Hippocampal neurons code individual episodic memories in humans.

The hippocampus is an essential hub for episodic memory processing. However, how human hippocampal single neurons code multi-element associations remains unknown. In particular, it is debated whether each hippocampal neuron represents an invariant element within an episode or whether single neurons bind together all the elements of a discrete episodic memory. Here we provide evidence for the latter hypothesis. Using single-neuron recordings from a total of 30 participants, we show that individual neurons, which we term episode-specific neurons, code discrete episodic memories using either a rate code or a temporal firing code. These neurons were observed exclusively in the hippocampus. Importantly, these episode-specific neurons do not reflect the coding of a particular element in the episode (that is, concept or time). Instead, they code for the conjunction of the different elements that make up the episode.

Cerebrospinal Fluid Diversion for Refractory Intracranial Hypertension in Traumatic Brain Injury: A Single Center Experience.

BACKGROUND: Diversion of cerebrospinal fluid (CSF) is a common neurosurgical procedure for control of intracranial pressure (ICP) in the acute phase after traumatic brain injury (TBI), where medical management is insufficient. CSF can be drained via an external ventricular drain (EVD) or, in selected patients, via a lumbar (external lumbar drain [ELD]) drainage catheter. Considerable variability exists in neurosurgical practice on their use. METHODS: A retrospective service evaluation was completed for patients receiving CSF diversion for ICP control after TBI, from April 2015 to August 2021. Patients were included whom fulfilled local criteria deeming them suitable for either ELD/EVD. Data were extracted from patient notes, including ICP values pre/postdrain insertion and safety data including infection or clinically/radiologically diagnosed tonsillar herniation. RESULTS: Forty-one patients were retrospectively identified (ELD = 30 and EVD = 11). All patients had parenchymal ICP monitoring. Both modalities affected statistically significant decreases in ICP, with relative reductions at 1, 6, and 24 hour pre/postdrainage (at 24-hour ELD P < 0.0001, EVD P < 0.01). Similar rates of ICP control failure, blockage and leak occurred in both groups. A greater proportion of patients with EVD were treated for CSF infection than with ELD. One event of clinical tonsillar herniation is reported, which may have been in part attributable to ELD overdrainage, but which did not result in adverse outcome. CONCLUSIONS: The data presented demonstrate that EVD and ELD can be successful in ICP control after TBI, with ELD limited to carefully selected patients with strict drainage protocols. The findings support prospective study to formally determine the relative risk-benefit profiles of CSF drainage modalities in TBI.

Volume maximised glycerol rhizolysis for trigeminal neuralgia: a single centre analysis of outcomes.

OBJECTIVES: Glycerol rhizotomy is an established treatment for medically refractory trigeminal neuralgia in select cases where microvascular decompression is contraindicated or not preferred. The standard approach is to inject a fixed volume of glycerol using Hartel's technique into Meckel's cave. We discuss a 'volume-maximised' technique of measuring the volume of Meckel's cave using intra-operative fluoroscopy and injecting an equivalent volume of glycerol such that every patient receives a tailored quantity of glycerol dependent on the volume of Meckel's cave. The safety and efficacy of this approach is analysed. METHODS: A retrospective analysis of 53 procedures where volume-maximised glycerol rhizolysis was utilised over a 7-year period (2012 -2018) at a single centre by the senior author was carried out. The incidence and duration of pain freedom and complications incurred over a median follow-up period of 8 years were analysed. RESULTS: 37 procedures were carried out for typical trigeminal neuralgia, 13 for secondary trigeminal neuralgia, and 3 for atypical trigeminal neuralgia. Overall, pain freedom was achieved in 85% cases, and 92% in patients with typical trigeminal neuralgia. Median duration of pain freedom in patients with typical trigeminal neuralgia was 63 months, versus 6 months in those with secondary trigeminal neuralgia (p < 0.00001). 14 procedures (26.4%) resulted in mild and temporary complications. 54.7% of cases experienced hypoaesthesia in a distribution similar to or less extensive than the distribution of trigeminal neuralgia. The presence of hypoaesthesia post-procedure was highly predictive of longer pain freedom (95 months versus 8 months median pain freedom (p = 0.00003)). CONCLUSIONS: Volume-maximised glycerol injection is safe and effective when compared to literature-reported outcomes post-standard volume glycerol injections. The duration of pain freedom achieved exceeds most literature-reported studies, with hypoaesthesia outcomes being comparable with previous studies. Pain freedom outcomes are more favourable in those with post-procedure hypoaesthesia.

External Lumbar Drainage for Refractory Intracranial Hypertension in Traumatic Brain Injury: A Systematic Review.

Considerable variation exists in the clinical practice of cerebrospinal fluid diversion for medically refractory intracranial hypertension in patients with acute traumatic brain injury (TBI), which is achievable via lumbar or ventricular drainage. This systematic review sought to compile the available evidence for the efficacy and safety of the use of lumbar drains for intracranial pressure (ICP) control. A systematic review of the literature was performed with the search and data extraction performed by two reviewers independently in duplicate. Nine independent studies were identified, enrolling 230 patients, 159 with TBI. Efficacy for ICP control was observed across all studies, with immediate and sustained effect, reducing medical therapy requirements. Lumbar drainage with medical therapy appears effective when used alone and as an adjunct to ventricular drainage. Safety reporting varied in quality. Clinical or radiological incidents of cerebral herniation (with an unclear relationship to lumbar drainage) were observed in 14/230 patients resulting in one incident of morbidity without adverse patient outcome. The available data is generally poor in quality and volume, but supportive of the efficacy of lumbar drainage for ICP control. Few reports of adverse outcomes are suggestive of, but are insufficient to confirm, the safety of use in the appropriate patient and clinical setting. Further large prospective observational studies are required to generate sufficient support of an acceptable safety profile.

Oscillations support short latency co-firing of neurons during human episodic memory formation.

Theta and gamma oscillations in the medial temporal lobe are suggested to play a critical role for human memory formation via establishing synchrony in neural assemblies. Arguably, such synchrony facilitates efficient information transfer between neurons and enhances synaptic plasticity, both of which benefit episodic memory formation. However, to date little evidence exists from humans that would provide direct evidence for such a specific role of theta and gamma oscillations for episodic memory formation. Here, we investigate how oscillations shape the temporal structure of neural firing during memory formation in the medial temporal lobe. We measured neural firing and local field potentials in human epilepsy patients via micro-wire electrode recordings to analyze whether brain oscillations are related to co-incidences of firing between neurons during successful and unsuccessful encoding of episodic memories. The results show that phase-coupling of neurons to faster theta and gamma oscillations correlates with co-firing at short latencies (~20-30 ms) and occurs during successful memory formation. Phase-coupling at slower oscillations in these same frequency bands, in contrast, correlates with longer co-firing latencies and occurs during memory failure. Thus, our findings suggest that neural oscillations play a role for the synchronization of neural firing in the medial temporal lobe during the encoding of episodic memories.

Cerebrospinal Fluid Diversion for Refractory Intracranial Hypertension: A United Kingdom and Ireland Survey on Practice Variation.

Introduction Diversion of cerebrospinal fluid (CSF) in a traumatic brain injury (TBI) is an established means for achieving control of intracranial pressure (ICP), aimed at improving intracranial homeostasis. The literature and anecdotal reports suggest a variation in practice between neurosurgical centres internationally, with current guidelines advocating ventricular drainage over lumbar drainage. We sought to establish the current neurosurgical practice in the United Kingdom regarding the methods of ICP control in TBI. Methods A 20-point survey was distributed electronically to British and Irish neurosurgeons after ratification by the Society of British Neurological Surgeons. Questions were directed at the clinician's opinion and experience of lumbar drain usage in patients with TBI: frequency, rationale, and experience of complications. Questions on lumbar drain usage in neurovascular patients were asked for practice comparison. Results Thirty-six responses from 21 neurosurgical centres were returned. Twenty-three per cent (23%) of responders reported using lumbar drains for refractory ICP in TBI patients: six units use lumbar drains and 15 do not. Three units showed partial usage, with mixed "yes/no" responses between consultants. Concerns of tonsillar herniation and familiarity with EVD were commonly given reasons against the usage of lumbar drains. Fifty-six per cent (56%) reported use in neurovascular patients. Conclusion This contemporary practice survey demonstrates mixed practice across the UK and within some centres. Responses and survey feedback demonstrate that the use of lumbar drains in TBI is a polarising topic. The variety of practice between and within neurosurgical units supports consideration of the prospective study of CSF diversion methods for control of refractory ICP in patients with TBI.

Theta rhythmicity governs human behavior and hippocampal signals during memory-dependent tasks.

Memory formation and reinstatement are thought to lock to the hippocampal theta rhythm, predicting that encoding and retrieval processes appear rhythmic themselves. Here, we show that rhythmicity can be observed in behavioral responses from memory tasks, where participants indicate, using button presses, the timing of encoding and recall of cue-object associative memories. We find no evidence for rhythmicity in button presses for visual tasks using the same stimuli, or for questions about already retrieved objects. The oscillations for correctly remembered trials center in the slow theta frequency range (1-5 Hz). Using intracranial EEG recordings, we show that the memory task induces temporally extended phase consistency in hippocampal local field potentials at slow theta frequencies, but significantly more for remembered than forgotten trials, providing a potential mechanistic underpinning for the theta oscillations found in behavioral responses.

The hippocampus as the switchboard between perception and memory.

Adaptive memory recall requires a rapid and flexible switch from external perceptual reminders to internal mnemonic representations. However, owing to the limited temporal or spatial resolution of brain imaging modalities used in isolation, the hippocampal-cortical dynamics supporting this process remain unknown. We thus employed an object-scene cued recall paradigm across two studies, including intracranial electroencephalography (iEEG) and high-density scalp EEG. First, a sustained increase in hippocampal high gamma power (55 to 110 Hz) emerged 500 ms after cue onset and distinguished successful vs. unsuccessful recall. This increase in gamma power for successful recall was followed by a decrease in hippocampal alpha power (8 to 12 Hz). Intriguingly, the hippocampal gamma power increase marked the moment at which extrahippocampal activation patterns shifted from perceptual cue toward mnemonic target representations. In parallel, source-localized EEG alpha power revealed that the recall signal progresses from hippocampus to posterior parietal cortex and then to medial prefrontal cortex. Together, these results identify the hippocampus as the switchboard between perception and memory and elucidate the ensuing hippocampal-cortical dynamics supporting the recall process.

The implementation of an external ventricular drain care bundle to reduce infection rates.

Background: The main complication of external ventricular drains (EVD) is infection. Implementation of evidence-based guidelines for central venous catheter (CVC) care resulted in significant declines in infections. We tested a comparable approach to EVD infection rates.Methods: An initial retrospective study evaluated the existing EVD infection rate, and identified contributory risk factors. Based on our results, and in corroboration with existing literature, an EVD care bundle was developed and implemented. A prospective study was then conducted to identify improvement.Results: A total of 275 EVDs (120 pre- and 155 post-EVD care bundle) inserted over a period of 1532 days were included. Pre-care bundle, the infection rate was 27%, with the predominant factor associated with infection being number cerebrospinal fluid sampling episodes. Following introduction of the EVD care bundle, the infection rate declined to 10% (p < 0.001) with the incidence from 21 to 9 cases per 1,000 EVD-days (p = 0.003). The infection rate was not found to be significantly associated with the number of accesses during this period (p = 0.910).Conclusions: Introduction of a well-implemented EVD care bundle can significantly decrease EVD infection rates.

Directional coupling of slow and fast hippocampal gamma with neocortical alpha/beta oscillations in human episodic memory.

Episodic memories hinge upon our ability to process a wide range of multisensory information and bind this information into a coherent, memorable representation. On a neural level, these 2 processes are thought to be supported by neocortical alpha/beta desynchronization and hippocampal theta/gamma synchronization, respectively. Intuitively, these 2 processes should couple to successfully create and retrieve episodic memories, yet this hypothesis has not been tested empirically. We address this by analyzing human intracranial electroencephalogram data recorded during 2 associative memory tasks. We find that neocortical alpha/beta (8 to 20 Hz) power decreases reliably precede and predict hippocampal "fast" gamma (60 to 80 Hz) power increases during episodic memory formation; during episodic memory retrieval, however, hippocampal "slow" gamma (40 to 50 Hz) power increases reliably precede and predict later neocortical alpha/beta power decreases. We speculate that this coupling reflects the flow of information from the neocortex to the hippocampus during memory formation, and hippocampal pattern completion inducing information reinstatement in the neocortex during memory retrieval.

Data-driven re-referencing of intracranial EEG based on independent component analysis (ICA).

BACKGROUND: Intracranial recordings from patients implanted with depth electrodes are a valuable source of information in neuroscience. They allow for the unique opportunity to record brain activity with high spatial and temporal resolution. A common pre-processing choice in stereotactic EEG (S-EEG) is to re-reference the data with a bipolar montage. In this, each channel is subtracted from its neighbor, to reduce commonalities between channels and isolate activity that is spatially confined. NEW METHOD: We challenge the assumption that bipolar reference effectively performs this task. To extract local activity, the distribution of the signal source of interest, interfering distant signals, and noise need to be considered. Referencing schemes with fixed coefficients can decrease the signal to noise ratio (SNR) of the data, they can lead to mislocalization of activity and consequently to misinterpretation of results. We propose to use Independent Component Analysis (ICA), to derive filter coefficients that reflect the statistical dependencies of the data at hand. RESULTS: We describe and demonstrate this on human S-EEG recordings. In a simulation with real data, we quantitatively show that ICA outperforms the bipolar referencing operation in sensitivity and importantly in specificity when revealing local time series from the superposition of neighboring channels. COMPARISON WITH EXISTING METHOD(S): We argue that ICA already performs the same task that bipolar referencing pursues, namely undoing the linear superposition of activity and will identify activity that is local. CONCLUSIONS: When investigating local sources in human S-EEG, ICA should be preferred over re-referencing the data with a bipolar montage.

Clinical outcomes of VNS therapy with AspireSR® (including cardiac-based seizure detection) at a large complex epilepsy and surgery centre.

PURPOSE: To compare the efficacy of AspireSR® to preceding VNS battery models for battery replacements, and to determine the efficacy of the AspireSR® for new implants. METHODS: Data were collected retrospectively from patients with epilepsy who had VNS AspireSR® implanted over a three-year period between June 2014 and June 2017 by a single surgeon. Cases were divided into two cohorts, those in whom the VNS was a new insertion, and those in whom the VNS battery was changed from a previous model to AspireSR®. Within each group, the seizure burden was compared between the periods before and after insertion of AspireSR®. RESULTS: Fifty-one patients with a newly inserted AspireSR® VNS model had a significant reduction in seizure frequency (p < 0.001), with 59% (n = 30) reporting ≥50% reduction. Of the 62 patients who had an existing VNS, 53% (n = 33) reported ≥50% reduction in seizure burden when the original VNS was inserted. After the battery was changed to the AspireSR®, 71% (n = 44) reported a further reduction of ≥50% in their seizure burden. The size of this reduction was at least as large as that resulting from the insertion of their existing VNS in 98% (61/62) of patients. CONCLUSION: The results suggest that approximately 70% of patients with existing VNS insertions could have significant additional benefit from cardiac based seizure detection and closed loop stimulation from the AspireSR® device. For new insertions, the AspireSR® device has efficacy in 59% of patients. The 'rule of thirds' used in counseling patients may need to be modified accordingly.

Subthalamic deep brain stimulation under general anesthesia and neurophysiological guidance while on dopaminergic medication: comparative cohort study.

OBJECTIVES: The authors have previously reported on the technical feasibility of subthalamic nucleus deep brain stimulation (STN DBS) under general anesthesia (GA) with microelectrode recording (MER) guidance in Parkinsonian patients who continued dopaminergic therapy until surgery. This paper presents the results of a prospective cohort analysis to verify the outcome of the initial study, and report on wider aspects of clinical outcome and postoperative recovery. METHODS: All patients in the study group continued dopaminergic therapy until GA was administered. Baseline characteristics, intraoperative neurophysiological markers, and perioperative complications were recorded. Long-term outcome was assessed using selective aspects of the unified Parkinson's disease rating scale motor score. Immediate postoperative recovery from GA was assessed using the "time needed for extubation" and "total time of recovery." Data for the "study group" was collected prospectively. Examined variables were compared between the "study group" and "historical control group" who stopped dopaminergic therapy preoperatively. RESULTS: The study group, n = 30 (May 2014-Jan 2016), were slightly younger than the "control group," 60 (51-64) vs. 64 (56-69) years respectively, p = 0.043. Both groups were comparable for the recorded intraoperative neurophysiological parameters; "number of MER tracks": 60% of the "study group" had single track vs. 58% in the "control" group, p = 1.0. Length of STN MER detected was 9 vs. 7 mm (median) respectively, p = 0.037. A trend towards better recovery from GA in the study group was noted, with shorter "total recovery time": 60 (50-84) vs. 89 (62-120) min, p = 0.09. Long-term improvement in motor scores and reduction in L-dopa daily equivalent dose were equally comparable between both groups. No cases of dopamine withdrawal or problems with immediate postop dyskinesia were recorded in the "on medications group." The observed rate of dopamine-withdrawal side effects in the "off-medications" group was 15%. CONCLUSIONS: The continuation of dopaminergic treatment for patients with PD does not affect the feasibility/outcome of the STN DBS surgery. This strategy appears to reduce the risk of dopamine-withdrawal adverse effects and may improve the recovery in the immediate postoperative period, which would help enhance patients' perioperative experience.

The effect of dopaminergic therapy on intraoperative microelectrode recordings for subthalamic deep brain stimulation under GA: can we operate on patients 'on medications'?

OBJECTIVES: Microelectrode recording (MER) plays an important role in target refinement in deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD). Traditionally, patients were operated on in the 'off-medication' state to allow intraoperative assessment of the patient response to direct STN stimulation. The development of intraoperative microelectrode recording (MER) has facilitated the introduction of general anaesthesia (GA). However, the routine withdrawal of dopaminergic medications has remained as standard practice. This retrospective review examines the effect of continuing these medications on intraoperative MER for subthalamic DBS insertion under GA and discusses the clinical implication of this approach. METHODS: Retrospective review of PD patients who had bilateral STN DBS insertion was conducted. A cohort of seven patients (14 STN microelectrodes) between 2012 and 2013, who inadvertently underwent the procedure while 'on medication', was identified. This 'on-medication' group was compared to all other patients who underwent the same procedure between 2012 and 2013 and had their medications withdrawn preoperatively, the 'off-medication' group, n = 26 (52 STN DBS). The primary endpoint was defined as the number of microelectrode tracks required to obtain adequate STN recordings. A second endpoint was the length of MERs that was finally used to guide the DBS lead insertion. The Reduction of the levo-dopa equivalent daily dose (LEDD) was also examined as a surrogate marker for clinical outcome 12 months postoperatively for both groups. For the on-medication group further analysis of the clinical outcome was done relying on the change in the motor examination at 12 months following STN DBS using the following parameters (Hoehn and Yahr scale, the number of waking hours spent in the OFF state as well as the duration of dyskinesia during the ON periods). RESULTS: The on-medication group was statistically comparable in all baseline characteristics to the off-medication group, including age at operation 57 ± 9.9 years vs. 61.5 ± 9.2 years, p = 0.34 (mean ± SD); duration of disease (11.6 ± 5 years vs. 11.3 ± 4 years, p = 0.68); gender F:M ratio (1:6 vs. 9:17, p = 0.40). Both groups had similar PD medication regimes preoperatively expressed as levodopa equivalent daily dose (LEDD) 916 mg (558-1850) vs. 744 mg (525-3591), respectively, p = 0.77. In the on-medication group, all seven patients (14 STN electrodes) had satisfactory STN recording from a single brain track versus 15 out of 26 patients (57.7 %) in the off-medication group, p = 0.06. The length of MER was 4.5 mm (3.0-5.5) in the on-medication group compared to 3.5 mm (3.0-4.5) in the off-medication group, p = 0.16. The percentage of reduction in LEDD postoperatively for the on-medication group was comparable to that in the off-medication group, 62 % versus 58 %, respectively, p > 0.05. All patients in the on-medication group had clinically significant improvement in their PD motor symptoms as assessed by the Hoehn and Yahr scale; the number of hours (of the waking day) spent in the OFF state dropped from 6.9 (±2.3) h to 0.9 (±1.6) h; the duration of dyskinesia during the ON state dropped from 64 % (±13 %) of the ON period to only 7 % (±12 %) at 12 months following STN DBS insertion. CONCLUSION: STN DBS insertion under GA can be performed without the need to withdraw dompaminergic treatment preoperatively. In this review the inadvertent continuation of medications did not affect the physiological localisation of the STN or the clinical effectiveness of the procedure. The continuation of dopamine therapy is likely to improve the perioperative experience for PD patients, avoid dopamine-withdrawal complications and improve recovery. A prospective study is needed to verify the results of this review.

Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies.

PURPOSE: Deep brain stimulation (DBS) of the thalamus is an emerging surgical option for people with medically refractory epilepsy that is not suitable for resective surgery, or in whom surgery has failed. Our main aim was to evaluate the efficacy of bilateral centromedian thalamic nucleus (CMN) DBS for seizure control in generalized epilepsy and frontal lobe epilepsy with a two-center, single-blind, controlled trial. METHODS: Participants were adults with refractory generalized or frontal lobe epilepsy. Seizure diaries were kept by patients/carers prospectively from enrollment. The baseline preimplantation period was followed by a control period consisting of a blind stimulation-OFF phase of at least 3 months, a 3-month blind stimulation-ON phase, and a 6-month unblinded stimulation-ON phase. The control period was followed by an unblinded long-term extension phase with stimulation-ON in those patients in whom stimulation was thought to be effective. KEY FINDINGS: Eleven patients were recruited at King's College Hospital (London, United Kingdom United Kingdom) and at University Hospital La Princesa (Madrid, Spain). Among the five patients with frontal lobe epilepsy, only one patient had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, two patients with frontal lobe epilepsy had >50% improvement in seizure frequency. All six patients with generalized epilepsy had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, five of the six patients showed >50% improvement in the frequency of major seizures (one became seizure free, one had >99% improvement, and three had 60-95% reduction in seizure frequency). Among patients with generalized epilepsy, the DBS implantation itself appears to be effective, as two patients remained seizure free during 12 and 50 months with DBS OFF, and the remaining four had 50-91% improvement in the initial 3 months with DBS OFF. SIGNIFICANCE: DBS implantation and stimulation of the CMN appears to be a safe and efficacious treatment, particularly in patients with refractory generalized epilepsy. CMN stimulation was not as effective in frontal lobe epilepsy, which requires further studies. DBS of the CMN should be considered as a treatment option, particularly in patients with refractory generalized epilepsy syndromes.

Haemangiopericytoma with no dural attachment.

The authors describe a case of a gentleman in his 40s who presented with a space-occupying lesion in the right precentral gyrus which showed no dural attachment and was well circumscribed, both on imaging and at surgery. This lesion was histologically challenging to diagnose but favoured to be a haemangiopericytoma. The lack of dural attachment is unusual for this tumour type but is typically associated with metastases to the brain, and less commonly a solid primary central nervous system tumour. The authors propose that haemangiopericytoma should be regularly considered as a differential diagnosis of cerebral metastases so that inadequate preoperative anticipation and planning is not encountered.

Shielded battery syndrome: a new hardware complication of deep brain stimulation.

BACKGROUND: Deep brain stimulation hardware is constantly advancing. The last few years have seen the introduction of rechargeable cell technology into the implanted pulse generator design, allowing for longer battery life and fewer replacement operations. The Medtronic® system requires an additional pocket adaptor when revising a non-rechargeable battery such as their Kinetra® to their rechargeable Activa® RC. This additional hardware item can, if it migrates superficially, become an impediment to the recharging of the battery and negate the intended technological advance. AIM: To report the emergence of the 'shielded battery syndrome', which has not been previously described. METHODS: We reviewed our deep brain stimulation database to identify cases of recharging difficulties reported by patients with Activa RC implanted pulse generators. RESULTS: Two cases of shielded battery syndrome were identified. The first required surgery to reposition the adaptor to the deep aspect of the subcutaneous pocket. In the second case, it was possible to perform external manual manipulation to restore the adaptor to its original position deep to the battery. CONCLUSIONS: We describe strategies to minimise the occurrence of the shielded battery syndrome and advise vigilance in all patients who experience difficulty with recharging after replacement surgery of this type for the implanted pulse generator.