Awake ripples enhance emotional memory encoding in the human brain.

Enhanced memory for emotional experiences is hypothesized to depend on amygdala-hippocampal interactions during memory consolidation. Here we show using intracranial recordings from the human amygdala and the hippocampus during an emotional memory encoding and discrimination task increased awake ripples after encoding of emotional, compared to neutrally-valenced stimuli. Further, post-encoding ripple-locked stimulus similarity is predictive of later memory discrimination. Ripple-locked stimulus similarity appears earlier in the amygdala than in hippocampus and mutual information analysis confirms amygdala influence on hippocampal activity. Finally, the joint ripple-locked stimulus similarity in the amygdala and hippocampus is predictive of correct memory discrimination. These findings provide electrophysiological evidence that post-encoding ripples enhance memory for emotional events.

Theta mediated dynamics of human hippocampal-neocortical learning systems in memory formation and retrieval.

Episodic memory arises as a function of dynamic interactions between the hippocampus and the neocortex, yet the mechanisms have remained elusive. Here, using human intracranial recordings during a mnemonic discrimination task, we report that 4-5 Hz (theta) power is differentially recruited during discrimination vs. overgeneralization, and its phase supports hippocampal-neocortical when memories are being formed and correctly retrieved. Interactions were largely bidirectional, with small but significant net directional biases; a hippocampus-to-neocortex bias during acquisition of new information that was subsequently correctly discriminated, and a neocortex-to-hippocampus bias during accurate discrimination of new stimuli from similar previously learned stimuli. The 4-5 Hz rhythm may facilitate the initial stages of information acquisition by neocortex during learning and the recall of stored information from cortex during retrieval. Future work should further probe these dynamics across different types of tasks and stimuli and computational models may need to be expanded accordingly to accommodate these findings.

Theta mediated dynamics of human hippocampal-neocortical learning systems in memory formation and retrieval.

Episodic memory arises as a function of dynamic interactions between the hippocampus and the neocortex, yet the mechanisms have remained elusive. Here, using human intracranial recordings during a mnemonic discrimination task, we report that 4-5 Hz (theta) power is differentially recruited during discrimination vs. overgeneralization, and its phase supports hippocampal-neocortical when memories are being formed and correctly retrieved. Interactions were largely bidirectional, with small but significant net directional biases; a hippocampus-to-neocortex bias during acquisition of new information that was subsequently correctly discriminated, and a neocortex-to-hippocampus bias during accurate discrimination of new stimuli from similar previously learned stimuli. The 4-5 Hz rhythm may facilitate the initial stages of information acquisition by neocortex during learning and the recall of stored information from cortex during retrieval. Future work should further probe these dynamics across different types of tasks and stimuli and computational models may need to be expanded accordingly to accommodate these findings.

Acute airway obstruction requiring nasotracheal intubation following hypoglossal neuromonitoring: a case report.

BACKGROUND: Intraoperative neurophysiological monitoring (IONM) is utilized for both the localization of critical structures and for real time detection and prevention of intraoperative neurological injury. Use of IONM to monitor the hypoglossal nerve is performed during neurosurgical, otolaryngological, and vascular procedures to improve surgical outcomes. There is a paucity of literature describing potential complications of IONM of the hypoglossal nerve, especially with respect to airway compromise. Here we present our findings regarding a case of acute airway obstruction following hypoglossal nerve monitoring. CASE PRESENTATION: A 54-year-old male was admitted for left far-lateral craniotomy and microsurgical clipping of a left posterior inferior cerebellar artery (PICA) aneurysm. Following induction and intubation but prior to the procedure start, the patient was placed in the ¾ prone position with the left side up and his neck was flexed approximately 10 degrees. He then underwent placement of subdermal needle electrodes into the facial muscles, trapezius muscles, soft palate, and tongue for IONM. The procedure lasted 523 minutes and was completed without complication. However, approximately one hour after emergence from general anesthesia, the patient experienced progressive difficulty breathing secondary to severe lingual swelling. He required emergent placement of a nasotracheal tube guided by a fiberoptic bronchoscope. He remained intubated for 3 days and was treated with dexamethasone, after which the swelling resolved, and the patient was successfully extubated. CONCLUSIONS: Acute lingual edema is a potentially life-threatening phenomenon that can lead to rapid airway compromise. Generally, causes of acute lingual swelling include hemorrhage, edema, infarction, and infection. In the case described above, we suspect traumatic injury to the tongue's vascular supply caused a deep tissue hematoma leading to postoperative acute lingual swelling and airway obstruction. With the widespread use of IONM, it becomes essential for providers to be aware that perioperative airway compromise is a potentially life-threatening complication, especially with respect to monitoring of the hypoglossal nerve. Awake fiberoptic nasotracheal intubation can successfully be employed to establish an emergency airway in such situations.

Polymerase Chain Reaction (PCR)-Negative Herpes Simplex Virus (HSV) Encephalitis in a 62-Year-Old Woman With p-ANCA Vasculitis.

We present the case of a 62-year-old woman with a past medical history significant for p-ANCA vasculitis (on immunosuppression) who was found to have polymerase chain reaction (PCR)-negative herpes simplex virus (HSV) encephalitis. We also present a review of all identifiable reports of PCR-negative HSV encephalitis in the past 20 years. To our knowledge, this is the first case of PCR-negative HSV encephalitis in a patient with p-ANCA vasculitis and the thirteenth overall in this timeframe. The patient presented with new-onset fever, encephalopathy, and a first-in-lifetime focal motor seizure progressing to status epilepticus. Cerebrospinal fluid (CSF) PCR was negative for HSV on three separate instances between the first and thirteenth days since symptom onset, and the CSF profile was not typical for HSV encephalitis. The patient underwent a brain biopsy, which confirmed the presence of HSV. She continued to worsen despite aggressive seizure control and six days of empiric acyclovir. Unfortunately, she expired despite the reinitiation of acyclovir. When faced with the classical features of encephalitis in the immunocompromised, the suspicion of HSV should remain high despite negative PCR results. The completion of a full course of acyclovir in the absence of clinical improvement should be considered.

Utility of video-fundoscopy and prospects of portable stereo-photography of the ocular fundus in neurological patients.

BACKGROUND: Proper evaluation of ocular fundi is an integral part of neurological examination. Unfortunately, neurology residents are increasingly uncomfortable performing fundoscopy and interpreting findings because of diminishing skills and lack of experience. This became more prominent during the COVID-19 pandemic as fundoscopy requires proximity to the patient. With the recent dramatic improvement of smartphone cameras, fundus photography using the PanOptic Ophthalmoscope (Welch Allyn, Skaneateles Falls, NY) with a smartphone adapter offered an alternative to direct fundoscopic examination. We present the first experience with our own design of a universal smartphone adapter. METHODS: This is a single-center case series, consecutive for a single user and certain presenting neurological symptoms, which is aimed to evaluate the feasibility and practicality of a new, universal PanOptic smartphone adapter. Presenting symptoms included headache, ocular symptoms, seizure, or encephalopathy. We used 3D modeling and printing techniques to create the adapter. We also developed a methodology of capturing stereoscopic images of the optic disc using a single smartphone camera, but the method was not systematically evaluated in this paper. RESULTS: Here we present our initial experience of fundus video/photography in patients, who presented with encephalopathy, headache, seizure, vision loss, and other ocular symptoms. Fundoscopic abnormalities were discovered in 11 out of 100 patients. Some were incidental findings and were unrelated to the presentation. In one case, fundoscopy played a critical role in establishing the correct diagnosis. CONCLUSIONS: Our custom-designed smartphone adapter allowed obtaining high-quality video and photo recordings using PanOptic Ophthalmoscope. The acquisition of high-quality photos enables a high-yield diagnostic tool and allows revisiting the image in the patient's chart. Improvement of smartphone cameras opens vast horizons for stereo-fundoscopy and 3D reconstruction of the ocular fundus without using sophisticated and costly equipment. Microscopic eye movements allow taking snapshots of two side-by-side photos for 3D reconstruction and stereoscopic image viewing, which is the next level of optic disc assessment.

Saphenous Nerve Somatosensory-Evoked Potentials Monitoring During Lateral Interbody Fusion.

STUDY DESIGN.: Retrospective cohort study. OBJECTIVES: To clinically evaluate saphenous nerve somatosensory-evoked potentials (SSEPs) as a reliable and predictable way to detect upper lumbar plexus injury intraoperatively during lateral lumbar trans-psoas interbody fusion (LLIF). METHODS: Saphenous nerve SSEPs were obtained by stimulation of inferior medial thigh with needle electrodes and recording from transcranial potentials. The primary outcome was measured by testing reproducibility of SSEPs at baseline, changes during the procedure, and relevance to standard modalities. Significant SSEP changes were compared with actual postoperative nerve complications. The sensitivity and specificity of saphenous SSEPs to detect postoperative lumbar plexus nerve injury was calculated. RESULTS: A total of 62 patients were included in the study. Reliable saphenous SSEPs were recorded on the LLIF approach side in 52/62 patients. Persistent saphenous SSEP reduction of amplitude of >50% in 6 cases was observed during expansion of the tubular retractor or during the procedure. Two of 6 patients postoperatively had femoral nerve sensory deficits, and 5 of 6 patients had mild femoral nerve motor weakness, all of which resolved at an average of 12 weeks postoperatively (range 2-24 weeks). One patient had saphenous SSEP changes but demonstrated intraoperative recovery and had no postoperative clinical deficits. Saphenous SSEPs demonstrated 52% to 100% sensitivity and 90% to 100% specificity for detecting postoperative femoral nerve complications. CONCLUSION: Saphenous SSEPs can be used to detect electrophysiological changes to prevent femoral nerve injury during LLIF. Intraoperative SSEP recovery after amplitude reduction or loss may be a prognostic factor for final clinical outcome.

Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System.

BACKGROUND: The responsive neurostimulation system (RNS) (NeuroPace Inc, Mountain View, California) was approved as an adjunctive therapy for medically refractory focal epilepsy. RNS detects epileptiform patterns and delivers electrical stimulation to abort seizures. OBJECTIVE: To describe a novel technique of RNS lead implantation using robotic-assisted targeting of ictal-onset zones based on stereoelectroencephalography (sEEG) localization. Secondary objectives are to report the accuracy of robotic-assisted lead implantation using the ROSA robot as well as to report the clinical outcome achieved after RNS implantation by this method. METHODS: A total of 16 patients with medically refractory focal epilepsy underwent sEEG implantation for ictal-onset localization followed by robotic RNS implantation. The electrode most correlative with ictal onset on sEEG was chosen as the target for the RNS electrode. Seizure control was measured at 6-mo and 1-yr follow-up. Ictal-onset electrocorticography (ECoG) data from RNS were compared with ictal onset from sEEG leads based on calculations of lead target to actual lead location from the ROSA robot. RESULTS: At 6-mo follow-up, the average percent seizure reduction was 82% based upon self-reported seizure diaries. At 1-yr follow-up, 8 patients had an average of 90% seizure reduction. The location of seizure onset from ECoG data show similar onset from sEEG leads within 0.165-mm discrepancy. CONCLUSION: The ROSA robot provides an ideal method for targeting subcortical ictal-onset zones. This method of RNS lead implantation achieves high accuracy and is associated with favorable clinical outcomes.

Bidirectional prefrontal-hippocampal dynamics organize information transfer during sleep in humans.

How are memories transferred from short-term to long-term storage? Systems-level memory consolidation is thought to be dependent on the coordinated interplay of cortical slow waves, thalamo-cortical sleep spindles and hippocampal ripple oscillations. However, it is currently unclear how the selective interaction of these cardinal sleep oscillations is organized to support information reactivation and transfer. Here, using human intracranial recordings, we demonstrate that the prefrontal cortex plays a key role in organizing the ripple-mediated information transfer during non-rapid eye movement (NREM) sleep. We reveal a temporally precise form of coupling between prefrontal slow-wave and spindle oscillations, which actively dictates the hippocampal-neocortical dialogue and information transfer. Our results suggest a model of the human sleeping brain in which rapid bidirectional interactions, triggered by the prefrontal cortex, mediate hippocampal activation to optimally time subsequent information transfer to the neocortex during NREM sleep.

Multiplexing of Theta and Alpha Rhythms in the Amygdala-Hippocampal Circuit Supports Pattern Separation of Emotional Information.

How do we remember emotional events? While emotion often leads to vivid recollection, the precision of emotional memories can be degraded, especially when discriminating among overlapping experiences in memory (i.e., pattern separation). Communication between the amygdala and the hippocampus has been proposed to support emotional memory, but the exact neural mechanisms remain unclear. Here, we used intracranial recordings in pre-surgical epilepsy patients to show that successful pattern separation of emotional stimuli is associated with theta band (3-7 Hz)-coordinated bidirectional interactions between the amygdala and the hippocampus. In contrast, discrimination errors (i.e., failure to discriminate similar stimuli) were associated with alpha band (7-13 Hz)-coordinated unidirectional influence from the amygdala to the hippocampus. These findings imply that alpha band synchrony may impair discrimination of similar emotional events via the amygdala-hippocampal directional coupling, which suggests a target for treatments of psychiatric conditions such as post-traumatic stress disorder, in which aversive experiences are often overgeneralized.

Hippocampal CA1 gamma power predicts the precision of spatial memory judgments.

The hippocampus plays a critical role in spatial memory. However, the exact neural mechanisms underlying high-fidelity spatial memory representations are unknown. We report findings from presurgical epilepsy patients with bilateral hippocampal depth electrodes performing an object-location memory task that provided a broad range of spatial memory precision. During encoding, patients were shown a series of objects along the circumference of an invisible circle. At test, the same objects were shown at the top of the circle (0°), and patients used a dial to move the object to its location shown during encoding. Angular error between the correct location and the indicated location was recorded as a continuous measure of performance. By registering pre- and postimplantation MRI scans, we were able to localize the electrodes to specific hippocampal subfields. We found a correlation between increased gamma power, thought to reflect local excitatory activity, and the precision of spatial memory retrieval in hippocampal CA1 electrodes. Additionally, we found a similar relationship between gamma power and memory precision in the dorsolateral prefrontal cortex and a directional relationship between activity in this region and in the CA1, suggesting that the dorsolateral prefrontal cortex is involved in postretrieval processing. These results indicate that local processing in hippocampal CA1 and dorsolateral prefrontal cortex supports high-fidelity spatial memory representations.

Using electrocorticogram baseline seizure frequency to assess the efficacy of responsive neurostimulation.

BACKGROUND: The effect of direct brain responsive neurostimulation on the frequency of electrographic seizures in patients with medically refractory focal epilepsy has not been evaluated by chronic ambulatory electrocorticographic monitoring. METHODS: This was a retrospective study of 9 patients who underwent implantation of the responsive neurostimulator (RNS) system from 2015 to 2017 at the University of California, Irvine. Leads were placed at the ictal onset zone as determined by intracranial electroencephalography (EEG). The neurostimulator was programmed to detect and deliver stimulation following identification of the individual's epileptiform patterns. Electrographic seizures were determined by review of all detections. The electrocorticography (ECoG) seizure frequency baseline was the average of the first 2 months postimplantation. The patient-reported seizure frequency baseline was the average of the 2 most recent months prior to RNS implantation. Seizure control was assessed at 3 months, 6 months, and 12 months. RESULTS: Nine patients were included in the study. All 9 patients have been treated with responsive stimulation for at least 3 months, 7/9 for 6 months, and 4/9 for 12 months. The mean change in seizure frequency was -10%, -19%, and -56% at 3, 6, and 12 months, respectively, using a self-reported seizure frequency baseline compared with -85%, -71%, and -56% at 3, 6, and 12 months, respectively, using the ECoG seizure frequency baseline. CONCLUSION: Chronic ECoG may provide a more accurate estimate of seizure frequency and provide additional insight into the true efficacy of the RNS system.

Language recovery after epilepsy surgery of the Broca's area.

Epilepsy surgery is indicated in select patients with drug-resistant focal epilepsy. Seizure freedom or significant reduction of seizure burden without risking new neurological deficits is the expected goal of epilepsy surgery. Typically, when the seizure onset zone overlaps with eloquent cortex, patients are excluded from surgery. We present a patient with drug-resistant frontal lobe epilepsy who underwent successful surgery with resection of Broca's area, primarily involving the pars triangularis (BA 45). We report transient expressive aphasia followed by recovery of speech. This case provides new insights into adult neuroplasticity of the language network.

Accuracy and Efficacy for Robotic Assistance in Implanting Responsive Neurostimulation Device Electrodes in Bilateral Mesial Temporal Lobe Epilepsy.

BACKGROUND: Responsive neurostimulation (RNS) is a relatively new treatment option that has been shown to be effective for patients with medically refractory focal epilepsy when resection is not possible, especially in bilateral mesial temporal onset. Robotic devices are becoming increasingly popular for use in stereotactic procedures such as stereoelectroencephalography, but have yet to be used when implanting RNS devices. OBJECTIVE: To show that these 2 forms of advanced technology were compatible and could be used effectively in patient care. METHODS: We implanted RNS devices in 3 patients with bilateral mesial temporal lobe epilepsy. Each patient was placed in the prone position, and electrode trajectories were planned via the robotic navigation system via a transoccipital approach. One lead was placed along each amygdalohippocampal complex. A small craniectomy was then created in the parietal region for RNS generator implantation. Actual and expected target locations and distance were calculated for each depth. There were no complications in this group. RESULTS: RNS devices with bilateral leads were successfully implanted in all 3 patients, with bilateral mesial temporal lobe onset. Follow-up ranged from 3 to 6 mo, and there were no complications in this group. The median distance between the estimate and actual targets was 2.18 (range = 1.11-3.27) mm. CONCLUSION: We show that implanting RNS devices with robotic assistance is feasible with excellent precision and accuracy. The advantages of using robotic assistance include higher flexibility, accuracy, precision, and consistency.

Length of stay for patients undergoing invasive electrode monitoring with stereoelectroencephalography and subdural grids correlates positively with increased institutional profitability.

OBJECTIVE: Lowering the length of stay (LOS) is thought to potentially decrease hospital costs and is a metric commonly used to manage capacity. Patients with epilepsy undergoing intracranial electrode monitoring may have longer LOS because the time to seizure is difficult to predict or control. This study investigates the effect of economic implications of increased LOS in patients undergoing invasive electrode monitoring for epilepsy. METHODS: We retrospectively collected and analyzed patient data for 76 patients who underwent invasive monitoring with either subdural grid (SDG) implantation or stereoelectroencephalography (SEEG) over 2 years at our institution. Data points collected included invasive electrode type, LOS, profit margin, contribution margins, insurance type, and complication rates. RESULTS: LOS correlated positively with both profit and contribution margins, meaning that as LOS increased, both the profit and contribution margins rose, and there was a low rate of complications in this patient group. This relationship was seen across a variety of insurance providers. SIGNIFICANCE: These data suggest that LOS may not be the best metric to assess invasive monitoring patients (i.e., SEEG or SDG), and increased LOS does not necessarily equate with lower or negative institutional financial gain. Further research into LOS should focus on specific specialties, as each may differ in terms of financial implications.

Amygdala-hippocampal dynamics during salient information processing.

Recognizing motivationally salient information is critical to guiding behaviour. The amygdala and hippocampus are thought to support this operation, but the circuit-level mechanism of this interaction is unclear. We used direct recordings in the amygdala and hippocampus from human epilepsy patients to examine oscillatory activity during processing of fearful faces compared with neutral landscapes. We report high gamma (70-180 Hz) activation for fearful faces with earlier stimulus evoked onset in the amygdala compared with the hippocampus. Attending to fearful faces compared with neutral landscape stimuli enhances low-frequency coupling between the amygdala and the hippocampus. The interaction between the amygdala and hippocampus is largely unidirectional, with theta/alpha oscillations in the amygdala modulating hippocampal gamma activity. Granger prediction, phase slope index and phase lag analysis corroborate this directional coupling. These results demonstrate that processing emotionally salient events in humans engages an amygdala-hippocampal network, with the amygdala influencing hippocampal dynamics during fear processing.

Axonal degeneration in peripheral nerves in a case of Leber hereditary optic neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) genetic disorder characterized by profound bilateral loss of central vision due to selective loss of retinal ganglion cells. Most patients with LHON do not have complaints related to the peripheral nervous system. We investigated possible qualitative and quantitative histological changes in the peripheral nerve of a patient with LHON as compared to normal controls. METHODS: Brachial plexus specimens were obtained at necropsy from a patient with LHON carrying the 3460/ND1 mtDNA mutation and age-matched controls without known history of neurological disease. The nerves were evaluated by light microscope coupled to a digital camera-based morphometric analysis and electron microscopy. RESULTS: Extensive axonal degeneration of the large heavily myelinated fibers was found in the brachial plexus from the patient with LHON. In LHON nerve fascicles, we counted over 10 times as many degenerated profiles as found in the control nerve fascicles. CONCLUSIONS: Microscopic examination of the brachial plexus in the patient with LHON clearly demonstrated a significant pattern of neurodegeneration. Our study suggests that peripheral neuropathy may be a subclinical feature associated with LHON.

Association of MBP peptides with Hsp70 in normal appearing human white matter.

Multiple Sclerosis is an autoimmune disease directed against myelin proteins. The etiology of MS is poorly defined though, with no definitive causative agent yet identified. It has been hypothesized that MS may be a multifactorial disease resulting in the same end product: the destruction of myelin by the immune system. In this report we describe a potential role for heat shock proteins in the pathogenesis of MS. We isolated Hsp70 from the normal appearing white matter of both MS and normal human brain and found this was actively associated with, among other things, immunodominant MBP peptides. Hsp70-MBP peptide complexes prepared in vitro were shown to be highly immunogenic, with adjuvant-like effects stimulating MBP peptide-specific T cell lines to respond to normally sub-optimal concentrations of peptide. This demonstration of a specific interaction between Hsp70 and different MBP peptides, coupled with the adjuvanticity of this association is suggestive of a possible role for Hsp70 in the immunopathology associated with MS.