Neurophysiologic Characteristics of the Anterior Nucleus of the Thalamus during Deep Brain Stimulation Surgery for Epilepsy.

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.

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.

Interstitial laser anterior capsulotomy for obsessive-compulsive disorder: lesion size and tractography correlate with outcome.

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.

Stereotactic laser anterior corpus callosotomy for Lennox-Gastaut syndrome.

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.

Stereotactic laser interstitial thermal therapy for epilepsy associated with solitary and multiple cerebral cavernous malformations.

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.

Technical note: accuracy and precision in stereotactic stem cell transplantation.

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.

Long-term effect of low frequency stimulation of STN on dysphagia, freezing of gait and other motor symptoms in PD.

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.

A role for glutamine 183 in the folate oxidative half-reaction of methylenetetrahydrofolate reductase from Escherichia coli.

The flavoprotein methylenetetrahydrofolate reductase (MTHFR) from Escherichia coli catalyzes a ping-pong reaction with NADH and 5,10-methylenetetrahydrofolate (CH2-H4folate) to produce NAD+ and 5-methyltetrahydrofolate (CH3-H4folate). This work focuses on the function of the invariant, active-site aminoacyl residue Gln183. X-ray structures of the enzyme complexes Ered(wild-type)•NADH and Eox(Glu28Gln)•CH3-H4folate indicate that Gln183 makes key hydrogen-bonding interactions with both NADH and folate in their respective half-reactions, suggesting roles in binding each substrate. We propose that the polarity of Gln183 may also aid in stabilizing the proposed 5-iminium cation intermediate during catalysis in the oxidative half-reaction with folate. We have prepared mutants Gln183Ala and Gln183Glu, which we hypothesize to have altered charge/polarity and hydrogen bonding properties. We have examined the enzymes by steady-state and stopped-flow kinetics and by measurement of the flavin redox potentials. In the reductive half-reaction, NADH binding affinity and the rate of flavin reduction have not been hindered by either mutation. By contrast, our results support a minor role for Gln183 in the oxidative half-reaction. The Gln183Ala variant exhibited a 6-10 fold lower rate of folate reduction and bound CH2-H4folate with 7-fold lower affinity, whereas the Gln183Glu mutant displayed catalytic constants within 3-fold of the wild-type enzyme.

Mania secondary to focal brain lesions: implications for understanding the functional neuroanatomy of bipolar disorder.

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.

Hearing loss in hydrocephalus: a review, with focus on mechanisms.

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.

T cell deficiency in spinal cord injury: altered locomotor recovery and whole-genome transcriptional analysis.

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.

Anatomic correlates of deep brain stimulation electrode impedance.

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.

Variation in deep brain stimulation electrode impedance over years following electrode implantation.

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.

A roadmap for implanting microelectrode arrays to evoke tactile sensations through intracortical microstimulation.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface 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 brain-computer interface studies to ensure successful placement of stimulation electrodes.

Tailored Hemispherotomy Using Tractography-Guided Laser Interstitial Thermal Therapy.

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.

Microstimulation of human somatosensory cortex evokes task-dependent, spatially patterned responses in motor cortex.

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.

Biomimetic multi-channel microstimulation of somatosensory cortex conveys high resolution force feedback for bionic hands.

Manual interactions with objects are supported by tactile signals from the hand. This tactile feedback can be restored in brain-controlled bionic hands via intracortical microstimulation (ICMS) of somatosensory cortex (S1). In ICMS-based tactile feedback, contact force can be signaled by modulating the stimulation intensity based on the output of force sensors on the bionic hand, which in turn modulates the perceived magnitude of the sensation. In the present study, we gauged the dynamic range and precision of ICMS-based force feedback in three human participants implanted with arrays of microelectrodes in S1. To this end, we measured the increases in sensation magnitude resulting from increases in ICMS amplitude and participant's ability to distinguish between different intensity levels. We then assessed whether we could improve the fidelity of this feedback by implementing "biomimetic" ICMS-trains, designed to evoke patterns of neuronal activity that more closely mimic those in natural touch, and by delivering ICMS through multiple channels at once. We found that multi-channel biomimetic ICMS gives rise to stronger and more distinguishable sensations than does its single-channel counterpart. Finally, we implemented biomimetic multi-channel feedback in a bionic hand and had the participant perform a compliance discrimination task. We found that biomimetic multi-channel tactile feedback yielded improved discrimination over its single-channel linear counterpart. We conclude that multi-channel biomimetic ICMS conveys finely graded force feedback that more closely approximates the sensitivity conferred by natural touch.

Tessellation of artificial touch via microstimulation of human somatosensory cortex.

When we interact with objects, we rely on signals from the hand that convey information about the object and our interaction with it. A basic feature of these interactions, the locations of contacts between the hand and object, is often only available via the sense of touch. Information about locations of contact between a brain-controlled bionic hand and an object can be signaled via intracortical microstimulation (ICMS) of somatosensory cortex (S1), which evokes touch sensations that are localized to a specific patch of skin. To provide intuitive location information, tactile sensors on the robotic hand drive ICMS through electrodes that evoke sensations at skin locations matching sensor locations. This approach requires that ICMS-evoked sensations be focal, stable, and distributed over the hand. To systematically investigate the localization of ICMS-evoked sensations, we analyzed the projected fields (PFs) of ICMS-evoked sensations - their location and spatial extent - from reports obtained over multiple years from three participants implanted with microelectrode arrays in S1. First, we found that PFs vary widely in their size across electrodes, are highly stable within electrode, are distributed over large swaths of each participant's hand, and increase in size as the amplitude or frequency of ICMS increases. Second, while PF locations match the locations of the receptive fields (RFs) of the neurons near the stimulating electrode, PFs tend to be subsumed by the corresponding RFs. Third, multi-channel stimulation gives rise to a PF that reflects the conjunction of the PFs of the component channels. By stimulating through electrodes with largely overlapping PFs, then, we can evoke a sensation that is experienced primarily at the intersection of the component PFs. To assess the functional consequence of this phenomenon, we implemented multichannel ICMS-based feedback in a bionic hand and demonstrated that the resulting sensations are more localizable than are those evoked via single-channel ICMS.

SEEG in 3D: Interictal Source Localization From Intracerebral Recordings.

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.

Source localization of ictal SEEG to predict postoperative seizure outcome.

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.