Publications by authors named "Bradley C Lega"

34 Publications

Cross-regional phase amplitude coupling supports the encoding of episodic memories.

Hippocampus 2021 Feb 5. Epub 2021 Feb 5.

Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hipo.23309DOI Listing
February 2021

Factors correlated with intracranial interictal epileptiform discharges in refractory epilepsy.

Epilepsia 2021 Feb 17;62(2):481-491. Epub 2020 Dec 17.

Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.16792DOI Listing
February 2021

Hippocampal Theta Oscillations Support Successful Associative Memory Formation.

J Neurosci 2020 12 6;40(49):9507-9518. Epub 2020 Nov 6.

Department of Neurosurgery, University of Texas Southwestern Medical Center, Dallas, Texas 75390

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. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.0767-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724134PMC
December 2020

Direct brain recordings identify hippocampal and cortical networks that distinguish successful versus failed episodic memory retrieval.

Neuropsychologia 2020 10 29;147:107595. Epub 2020 Aug 29.

Department of Neurosurgery, University of Texas Southwestern, Dallas, TX 75390, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuropsychologia.2020.107595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554101PMC
October 2020

The effects of direct brain stimulation in humans depend on frequency, amplitude, and white-matter proximity.

Brain Stimul 2020 Sep - Oct;13(5):1183-1195. Epub 2020 May 21.

Department of Biomedical Engineering, Columbia University, New York, 10027, USA. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brs.2020.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494653PMC
May 2020

Commentary: Awake Craniotomy and Memory Induction Through Electrical Stimulation: Why Are Penfield's Findings Not Replicated in the Modern Era?

Neurosurgery 2020 08;87(2):E138-E139

Department of Neurosurgery, University of Texas Southwestern Medical Center, Dallas, Texas.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyaa122DOI Listing
August 2020

Comparison of fMRI correlates of successful episodic memory encoding in temporal lobe epilepsy patients and healthy controls.

Neuroimage 2020 02 23;207:116397. Epub 2019 Nov 23.

Center for Vital Longevity, University of Texas at Dallas, 1600 Viceroy Dr. #800, Dallas, TX, 75235, USA; School of Behavioral and Brain Sciences, University of Texas at Dallas, 800 W Campbell Rd, Richardson, TX, 75080, USA; Department of Psychiatry, University of Texas Southwestern Medical Center, 6363 Forest Park Rd 7th Floor Suite 749, Dallas, TX, 75235, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2019.116397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238288PMC
February 2020

Hippocampal theta codes for distances in semantic and temporal spaces.

Proc Natl Acad Sci U S A 2019 11 13;116(48):24343-24352. Epub 2019 Nov 13.

Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1906729116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883851PMC
November 2019

Risk of seizures induced by intracranial research stimulation: analysis of 770 stimulation sessions.

J Neural Eng 2019 11 11;16(6):066039. Epub 2019 Nov 11.

Department of Neurological Surgery, Columbia University, New York, NY, United States of America.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1741-2552/ab4365DOI Listing
November 2019

Functional control of electrophysiological network architecture using direct neurostimulation in humans.

Netw Neurosci 2019 1;3(3):848-877. Epub 2019 Jul 1.

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1162/netn_a_00089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663306PMC
July 2019

Autofluorescence Technology in Glioblastoma Resection: Evolution of New Tool and Approach.

World Neurosurg 2019 06 9;126:139-141. Epub 2019 Mar 9.

Department of Neurological Surgery, The University of Texas Southwestern, Zale Lipshy Hospital, Dallas, Texas, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2019.02.158DOI Listing
June 2019

Neural activity reveals interactions between episodic and semantic memory systems during retrieval.

J Exp Psychol Gen 2019 Jan;148(1):1-12

Department of Psychology, University of Pennsylvania.

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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/xge0000480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419095PMC
January 2019

Ripple oscillations in the left temporal neocortex are associated with impaired verbal episodic memory encoding.

Epilepsy Behav 2018 11 11;88:33-40. Epub 2018 Sep 11.

Dept. of Neurology and Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2018.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240385PMC
November 2018

Closed-loop stimulation of temporal cortex rescues functional networks and improves memory.

Nat Commun 2018 02 6;9(1):365. Epub 2018 Feb 6.

Department of Psychology, University of Pennsylvania, 433 South University Avenue, Philadelphia, PA, 19104, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-017-02753-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802791PMC
February 2018

Theta band power increases in the posterior hippocampus predict successful episodic memory encoding in humans.

Hippocampus 2017 10 30;27(10):1040-1053. Epub 2017 Jun 30.

Department of Neurological Surgery, University of Texas, Southwestern Medical Center, Dallas, Texas, 75390.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hipo.22751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517838PMC
October 2017

Direct Brain Stimulation Modulates Encoding States and Memory Performance in Humans.

Curr Biol 2017 May 20;27(9):1251-1258. Epub 2017 Apr 20.

Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2017.03.028DOI Listing
May 2017

Human Genomic Signatures of Brain Oscillations During Memory Encoding.

Cereb Cortex 2018 05;28(5):1733-1748

Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhx083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907355PMC
May 2018

Contextually Mediated Spontaneous Retrieval Is Specific to the Hippocampus.

Curr Biol 2017 Apr 23;27(7):1074-1079. Epub 2017 Mar 23.

Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2017.02.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789776PMC
April 2017

Neuronal activity in the human subthalamic nucleus encodes decision conflict during action selection.

J Neurosci 2012 Feb;32(7):2453-60

Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA. kareem.zaghloul@

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.5815-11.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296967PMC
February 2012

A patient with thoracic intradural disc herniation.

J Clin Neurosci 2011 Dec 15;18(12):1730-2. Epub 2011 Oct 15.

Department of Neurosurgery, Hospital of The University of Pennsylvania, 3400 Spruce Street, 3rd Floor Silverstein, Philadelphia, PA 19104, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2011.04.021DOI Listing
December 2011

Neuronal and oscillatory activity during reward processing in the human ventral striatum.

Neuroreport 2011 Nov;22(16):795-800

Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNR.0b013e32834b2975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188759PMC
November 2011

Human hippocampal theta oscillations and the formation of episodic memories.

Hippocampus 2012 Apr 27;22(4):748-61. Epub 2011 Apr 27.

Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hipo.20937DOI Listing
April 2012

Brain-machine interfaces: electrophysiological challenges and limitations.

Crit Rev Biomed Eng 2011 ;39(1):5-28

Department of Neurosurgery, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA 19103, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1615/critrevbiomedeng.v39.i1.20DOI Listing
August 2011

Morphometric measurements of the anterior skull base for endoscopic transoral and transnasal approaches.

Skull Base 2011 Jan;21(1):65-70

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0030-1265825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312413PMC
January 2011

Isolated lower extremity monoplegia due to a traumatic intraparenchymal contusion: report of two cases.

Brain Inj 2010 ;24(10):1231-5

Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19105, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/02699052.2010.495698DOI Listing
January 2011

Choosing the best operation for chronic subdural hematoma: a decision analysis.

J Neurosurg 2010 Sep;113(3):615-21

Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2009.9.JNS08825DOI Listing
September 2010

Deep brain stimulation in the treatment of refractory epilepsy: update on current data and future directions.

Neurobiol Dis 2010 Jun 23;38(3):354-60. Epub 2009 Jul 23.

Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19107, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nbd.2009.07.007DOI Listing
June 2010

Quality of life after hemicraniectomy for traumatic brain injury in adults. A review of the literature.

Neurosurg Focus 2009 Jun;26(6):E2

Division of Neurosurgery University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2009.3.FOCUS945DOI Listing
June 2009

Cortical resection tailored to awake, intraoperative ictal recordings and motor mapping in the treatment of intractable epilepsia partialis continua: technical case report.

Neurosurgery 2009 Mar;64(3 Suppl):ons195-6; discussion ons196

Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1227/01.NEU.0000335656.12271.A9DOI Listing
March 2009

Recurrent hemifacial spasm following minor trauma: report of a case.

Stereotact Funct Neurosurg 2008 25;86(6):394-6. Epub 2008 Nov 25.

Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000175803DOI Listing
June 2009