A novel neural prosthesis providing long-term electrocorticography recording and cortical stimulation for epilepsy and brain-computer interface

J Neurosurg 130:1166–1179, 2019

Wireless technology is a novel tool for the transmission of cortical signals. Wireless electrocorticography (ECoG) aims to improve the safety and diagnostic gain of procedures requiring invasive localization of seizure foci and also to provide long-term recording of brain activity for brain-computer interfaces (BCIs). However, no wireless devices aimed at these clinical applications are currently available. The authors present the application of a fully implantable and externally rechargeable neural prosthesis providing wireless ECoG recording and direct cortical stimulation (DCS). Prolonged wireless ECoG monitoring was tested in nonhuman primates by using a custom-made device (the ECoG im- plantable wireless 16-electrode [ECOGIW-16E] device) containing a 16-contact subdural grid. This is a preliminary step toward large-scale, long-term wireless ECoG recording in humans.

METHODS The authors implanted the ECOGIW-16E device over the left sensorimotor cortex of a nonhuman primate (Macaca fascicularis), recording ECoG signals over a time span of 6 months. Daily electrode impedances were mea- sured, aiming to maintain the impedance values below a threshold of 100 KW. Brain mapping was obtained through wireless cortical stimulation at fixed intervals (1, 3, and 6 months). After 6 months, the device was removed. The authors analyzed cortical tissues by using conventional histological and immunohistological investigation to assess whether there was evidence of damage after the long-term implantation of the grid.

RESULTS The implant was well tolerated; no neurological or behavioral consequences were reported in the monkey, which resumed his normal activities within a few hours of the procedure. The signal quality of wireless ECoG remained excellent over the 6-month observation period. Impedance values remained well below the threshold value; the average impedance per contact remains approximately 40 KW. Wireless cortical stimulation induced movements of the upper and lower limbs, and elicited fine movements of the digits as well. After the monkey was euthanized, the grid was found to be encapsulated by a newly formed dural sheet. The grid removal was performed easily, and no direct adhesions of the grid to the cortex were found. Conventional histological studies showed no cortical damage in the brain region covered by
the grid, except for a single microscopic spot of cortical necrosis (not visible to the naked eye) in a region that had under- gone repeated procedures of electrical stimulation. Immunohistological studies of the cortex underlying the grid showed
a mild inflammatory process.

CONCLUSIONS This preliminary experience in a nonhuman primate shows that a wireless neuroprosthesis, with related long-term ECoG recording (up to 6 months) and multiple DCSs, was tolerated without sequelae. The authors predict that epilepsy surgery could realize great benefit from this novel prosthesis, providing an extended time span for ECoG recording.

Continuous subcortical motor evoked potential stimulation using the tip of an ultrasonic aspirator for the resection of motor eloquent lesions

Continuous subcortical motor evoked potential stimulation

J Neurosurg 123:301–306, 2015

Resection of a motor eloquent lesion has become safer because of intraoperative neurophysiological monitoring (IOM). Stimulation of subcortical motor evoked potentials (scMEPs) is increasingly used to optimize patient safety. So far, scMEP stimulation has been performed intermittently during resection of eloquently located lesions. Authors of the present study assessed the possibility of using a resection instrument for continuous stimulation of scMEPs.

Methods An ultrasonic surgical aspirator was attached to an IOM stimulator and was used as a monopolar subcortical stimulation probe. The effect of the aspirator’s use at different ultrasound power levels (0%, 25%, 50%, 75%, and 100%) on stimulation intensity was examined in a saline bath. Afterward monopolar stimulation with the surgical aspirator was used during the resection of subcortical lesions in the vicinity of the corticospinal tract in 14 patients in comparison with scMEP stimulation via a standard stimulation electrode. During resection, the stimulation current at which an MEP response was still measurable with subcortical stimulation using the surgical aspirator was compared with the corresponding stimulation current needed using a standard monopolar subcortical stimulation probe at the same location.

Results The use of ultrasound at different energy levels did result in a slight but irrelevant increase in stimulation energy via the tip of the surgical aspirator in the saline bath. Stimulation of scMEPs using the surgical aspirator or monopolar probe was successful and almost identical in all patients. One patient developed a new permanent neurological deficit. Transient new postoperative paresis was observed in 28% (4 of 14) of cases. Gross-total resection was achieved in 64% (9 of 14) cases and subtotal resection (> 80% of tumor mass) in 35% (5 of 14).

Conclusions Continuous motor mapping using subcortical stimulation via a surgical aspirator, in comparison with the sequential use of a standard monopolar stimulation probe, is a feasible and safe method without any disadvantages. Compared with the standard probe, the aspirator offers continuous information on the distance to the corticospinal tract.

Epidural Cortical Stimulation of the Left Dorsolateral Prefrontal Cortex for Refractory Major Depressive Disorder

Neurosurgery 69:1015–1029, 2011 DOI: 10.1227/NEU.0b013e318229cfcd

A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated.

OBJECTIVE: To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study.

METHODS: Twelve patients were recruited in this randomized, single-blind, shamcontrolled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest.

RESULTS: During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P . .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had ≥40% improvement, 5 patients had ≥ 50% improvement, and 4 subjects achieved remission (HDRS , 10) at some point during the study.

CONCLUSION: Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment- refractory major depressive disorder.

Resection of malignant brain tumors in eloquent cortical areas: a new multimodal approach combining 5-aminolevulinic acid and intraoperative monitoring

J Neurosurg 113:352–357, 2010.DOI: 10.3171/2009.10.JNS09447

Object. Several studies have revealed that the gross-total resection (GTR) of malignant brain tumors has a significant influence on patient survival. Frequently, however, GTR cannot be achieved because the borders between healthy brain and diseased tissue are blurred in the infiltration zones of malignant brain tumors. Especially in eloquent cortical areas, resection is frequently stopped before total removal is achieved to avoid causing neurological deficits. Interestingly, 5-aminolevulinic acid (5-ALA) has been shown to help visualize tumor tissue intraoperatively and, thus, can significantly improve the possibility of achieving GTR of primary malignant brain tumors. The aim of this study was to go one step further and evaluate the utility and limitations of fluorescence-guided resections of primary malignant brain tumors in eloquent cortical areas in combination with intraoperative monitoring based on multimodal functional imaging data. Methods. Eighteen patients with primary malignant brain tumors in eloquent areas were included in this prospective study. Preoperative neuroradiological examinations included MR imaging with magnetization-prepared rapid gradient echo (MPRAGE), functional MR, and diffusion tensor imaging sequences to visualize functional areas and fiber tracts. Imaging data were analyzed offline, loaded into a neuronavigational system, and used intraoperatively during resections. All patients received 5-ALA 6 hours before surgery. Fluorescence-guided tumor resections were combined with intraoperative monitoring and cortical as well as subcortical stimulation to localize functional areas and fiber tracts during surgery. Results. Twenty-five procedures were performed in 18 consecutive patients. In 24% of all surgeries, resection was stopped because a functional area or cortical tract was identified in the resection area or because motor evoked potential amplitudes were reduced in an area where fluorescent tumor cells were still seen intraoperatively. Grosstotal resection could be achieved in 16 (64%) of the surgeries with preservation of all functional areas and fiber tracts. In 2 patients presurgical hemiparesis became accentuated postoperatively, and 1 of these patients also suffered from a new homonymous hemianopia following a second resection. Conclusions. The authors’ first results show that tumor resections with 5-ALA in combination with intraoperative cortical stimulation have the advantages of both methods and, thus, provide additional safety for the neurosurgeon during resections of primary malignant brain tumors in eloquent areas. Nonetheless, more cases and additional studies are necessary to further prove the advantages of this multimodal strategy.