Subthalamic nucleus synchronization between beta band local field potential and single-unit activity in Parkinson's disease.

Local field potential (LFP) oscillations in the beta band (13-30 Hz) in the subthalamic nucleus (STN) of Parkinson's disease patients have been implicated in disease severity and treatment response. The relationship between single-neuron activity in the STN and regional beta power changes remains unclear. We used spike-triggered average (STA) to assess beta synchronization in STN. Beta power and STA magnitude at the beta frequency range were compared in three conditions: STN versus other subcortical structures, dorsal versus ventral STN, and high versus low beta power STN recordings. Magnitude of STA-LFP was greater within the STN compared to extra-STN structures along the trajectory path, despite no difference in percentage of the total power. Within the STN, there was a higher percent beta power in dorsal compared to ventral STN but no difference in STA-LFP magnitude. Further refining the comparison to high versus low beta peak power recordings inside the STN to evaluate if single-unit activity synchronized more strongly with beta band activity in areas of high beta power resulted in a significantly higher STA magnitude for areas of high beta power. Overall, these results suggest that STN single units strongly synchronize to beta activity, particularly units in areas of high beta power.

Brain Shift during Staged Deep Brain Stimulation for Movement Disorders.

INTRODUCTION: Deep brain stimulation (DBS) is a routine neurosurgical procedure utilized to treat various movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. Treatment efficacy is dependent on stereotactic accuracy of lead placement into the deep brain target of interest. However, brain shift attributed to pneumocephalus can introduce unpredictable inaccuracies during DBS lead placement. This study aimed to determine whether intracranial air is associated with brain shift in patients undergoing staged DBS surgery. METHODS: We retrospectively evaluated 46 patients who underwent staged DBS surgery for PD, ET, and dystonia. Due to the staged nature of DBS surgery at our institution, the first electrode placement is used as a concrete fiducial marker for movement in the target location. Postoperative computed tomography (CT) images after the first electrode implantation, as well as preoperative, and postoperative CT images after the second electrode implantation were collected. Images were analyzed in stereotactic targeting software (BrainLab); intracranial air was manually segmented, and electrode shift was measured in the x, y, and z plane, as well as a Euclidian distance on each set of merged CT scans. A Pearson correlation analysis was used to determine the relationship between intracranial air and brain shift, and student's t test was used to compare means between patients with and without radiographic evidence of intracranial air. RESULTS: Thirty-six patients had pneumocephalus after the first electrode implantation, while 35 had pneumocephalus after the second electrode implantation. Accumulation of intracranial air following the first electrode implantation (4.49 ± 6.05 cm3) was significantly correlated with brain shift along the y axis (0.04 ± 0.35 mm; r (34) = 0.36; p = 0.03), as well as the Euclidean distance of deviation (0.57 ± 0.33 mm; r (34) = 0.33; p = 0.05) indicating statistically significant shift on the ipsilateral side. However, there was no significant correlation between intracranial air and brain shift following the second electrode implantation, suggesting contralateral shift is minimal. Furthermore, there was no significant difference in brain shift between patients with and without radiographic evidence of intracranial air following both electrode implantation surgeries. CONCLUSION: Despite observing volumes as high as 22.0 cm3 in patients with radiographic evidence of pneumocephalus, there was no significant difference in brain shift when compared to patients without pneumocephalus. Furthermore, the mean magnitude of brain shift was <1.0 mm regardless of whether pneumocephalus was presenting, suggesting that intracranial air accumulation may not produce clinical significant brain shift in our patients.

Primary somatosensory cortex organization for engineering artificial somatosensation.

Somatosensory deficits from stroke, spinal cord injury, or other neurologic damage can lead to a significant degree of functional impairment. The primary (SI) and secondary (SII) somatosensory cortices encode information in a medial to lateral organization. SI is generally organized topographically, with more discrete cortical representations of specific body regions. SII regions corresponding to anatomical areas are less discrete and may represent a more functional rather than topographic organization. Human somatosensory research continues to map cortical areas of sensory processing with efforts primarily focused on hand and upper extremity information in SI. However, research into SII and other body regions is lacking. In this review, we synthesize the current state of knowledge regarding the cortical organization of human somatosensation and discuss potential applications for brain computer interface. In addition to accurate individualized mapping of cortical somatosensation, further research is required to uncover the neurophysiological mechanisms of how somatosensory information is encoded in the cortex.

Pilot Study to Investigate the Use of In-Clinic Sensing to Identify Optimal Stimulation Parameters for Deep Brain Stimulation Therapy in Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) programming is time intensive. Recent advances in sensing technology of local field potentials (LFPs) may enable improvements. Few studies have compared the use of this technology with standard of care. OBJECTIVE/HYPOTHESIS: Sensing technology of subthalamic nucleus (STN) DBS leads in Parkinson's disease (PD) is reliable and predicts the optimal contacts and settings as predicted by clinical assessment. MATERIALS AND METHODS: Five subjects with PD (n = 9 hemispheres) with bilateral STN DBS and sensing capable battery replacement were recruited. An LFP sensing review of all bipolar contact pairs was performed three times. Contact with the maximal beta peak power (MBP) was then clinically assessed in a double-blinded fashion, and five conditions were tested: 1) entry settings, 2) off stimulation, 3) MBP at 30 µs, 4) MBP at 60 µs, and 5) MBP at 90 µs. RESULTS: Contact and frequency of the MBP power in all hemispheres did not differ across sessions. The entry settings matched with the contact with the MBP power in 5 of 9 hemispheres. No clinical difference was evident in the stimulation conditions. The clinician and subject preferred settings determined by MBP power in 7 of 9 and 5 of 7 hemispheres, respectively. CONCLUSIONS: This study indicates that STN LFPs in PD recorded directly from contacts of the DBS lead provide consistent recordings across the frequency range and a reliably detected beta peak. Furthermore, programming based on the MBP power provides at least clinical equivalence to standard of care programming with STN DBS.

Comparison of Monopolar Review to Fixed Parameter Fractionation in Deep Brain Stimulation.

Background: Technological advancements in deep brain stimulation (DBS) require methodological changes in programming. Fractionalization poses significant practical challenges for the most common approach for assessing DBS efficacy, monopolar review (MR). Objectives: Two DBS programming methods: MR and fixed parameter vertical and horizontal fractionalization (FPF) were compared. Methods: A two-phase process of vertical and horizontal FPF was performed. MR was conducted thereafter. After a short wash-out period, both optimal configurations determined by MR and FPF were tested in a double-blind randomized manner. Results: Seven PD patients were enrolled, providing 11 hemispheres to compare the two conditions. In all subjects, the blinded examiner selected a directional or fractionalization configuration. There was no significant difference in clinical benefits between MR and FPF. FPF was the preferred method for initial programming as selected by subject and clinician. Conclusions: FPF programming is a viable and efficient methodology that may be incorporated into clinical practice.

Oscillatory beta dynamics inform biomarker-driven treatment optimization for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons and dysregulation of the basal ganglia. Cardinal motor symptoms include bradykinesia, rigidity, and tremor. Deep brain stimulation (DBS) of select subcortical nuclei is standard of care for medication-refractory PD. Conventional open-loop DBS delivers continuous stimulation with fixed parameters that do not account for a patient's dynamic activity state or medication cycle. In comparison, closed-loop DBS, or adaptive DBS (aDBS), adjusts stimulation based on biomarker feedback that correlates with clinical state. Recent work has identified several neurophysiological biomarkers in local field potential recordings from PD patients, the most promising of which are 1) elevated beta (∼13-30 Hz) power in the subthalamic nucleus (STN), 2) increased beta synchrony throughout basal ganglia-thalamocortical circuits, notably observed as coupling between the STN beta phase and cortical broadband gamma (∼50-200 Hz) amplitude, and 3) prolonged beta bursts in the STN and cortex. In this review, we highlight relevant frequency and time domain features of STN beta measured in PD patients and summarize how spectral beta power, oscillatory beta synchrony, phase-amplitude coupling, and temporal beta bursting inform PD pathology, neurosurgical targeting, and DBS therapy. We then review how STN beta dynamics inform predictive, biomarker-driven aDBS approaches for optimizing PD treatment. We therefore provide clinically useful and actionable insight that can be applied toward aDBS implementation for PD.

Corrigendum: The role of the piriform cortex in temporal lobe epilepsy: A current literature review.

[This corrects the article DOI: 10.3389/fneur.2022.1042887.].

The role of the piriform cortex in temporal lobe epilepsy: A current literature review.

Temporal lobe epilepsy is the most common form of focal epilepsy and can have various detrimental consequences within many neurologic domains. Recent evidence suggests that the piriform cortex may also be implicated in seizure physiology. The piriform cortex is a primary component of the olfactory network and is located at the junction of the frontal and temporal lobes, wrapping around the entorhinal sulcus. Similar to the hippocampus, it is a tri-layered allocortical structure, with connections to many adjacent regions including the orbitofrontal cortex, amygdala, peri- and entorhinal cortices, and insula. Both animal and human studies have implicated the piriform cortex as a critical node in the temporal lobe epilepsy network. It has additionally been shown that resection of greater than half of the piriform cortex may significantly increase the odds of achieving seizure freedom. Laser interstitial thermal therapy has also been shown to be an effective treatment strategy with recent evidence hinting that ablation of the piriform cortex may be important for seizure control as well. We propose that sampling piriform cortex in intracranial stereoelectroencephalography (sEEG) procedures with the use of a temporal pole or amygdalar electrode would be beneficial for further understanding the role of the piriform cortex in temporal lobe epilepsy.

Automatic extraction of upper-limb kinematic activity using deep learning-based markerless tracking during deep brain stimulation implantation for Parkinson's disease: A proof of concept study.

Optimal placement of deep brain stimulation (DBS) therapy for treating movement disorders routinely relies on intraoperative motor testing for target determination. However, in current practice, motor testing relies on subjective interpretation and correlation of motor and neural information. Recent advances in computer vision could improve assessment accuracy. We describe our application of deep learning-based computer vision to conduct markerless tracking for measuring motor behaviors of patients undergoing DBS surgery for the treatment of Parkinson's disease. Video recordings were acquired during intraoperative kinematic testing (N = 5 patients), as part of standard of care for accurate implantation of the DBS electrode. Kinematic data were extracted from videos post-hoc using the Python-based computer vision suite DeepLabCut. Both manual and automated (80.00% accuracy) approaches were used to extract kinematic episodes from threshold derived kinematic fluctuations. Active motor epochs were compressed by modeling upper limb deflections with a parabolic fit. A semi-supervised classification model, support vector machine (SVM), trained on the parameters defined by the parabolic fit reliably predicted movement type. Across all cases, tracking was well calibrated (i.e., reprojection pixel errors 0.016-0.041; accuracies >95%). SVM predicted classification demonstrated high accuracy (85.70%) including for two common upper limb movements, arm chain pulls (92.30%) and hand clenches (76.20%), with accuracy validated using a leave-one-out process for each patient. These results demonstrate successful capture and categorization of motor behaviors critical for assessing the optimal brain target for DBS surgery. Conventional motor testing procedures have proven informative and contributory to targeting but have largely remained subjective and inaccessible to non-Western and rural DBS centers with limited resources. This approach could automate the process and improve accuracy for neuro-motor mapping, to improve surgical targeting, optimize DBS therapy, provide accessible avenues for neuro-motor mapping and DBS implantation, and advance our understanding of the function of different brain areas.

Quantifying neuro-motor correlations during awake deep brain stimulation surgery using markerless tracking.

The expanding application of deep brain stimulation (DBS) therapy both drives and is informed by our growing understanding of disease pathophysiology and innovations in neurosurgical care. Neurophysiological targeting, a mainstay for identifying optimal, motor responsive targets, has remained largely unchanged for decades. Utilizing deep learning-based computer vision and related computational methods, we developed an effective and simple intraoperative approach to objectively correlate neural signals with movements, automating and standardizing the otherwise manual and subjective process of identifying ideal DBS electrode placements. Kinematics are extracted from video recordings of intraoperative motor testing using a trained deep neural network and compared to multi-unit activity recorded from the subthalamic nucleus. Neuro-motor correlations were quantified using dynamic time warping with the strength of a given comparison measured by comparing against a null distribution composed of related neuro-motor correlations. This objective measure was then compared to clinical determinations as recorded in surgical case notes. In seven DBS cases for treatment of Parkinson's disease, 100 distinct motor testing epochs were extracted for which clear clinical determinations were made. Neuro-motor correlations derived by our automated system compared favorably with expert clinical decision making in post-hoc comparisons, although follow-up studies are necessary to determine if improved correlation detection leads to improved outcomes. By improving the classification of neuro-motor relationships, the automated system we have developed will enable clinicians to maximize the therapeutic impact of DBS while also providing avenues for improving continued care of treated patients.

Melanoma metastasis to a nonfunctioning pituitary macroadenoma: illustrative case.

BACKGROUND: Metastases to the central nervous system are often multiple in number and typically favor the gray-white matter junction. Collision tumors, defined as the coexistence of two morphologically different tumors, such as metastases to a known pituitary adenoma (PA), are exceedingly rare. Only a few reported cases of metastases to a PA exist in the literature. OBSERVATIONS: The authors present the case of a 64-year-old man with a known history of stage IV metastatic melanoma who was found to have hypermetabolic activity in the sellar region on surveillance positron emission tomography. On laboratory evaluation, he had clear evidence of pituitary axis dysfunction without diabetes insipidus. Subsequent magnetic resonance imaging showed a 2.4-cm sellar mass with features of a pituitary macroadenoma and internal hemorrhage, although no clinical symptoms of apoplexy were noted. He underwent a transsphenoidal endoscopic endonasal approach for resection of the sellar lesion. Final pathology showed a collision tumor with melanoma cells intermixed with PA cells. LESSONS: Histological analysis verified the rare presence of a collision tumor of a melanoma metastasis to a nonfunctional pituitary macroadenoma. Metastasis to a preexisting PA, although rare, should be considered in the differential diagnosis in patients with sellar lesions and a known cancer history.

Mapping of primary somatosensory cortex of the hand area using a high-density electrocorticography grid for closed-loop brain computer interface.

Objective.The ideal modality for generating sensation in sensorimotor brain computer interfaces (BCI) has not been determined. Here we report the feasibility of using a high-density 'mini'-electrocorticography (mECoG) grid in a somatosensory BCI system.Approach.Thirteen subjects with intractable epilepsy underwent standard clinical implantation of subdural electrodes for the purpose of seizure localization. An additional high-density mECoG grid was placed (Adtech, 8 by 8, 1.2 mm exposed, 3 mm center-to-center spacing) over the hand area of primary somatosensory cortex. Following implantation, cortical mapping was performed with stimulation parameters of frequency: 50 Hz, pulse-width: 250µs, pulse duration: 4 s, polarity: alternating, and current that ranged from 0.5 mA to 12 mA at the discretion of the epileptologist. Location of the evoked sensory percepts was recorded along with a description of the sensation. The hand was partitioned into 48 distinct boxes. A box was included if sensation was felt anywhere within the box.Main results.The percentage of the hand covered was 63.9% (± 34.4%) (mean ± s.d.). Mean redundancy, measured as electrode pairs stimulating the same box, was 1.9 (± 2.2) electrodes per box; and mean resolution, measured as boxes included per electrode pair stimulation, was 11.4 (± 13.7) boxes with 8.1 (± 10.7) boxes in the digits and 3.4 (± 6.0) boxes in the palm. Functional utility of the system was assessed by quantifying usable percepts. Under the strictest classification, 'dermatomally exclusive' percepts, the mean was 2.8 usable percepts per grid. Allowing 'perceptually unique' percepts at the same anatomical location, the mean was 5.5 usable percepts per grid.Significance.Compared to the small area of coverage and redundancy of a microelectrode system, or the poor resolution of a standard ECoG grid, a mECoG is likely the best modality for a somatosensory BCI system with good coverage of the hand and minimal redundancy.

Gamma-band modulation in the human amygdala during reaching movements.

OBJECTIVE: Motor brain-computer interface (BCI) represents a new frontier in neurological surgery that could provide significant benefits for patients living with motor deficits. Both the primary motor cortex and posterior parietal cortex have successfully been used as a neural source for human motor BCI, leading to interest in exploring other brain areas involved in motor control. The amygdala is one area that has been shown to have functional connectivity to the motor system; however, its role in movement execution is not well studied. Gamma oscillations (30-200 Hz) are known to be prokinetic in the human cortex, but their role is poorly understood in subcortical structures. Here, the authors use direct electrophysiological recordings and the classic "center-out" direct-reach experiment to study amygdaloid gamma-band modulation in 8 patients with medically refractory epilepsy. METHODS: The study population consisted of 8 epilepsy patients (2 men; age range 21-62 years) who underwent implantation of micro-macro depth electrodes for seizure localization and EEG monitoring. Data from the macro contacts sampled at 2000 Hz were used for analysis. The classic center-out direct-reach experiment was used, which consists of an intertrial interval phase, a fixation phase, and a response phase. The authors assessed the statistical significance of neural modulation by inspecting for nonoverlapping areas in the 95% confidence intervals of spectral power for the response and fixation phases. RESULTS: In 5 of the 8 patients, power spectral analysis showed a statistically significant increase in power within regions of the gamma band during the response phase compared with the fixation phase. In these 5 patients, the 95% bootstrapped confidence intervals of trial-averaged power in contiguous frequencies of the gamma band during the response phase were above, and did not overlap with, the confidence intervals of trial-averaged power during the fixation phase. CONCLUSIONS: To the authors' knowledge, this is the first time that direct neural recordings have been used to show gamma-band modulation in the human amygdala during the execution of voluntary movement. This work indicates that gamma-band modulation in the amygdala could be a contributing source of neural signals for use in a motor BCI system.

Beta-band power modulation in the human hippocampus during a reaching task.

OBJECTIVE: Characterize the role of the beta-band (13-30 Hz) in the human hippocampus during the execution of voluntary movement. APPROACH: We recorded electrophysiological activity in human hippocampus during a reach task using stereotactic electroencephalography (SEEG). SEEG has previously been utilized to study the theta band (3-8 Hz) in conflict processing and spatial navigation, but most studies of hippocampal activity during movement have used noninvasive measures such as fMRI. We analyzed modulation in the beta band (13-30 Hz), which is known to play a prominent role throughout the motor system including the cerebral cortex and basal ganglia. We conducted the classic 'center-out' direct-reach experiment with nine patients undergoing surgical treatment for medically refractory epilepsy. MAIN RESULTS: In seven of the nine patients, power spectral analysis showed a statistically significant decrease in power within the beta band (13-30 Hz) during the response phase, compared to the fixation phase, of the center-out direct-reach task using the Wilcoxon signed-rank hypothesis test (p < 0.05). SIGNIFICANCE: This finding is consistent with previous literature suggesting that the hippocampus may be involved in the execution of movement, and it is the first time that changes in beta-band power have been demonstrated in the hippocampus using human electrophysiology. Our findings suggest that beta-band modulation in the human hippocampus may play a role in the execution of voluntary movement.

A Phantom Study of the Spatial Precision and Accuracy of Stereotactic Localization Using Computed Tomography Imaging with the Leksell Stereotactic System.

BACKGROUND: Stereotactic localization of neurosurgical targets traditionally relies on computed tomography (CT), which is considered the optimal imaging modality for geometric accuracy. However, in-depth investigations that characterize the precision and accuracy of CT images are lacking. We used a CT phantom to examine interscanner precision and interprotocol accuracy in coordinate localization. METHODS: A polymethylacrylate phantom was scanned with Toshiba Aquilion 64 and GE Healthcare LightSpeed 16 CT scanners, using both helical and incremental single-slice (SS) image acquisition protocols. The X, Y, and Z coordinates of 94 points across 6 surfaces of the phantom were physically measured. The CT scan-derived coordinates were compared with the phantom coordinates and with each other to determine accuracy and precision, respectively. RESULTS: Using the SS imaging protocol, the mean (SD) interscanner disparity in localization was 0.93 (0.39) mm, given by the average Euclidean distance between the coordinates of the 2 scanners. This discrepancy significantly varied by axis and surface, with the greatest discrepancy in the Z-axis of 0.30 mm (95% confidence interval, 0.25-0.35; P = 0.05) and on the superior surface of 1.30 mm (95% confidence interval, 1.15-1.45; P = 0.05). SS acquisition was significantly more accurate than the helical protocol. CONCLUSIONS: We found evidence of clinically relevant inconsistency between 2 CT scanners used for stereotactic localization. SS image acquisition was superior to helical scanning with respect to localization accuracy. Interscanner consistency cannot be assumed. Institutions would benefit from identifying the errors inherent in their CT scanners.

Utility and lower limits of frequency detection in surface electrode stimulation for somatosensory brain-computer interface in humans.

OBJECTIVE: Stimulation of the primary somatosensory cortex (S1) has been successful in evoking artificial somatosensation in both humans and animals, but much is unknown about the optimal stimulation parameters needed to generate robust percepts of somatosensation. In this study, the authors investigated frequency as an adjustable stimulation parameter for artificial somatosensation in a closed-loop brain-computer interface (BCI) system. METHODS: Three epilepsy patients with subdural mini-electrocorticography grids over the hand area of S1 were asked to compare the percepts elicited with different stimulation frequencies. Amplitude, pulse width, and duration were held constant across all trials. In each trial, subjects experienced 2 stimuli and reported which they thought was given at a higher stimulation frequency. Two paradigms were used: first, 50 versus 100 Hz to establish the utility of comparing frequencies, and then 2, 5, 10, 20, 50, or 100 Hz were pseudorandomly compared. RESULTS: As the magnitude of the stimulation frequency was increased, subjects described percepts that were "more intense" or "faster." Cumulatively, the participants achieved 98.0% accuracy when comparing stimulation at 50 and 100 Hz. In the second paradigm, the corresponding overall accuracy was 73.3%. If both tested frequencies were less than or equal to 10 Hz, accuracy was 41.7% and increased to 79.4% when one frequency was greater than 10 Hz (p = 0.01). When both stimulation frequencies were 20 Hz or less, accuracy was 40.7% compared with 91.7% when one frequency was greater than 20 Hz (p < 0.001). Accuracy was 85% in trials in which 50 Hz was the higher stimulation frequency. Therefore, the lower limit of detection occurred at 20 Hz, and accuracy decreased significantly when lower frequencies were tested. In trials testing 10 Hz versus 20 Hz, accuracy was 16.7% compared with 85.7% in trials testing 20 Hz versus 50 Hz (p < 0.05). Accuracy was greater than chance at frequency differences greater than or equal to 30 Hz. CONCLUSIONS: Frequencies greater than 20 Hz may be used as an adjustable parameter to elicit distinguishable percepts. These findings may be useful in informing the settings and the degrees of freedom achievable in future BCI systems.

Comparison of Intraoperative 3-Dimensional Fluoroscopy With Standard Computed Tomography for Stereotactic Frame Registration.

BACKGROUND: Three-dimensional fluoroscopy via the O-arm (Medtronic, Dublin, Ireland) has been validated for intraoperative confirmation of successful lead placement in stereotactic electrode implantation. However, its role in registration and targeting has not yet been studied. After frame placement, many stereotactic neurosurgeons obtain a computed tomography (CT) scan and merge it with a preoperative magnetic resonance imaging (MRI) scan to generate planning coordinates; potential disadvantages of this practice include increased procedure time and limited scanner availability. OBJECTIVE: To evaluate whether the second-generation O-arm (O2) can be used in lieu of a traditional CT scan to obtain accurate frame-registration scans. METHODS: In 7 patients, a postframe placement CT scan was merged with preoperative MRI and used to generate lead implantation coordinates. After implantation, the fiducial box was again placed on the patient to obtain an O2 confirmation scan. Vector, scalar, and Euclidean differences between analogous X, Y, and Z coordinates from fused O2/MRI and CT/MRI scans were calculated for 33 electrode target coordinates across 7 patients. RESULTS: Marginal means of difference for vector (X = -0.079 ± 0.099 mm; Y = -0.076 ± 0.134 mm; Z = -0.267 ± 0.318 mm), scalar (X = -0.146 ± 0.160 mm; Y = -0.306 ± 0.106 mm; Z = 0.339 ± 0.407 mm), and Euclidean differences (0.886 ± 0.190 mm) remained within the predefined equivalence margin differences of -2 mm and 2 mm. CONCLUSION: This study demonstrates that O2 may emerge as a viable alternative to the traditional CT scanner for generating planning coordinates. Adopting the O2 as a perioperative tool may offer reduced transport risks, decreased anesthesia time, and greater surgical efficiency.

Functional Frequency Discrimination From Cortical Somatosensory Stimulation in Humans.

Recently, efforts to produce artificial sensation through cortical stimulation of primary somatosensory cortex (PSC) in humans have proven safe and reliable. Changes in stimulation parameters like frequency and amplitude have been shown to elicit different percepts, but without clearly defined psychometric profiles. This study investigates the functionally useful limits of frequency changes on the percepts felt by three epilepsy patients with subdural electrocorticography (ECoG) grids. Subjects performing a hidden target task were stimulated with parameters of constant amplitude, pulse-width, and pulse-duration, and a randomly selected set of two frequencies (20, 30, 40, 50, 60, and 100 Hz). They were asked to decide which target had the "higher" frequency. Objectively, an increase in frequency differences was associated with an increase in perceived intensity. Reliable detection of stimulation occurred at and above 40 Hz with a lower limit of detection around 20 Hz and a just-noticeable difference estimated at less than 10 Hz. These findings suggest that frequency can be used as a reliable, adjustable parameter and may be useful in establishing settings and thresholds of functionality in future BCI systems.

Clinical neuroprosthetics: Today and tomorrow.

Implantable neurostimulation devices provide a direct therapeutic link to the nervous system and can be considered brain-computer interfaces (BCI). Under this definition, BCI are not simply science fiction, they are part of existing neurosurgical practice. Clinical BCI are standard of care for historically difficult to treat neurological disorders. These systems target the central and peripheral nervous system and include Vagus Nerve Stimulation, Responsive Neurostimulation, and Deep Brain Stimulation. Recent advances in clinical BCI have focused on creating "closed-loop" systems. These systems rely on biomarker feedback and promise individualized therapy with optimal stimulation delivery and minimal side effects. Success of clinical BCI has paralleled research efforts to create BCI that restore upper extremity motor and sensory function to patients. Efforts to develop closed loop motor/sensory BCI is linked to the successes of today's clinical BCI.

Directional tuning during reach planning in the supramarginal gyrus using local field potentials.

Previous work in directional tuning for brain machine interfaces has primarily relied on algorithm sorted neuronal action potentials in primary motor cortex. However, local field potential has been utilized to show directional tuning in macaque studies, and inferior parietal cortex has shown increased neuronal activity in reaching tasks that relied on MRI imaging. In this study we utilized local field potential recordings from a human subject performing a delayed reach task and show that high frequency band (76-100 Hz) spectral power is directionally tuned to different reaching target locations during an active reach. We also show that during the delay phase of the task, directional tuning is present in areas of the inferior parietal cortex, in particular, the supramarginal gyrus.