Jimmy C. Yang

Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time-consuming. In addition, the electrode grids that are used to measure brain activity and to identify the boundaries of pathological versus functional brain regions have low resolution and limited conformity to the brain surface. Here, we present the development of an intracranial electroencephalogram (iEEG)–microdisplay that consists of freestanding arrays of 2048 GaN light-emitting diodes laminated on the back of micro-electrocorticography electrode grids. With a series of proof-of-concept experiments in rats and pigs, we demonstrate that these iEEG-microdisplays allowed us to perform real-time iEEG recordings and display cortical activities by spatially corresponding light patterns on the surface of the brain in the surgical field. Furthermore, iEEG-microdisplays allowed us to identify and display cortical landmarks and pathological activities from rat and pig models. Using a dual-color iEEG-microdisplay, we demonstrated coregistration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The iEEG-microdisplay holds promise to facilitate monitoring of pathological brain activity in clinical settings.

Objective: Based on the promising results of randomized controlled trials, deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used increasingly in the treatment of patients with drug‐resistant epilepsy. Drug‐resistant temporal lobe epilepsy (TLE) is an indication for either DBS of the anterior nucleus of the thalamus (ANT) or temporal lobe (TL) RNS, but there are no studies that directly compare the seizure benefits and adverse effects associated with these therapies in this patient population. We, therefore, examined all patients who underwent ANT‐DBS or TL‐RNS for drug‐resistant TLE at our center.Methods: We performed a retrospective review of patients who were treated with either ANT‐DBS or TL‐RNS for drug‐resistant TLE with at least 12 months of follow‐up. Along with the clinical characteristics of each patient's epilepsy, seizure frequency was recorded throughout each patient's postoperative clinical course.Results: Twenty‐six patients underwent ANT‐DBS implantation and 32 patients underwent TL‐RNS for drug‐resistant TLE. The epilepsy characteristics of both groups were similar. Patients who underwent ANT‐DBS demonstrated a median seizure reduction of 58% at 12–15 months, compared to a median seizure reduction of 70% at 12–15 months in patients treated with TL‐RNS (p > .05). The responder rate (percentage of patients with a 50% decrease or more in seizure frequency) was 54% for ANT‐DBS and 56% for TL‐RNS (p > .05). The incidence of complications and stimulation‐related side effects did not significantly differ between therapies.Significance: We demonstrate in our single‐center experience that patients with drug‐resistant TLE benefit similarly from either ANT‐DBS or TL‐RNS. Selection of either ANT‐DBS or TL‐RNS may, therefore, depend more heavily on patient and provider preference, as each has unique capabilities and configurations. Future studies will consider subgroup analyses to determine if specific patients have greater seizure frequency reduction from one form of neuromodulation strategy over another.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Despite improvements in survival, treatments that improve functional outcome remain lacking. There is, therefore, a pressing need to develop novel treatments to improve functional recovery. Here, we investigated task-matched deep-brain stimulation of the nucleus accumbens (NAc) to augment reinforcement learning in a rodent model of TBI. We demonstrate that task-matched deep brain stimulation (DBS) of the NAc can enhance learning following TBI. We further demonstrate that animals receiving DBS exhibited greater behavioral improvement and enhanced neural proliferation. Treated animals recovered to an uninjured behavioral baseline and showed retention of improved performance even after stimulation was stopped. These results provide encouraging early evidence for the potential of NAc DBS to improve functional outcomes following TBI and that its effects may be broad, with alterations in neurogenesis and synaptogenesis.

Electrophysiological devices are critical for mapping eloquent and diseased brain regions and for therapeutic neuromodulation in clinical settings and are extensively used for research in brain-machine interfaces. However, the existing clinical and experimental devices are often limited in either spatial resolution or cortical coverage. Here, we developed scalable manufacturing processes with a dense electrical connection scheme to achieve reconfigurable thin-film, multithousand-channel neurophysiological recording grids using platinum nanorods (PtNRGrids). With PtNRGrids, we have achieved a multithousand-channel array of small (30 μm) contacts with low impedance, providing high spatial and temporal resolution over a large cortical area. We demonstrated that PtNRGrids can resolve submillimeter functional organization of the barrel cortex in anesthetized rats that captured the tissue structure. In the clinical setting, PtNRGrids resolved fine, complex temporal dynamics from the cortical surface in an awake human patient performing grasping tasks. In addition, the PtNRGrids identified the spatial spread and dynamics of epileptic discharges in a patient undergoing epilepsy surgery at 1-mm spatial resolution, including activity induced by direct electrical stimulation. Collectively, these findings demonstrated the power of the PtNRGrids to transform clinical mapping and research with brain-machine interfaces.

No clear evidence‐based treatment paradigm currently exists for refractory and super‐refractory status epilepticus, which can result in significant mortality and morbidity. While patients are typically treated with antiepileptic drugs and anesthetics, neurosurgical neuromodulation techniques can also be considered. We present a novel case in which responsive neurostimulation was used to effectively treat a patient who had developed super‐refractory status epilepticus, later consistent with epilepsia partialis continua, that was refractory to antiepileptic drugs, immunomodulatory therapies, and transcranial magnetic stimulation. This case demonstrates how regional therapy provided by responsive neurostimulation can be effective in treating super‐refractory status epilepticus through neuromodulation of seizure networks.

Objective: Interictal discharges (IIDs) and high frequency oscillations (HFOs) are neurophysiologic biomarkers of epilepsy. In this study, we use custom poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) microelectrodes to better understand their microscale dynamics. Methods: Electrodes with spatial resolution down to 50µm were used to record intraoperatively in 30 subjects. For IIDs, putative spatiotemporal paths were generated by peak-tracking, followed by clustering. For HFOs, repeating patterns were elucidated by clustering similar time windows. Fast events, consistent with multi-unit activity (MUA), were covaried with either IIDs or HFOs. Results: IIDs seen across the entire array were detected in 93% of subjects. Local IIDs, observed across <50% of the array, were seen in 53% of subjects. IIDs appeared to travel across the array in specific paths, and HFOs appeared in similar repeated spatial patterns. Finally, microseizure events were identified spanning 50-100µm. HFOs covaried with MUA, but not with IIDs. Conclusions: Overall, these data suggest micro-domains of irritable cortex that form part of an underlying pathologic architecture that contributes to the seizure network. Significance: Microelectrodes in cases of human epilepsy can reveal dynamics that are not seen by conventional electrocorticography and point to new possibilities for their use in the diagnosis and treatment of epilepsy. Highlights: PEDOT:PSS microelectrodes with at least 50µm spatial resolution uniquely reveal spatiotemporal patterns of markers of epilepsy High spatiotemporal resolution allows interictal discharges to be tracked and reveal cortical domains involved in microseizures High frequency oscillations detected by microelectrodes demonstrate localized clustering on the cortical surface