Search

Closed-loop direct brain stimulation is a promising tool for modulating neural activity and behavior. However, it remains unclear how to optimally target stimulation to modulate brain activity in particular brain networks that underlie particular cognitive functions. Here, we test the hypothesis that stimulation's behavioral and physiological effects depend on the stimulation target's anatomical and functional network properties. We delivered closed-loop stimulation as 47 neurosurgical patients studied and recalled word lists. Multivariate classifiers, trained to predict momentary lapses in memory function, triggered the stimulation of the lateral temporal cortex (LTC) during the study phase of the task. We found that LTC stimulation specifically improved memory when delivered to targets near white matter pathways. Memory improvement was largest for targets near white matter that also showed high functional connectivity to the brain's memory network. These targets also reduced low-frequency activity in this network, an established marker of successful memory encoding. These data reveal how anatomical and functional networks mediate stimulation's behavioral and physiological effects, provide further evidence that closed-loop LTC stimulation can improve episodic memory, and suggest a method for optimizing neuromodulation through improved stimulation targeting., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: A major critique of the h-index is that it may be inflated by noncritical authorship. We propose a modified h-index (h m ), incorporating critical authorship, complementary to the h-index. We analyze its relationship to the traditional h-index, and how each varies across professional categories relevant to academic neurosurgery. This analysis is not meant to critique authorship decisions, affect career development, alter academic legacy, or imply that the concepts of team science or midlevel authorship contributions are not valuable., Methods: H-indices and h m s were gathered and computed for clinical neurosurgical faculty at the top 32 ranked academic neurosurgical programs based on the current literature. H m was computed for faculty at each program, using articles in which the individual was first, second, last, or co-corresponding author. Individuals were further identified based on chair status, leadership status, neurosurgical subspecialty, and National Institutes of Health funding status. Further analysis was performed to determine factors influencing h-index and h m ., Results: The median h-index for the 225 physicians included in the final dataset is 48 (interquartile range [IQR], 39-61), whereas the median h m was 32 (IQR, 24-43). The median difference between h-index and h m is 15 (IQR, 10-23). The median h m /h was 64% (IQR, 57-74). National Institutes of Health funding and subspecialty (neurosurgical oncology, neurocritical care, and cerebrovascular) were associated with significant change from h to h m ., Conclusions: The h-index can be influenced by noncritical authorship, and h m , using critical contributions, can be used as a complement reflecting critical academic output in neurosurgery. Leaders deciding on hiring or promotion should consider disparities in productivity predicated on noncritical authorship contributions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Decades of work in rodents suggest that movement is a powerful driver of hippocampal low-frequency "theta" oscillations. Puzzlingly, such movement-related theta increases in primates are less sustained and of lower frequency, leading to questions about their functional relevance. Verbal memory encoding and retrieval lead to robust increases in low-frequency oscillations in humans, and one possibility is that memory might be a stronger driver of hippocampal theta oscillations in humans than navigation. Here, neurosurgical patients navigated routes and then immediately mentally simulated the same routes while undergoing intracranial recordings. We found that mentally simulating the same route that was just navigated elicited oscillations that were of greater power, higher frequency, and longer duration than those involving navigation. Our findings suggest that memory is a more potent driver of human hippocampal theta oscillations than navigation, supporting models of internally generated theta oscillations in the human hippocampus., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is a leading cause of cognitive disability in adults, often characterized by marked deficits in episodic memory and executive function. Prior studies have found that direct electrical stimulation of the temporal cortex yielded improved memory in epilepsy patients, but it is not clear if these results generalize to patients with a specific history of TBI. Here we asked whether applying closed-loop, direct electrical stimulation to lateral temporal cortex could reliably improve memory in a TBI cohort. Among a larger group of patients undergoing neurosurgical evaluation for refractory epilepsy, we recruited a subset of patients with a history of moderate-to-severe TBI. By analyzing neural data from indwelling electrodes as patients studied and recalled lists of words, we trained personalized machine-learning classifiers to predict momentary fluctuations in mnemonic function in each patient. We subsequently used these classifiers to trigger high-frequency stimulation of the lateral temporal cortex (LTC) at moments when memory was predicted to fail. This strategy yielded a 19% boost in recall performance on stimulated as compared with non-stimulated lists (P = 0.012). These results provide a proof-of-concept for using closed-loop stimulation of the brain in treatment of TBI-related memory impairment., Competing Interests: Declaration of competing interest B.C.J. receives research funding from NeuroPace, Inc. and Harvard Pilgrim, Inc. not relating to this research. R.E.G. serves as a consultant to Medtronic, which was previously a subcontractor on this project, and receives compensation for these services. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. M.J.K. holds a greater than 5% equity interest in Nia Therapeutics Inc., a company intended to develop and commercialize brain stimulation therapies for memory restoration. R.E.G. holds a less than 5% equity interest in Nia Therapeutics, Inc. P.A.W. is employed by Blackrock Microsystems Europe GmbH. E.A.S. has served as a compensated technical consultant to Nia Therapeutics Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Successful neuromodulation approaches to alter episodic memory require closed-loop stimulation predicated on the effective classification of brain states. The practical implementation of such strategies requires prior decisions regarding electrode implantation locations. Using a data-driven approach, we employ support vector machine (SVM) classifiers to identify high-yield brain targets on a large data set of 75 human intracranial electroencephalogram subjects performing the free recall (FR) task. Further, we address whether the conserved brain regions provide effective classification in an alternate (associative) memory paradigm along with FR, as well as testing unsupervised classification methods that may be a useful adjunct to clinical device implementation. Finally, we use random forest models to classify functional brain states, differentiating encoding versus retrieval versus non-memory behavior such as rest and mathematical processing. We then test how regions that exhibit good classification for the likelihood of recall success in the SVM models overlap with regions that differentiate functional brain states in the random forest models. Finally, we lay out how these data may be used in the design of neuromodulation devices., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

While there is extensive research on memory-related oscillations and brain gene expression, the relationship between oscillations and gene expression has rarely been studied. Recently, progress has been made to identify specific genes associated with oscillations that are correlated with episodic memory. Neocortical regions, in particular the temporal pole, have been examined in this line of research due to their accessibility during neurosurgical procedures. By harnessing this accessibility, a unique and powerful study design has allowed gene expression and intracranial oscillatory data to be sourced from the same human patients. These studies have identified a plethora of understudied gene targets that should be further characterized with respect to human brain function. Future work should extend to other brain regions to increase our understanding of the genetic signatures of oscillations and, ultimately, human cognition., Competing Interests: Conflicts of interest statement Nothing declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Closed-loop stimulation for targeted modulation of brain signals has emerged as a promising strategy for episodic memory restoration. In parallel, closed-loop neuromodulation strategies have been applied to treat brain conditions including drug-resistant depression, Parkinson's Disease, and epilepsy. In this study, we seek to apply control theoretical principles to achieve closed loop modulation of hippocampal oscillatory activity. We focus on hippocampal gamma power, a signal with an established association for episodic memory processing, which may be a promising 'biomarker' for the modulation of memory performance. To develop a closed-loop stimulation paradigm that effectively modulates hippocampal gamma power, we use a novel data-set in which open-loop stimulation was applied to the posterior cingulate cortex and hippocampal gamma power was recorded during the encoding of episodic memories. The dataset was used to design and evaluate a linear quadratic integral (LQI) servo-controller in order to determine its viability for in-vivo use. In our simulation framework, we demonstrate that applying an LQI servo controller based on an autoregressive with exogenous input (ARX) plant model achieves effective control of hippocampal gamma power in 15 out of 17 experimental subjects. We demonstrate that we are able to modulate gamma power using stimulation thresholds that are physiologically safe and on time scales that are reasonable for application in a clinical system. We outline further experimentation to test our proposed system and compare our findings to emerging closed-loop neuromodulation strategies.

Objective: Interictal epileptiform discharges (IEDs) were shown to be associated with cognitive impairment in persons with epilepsy. Previous studies indicated that IED rate, location, timing, and spatial relation to the seizure onset zone could predict an IED's impact on memory encoding and retrieval if they occurred in lateral temporal, mesial temporal, or parietal regions. In this study, we explore the influence that other IED properties (e.g., amplitude, duration, white matter classification) have on memory performance. We were specifically interested in investigating the influence that lateral temporal IEDs have on memory encoding., Methods: Two hundred sixty-one subjects with medication-refractory epilepsy undergoing intracranial electroencephalographic monitoring performed multiple sessions of a delayed free-recall task (n = 671). Generalized linear mixed models were utilized to examine the relationship between IED properties and memory performance., Results: We found that increased IED rate, IEDs propagating in white matter, and IEDs localized to the left middle temporal region were associated with poorer memory performance. For lateral temporal IEDs, we observed a significant interaction between IED white matter categorization and amplitude, where IEDs with an increased amplitude and white matter propagation were associated with reduced memory performance. Additionally, changes in alpha power after an IED showed a significant positive correlation with memory performance., Significance: Our results suggest that IED properties may be useful for predicting the impact an IED has on memory encoding. We provide an essential step toward understanding pathological versus potentially beneficial interictal epileptiform activity., (© 2021 International League Against Epilepsy.)

Single-nucleus RNA sequencing (snRNA-seq), where nuclear transcriptomes are a proxy to cellular transcriptomes, has been used to profile human brain. snRNA-seq is sensitive to tissue processing, tissue quality, postmortem interval time, and cellular debris. This protocol outlines steps for the isolation of high-quality nuclei from surgically resected human brain tissue followed by a sucrose gradient yielding neuronal and non-neuronal nuclei enabling unbiased analysis of various cell types. For complete details on the use and execution of this protocol, please refer to Ayhan et al. (2021)., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Episodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. Evidence from functional neuroimaging and invasive recordings in humans suggest that reinstatement organizes our memories by time or content, yet the neural systems involved in reinstating these unique types of information remain unclear. Here, combining computational modeling and intracranial recordings from 69 epilepsy patients, we show that two cortical systems uniquely reinstate the semantic content and temporal context of previously studied items during free recall. Examining either the posterior medial or anterior temporal networks, we find that forward encoding models trained on the brain's response to the temporal and semantic attributes of items can predict the serial position and semantic category of unseen items. During memory recall, these models uniquely link reinstatement of temporal context and semantic content to these posterior and anterior networks, respectively. These findings demonstrate how specialized cortical systems enable the human brain to target specific memories., (© 2021. The Author(s).)

Functional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood oxygenation level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modeling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70-150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30-70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex. SIGNIFICANCE STATEMENT The BOLD signal forms the basis of fMRI but provides only an indirect measure of neural activity. Task-related modulation of BOLD signals are typically equated with changes in gamma-band activity; however, relevant empirical evidence comes largely from the neocortex. We examined neurophysiological correlates of the BOLD signal in the hippocampus, where the differing neural architecture might result in a different relationship between the respective signals. We identified a positive relationship between encoding-related changes in BOLD and gamma-band activity in the frontal and parietal cortices. This effect was reversed in the hippocampus, where BOLD and gamma-band effects negatively covaried. These results suggest regional variability in the transfer function between neural activity and the BOLD signal in the hippocampus and neocortex., (Copyright © 2021 the authors.)

The hippocampus supports many facets of cognition, including learning, memory, and emotional processing. Anatomically, the hippocampus runs along a longitudinal axis, posterior to anterior in primates. The structure, function, and connectivity of the hippocampus vary along this axis. In human hippocampus, longitudinal functional heterogeneity remains an active area of investigation, and structural heterogeneity has not been described. To understand the cellular and molecular diversity along the hippocampal long axis in human brain and define molecular signatures corresponding to functional domains, we performed single-nuclei RNA sequencing on surgically resected human anterior and posterior hippocampus from epilepsy patients, identifying differentially expressed genes at cellular resolution. We further identify axis- and cell-type-specific gene expression signatures that differentially intersect with human genetic signals, identifying cell-type-specific genes in the posterior hippocampus for cognitive function and the anterior hippocampus for mood and affect. These data are accessible as a public resource through an interactive website., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Phase amplitude coupling (PAC) between theta and gamma oscillations represents a key neurophysiological mechanism that promotes the temporal organization of oscillatory activity. For this reason, PAC has been implicated in item/context integration for episodic processes, including coordinating activity across multiple cortical regions. While data in humans has focused principally on PAC within a single brain region, data in rodents has revealed evidence that the phase of the hippocampal theta oscillation modulates gamma oscillations in the cortex (and vice versa). This pattern, termed cross-regional PAC (xPAC), has not previously been observed in human subjects engaged in mnemonic processing. We use a unique dataset with intracranial electrodes inserted simultaneously into the hippocampus and seven cortical regions across 40 human subjects to (1) test for the presence of significant cross-regional PAC (xPAC), (2) to establish that the magnitude of xPAC predicts memory encoding success, (3) to describe specific frequencies within the broad 2-9 Hz theta range that govern hippocampal-cortical interactions in xPAC, and (4) compare anterior versus posterior hippocampal xPAC patterns. We find that strong functional xPAC occurs principally between the hippocampus and other mesial temporal structures, namely entorhinal and parahippocampal cortices, and that xPAC is overall stronger for posterior hippocampal connections. We also show that our results are not confounded by alternative factors such as inter-regional phase synchrony, local PAC occurring within cortical regions, or artifactual theta oscillatory waveforms., (© 2021 Wiley Periodicals LLC.)

In humans, brain oscillations support critical features of memory formation. However, understanding the molecular mechanisms underlying this activity remains a major challenge. Here, we measured memory-sensitive oscillations using intracranial electroencephalography recordings from the temporal cortex of patients performing an episodic memory task. When these patients subsequently underwent resection, we employed transcriptomics on the temporal cortex to link gene expression with brain oscillations and identified genes correlated with oscillatory signatures of memory formation across six frequency bands. A co-expression analysis isolated oscillatory signature-specific modules associated with neuropsychiatric disorders and ion channel activity, with highly correlated genes exhibiting strong connectivity within these modules. Using single-nucleus transcriptomics, we further revealed that these modules are enriched for specific classes of both excitatory and inhibitory neurons, and immunohistochemistry confirmed expression of highly correlated genes. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding.

The factors that control the occurrence of interictal epileptiform discharges (IEDs) are not well understood. We suspected that this phenomenon reflects an attention-dependent suppression of interictal epileptiform activity. We hypothesized that IEDs would occur less frequently when a subject viewed a task-relevant stimulus compared with viewing a blank screen. Furthermore, IEDs have been shown to impair memory when they occur in certain regions during the encoding or recall phases of a memory task. Although these discharges have a short duration, their impact on memory suggests that they have longer lasting electrophysiological effects. We found that IEDs were associated with an increase in low-frequency power and a change in the balance between low- and high-frequency oscillations for several seconds. We found that the occurrence of IEDs is modified by whether a subject is attending to a word displayed on screen or is observing a blank screen. In addition, we found that discharges in brain regions in every lobe impair memory. These findings elucidate the relationship between IEDs and memory impairment and reveal the task dependence of the occurrence of IEDs., (© The Author(s) 2021. Published by Oxford University Press.)

Objective: This study was undertaken to evaluate the influence that subject-specific factors have on intracranial interictal epileptiform discharge (IED) rates in persons with refractory epilepsy., Methods: One hundred fifty subjects with intracranial electrodes performed multiple sessions of a free recall memory task; this standardized task controlled for subject attention levels. We utilized a dominance analysis to rank the importance of subject-specific factors based on their relative influence on IED rates. Linear mixed-effects models were employed to comprehensively examine factors with highly ranked importance., Results: Antiseizure medication (ASM) status, time of testing, and seizure onset zone (SOZ) location were the highest-ranking factors in terms of their impact on IED rates. The average IED rate of electrodes in SOZs was 34% higher than the average IED rate of electrodes outside of SOZs (non-SOZ; p < .001). However, non-SOZ electrodes had similar IED rates regardless of the subject's SOZ location (p = .99). Subjects on older generation (p < .001) and combined generation (p < .001) ASM regimens had significantly lower IED rates relative to the group taking no ASMs; newer generation ASM regimens demonstrated a nonsignificant association with IED rates (p = .13). Of the ASMs included in this study, the following ASMs were associated with significant reductions in IED rates: levetiracetam (p < .001), carbamazepine (p < .001), lacosamide (p = .03), zonisamide (p = .01), lamotrigine (p = .03), phenytoin (p = .03), and topiramate (p = .01). We observed a nonsignificant association between time of testing and IED rates (morning-afternoon p = .15, morning-evening p = .85, afternoon-evening p = .26)., Significance: The current study ranks the relative influence that subject-specific factors have on IED rates and highlights the importance of considering certain factors, such as SOZ location and ASM status, when analyzing IEDs for clinical or research purposes., (© 2020 International League Against Epilepsy.)

Models of memory formation posit that episodic memory formation depends critically on the hippocampus, which binds features of an event to its context. For this reason, the contrast between study items that are later recollected with their associative pair versus those for which no association is made fails should reveal electrophysiological patterns in the hippocampus selectively involved in associative memory encoding. Extensive data from studies in rodents support a model in which theta oscillations fulfill this role, but results in humans have not been as clear. Here, we used an associative recognition memory procedure to identify hippocampal correlates of successful associative memory encoding and retrieval in patients (10 females and 9 males) undergoing intracranial EEG monitoring. We identified a dissociation between 2-5 Hz and 5-9 Hz theta oscillations, by which power increases in 2-5 Hz oscillations were uniquely linked with successful associative memory in both the anterior and posterior hippocampus. These oscillations exhibited a significant phase reset that also predicted successful associative encoding and distinguished recollected from nonrecollected items at retrieval, as well as contributing to relatively greater reinstatement of encoding-related patterns for recollected versus nonrecollected items. Our results provide direct electrophysiological evidence that 2-5 Hz hippocampal theta oscillations preferentially support the formation of associative memories, although we also observed memory-related effects in the 5-9 Hz frequency range using measures such as phase reset and reinstatement of oscillatory activity. SIGNIFICANCE STATEMENT Models of episodic memory encoding predict that theta oscillations support the formation of interitem associations. We used an associative recognition task designed to elicit strong hippocampal activation to test this prediction in human neurosurgical patients implanted with intracranial electrodes. The findings suggest that 2-5 Hz theta oscillatory power and phase reset in the hippocampus are selectively associated with associative memory judgments. Furthermore, reinstatement of oscillatory patterns in the hippocampus was stronger for successful recollection. Collectively, the findings support a role for hippocampal theta oscillations in human associative memory., (Copyright © 2020 the authors.)

Human data collected using noninvasive imaging techniques have established the importance of parietal regions towards episodic memory retrieval, including the angular gyrus and posterior cingulate cortex. Such regions comprise part of a putative core episodic retrieval network. In free recall, comparisons between contextually appropriate and inappropriate recall events (i.e. prior list intrusions) provide the opportunity to study memory retrieval networks supporting veridical recall, and existing findings predict that differences in electrical activity in these brain regions should be identified according to the accuracy of recall. However, prior iEEG studies, utilizing principally subdural grid electrodes, have not fully characterized brain activity in parietal regions during memory retrieval and have not examined connectivity between core recollection areas and the hippocampus or prefrontal cortex. Here, we employed a data set obtained from 100 human patients implanted with stereo EEG electrodes for seizure mapping purposes as they performed a free recall task. This data set allowed us to separately analyze activity in midline versus lateral parietal brain regions, and in anterior versus posterior hippocampus, to identify areas in which retrieval-related activity predicted the recollection of a correct versus an incorrect memory. With the wide coverage afforded by the stereo EEG approach, we were also able to examine interregional connectivity. Our key findings were that differences in gamma band activity in the angular gyrus, precuneus, posterior temporal cortex, and posterior (more than anterior) hippocampus discriminated accurate versus inaccurate recall as well as active retrieval versus memory search. The left angular gyrus exhibited a significant power decrease preceding list intrusions as well as unique phase-amplitude coupling properties, whereas the prefrontal cortex was unique in exhibiting a power increase during list intrusions. Analysis of connectivity revealed significant hemispheric asymmetry, with relatively sparse left-sided functional connections compared to the right hemisphere. One exception to this finding was elevated connectivity between the prefrontal cortex and left angular gyrus. This finding is interpreted as evidence for the engagement of prefrontal cortex in memory monitoring and mnemonic decision-making., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes., Objective: The goal of our large-scale study was to comprehensively evaluate the effects of stimulation at different parameters and locations on neuronal activity across the human brain., Methods: To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations., Results: Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity., Conclusion: By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results provide an electrophysiological framework that clinicians and researchers may consider when designing stimulation protocols to cause precisely targeted changes in human brain activity., Competing Interests: Declaration of competing interest M.K. and D.R. have started a company, Nia Therapeutics, Inc., intended to develop and commercialize brain stimulation therapies for memory restoration. Each of them holds >5% equity interest in Nia. R.E.G. serves as a consultant to Medtronic, which was a subcontractor on the RAM project. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. B.J. receives research funding from NeuroPace and Medtronic not relating to this research. G.W. has rights to receive future royalties from the licensing of brain stimulation technology. Mayo Clinic has a financial interest related to brain stimulation technology, and is co-owner of Cadence Neuroscience Inc, the development of which has been assisted by G.W. The remaining authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Intra-cranial electroencephalographic brain recordings (iEEG) provide a powerful tool for investigating the neural processes supporting episodic memory encoding and form the basis of experimental therapies aimed at improving memory dysfunction. However, given the invasiveness of iEEG, investigations are constrained to patients with drug-resistant epilepsy for whom such recordings are clinically indicated. Particularly in the case of temporal lobe epilepsy (TLE), neuropathology and the possibility of functional reorganization are potential constraints on the generalizability of intra-cerebral findings and pose challenges to the development of therapies for memory disorders stemming from other etiologies. Here, samples of TLE (N ​= ​16; all of whom had undergone iEEG) and age-matched healthy control (N ​= ​19) participants underwent fMRI as they studied lists of concrete nouns. fMRI BOLD responses elicited by the study words were segregated according to subsequent performance on tests of delayed free recall and recognition memory. Subsequent memory effects predictive of both successful recall and recognition memory were evident in several neural regions, most prominently in the left inferior frontal gyrus, and did not demonstrate any group differences. Behaviorally, the groups did not differ in overall recall performance or in the strength of temporal contiguity effects. However, group differences in serial position effects and false alarm rates were evident during the free recall and recognition memory tasks, respectively. Despite these behavioral differences, neuropathology associated with temporal lobe epilepsy was apparently insufficient to give rise to detectable differences in the functional neuroanatomy of episodic memory encoding relative to neurologically healthy controls. The findings provide reassurance that iEEG findings derived from experimental paradigms similar to those employed here generalize to the neurotypical population., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier Inc.)

The medial temporal lobe (MTL) is known to support episodic memory and spatial navigation, raising the possibility that its true function is to form "cognitive maps" of any kind of information. Studies in humans and animals support the idea that the hippocampal theta rhythm (4 to 8 Hz) is key to this mapping function, as it has been repeatedly observed during spatial navigation tasks. If episodic memory and spatial navigation are 2 sides of the same coin, we hypothesized that theta oscillations might reflect relations between explicitly nonspatial items, such as words. We asked 189 neurosurgical patients to perform a verbal free-recall task, of which 96 had indwelling electrodes placed in the MTL. Subjects were instructed to remember short lists of sequentially presented nouns. We found that hippocampal theta power and connectivity during item retrieval coded for semantic distances between words, as measured using word2vec-derived subspaces. Additionally, hippocampal theta indexed temporal distances between words after filtering lists on recall performance, to ensure adequate dynamic range in time. Theta effects were noted only for semantic subspaces of 1 dimension, indicating a substantial compression of the possible semantic feature space. These results lend further support to our growing confidence that the MTL forms cognitive maps of arbitrary representational spaces, helping to reconcile longstanding differences between the spatial and episodic memory literatures., Competing Interests: The authors declare no competing interest.

Objective: Patients with medically refractory epilepsy often undergo intracranial electroencephalography (iEEG) monitoring to identify a seizure focus and determine their candidacy for surgical intervention. This clinically necessary monitoring period provides an increasingly utilized research opportunity to study human neurophysiology, however ethical concerns demand a thorough appreciation of the associated risks. We measured the incidence of research stimulation-associated seizures in a large multi-institutional dataset in order to determine whether brain stimulation was statistically associated with seizure incidence and identify potential risk factors for stimulation-associated seizures., Approach: 188 subjects undergoing iEEG monitoring across ten institutions participated in 770 research stimulation sessions over 3.5 yr. Seizures within 30 min of a stimulation session were included in our retrospective analysis. We analyzed stimulation parameters, seizure incidence, and typical seizure patterns, to assess the likelihood that recorded seizures were stimulation-induced, rather than events that occurred by chance in epilepsy patients prone to seizing., Main Results: In total, 14 seizures were included in our analysis. All events were single seizures, and no adverse events occurred. The mean amplitude of seizure-associated stimulation did not differ significantly from the mean amplitude delivered in sessions without seizures. In order to determine the likelihood that seizures were stimulation induced, we used three sets of analyses: visual iEEG analysis, statistical frequency, and power analyses. We determined that three of the 14 seizures were likely stimulation-induced, five were possibly stimulation-induced, and six were unlikely stimulation-induced. Overall, we estimate a rate of stimulation-induced seizures between 0.39% and 1.82% of sessions., Significance: The rarity of stimulation-associated seizures and the fact that none added morbidity or affected the clinical course of any patient are important findings for understanding the feasibility and safety of intracranial stimulation for research purposes.

Chronically implantable neurostimulation devices are becoming a clinically viable option for treating patients with neurological disease and psychiatric disorders. Neurostimulation offers the ability to probe and manipulate distributed networks of interacting brain areas in dysfunctional circuits. Here, we use tools from network control theory to examine the dynamic reconfiguration of functionally interacting neuronal ensembles during targeted neurostimulation of cortical and subcortical brain structures. By integrating multimodal intracranial recordings and diffusion-weighted imaging from patients with drug-resistant epilepsy, we test hypothesized structural and functional rules that predict altered patterns of synchronized local field potentials. We demonstrate the ability to predictably reconfigure functional interactions depending on stimulation strength and location. Stimulation of areas with structurally weak connections largely modulates the functional hubness of downstream areas and concurrently propels the brain towards more difficult-to-reach dynamical states. By using focal perturbations to bridge large-scale structure, function, and markers of behavior, our findings suggest that stimulation may be tuned to influence different scales of network interactions driving cognition., Competing Interests: Competing Interests: The authors have declared that no competing interests exist.

Whereas numerous findings support a distinction between episodic and semantic memory, it is now widely acknowledged that these two forms of memory interact during both encoding and retrieval. The precise nature of this interaction, however, remains poorly understood. To examine the role of semantic organization during episodic encoding and retrieval, we recorded intracranial encephalographic signals as 69 neurosurgical patients studied and subsequently recalled categorized and unrelated word lists. Applying multivariate classifiers to neural recordings, we were able to reliably predict encoding success, retrieval success, and temporal and categorical clustering during recall. By assessing how these classifiers generalized across list types, we identified specific retrieval processes that predicted recall of categorized lists and distinguished between recall transitions within and between category clusters. These results particularly implicate retrieval (rather than encoding) processes in the categorical organization of episodic memories. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Background: We sought to determine if ripple oscillations (80-120 Hz), detected in intracranial electroencephalogram (iEEG) recordings of patients with epilepsy, correlate with an enhancement or disruption of verbal episodic memory encoding., Methods: We defined ripple and spike events in depth iEEG recordings during list learning in 107 patients with focal epilepsy. We used logistic regression models (LRMs) to investigate the relationship between the occurrence of ripple and spike events during word presentation and the odds of successful word recall following a distractor epoch and included the seizure onset zone (SOZ) as a covariate in the LRMs., Results: We detected events during 58,312 word presentation trials from 7630 unique electrode sites. The probability of ripple on spike (RonS) events was increased in the SOZ (p < 0.04). In the left temporal neocortex, RonS events during word presentation corresponded with a decrease in the odds ratio (OR) of successful recall, however, this effect only met significance in the SOZ (OR of word recall: 0.71, 95% confidence interval (CI): 0.59-0.85, n = 158 events, adaptive Hochberg, p < 0.01). Ripple on oscillation (RonO) events that occurred in the left temporal neocortex non-SOZ also correlated with decreased odds of successful recall (OR: 0.52, 95% CI: 0.34-0.80, n = 140, adaptive Hochberg, p < 0.01). Spikes and RonS that occurred during word presentation in the left middle temporal gyrus (MTG) correlated with the most significant decrease in the odds of successful recall, irrespective of the location of the SOZ (adaptive Hochberg, p < 0.01)., Conclusion: Ripples and spikes generated in the left temporal neocortex are associated with impaired verbal episodic memory encoding. Although physiological and pathological ripple oscillations were not distinguished during cognitive tasks, our results show an association of undifferentiated ripples with impaired encoding. The effect was sometimes specific to regions outside the SOZ, suggesting that widespread effects of epilepsy outside the SOZ may contribute to cognitive impairment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Memory encoding is an essential step for all learning. However, the genetic and molecular mechanisms underlying human memory encoding remain poorly understood, and how this molecular framework permits the emergence of specific patterns of brain oscillations observed during mnemonic processing is unknown. Here, we directly compare intracranial electroencephalography recordings from the neocortex in individuals performing an episodic memory task with human gene expression from the same areas. We identify genes correlated with oscillatory memory effects across 6 frequency bands. These genes are enriched for autism-related genes and have preferential expression in neurons, in particular genes encoding synaptic proteins and ion channels, supporting the idea that the genes regulating voltage gradients are involved in the modulation of oscillatory patterns during successful memory encoding across brain areas. Memory-related genes are distinct from those correlated with other forms of cognitive processing and resting state fMRI. These data are the first to identify correlations between gene expression and active human brain states as well as provide a molecular window into memory encoding oscillations in the human brain.

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target for memory enhancement. Taken together, our results suggest that such systems may provide a therapeutic approach for treating memory dysfunction.

Functional differences in the anterior and posterior hippocampus during episodic memory processing have not been examined in human electrophysiological data. This is in spite of strong evidence for such differences in rodent data, including greater place cell specificity in the dorsal hippocampus, greater sensitivity to the aversive or motivational content of memories in ventral regions, connectivity analyses identifying preferential ventral hippocampal connections with the amygdala, and gene expression analyses identifying a dorsal-ventral gradient. We asked if memory-related oscillatory patterns observed in human hippocampal recordings, including the gamma band and slow-theta (2.5-5 Hz) subsequent memory effects, would exhibit differences along the longitudinal axis and between hemispheres. We took advantage of a new dataset of stereo electroencephalography patients with simultaneous, robotically targeted anterior, and posterior hippocampal electrodes to directly compare oscillatory subsequent memory effects during item encoding. This same data set allowed us to examine left-right connectivity and hemispheric differences in hippocampal oscillatory patterns. Our data suggest that a power increase during successful item encoding in the 2.5-5 Hz slow-theta frequency range preferentially occurs in the posterior hippocampus during the first 1,000 ms after item presentation, while a gamma band power increase is stronger in the dominant hemisphere. This dominant-nondominant pattern in the gamma range appears to reverse during item retrieval, however. Intrahippocampal phase coherence was found to be stronger during successful item encoding. Our phase coherence data are also consistent with existing reports of a traveling wave for theta oscillations propagating along the septotemporal (longitudinal) axis of the human hippocampus. We examine how our findings fit with theories of functional specialization along the hippocampal axis., (© 2017 Wiley Periodicals, Inc.)

People often forget information because they fail to effectively encode it. Here, we test the hypothesis that targeted electrical stimulation can modulate neural encoding states and subsequent memory outcomes. Using recordings from neurosurgical epilepsy patients with intracranially implanted electrodes, we trained multivariate classifiers to discriminate spectral activity during learning that predicted remembering from forgetting, then decoded neural activity in later sessions in which we applied stimulation during learning. Stimulation increased encoding-state estimates and recall if delivered when the classifier indicated low encoding efficiency but had the reverse effect if stimulation was delivered when the classifier indicated high encoding efficiency. Higher encoding-state estimates from stimulation were associated with greater evidence of neural activity linked to contextual memory encoding. In identifying the conditions under which stimulation modulates memory, the data suggest strategies for therapeutically treating memory dysfunction., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Although it is now well established that the hippocampus supports memory encoding [1, 2], little is known about hippocampal activity during spontaneous memory retrieval. Recent intracranial electroencephalographic (iEEG) work has shown that hippocampal activity during encoding predicts subsequent temporal organization of memories [3], supporting a role in contextual binding. It is an open question, however, whether the hippocampus similarly supports contextually mediated processes during retrieval. Here, we analyzed iEEG recordings obtained from 215 epilepsy patients as they performed a free recall task. To identify neural activity specifically associated with contextual retrieval, we compared correct recalls, intrusions (incorrect recall of either items from prior lists or items not previously studied), and deliberations (matched periods during recall when no items came to mind). Neural signals that differentiate correct recalls from both other retrieval classes reflect contextual retrieval, as correct recalls alone arise from the correct context. We found that in the hippocampus, high-frequency activity (HFA, 44-100 Hz), a proxy for neural activation [4], was greater prior to correct recalls relative to the other retrieval classes, with no differentiation between intrusions and deliberations. This pattern was not observed in other memory-related cortical regions, including DLPFC, thus supporting a specific hippocampal contribution to contextually mediated memory retrieval., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The importance of the hippocampal theta oscillation (4-8 Hz) to memory formation has been well-established through studies in animals, prompting researchers to propose comprehensive theories of memory and learning that rely on theta oscillations for integrating information in the hippocampus and neocortex. Yet, empirical evidence for the importance of 4-8 Hz hippocampal theta oscillations to memory formation in humans is equivocal at best. To clarify this apparent interspecies discrepancy, we recorded intracranial EEG (iEEG) data from 237 hippocampal electrodes in 33 neurosurgical patients as they performed an episodic memory task. We identified two distinct patterns of hippocampal oscillations, at ∼3 and ∼8 Hz, which are at the edges of the traditional 4-8 Hz human theta band. The 3 Hz "slow-theta" oscillation exhibited higher power during successful memory encoding and was functionally linked to gamma oscillations, but similar patterns were not present for the 8 Hz "fast-theta" oscillation. For episodic memory, slow-theta oscillations in the human hippocampus appear to be analogous to the memory-related theta oscillations observed in animals. Both fast-theta and slow-theta oscillations exhibit evidence of phase synchrony with oscillations in the temporal cortex. We discuss our findings in the context of recent research on the electrophysiology of human memory and spatial navigation, and explore the implications of this result for theories of cortico-hippocampal communication., (Copyright © 2011 Wiley Periodicals, Inc.)

The subthalamic nucleus (STN), which receives excitatory inputs from the cortex and has direct connections with the inhibitory pathways of the basal ganglia, is well positioned to efficiently mediate action selection. Here, we use microelectrode recordings captured during deep brain stimulation surgery as participants engage in a decision task to examine the role of the human STN in action selection. We demonstrate that spiking activity in the STN increases when participants engage in a decision and that the level of spiking activity increases with the degree of decision conflict. These data implicate the STN as an important mediator of action selection during decision processes.

Intradural disc herniation is a rare disease that occurs most commonly in the lumbar region, while fewer than 5% occur in the thoracic and cervical regions. We report a patient with thoracic intradural disc herniation at T12-L1 who presented with radiculopathy and motor weakness. The preoperative MRI did not demonstrate an intradural lesion, and it was identified intraoperatively by inspection and palpation of the thecal sac. The disc was removed, and the patient experienced good neurological recovery and remains pain free 1 year after surgery., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Accumulated evidence from animal studies implicates the ventral striatum in the processing of reward information. Recently, deep brain stimulation (DBS) surgery has enabled researchers to analyze neurophysiological recordings from humans engaged in reward tasks. We present data recorded from the human ventral striatum during deep brain stimulation surgery as a participant played a video game coupled to the receipt of visual reward images. To our knowledge, we identify the first instances of reward-sensitive single unit activity in the human ventral striatum. Local field potential data suggest that alpha oscillations are sensitive to positive feedback, whereas beta oscillations exhibit significantly higher power during unrewarded trials. We report evidence of alpha-gamma cross-frequency coupling that differentiates between positive and negative feedback., (© 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.)

The objective of this study is to determine the bony limits of the transnasal and transoral approaches to the anterior skull base. The data we present are meant to assist surgeons in preoperative planning for lesions of the sella, clivus, foramen magnum, and odontoid. Using precise measurements undertaken on 41 high-resolution computed tomography scans from patients at the University of Pennsylvania without any history of sinus or sellar pathology, we sought to define the bony limits of transoral and transnasal approaches. Direct measurements and calculated angles were used to assess the dimensions of the anterior skull base. Using our measurements, a transnasal approach can reach an average of 22.5 mm below the plane of the hard palate to the body of C2, and a transoral route can reach 38 mm above the basion along the length of the clivus. Analysis of variance demonstrated no significant differences when subjects were grouped based on race or gender. The measurements outlined within this article help to define the relative dimensions necessary for adapted transoral and transnasal skull base surgeries.

Brain-machine interfaces (BMI) seek to directly communicate with the human nervous system in order to diagnose and treat intrinsic neurological disorders. While the first generation of these devices has realized significant clinical successes, they often rely on gross electrical stimulation using empirically derived parameters through open-loop mechanisms of action that are not yet fully understood. Their limitations reflect the inherent challenge in developing the next generation of these devices. This review identifies lessons learned from the first generation of BMI devices (chiefly deep brain stimulation), identifying key problems for which the solutions will aid the development of the next generation of technologies. Our analysis examines four hypotheses for the mechanism by which brain stimulation alters surrounding neurophysiologic activity. We then focus on motor prosthetics, describing various approaches to overcoming the problems of decoding neural signals. We next turn to visual prosthetics, an area for which the challenges of signal coding to match neural architecture has been partially overcome. Finally, we close with a review of cortical stimulation, examining basic principles that will be incorporated into the design of future devices. Throughout the review, we relate the issues of each specific topic to the common thread of BMI research: translating new knowledge of network neuroscience into improved devices for neuromodulation.

Object: Chronic subdural hematoma (CSDH), a condition much more common in the elderly, presents an increasing challenge as the population ages. Treatment strategies for CSDH include bur-hole craniostomy (BHC), twist-drill craniostomy (TDC), and craniotomy. Decision analysis was used to organize existing data and develop recommendations for effective treatment., Methods: A Medline search was used to identify articles about treatment of CSDH. Direct assessment by health care professionals of the relative health impact of common complications and recurrences was used to generate utility values for treatment outcomes. Monte Carlo simulation and sensitivity analyses allowed comparisons across treatment strategies. A second simulation examined whether intraoperative irrigation or postoperative drainage affect the outcomes following BHC., Results: On a scale from 0 to 1, the utility of BHC was found to be 0.9608, compared with 0.9202 for TDC (p = 0.001) and 0.9169 for craniotomy (p = 0.006). Sensitivity analysis confirmed the robustness of these values. Craniotomy yielded fewer recurrences, but more frequent and more serious complications than did BHC. There were no significant differences for BHC with or without irrigation or postoperative drainage., Conclusions: Bur-hole craniostomy is the most efficient choice for surgical drainage of uncomplicated CSDH. Bur-hole craniostomy balances a low recurrence rate with a low incidence of highly morbid complications. Decision analysis provides statistical and empirical guidance in the absence of well-controlled large trials and despite a confusing range of previously reported morbidity and recurrence.

Deep brain stimulation for epilepsy has garnered attention from epileptologists due to its well-documented success in treating movement disorders and the low morbidity associated with the implantation of electrodes. Given the large proportion of patients who fail medical therapy and are not candidates for surgical amelioration, as well as the suboptimal seizure control offered by vagus nerve stimulation, the search for appropriate brain structures to serve as targets for deep brain stimulation has generated a useful body of evidence to serve as the basis for larger investigations. Early results of the SANTE trial should lay the foundation for widespread implementation of DBS for epilepsy targeting the anterior thalamic nucleus. Other targets also offer promise, including the caudate nucleus, the subthalamic nucleus, the cerebellum, the centromedian nucleus of the thalamus, and the hippocampus. This paper reviews the logic which underlies these potential targets and recapitulates the current data from limited human trials supporting each one. It also provides a succinct overview of the surgical procedure used for electrode implantation.

Background: Although existing literature includes reports of isolated lower extremity monoparesis/monoplegia (MP) due to epidural or subdural haematomas, instances due to traumatic intraparenchymal contusions near the vertex have not been described [corrected].Due to the limitations of conventional axial computed tomographic (CT) imaging, the evidence of a vertex contusion may be under-appreciated if an overlying skull fracture is absent., Case Description: Two cases of isolated MP due to vertex contusions are described and the physical forces involved in the head trauma are described to explain the location of the contusions. Vertex intraparenchymal contusions are rare because of the way the brain deforms in response to the accelerational forces acting on it during head trauma. This study analyses patients' injuries and addresses the importance of considering the forces acting on the brain when evaluating a victim of head trauma., Conclusion: Isolated lower extremity MP following head trauma is rare because haematomas in the fronto-parietal cortex near the midline that could produce such a deficit are rare. The limitations of typical axial CT imaging can be overcome with coronal reconstructions. Practitioners who evaluate patients with isolated MP after head injury should be aware of the possibility of an intraparenchymal lesion near the vertex as the cause of this deficit.

Decompressive hemicraniectomy is well accepted for the surgical treatment of intractable intracranial hypertension in cases in which medical management fails. Although it is performed as a life-saving procedure when death is imminent from intracranial hypertension, little is known about the functional outcomes for these patients on long-term follow-up. In this study, the authors performed a systematic review of the literature to examine neurological outcome after hemicraniectomy. A literature search revealed 29 studies that reported outcomes using GOS scores. The GOS scores were transformed to utility values for quality of life using a conversion method based on decision analysis modeling. Based on the literature, 1422 cases were analyzed. The average 6-month-postoperative mortality rate was 28.2%. The mean QOL value among survivors was 0.592, which corresponds roughly to a GOS score of 4. Although more studies are needed for validation of long-term neurological outcome after hemicraniectomy, the assumption that most patients remain in a vegetative state after this intervention is clearly incorrect.

Objective: Epilepsia partialis continua (EPC) is a form of status epilepticus that is characterized by continuous simple partial seizures and can occur as a manifestation of a variety of underlying pathological processes. Because these seizures typically take onset within or close to motor cortex, the treatment of refractory EPC with resective surgery risks significant postoperative deficits., Clinical Presentation: We describe our experience using ictal recordings obtained intraoperatively during awake craniotomy, in conjunction with direct cortical stimulation mapping, to tailor surgical resections in 2 patients with refractory EPC. Both patients had pan-hemispheric pathologies that made extraoperative recording difficult., Intervention: Awake craniotomy takes advantage of a unique feature of refractory EPC, namely the near-continuous presence of focal seizure activity. It allows the surgeon to record seizures in the operating room and precisely define the anatomic location of epileptic activity, to resect the seizure focus, and to both visually and electrographically confirm successful cessation of EPC after resection, all within a single operation. We used standard methods of awake craniotomy to finely tailor a cortical resection to the epileptogenic cortex while sparing nearby eloquent motor areas. The precision of awake mapping made this approach safe and effective., Conclusion: The cases we describe demonstrate the role of focal resection in the treatment of EPC. Standard techniques of awake craniotomy have application in the treatment of this challenging problem.

Object: Microvascular decompression (MVD) of the facial nerve is an effective treatment for hemifacial spasm (HFS), but the procedure is associated with a significant risk of complications such as hearing loss and facial weakness. Many surgeons advocate the use of intraoperative brainstem auditory evoked response (BAER) monitoring in an attempt to improve surgical outcomes. The authors critically assessed a large series of patients with HFS who underwent MVD without neurophysiological monitoring., Methods: The authors retrospectively identified 114 consecutive patients, with a history of HFS and without a history of HFS surgery, in whom MVD was performed by a single surgeon without the use of neurophysiological monitoring. Postoperative outcomes were determined by reviewing records and through telephone interviews. At least 1 year of postoperative follow-up data were available for 91 of the 114 patients, and the median follow-up duration in all cases was 8 years (range 3 months-23 years). A Kaplan-Meier analysis showed that 86% of the patients were spasm free at 10 years postoperatively., Results: There were no surgical deaths or major deficits, and complications included 1 case of postoperative deafness, 1 of permanent subtotal hearing loss, and 10 of delayed facial palsy, 2 of which did not completely resolve at last follow-up. The outcomes, rates of hearing loss, and other complications compared well with those reported in studies in which investigators used intraoperative monitoring., Conclusions: The results suggest that MVD without neurophysiological monitoring is a safe and effective treatment option in patients with HFS. Although BAER monitoring may be a valuable adjunct to surgery at centers experienced with the modality, the absence of intraoperative monitoring should not prevent neurosurgeons from performing MVD in patients with HFS.

Late recurrences after microvascular decompression for hemifacial spasm or trigeminal neuralgia are rare. We present an atypical case of recurrence one and a half years after successful microvascular decompression for hemifacial spasm associated with direct trauma. Implications for the management of recurrences and the judicious use of polymer adhesives such as fibrin glue are discussed., (Copyright 2008 S. Karger AG, Basel.)

Objectives: Although subdural electrodes are routinely used to map regional brain function, it is unknown if the presence of these implants hinders local cortical function. The authors used psychophysical methods to measure the effect of uncomplicated electrode implantation on local cortical function., Methods: Local field potentials were used to map receptive fields (RFs) for subdural electrodes that were unilaterally implanted on early visual cortex in 4 patients. After electrode implantation, patients did a task that required them to detect an orientation change in a flashing visual stimulus that was presented either inside the mapped RF or outside the RF in the diametrically opposite portion of the other hemifield. The size of the orientation change was varied to span a wide range of behavioral performance. Psychometric curves were generated by fitting behavioral responses to a logistic function. The threshold was defined as the point at which the fitted function crossed 50% detection., Results: Data were well fit by the logistic function in all 4 patients for both RF and non-RF conditions. None of the volunteers tested showed a statistically significant difference in detection threshold, reaction time, or in the slope of the psychometric function for stimuli presented inside or outside the RF., Conclusions: Subdural electrodes implanted for extraoperative monitoring do not impair psychophysical performance for a task based on stimuli lying within the RF for recording electrodes. This finding suggests that these electrodes can be used reliably for accurate assessment of regional neurological function.

Spontaneous cerebral venous sinus thrombosis is a rare problem that may be encountered in patients with underlying thrombophilic disorders. It has also been reported as a postoperative complication following suboccipital, transpetrosal, and transcallosal approaches. The authors report on a 67-year-old man with two prior episodes of lower-extremity deep venous thrombosis who underwent transcallosal resection of a colloid cyst and in whom sagittal sinus thrombosis developed 2 weeks thereafter. Results of a subsequent hematological workup revealed both a factor V Leiden mutation and the presence of antiphospholipid antibodies, two thrombophilic risk factors that likely contributed to the development of delayed postoperative sinus thrombosis. Although the safety of low-molecular-weight heparin (LMWH) after craniotomy has not been established in a randomized, controlled study, there is sufficient evidence to justify its use for prophylactic anticoagulation therapy in patients at high risk for postoperative cerebral venous thrombosis. The authors propose using LMWH prophylaxis in patients with thrombophilic disorders who undergo neurosurgical procedures in proximity to dural sinuses in an effort to prevent catastrophic venous infarction.