 0.04). Subregion analysis revealed that extent of ablation in the parahippocampal cortex (35% vs 19%, p = 0.03) and angular bundle (64% vs 43%, p = 0.02) was positively associated with Engel class I outcome. The degree of amygdalohippocampal complex (AHC) ablated was not associated with seizure outcome (p = 0.30)., Conclusions: Although the AHC was the described target of SLAH, seizure outcome in this cohort was associated with degree of ablation for the PHG, not the AHC. Complete coverage of both the AHC and PHG is technically challenging, and more work is needed to optimize seizure outcome after SLAH.

Objective: To assess the seizure outcomes of stereotactic laser amygdalohippocampectomy (SLAH) in consecutive patients with mesial temporal lobe epilepsy (mTLE) in a single center and identify scalp EEG and imaging factors in the presurgical evaluation that correlate with post-surgical seizure recurrence. Methods: We retrospectively reviewed the medical and EEG records of 30 patients with drug-resistant mTLE who underwent SLAH and had at least 1 year of follow-up. Surgical outcomes were classified using the Engel scale. Univariate hazard ratios were used to evaluate the risk factors associated with seizure recurrence after SLAH. Results: The overall Engel class I outcome after SLAH was 13/30 (43%), with a mean postoperative follow-up of 48.9 ± 17.6 months. Scalp EEG findings of interictal regional slow activity (IRSA) on the side of surgery ( HR = 4.05, p = 0.005) and non-lateralizing or contra-lateralizing seizure onset ( HR = 4.31, p = 0.006) were negatively correlated with postsurgical seizure freedom. Scalp EEG with either one of the above features strongly predicted seizure recurrence after surgery (HR = 7.13, p < 0.001) with 100% sensitivity and 71% specificity. Significance: Understanding the factors associated with good or poor surgical outcomes can help choose the best candidates for SLAH. Of the variables assessed, scalp EEG findings were the most clearly associated with seizure outcomes after SLAH., Competing Interests: SW, NI, ML, SR, JC, PW, and JT are investigators in the Stereotactic Laser Ablation for Temporal Lobe Epilepsy (SLATE) trial funded by Medtronic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Issa, Lacy, Satzer, Rose, Yang, Collins, Liu, Sun, Towle, Nordli, Warnke and Tao.)

Objectives : To study whether and to what extent the therapeutic impedance and current change under long-term deep brain stimulation (DBS) with constant stimulation settings, which could inform the role of constant current stimulation. Methods : Therapy impedance and current measurements were retrospectively collected from patients with Parkinson's disease (PD) undergoing DBS of the subthalamic nucleus (STN) or essential tremor (ET) undergoing ventral intermediate nucleus (VIM). Baseline and follow-up measurements were obtained for intervals of at least 6 months without changes in stimulation settings. The single longest interval of constant stimulation for each electrode was included. Temporal trends in impedance and current were analyzed as absolute and relative differences and as the rate of change. Results : Impedance and current data from 79 electrodes (60 in STN, 19 in VIM) in 44 patients (32 with PD, 12 with ET) met inclusion criteria. The duration between baseline and follow-up measurements with constant stimulation settings was 17 months (median, with an interquartile range of 12-26 months) in the mixed group. Therapy impedance decreased by 27 ± 12 Ω/year (mean ± 2 standard errors; p < 0.0001), and therapy current increased at a rate of 0.142 ± 0.063 mA/year ( p < 0.0001). Similar results were observed in the STN and VIM subgroups. Conclusions : Impedance decreases gradually over time, even when stimulation settings are kept constant. The rate of decrease is smaller than previously reported, suggesting that changes in stimulation settings contribute to impedance drift. Stimulation-independent impedance drift is gradual but relevant to constant-current programming., (Copyright © 2020 Satzer, Yu, Wells, Padmanaban, Burns, Warnke and Xie.)

Objective: Corpus callosotomy is an effective palliative treatment for drug-resistant Lennox-Gastaut syndrome (LGS). Laser interstitial thermal therapy has been increasingly used in the treatment of epilepsy. Here, we assess the safety and effectiveness of minimally invasive stereotactic laser anterior corpus callosotomy (SLACC) for drop attacks in LGS., Methods: We reviewed sequential cases of patients with medically intractable LGS who underwent SLACC using a two-cannula technique between November 2014 and July 2019. Pre- and postoperative magnetic resonance imaging was used to measure the anteroposterior length of callosal ablation (contrast-enhancing lesion) and estimated disconnection (gap in tract projections on diffusion tensor imaging). Patients were followed longitudinally to assess clinical outcomes., Results: Ten patients were included in this study. The median age was 33 (range = 11-52) years, median duration of epilepsy was 26 (range = 10-49) years, and median duration of postoperative follow-up was 19 (range = 6-40) months. In the anteroposterior direction, 53 ± 7% (mean ± SD) of the corpus callosum was ablated and 62 ± 19% of the corpus callosum was estimated to be disconnected. Six (60%) of 10 patients achieved >80% seizure reduction, two (20%) of whom became seizure-free. Eight (80%) patients had >80% reduction in drop attacks, five (50%) of whom became free of drop attacks. Three patients subsequently underwent laser posterior callosotomy with further improvement in drop attacks and/or overall seizure frequency. One patient had an asymptomatic intracerebral hemorrhage along the cannula tract. One patient developed significant aggression after becoming seizure-free., Significance: Seizure outcomes following SLACC were comparable to previously reported outcomes of open callosotomy, with reasonable safety profile. SLACC appears to be an effective alternative to open anterior corpus callosotomy with minimal postoperative discomfort and a short recovery period., (© 2020 International League Against Epilepsy.)

Objective: The authors sought to perform a preliminary assessment of the safety and effectiveness of stereotactic laser interstitial thermal therapy (LITT) for patients with cerebral cavernous malformation (CCM)-related epilepsy., Methods: The authors retrospectively analyzed 6 patients with CCM-related epilepsy who underwent LITT. Pre-, intra-, and postoperative brain MRI studies were used to characterize preoperative CCM volume, ablation volume, and postablation hemosiderin volume. Clinical outcomes were assessed postoperatively during clinic follow-up visits or phone interviews., Results: LITT was performed in 7 CCMs in 6 patients. Two patients had familial CCM disease with multifocal lesions. Four treated CCMs were extratemporal, and 3 were in or near the visual pathways. The median follow-up was 25 (range 12-39) months. Five of 6 (83%) patients achieved seizure freedom (Engel I classification), of whom 4 (67%) were Engel IA and 1 was Engel IC after a single seizure on postoperative day 4. The remaining patient had rare seizures (Engel II). One patient had a nondisabling visual field deficit. There were no hemorrhagic complications. All patients were discharged within 24 hours postablation. MRI 3-11 months after ablation demonstrated expected focal necrosis and trace hemosiderin-related T2 hypointensity measuring 9%-44% (median 24%) of the original lesion volume, with significant (p = 0.04) volume reduction., Conclusions: LITT is a minimally invasive option for treating CCM-related epilepsy with seizure outcomes comparable to those achieved with open lesionectomy. The precision of LITT allows for the obliteration of eloquent, deep, small, and multifocal lesions with low complication rates, minimal postoperative discomfort, and short hospital stays. In this study the feasibility and benefits of this method were demonstrated in 2 patients with multifocal lesions.

Background: While multiple trials have employed stereotactic stem cell transplantation, injection techniques have received little critical attention. Precise cell delivery is critical for certain applications, particularly when targeting deep nuclei., Methods: Ten patients with a history of ischemic stroke underwent CT-guided stem cell transplantation. Cells were delivered along 3 tracts adjacent to the infarcted area. Intraoperative air deposits and postoperative T2-weighted MRI fluid signals were mapped in relation to calculated targets., Results: The deepest air deposit was found 4.5 ± 1.0 mm (mean ± 2 SEM) from target. The apex of the T2-hyperintense tract was found 2.8 ± 0.8 mm from target. On average, air pockets were found anterior (1.2 ± 1.1 mm, p = 0.04) and superior (2.4 ± 1.0 mm, p < 0.001) to the target; no directional bias was noted for the apex of the T2-hyperintense tract. Location and distribution of air deposits were variable and were affected by the relationship of cannula trajectory to stroke cavity., Conclusions: Precise stereotactic cell transplantation is a little-studied technical challenge. Reflux of cell suspension and air, and the structure of the injection tract affect delivery of cell suspensions. Intraoperative CT allows assessment of delivery and potential trajectory correction.

Objective: To evaluate the long-term effect of 60 Hz stimulation of the subthalamic nucleus (STN) on dysphagia, freezing of gait (FOG) and other motor symptoms in patients with Parkinson's disease (PD) who have FOG at the usual 130 Hz stimulation., Methods: This is a prospective, sequence randomised, crossover, double-blind study. PD patients with medication refractory FOG at 130 Hz stimulation of the STN were randomised to the sequences of 130 Hz, 60 Hz or deep brain stimulation off to assess swallowing function (videofluoroscopic evaluation and swallowing questionnaire), FOG severity (stand-walk-sit test and FOG questionnaire) and motor function (Unified PD Rating Scale, Part III motor examination (UPDRS-III)) at initial visit (V1) and follow-up visit (V2, after being on 60 Hz stimulation for an average of 14.5 months), in their usual medications on state. The frequency of aspiration events, perceived swallowing difficulty and FOG severity at 60 Hz compared with 130 Hz stimulation at V2, and their corresponding changes at V2 compared with V1 at 60 Hz were set as primary outcomes, with similar comparisons in UPDRS-III and its subscores as secondary outcomes., Results: All 11 enrolled participants completed V1 and 10 completed V2. We found the benefits of 60 Hz stimulation compared with 130 Hz in reducing aspiration frequency, perceived swallowing difficulty, FOG severity, bradykinesia and overall axial and motor symptoms at V1 and persistent benefits on all of them except dysphagia at V2, with overall decreasing efficacy when comparing V2 to V1., Conclusions: The 60 Hz stimulation, when compared with 130 Hz, has long-term benefits on reducing FOG, bradykinesia and overall axial and motor symptoms except dysphagia, although the overall benefits decrease with long-term use., Clinical Trial Registration: NCT02549859; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Approximately 3.5 million Americans will experience a manic episode during their lifetimes. The most common causes are psychiatric illnesses such as bipolar I disorder and schizoaffective disorder, but mania can also occur secondary to neurological illnesses, brain injury, or neurosurgical procedures., Methods: For this narrative review, we searched Medline for articles on the association of mania with stroke, brain tumors, traumatic brain injury, multiple sclerosis, neurodegenerative disorders, epilepsy, and neurosurgical interventions. We discuss the epidemiology, features, and treatment of these cases. We also review the anatomy of the lesions, in light of what is known about the neurobiology of bipolar disorder., Results: The prevalence of mania in patients with brain lesions varies widely by condition, from <2% in stroke to 31% in basal ganglia calcification. Mania occurs most commonly with lesions affecting frontal, temporal, and subcortical limbic brain areas. Right-sided lesions causing hypo-functionality or disconnection (e.g., stroke; neoplasms) and left-sided excitatory lesions (e.g., epileptogenic foci) are frequently observed., Conclusions: Secondary mania should be suspected in patients with neurological deficits, histories atypical for classic bipolar disorder, and first manic episodes after the age of 40 years. Treatment with antimanic medications, along with specific treatment for the underlying neurologic condition, is typically required. Typical lesion locations fit with current models of bipolar disorder, which implicate hyperactivity of left-hemisphere reward-processing brain areas and hypoactivity of bilateral prefrontal emotion-modulating regions. Lesion studies complement these models by suggesting that right-hemisphere limbic-brain hypoactivity, or a left/right imbalance, may be relevant to the pathophysiology of mania., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

While neither hydrocephalus nor cerebrospinal fluid (CSF) shunt placement is traditionally considered in the differential diagnosis of hearing loss, there is substantial evidence that CSF circulation and pressure abnormalities can produce auditory dysfunction. Several indirect mechanisms may explain association between hydrocephalus and hearing loss, including mass effect, compromise of the auditory pathway, complications of prematurity, and genetically mediated hydrocephalus and hearing loss. Nevertheless, researchers have proposed a direct mechanism, which we term the hydrodynamic theory. In this hypothesis, the intimate relationship between CSF and inner ear fluids permits relative endolymphatic or perilymphatic hydrops in the setting of CSF pressure disturbances. CSF is continuous with perilymph, and CSF pressure changes are known to produce parallel perilymphatic pressure changes. In support of the hydrodynamic theory, some studies have found an independent association between hydrocephalus and hearing loss. Moreover, surgical shunting of CSF has been linked to both resolution and development of auditory dysfunction. The disease burden of hydrocephalus-associated hearing loss may be large, and because hydrocephalus and over-shunting are reversible, this relationship merits broader recognition. Hydrocephalic patients should be monitored for hearing loss, and hearing loss in a patient with shunted hydrocephalus should prompt further evaluation and possibly adjustment of shunt settings.

Background: T cells undergo autoimmunization following spinal cord injury (SCI) and play both protective and destructive roles during the recovery process. T cell-deficient athymic nude (AN) rats exhibit improved functional recovery when compared to immunocompetent Sprague-Dawley (SD) rats following spinal cord transection., Methods: In the present study, we evaluated locomotor recovery in SD and AN rats following moderate spinal cord contusion. To explain variable locomotor outcome, we assessed whole-genome expression using RNA sequencing, in the acute (1 week post-injury) and chronic (8 weeks post-injury) phases of recovery., Results: Athymic nude rats demonstrated greater locomotor function than SD rats only at 1 week post-injury, coinciding with peak T cell infiltration in immunocompetent rats. Genetic markers for T cells and helper T cells were acutely enriched in SD rats, while AN rats expressed genes for T(h)2 cells, cytotoxic T cells, NK cells, mast cells, IL-1a, and IL-6 at higher levels. Acute enrichment of cell death-related genes suggested that SD rats undergo secondary tissue damage from T cells. Additionally, SD rats exhibited increased acute expression of voltage-gated potassium (Kv) channel-related genes. However, AN rats demonstrated greater chronic expression of cell death-associated genes and less expression of axon-related genes. Immunostaining for macrophage markers revealed no T cell-dependent difference in the acute macrophage infiltrate., Conclusions: We put forth a model in which T cells facilitate early tissue damage, demyelination, and Kv channel dysregulation in SD rats following contusion SCI. However, compensatory features of the immune response in AN rats cause delayed tissue death and limit long-term recovery. T cell inhibition combined with other neuroprotective treatment may thus be a promising therapeutic avenue.

Background: The location of the optimal target for deep brain stimulation (DBS) of the subthalamic nucleus (STN) remains controversial. Electrode impedance affects tissue activation by DBS and has been found to vary by contact number, but no studies have examined association between impedance and anatomic location., Objectives: To evaluate the relationship between electrode impedance and anatomic contact location, and to assess the clinical significance of impedance., Methods: We gathered retrospective impedance data from 101 electrodes in 73 patients with Parkinson's disease. We determined contact location using microelectrode recording (MER) and high-field 7T MRI, and assessed the relationship between impedance and contact location., Results: For contact location as assessed via MER, impedance was significantly higher for contacts in STN, at baseline (111 Ω vs STN border, p=0.03; 169 Ω vs white matter, p<0.001) and over time (90 Ω vs STN border, p<0.001; 54 Ω vs white matter, p<0.001). Over time, impedance was lowest in contacts situated at STN border (p=0.03). Impedance did not vary by contact location as assessed via imaging. Location determination was 75% consistent between MER and imaging. Impedance was inversely related to absolute symptom reduction during stimulation (-2.5 motor portion of the Unified Parkinson's Disease Rating Scale (mUPDRS) points per 1000 Ω, p=0.01)., Conclusions: In the vicinity of DBS electrodes chronically implanted in STN, impedance is lower at the rostral STN border and in white matter, than in STN. This finding suggests that current reaches white matter fibres more readily than neuronal cell bodies in STN, which may help explain anatomic variation in stimulation efficacy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Type I mucopolysaccharidosis (MPS I) is an autosomal recessive lysosomal storage disorder with neurological features. Humans and laboratory animals with MPS I exhibit various white matter abnormalities involving the corpus callosum and other regions. In this study, we first validated a novel MRI technique, entitled Relaxation Along a Fictitious Field in the rotating frame of rank n (RAFFn), as a measure of myelination and dysmyelination in mice. We then examined differences between MPS I mice and heterozygotes using RAFF5 and histology. RAFF5 (i.e., RAFFn with n = 5) relaxation time constants were highly correlated with histological myelin density (R2 = 0.68, P<0.001), and RAFF5 clearly distinguished between the hypomyelinated and dysmyelinated shiverer mouse and the wild-type mouse. Bloch-McConnell theoretical analysis revealed slower exchange correlation times and smaller exchange-induced relaxation rate constants for RAFF4 and RAFF5 compared to RAFF1-3, T1ρ, and T2ρ. These data suggest that RAFF5 may assess methylene protons in myelin lipids and proteins, though other mechanisms (e.g. detection of myelin-bound water) may also explain the sensitivity of RAFF5 to myelin. In MPS I mice, mean RAFF5 relaxation time constants were significantly larger for the striatum (P = 0.004) and internal capsule (P = 0.039), and marginally larger for the fornix (P = 0.15). Histological assessment revealed no differences between MPS I mice and heterozygotes in myelin density or corpus callosum thickness. Taken together, these findings support subtle dysmyelination in the brains of mice with MPS I. Dysmyelination may result from myelin lipid abnormalities caused by the absence of α-L-iduronidase. Our findings may help to explain locomotor and cognitive deficits seen in mice with MPS I.

Object: Brainstem dysfunction occurs in a minority of patients with myelomeningocele (MMC), most of whom have Chiari Type II malformation. Some surgeons advocate early identification of these patients for craniocervical decompression to avoid significant mortality. The auditory brainstem response has been found to be abnormal in most children with MMC. The present study examines whether failure of routine newborn hearing screening (NHS) predicts brainstem dysfunction in MMC patients., Methods: The charts of 40 newborns with MMC and 50 newborns without MMC who stayed in the neonatal intensive care unit were reviewed. Results of NHS, brainstem symptoms, birth demographics, and surgical history were retrospectively examined. Differences in the presence and onset of brainstem symptoms by NHS result were assessed., Results: Failure of NHS was more common among newborns with MMC who developed brainstem symptoms (31%, 4 of 13 patients) than among newborns without MMC (0%, 0 of 50 patients; p = 0.001). Among the 40 newborns with MMC, brainstem symptoms were more common in those who failed NHS (80%, 4 of 5 patients) than in those who passed (26%, 9 of 35 patients; p = 0.031). Respiratory symptom onset occurred later in patients who failed NHS (median 16 months) than among those who passed (median 0 months; p = 0.022). The positive and negative predictive values of NHS for brainstem dysfunction in MMC were 0.80 and 0.74, respectively., Conclusions: Results of NHS may help predict future brainstem dysfunction in patients with MMC and may be useful to incorporate into prognostic assessment and surgical decision making.

Background: Deep brain stimulation (DBS) electrode impedance is a major determinant of current delivery to target tissues, but long-term variation in impedance has received little attention., Objectives: To assess the relationship between electrode impedance and time in a large DBS patient population and characterize the relationship between contact activity and impedance., Methods: We collected retrospective impedance and programming data from 128 electrodes in 84 patients with Parkinson's disease, essential tremor or dystonia. Effects of time, contact activity, stimulation voltage and other parameters on impedance were assessed. We also examined impedance changes following contact activation and deactivation., Results: Impedance decreased by 73 Ω/year (p < 0.001), with 72% of contacts following a downward trend. Impedance was on average 163 Ω lower in active contacts (p < 0.001). Contact activation and inactivation were associated with a more (p < 0.001) and less (p = 0.016) rapid decline in impedance, respectively. Higher stimulation voltages were associated with lower impedance values (p < 0.001). Contact number and electrode model were also significant predictors of impedance., Conclusions: Impedance decreases gradually in a stimulation-dependent manner. These trends have implications for long-term programming, the development of a closed-loop DBS device and current understanding of the electrode-tissue interface., (© 2014 S. Karger AG, Basel.)