Thalamic Stimulation Improves Postictal Cortical Arousal and Behavior.

The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. Previous work in disorders of consciousness including the postictal state suggests that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) may improve level of arousal. We tested the effects of postictal thalamic CL DBS in a rat model of secondarily generalized seizures elicited by electrical hippocampal stimulation. Thalamic CL DBS was delivered at 100 Hz during the postictal period in 21 female rats while measuring cortical electrophysiology and behavior. The postictal period was characterized by frontal cortical slow waves, like other states of depressed consciousness. In addition, rats exhibited severely impaired responses on two different behavioral tasks in the postictal state. Thalamic CL stimulation prevented postictal cortical slow wave activity but produced only modest behavioral improvement on a spontaneous licking sucrose reward task. We therefore also tested responses using a lever-press shock escape/avoidance (E/A) task. Rats achieved high success rates responding to the sound warning on the E/A task even during natural slow wave sleep but were severely impaired in the postictal state. Unlike the spontaneous licking task, thalamic CL DBS during the E/A task produced a marked improvement in behavior, with significant increases in lever-press shock avoidance with DBS compared with sham controls. These findings support the idea that DBS of subcortical arousal structures may be a novel therapeutic strategy benefitting patients with medically and surgically refractory epilepsy.SIGNIFICANCE STATEMENT The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. For the first time, we developed two behavioral tasks and demonstrate that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) decreased cortical slow wave activity and improved task performance in the postictal period. Because preclinical task performance studies are crucial to explore the effectiveness and safety of DBS treatment, our work is clinically relevant as it could support and help set the foundations for a human neurostimulation trial to improve postictal responsiveness in patients with medically and surgically refractory epilepsy.

Cortical low-frequency power correlates with behavioral impairment in animal model of focal limbic seizures.

OBJECTIVE: Impairment in consciousness is a debilitating symptom during and after seizures; however, its mechanism remains unclear. Limbic seizures have been shown to spread to arousal circuitry to result in a "network inhibition" phenomenon. However, prior animal model studies did not relate physiological network changes to behavioral responses during or following seizures. METHODS: Focal onset limbic seizures were induced while rats were performing an operant conditioned behavioral task requiring response to an auditory stimulus to quantify how and when impairment of behavioral response occurs. Correct responses were rewarded with sucrose. Cortical and hippocampal electrophysiology measured by local field potential recordings was analyzed for changes in low- and high-frequency power in relation to behavioral responsiveness during seizures. RESULTS: As seen in patients with seizures, ictal (p < .0001) and postictal (p = .0015) responsiveness was variably impaired. Analysis of cortical and hippocampal electrophysiology revealed that ictal (p = .002) and postictal (p = .009) frontal cortical low-frequency 3-6-Hz power was associated with poor behavioral performance. In contrast, the hippocampus showed increased power over a wide frequency range during seizures, and suppression postictally, neither of which were related to behavioral impairment. SIGNIFICANCE: These findings support prior human studies of temporal lobe epilepsy as well as anesthetized animal models suggesting that focal limbic seizures depress consciousness through remote network effects on the cortex, rather than through local hippocampal involvement. By identifying the cortical physiological changes associated with impaired arousal and responsiveness in focal seizures, these results may help guide future therapies to restore ictal and postictal consciousness, improving quality of life for people with epilepsy.

A Switch and Wave of Neuronal Activity in the Cerebral Cortex During the First Second of Conscious Perception.

Conscious perception occurs within less than 1 s. To study events on this time scale we used direct electrical recordings from the human cerebral cortex during a conscious visual perception task. Faces were presented at individually titrated visual threshold for 9 subjects while measuring broadband 40-115 Hz gamma power in a total of 1621 intracranial electrodes widely distributed in both hemispheres. Surface maps and k-means clustering analysis showed initial activation of visual cortex for both perceived and non-perceived stimuli. However, only stimuli reported as perceived then elicited a forward-sweeping wave of activity throughout the cerebral cortex accompanied by large-scale network switching. Specifically, a monophasic wave of broadband gamma activation moves through bilateral association cortex at a rate of approximately 150 mm/s and eventually reenters visual cortex for perceived but not for non-perceived stimuli. Meanwhile, the default mode network and the initial visual cortex and higher association cortex networks are switched off for the duration of conscious stimulus processing. Based on these findings, we propose a new "switch-and-wave" model for the processing of consciously perceived stimuli. These findings are important for understanding normal conscious perception and may also shed light on its vulnerability to disruption by brain disorders.

Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders.

OBJECTIVE: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016. DESIGN: Here we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses. CONCLUSION: Interest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

Seizure susceptibility and infraslow modulatory activity in the intracranial electroencephalogram.

OBJECTIVE: Studies of infraslow amplitude modulations (<0.15 Hz) of band power time series suggest that these envelope correlations may form a basis for distant spatial coupling in the brain. In this study, we sought to determine how infraslow relationships are affected by antiepileptic drug (AED) taper, time of day, and seizure. METHODS: We studied intracranial electroencephalographic (icEEG) data collected from 13 medically refractory adult epilepsy patients who underwent monitoring at Yale-New Haven Hospital. We estimated the magnitude-squared coherence (MSC) at <0.15 Hz of traditional EEG frequency band power time series for all electrode contact pairs to quantify infraslow envelope correlations between them. We studied, first, hour-long background icEEG epochs before and after AED taper to understand the effect of taper. Second, we analyzed the entire record for each patient to study the effect of time of day. Finally, for each patient, we reviewed the clinical record to find all seizures that were at least 6 hours removed from other seizures and analyzed infraslow envelope MSC before and after them. RESULTS: Infraslow envelope MSC increased slightly, but significantly, after AED taper, and increased on average during the night and decreased during the day. It was also increased significantly in all frequency bands up to 3 hours preseizure and 1 hour postseizure as compared to background icEEG (61 seizures studied). These changes occurred for both daytime and nighttime seizures (28 daytime, 33 nighttime). Interestingly, there was significant spatial variability to these changes, with the seizure onset area peaking at 3 hours preseizure, then showing progressive desynchronization from 3 hours preseizure to 1 hour postseizure. SIGNIFICANCE: Infraslow envelope analysis may be used to understand long-term changes over the course of icEEG monitoring, provide unique insight into interictal electrophysiological changes related to ictogenesis, and contribute to the development of novel seizure forecasting algorithms.

Sharp Wave Ripples during Visual Exploration in the Primate Hippocampus.

Hippocampal sharp-wave ripples (SWRs) are highly synchronous oscillatory field potentials that are thought to facilitate memory consolidation. SWRs typically occur during quiescent states, when neural activity reflecting recent experience is replayed. In rodents, SWRs also occur during brief locomotor pauses in maze exploration, where they appear to support learning during experience. In this study, we detected SWRs that occurred during quiescent states, but also during goal-directed visual exploration in nonhuman primates (Macaca mulatta). The exploratory SWRs showed peak frequency bands similar to those of quiescent SWRs, and both types were inhibited at the onset of their respective behavioral epochs. In apparent contrast to rodent SWRs, these exploratory SWRs occurred during active periods of exploration, e.g., while animals searched for a target object in a scene. SWRs were associated with smaller saccades and longer fixations. Also, when they coincided with target-object fixations during search, detection was more likely than when these events were decoupled. Although we observed high gamma-band field potentials of similar frequency to SWRs, only the SWRs accompanied greater spiking synchrony in neural populations. These results reveal that SWRs are not limited to off-line states as conventionally defined; rather, they occur during active and informative performance windows. The exploratory SWR in primates is an infrequent occurrence associated with active, attentive performance, which may indicate a new, extended role of SWRs during exploration in primates. SIGNIFICANCE STATEMENT: Sharp-wave ripples (SWRs) are high-frequency oscillations that generate highly synchronized activity in neural populations. Their prevalence in sleep and quiet wakefulness, and the memory deficits that result from their interruption, suggest that SWRs contribute to memory consolidation during rest. Here, we report that SWRs from the monkey hippocampus occur not only during behavioral inactivity but also during successful visual exploration. SWRs were associated with attentive, focal search and appeared to enhance perception of locations viewed around the time of their occurrence. SWRs occurring in rest are noteworthy for their relation to heightened neural population activity, temporally precise and widespread synchronization, and memory consolidation; therefore, the SWRs reported here may have a similar effect on neural populations, even as experiences unfold.

Delta rhythm in wakefulness: evidence from intracranial recordings in human beings.

A widely accepted view is that wakefulness is a state in which the entire cortical mantle is persistently activated, and therefore desynchronized. Consequently, the EEG is dominated by low-amplitude, high-frequency fluctuations. This view is currently under revision because the 1-4 Hz delta rhythm is often evident during "quiet" wakefulness in rodents and nonhuman primates. Here we used intracranial EEG recordings to assess the occurrence of delta rhythm in 18 awake human beings. Our recordings reveal rhythmic delta during wakefulness at 10% of all recording sites. Delta rhythm could be observed in a single cortical lobe or in multiple lobes. Sites with high delta could flip between high and low delta power or could be in a persistently high delta state. Finally, these sites were rarely identified as the sites of seizure onset. Thus rhythmic delta can dominate the background operation and activity of some neocortical circuits in awake human beings.

Neurostimulation to improve level of consciousness in patients with epilepsy.

When drug-resistant epilepsy is poorly localized or surgical resection is contraindicated, current neurostimulation strategies such as deep brain stimulation and vagal nerve stimulation can palliate the frequency or severity of seizures. However, despite medical and neuromodulatory therapy, a significant proportion of patients continue to experience disabling seizures that impair awareness, causing disability and risking injury or sudden unexplained death. We propose a novel strategy in which neuromodulation is used not only to reduce seizures but also to ameliorate impaired consciousness when the patient is in the ictal and postictal states. Improving or preventing alterations in level of consciousness may have an effect on morbidity (e.g., accidents, drownings, falls), risk for death, and quality of life. Recent studies may have elucidated underlying networks and mechanisms of impaired consciousness and yield potential novel targets for neuromodulation. The feasibility, benefits, and pitfalls of potential deep brain stimulation targets are illustrated in human and animal studies involving minimally conscious/vegetative states, movement disorders, depth of anesthesia, sleep-wake regulation, and epilepsy. We review evidence that viable therapeutic targets for impaired consciousness associated with seizures may be provided by key nodes of the consciousness system in the brainstem reticular activating system, hypothalamus, basal ganglia, thalamus, and basal forebrain.

The spatial and signal characteristics of physiologic high frequency oscillations.

OBJECTIVES: To study the incidence, spatial distribution, and signal characteristics of high frequency oscillations (HFOs) outside the epileptic network. METHODS: We included patients who underwent invasive evaluations at Yale Comprehensive Epilepsy Center from 2012 to 2013, had all major lobes sampled, and had localizable seizure onsets. Segments of non-rapid eye movement (NREM) sleep prior to the first seizure were analyzed. We implemented a semiautomated process to analyze oscillations with peak frequencies >80 Hz (ripples 80-250 Hz; fast ripples 250-500 Hz). A contact location was considered epileptic if it exhibited epileptiform discharges during the intracranial evaluation or was involved ictally within 5 s of seizure onset; otherwise it was considered nonepileptic. RESULTS: We analyzed recordings from 1,209 electrode contacts in seven patients. The nonepileptic contacts constituted 79.1% of the total number of contacts. Ripples constituted 99% of total detections. Eighty-two percent of all HFOs were seen in 45.2% of the nonepileptic contacts (82.1%, 47%, 34.6%, and 34% of the occipital, parietal, frontal, and temporal nonepileptic contacts, respectively). The following sublobes exhibited physiologic HFOs in all patients: Perirolandic, basal temporal, and occipital subregions. The ripples from nonepileptic sites had longer duration, higher amplitude, and lower peak frequency than ripples from epileptic sites. A high HFO rate (>1/min) was seen in 110 nonepileptic contacts, of which 68.2% were occipital. Fast ripples were less common, seen in nonepileptic parietooccipital regions only in two patients and in the epileptic mesial temporal structures. CONCLUSIONS: There is consistent occurrence of physiologic HFOs over vast areas of the neocortex outside the epileptic network. HFOs from nonepileptic regions were seen in the occipital lobes and in the perirolandic region in all patients. Although duration of ripples and peak frequency of HFOs are the most effective measures in distinguishing pathologic from physiologic events, there was significant overlap between the two groups.

Ictal spread of medial temporal lobe seizures with and without secondary generalization: an intracranial electroencephalography analysis.

OBJECTIVE: Secondary generalization of seizures has devastating consequences for patient safety and quality of life. The aim of this intracranial electroencephalography (icEEG) study was to investigate the differences in onset and propagation patterns of temporal lobe seizures that remained focal versus those with secondary generalization, in order to better understand the mechanism of secondary generalization. METHODS: A total of 39 seizures were analyzed in nine patients who met the following criteria: (1) icEEG-video monitoring with at least one secondarily generalized tonic-clonic seizure (GTCS), (2) pathologically proven hippocampal sclerosis, and (3) no seizures for at least 1 year after anteromedial temporal lobe resection. Seizures were classified as focal or secondary generalized by behavioral analysis of video. Onset and propagation patterns were compared by analysis of icEEG. RESULTS: We obtained data from 22 focal seizures without generalization (FS), and 17 GTCS. Seizure-onset patterns did not differ between FS and GTCS, but there were differences in later propagation. All seizures started with low voltage fast activity, except for seven seizures in one patient (six FS, one GTCS), which started with sharply contoured theta activity. Fifteen of 39 seizures started from the hippocampus, and 24 seizures (including six seizures in a patient without hippocampal contacts) started from other medial temporal lobe areas. We observed involvement or more prominent activation of the posterior-lateral temporal regions in GTCS prior to propagation to the other cortical regions, versus FS, which had no involvement or less prominent activation of the posterior lateral temporal cortex. Occipital contacts were not involved at the time of clinical secondary generalization. SIGNIFICANCE: The posterior-lateral temporal cortex may serve as an important "gateway" controlling propagation of medial temporal lobe seizures to other cortical regions. Identifying the mechanisms of secondary generalization of focal seizures could lead to improved treatments to confine seizure spread.

Hemifacial spasm and neurovascular compression.

Hemifacial spasm (HFS) is characterized by involuntary unilateral contractions of the muscles innervated by the ipsilateral facial nerve, usually starting around the eyes before progressing inferiorly to the cheek, mouth, and neck. Its prevalence is 9.8 per 100,000 persons with an average age of onset of 44 years. The accepted pathophysiology of HFS suggests that it is a disease process of the nerve root entry zone of the facial nerve. HFS can be divided into two types: primary and secondary. Primary HFS is triggered by vascular compression whereas secondary HFS comprises all other causes of facial nerve damage. Clinical examination and imaging modalities such as electromyography (EMG) and magnetic resonance imaging (MRI) are useful to differentiate HFS from other facial movement disorders and for intraoperative planning. The standard medical management for HFS is botulinum neurotoxin (BoNT) injections, which provides low-risk but limited symptomatic relief. The only curative treatment for HFS is microvascular decompression (MVD), a surgical intervention that provides lasting symptomatic relief by reducing compression of the facial nerve root. With a low rate of complications such as hearing loss, MVD remains the treatment of choice for HFS patients as intraoperative technique and monitoring continue to improve.

Combined neuromodulation and resection for functional cortex epilepsy: a case series.

OBJECTIVE: Medically refractory epilepsy (MRE) often requires resection of the seizure onset zone (SOZ) for effective treatment. However, when the SOZ is in functional cortex (FC), achieving complete and safe resection becomes difficult, due to the seizure network overlap with function. The authors aimed to assess the safety and outcomes of a combined approach involving partial resection combined with focal neuromodulation for FC refractory epilepsy. METHODS: The authors performed a retrospective analysis of individuals diagnosed with MRE who underwent surgical intervention from January 2015 to December 2022. Patients whose SOZ was located in FC and were treated with resection combined with simultaneous implantation of a focal neuromodulation device (responsive neurostimulation [RNS] device) with more than 12 months of follow-up data were included. All patients underwent a standard epilepsy preoperative assessment including intracranial electroencephalography and extraoperative stimulation mapping. Resections were performed under general anesthesia, followed by the concurrent implantation of an RNS device. RESULTS: Seven patients (4 males, median age 32.3 years, all right-handed) were included. The median interval from seizure onset to surgery was 17.4 years. The epileptogenic network included sensorimotor areas (cases 2, 3, and 6), visual cortex (case 1), language areas (cases 4 and 7), and the insula (case 5). The median follow-up was 3 years (range 1-5.8 years). No significant changes in neuropsychological tests were reported. One permanent nondisabling planned neurological deficit (left inferior quadrantanopia) was observed. Six patients had stimulation activated at a median of 4.7 months after resection. All patients achieved good seizure outcomes (5 with Engel class I and 2 with Engel class II outcomes). CONCLUSIONS: Maximal safe resection combined with focal neuromodulation presents a promising alternative to stand-alone resections for MRE epileptogenic zones overlapping with functional brain. This combined approach prioritizes the preservation of function while improving seizure outcomes.

ASSFN Position Statement on Deep Brain Stimulation for Medication-Refractory Epilepsy.

Neuromodulation has taken a foothold in the landscape of surgical treatment for medically refractory epilepsies and offers additional surgical treatment options for patients who are not candidates for resective/ablative surgery. Approximately one third of patients with epilepsy suffer with medication-refractory epilepsy. A persistent underuse of epilepsy surgery exists. Neuromodulation treatments including deep brain stimulation (DBS) expand the surgical options for patients with epilepsy and provide options for patients who are not candidates for resective surgery. DBS of the bilateral anterior nucleus of the thalamus is an Food and Drug Administration-approved, safe, and efficacious treatment option for patients with refractory focal epilepsy. The purpose of this consensus position statement is to summarize evidence, provide recommendations, and identify indications and populations for future investigation in DBS for epilepsy. The recommendations of the American Society of Functional and Stereotactic Neurosurgeons are based on several randomized and blinded clinical trials with high-quality data to support the use of DBS to the anterior nucleus of the thalamus for the treatment of refractory focal-onset seizures.

Preresidency Publication Productivity of U.S. Neurosurgery Interns.

BACKGROUND: Research experience is believed to be an important component of the neurosurgery residency application process. One measure of research productivity is publication volume. The preresidency publication volume of U.S. neurosurgery interns and any potential association between applicant publication volume and the match results of top-ranked residency programs have not been well characterized. OBJECTIVE: In this study, we sought to characterize the preresidency publication volume of U.S. neurosurgery residents in the 2018-2019 intern class using the Scopus database. METHODS: For each intern, we recorded the total number of publications, total number of first or last author publications, total number of neuroscience-related publications, mean number of citations per publication, and mean impact factor of the journal per publication. Preresidency publication volumes of interns at the top-25 programs (based on a composite ranking score according to 4 different ranking metrics) were compared with those at all other programs. RESULTS: We found that 82% of neurosurgery interns included in the analysis (190 interns from 95 programs) had at least 1 publication. The average number of publications per intern among all programs was 6 ± 0.63 (mean ± standard error of the mean). We also found that interns at top-25 neurosurgery residency programs tended to have a higher number of publications (8.3 ± 1.2 vs. 4.8 ± 0.7, P = 0.0137), number of neuroscience-related publications (6.8 ± 1.1 vs. 4.1 ± 0.7, P = 0.0419), and mean number of citations per publication (9.8 ± 1.7 vs. 5.7 ± 0.8, P = 0.0267) compared with interns at all other programs. CONCLUSIONS: Our results provide a general estimate of the preresidency publication volume of U.S. neurosurgery interns and suggest a potential association between publication volume and matching in the top-25 neurosurgery residency programs.

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl- channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.

Sequence reactivation in the hippocampus is impaired in aged rats.

The hippocampus is thought to coordinate memory consolidation by reactivating traces from behavioral experience when the brain is not actively processing new input. In fact, during slow-wave sleep, the patterns of CA1 pyramidal cell ensemble activity correlations are reactivated in both young and aged rats. In addition to correlated activity patterns, repetitive track running also creates a recurring sequence of pyramidal cell activity. The present study compared CA1 sequence activity pattern replay in young and old animals during rest periods after behavior. Whereas the young rats exhibited significant sequence reactivation, it was markedly impaired in the aged animals. When the spatial memory scores of all animals were compared with the degree of sequence reactivation, there was a significant correlation. The novel finding that weak replay of temporal patterns has behavioral consequences, strengthens the idea that reactivation processes are integral to memory consolidation.

The roles of surgery and technology in understanding focal epilepsy and its comorbidities.

Intracranial electrophysiological recording in patients with refractory focal epilepsy is the gold standard for defining epileptogenic tissue. Although the concordance of intracranial electrophysiology, structural MRI, and pathology can identify brain regions for resection, complete seizure control after surgery is not achieved in all patients with focal epilepsy. Repetitive identical behavioural seizures suggest one onset area, but epileptogenesis might be distributed and connected by functional and structural brain networks outside the seizure onset area, which could explain poor postsurgical outcomes in some patients. Similar networks are postulated in neuropsychiatric disorders, such as depression and anxiety, and seem to overlap with posited epilepsy networks, perhaps explaining the high prevalence of comorbid neuropsychiatric disorders in patients with epilepsy. These networks are difficult to verify with available electrophysiological recording approaches. Advances in intracranial technology are needed to confirm the epilepsy network hypothesis and improve surgical outcomes by providing individualised therapies based on specific network contributions.

Expanding Brain-Computer Interfaces for Controlling Epilepsy Networks: Novel Thalamic Responsive Neurostimulation in Refractory Epilepsy.

Seizures have traditionally been considered hypersynchronous excitatory events and epilepsy has been separated into focal and generalized epilepsy based largely on the spatial distribution of brain regions involved at seizure onset. Epilepsy, however, is increasingly recognized as a complex network disorder that may be distributed and dynamic. Responsive neurostimulation (RNS) is a recent technology that utilizes intracranial electroencephalography (EEG) to detect seizures and delivers stimulation to cortical and subcortical brain structures for seizure control. RNS has particular significance in the clinical treatment of medically refractory epilepsy and brain-computer interfaces in epilepsy. Closed loop RNS represents an important step forward to understand and target nodes in the seizure network. The thalamus is a central network node within several functional networks and regulates input to the cortex; clinically, several thalamic nuclei are safe and feasible targets. We highlight the network theory of epilepsy, potential targets for neuromodulation in epilepsy and the first reported use of RNS as a first generation brain-computer interface to detect and stimulate the centromedian intralaminar thalamic nucleus in a patient with bilateral cortical onset of seizures. We propose that advances in network analysis and neuromodulatory techniques using brain-computer interfaces will significantly improve outcomes in patients with epilepsy. There are numerous avenues of future direction in brain-computer interface devices including multi-modal sensors, flexible electrode arrays, multi-site targeting, and wireless communication.

Management of Subdural Hematomas: Part II. Surgical Management of Subdural Hematomas.

PURPOSE OF REVIEW: Management of patients with subdural hematomas starts with Emergency Neurological Life Support guidelines. Patients with acute or chronic subdural hematomas (SDHs) associated with rapidly deteriorating neurologic exam, unilaterally or bilaterally dilated nonreactive pupils, and extensor posturing are considered imminently surgical; likewise, SDHs more than 10 mm in size or those associated with more than 5-mm midline shift are deemed operative. RECENT FINDINGS: While twist drill craniostomy and placement of subdural evacuating vport system (SEPS) are quick, bedside procedures completed under local anesthesia and appropriate for patients with chronic SDH or patients that cannot tolerate anesthesia, these techniques are not optimal for patients with acute SDH or chronic SDH with septations. Burr hole SDH evacuation under conscious sedation or general anesthesia is an analogous technique; however, it requires basic surgical equipment and operating room staff, with a focus on a closed system with burr hole followed by rapid drain placement to avoid introduction of air into the subdural space, or multiple burr holes with extensive irrigation to reduce pneumocephalus and continue SDH evacuation via drain for several days. Acute SDH associated with significant mass effect and cerebral edema requires aggressive decompression via craniotomy with clot evacuation and frequently a craniectomy. Chronic SDHs that fail conservative management and progress clinically or radiographically are addressed with craniotomy with or without membranectomy. Surgical SDH management is variable depending on its characteristics and etiology, patient's functional status, comorbidities, goals of care, institutional preferences, and availability of specialized surgical equipment and adjunct therapies. Rapid access to surgical suites and trained staff to address surgical hemorrhages in a timely manner, with appropriate post-operative care by a specialized team including neurosurgeons and neurointensivists, is of paramount importance for successful patient outcomes. Here, we review various aspects of surgical SDH management.