Publications by authors named "Paul A Wanda"

11 Publications

  • Page 1 of 1

Biomarkers of memory variability in traumatic brain injury.

Brain Commun 2021 15;3(1):fcaa202. Epub 2020 Dec 15.

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

Traumatic brain injury is a leading cause of cognitive disability and is often associated with significant impairment in episodic memory. In traumatic brain injury survivors, as in healthy controls, there is marked variability between individuals in memory ability. Using recordings from indwelling electrodes, we characterized and compared the oscillatory biomarkers of mnemonic variability in two cohorts of epilepsy patients: a group with a history of moderate-to-severe traumatic brain injury ( = 37) and a group of controls without traumatic brain injury ( = 111) closely matched for demographics and electrode coverage. Analysis of these recordings demonstrated that increased high-frequency power and decreased theta power across a broad set of brain regions mark periods of successful memory formation in both groups. As features in a logistic-regression classifier, spectral power biomarkers effectively predicted recall probability, with little difference between traumatic brain injury patients and controls. The two groups also displayed similar patterns of theta-frequency connectivity during successful encoding periods. These biomarkers of successful memory, highly conserved between traumatic brain injury patients and controls, could serve as the basis for novel therapies that target disordered memory across diverse forms of neurological disease.
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http://dx.doi.org/10.1093/braincomms/fcaa202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850041PMC
December 2020

Contribution of left supramarginal and angular gyri to episodic memory encoding: An intracranial EEG study.

Neuroimage 2021 01 1;225:117514. Epub 2020 Nov 1.

Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States.

The role of the left ventral lateral parietal cortex (VPC) in episodic memory is hypothesized to include bottom-up attentional orienting to recalled items, according to the dual-attention model (Cabeza et al., 2008). However, its role in memory encoding could be further clarified, with studies showing both positive and negative subsequent memory effects (SMEs). Furthermore, few studies have compared the relative contributions of sub-regions in this functionally heterogeneous area, specifically the anterior VPC (supramarginal gyrus/BA40) and the posterior VPC (angular gyrus/BA39), on a within-subject basis. To elucidate the role of the VPC in episodic encoding, we compared SMEs in the intracranial EEG across multiple frequency bands in the supramarginal gyrus (SmG) and angular gyrus (AnG), as twenty-four epilepsy patients with indwelling electrodes performed a free recall task. We found a significant SME of decreased theta power and increased high gamma power in the VPC overall, and specifically in the SmG. Furthermore, SmG exhibited significantly greater spectral tilt SME from 0.5 to 1.6 s post-stimulus, in which power spectra slope differences between recalled and unrecalled words were greater than in the AnG (p = 0.04). These results affirm the contribution of VPC to episodic memory encoding, and suggest an anterior-posterior dissociation within VPC with respect to its electrophysiological underpinnings.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117514DOI Listing
January 2021

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

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.
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http://dx.doi.org/10.1088/1741-2552/ab4365DOI Listing
November 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).
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http://dx.doi.org/10.1037/xge0000480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419095PMC
January 2019

Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation.

Nat Commun 2018 06 21;9(1):2423. Epub 2018 Jun 21.

Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY, 10027, USA.

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.
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http://dx.doi.org/10.1038/s41467-018-04847-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013427PMC
June 2018

Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and Temporal Memory.

J Neurosci 2018 05 10;38(19):4471-4481. Epub 2018 Apr 10.

Department of Biomedical Engineering, Columbia University, New York, New York 10027,

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred. Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory.
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http://dx.doi.org/10.1523/JNEUROSCI.3049-17.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943975PMC
May 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.
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http://dx.doi.org/10.1038/s41467-017-02753-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802791PMC
February 2018

Uncertainty leads to persistent effects on reach representations in dorsal premotor cortex.

Elife 2016 07 15;5. Epub 2016 Jul 15.

Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, United States.

Every movement we make represents one of many possible actions. In reaching tasks with multiple targets, dorsal premotor cortex (PMd) appears to represent all possible actions simultaneously. However, in many situations we are not presented with explicit choices. Instead, we must estimate the best action based on noisy information and execute it while still uncertain of our choice. Here we asked how both primary motor cortex (M1) and PMd represented reach direction during a task in which a monkey made reaches based on noisy, uncertain target information. We found that with increased uncertainty, neurons in PMd actually enhanced their representation of unlikely movements throughout both planning and execution. The magnitude of this effect was highly variable across sessions, and was correlated with a measure of the monkeys' behavioral uncertainty. These effects were not present in M1. Our findings suggest that PMd represents and maintains a full distribution of potentially correct actions.
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http://dx.doi.org/10.7554/eLife.14316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946902PMC
July 2016

State dependence of adaptation of force output following movement observation.

J Neurophysiol 2013 Sep 12;110(5):1246-56. Epub 2013 Jun 12.

Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, MO 63130, USA.

Humans readily learn to move through direct physical practice and by watching the movements of others. Some researchers have proposed that action observation can inform subsequent changes in control through the acquisition of a neural representation of the novel dynamics, but to date learning following observation has been described by kinematic metrics. Here we designed an experiment to consider the specificity of adaptation to novel dynamic perturbations at the level of force generation. We measured changes in temporal patterns of force output following either the performance or observation of movements perturbed by either position- or velocity-dependent dynamic environments to 1) establish whether previously described observational motor learning effects were attributable to changes in predictive limb control and 2) determine whether such adaptation reflected a learned dependence on limb states appropriate to the haptic environment. We found that subjects who observed perturbed movements produced significant compensatory changes in their lateral force output, despite never directly experiencing force perturbations firsthand while performing the motor task. The time series of observers' adapted force outputs suggested that the state dependence of observed dynamics shapes adaptation. We conclude that the brain can transform observation of kinematics into state-dependent adaptation of reach dynamics.
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http://dx.doi.org/10.1152/jn.00353.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763093PMC
September 2013

Brevity of haptic force perturbations induces heightened adaptive sensitivity.

Exp Brain Res 2013 May 7;226(3):407-20. Epub 2013 Mar 7.

Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, Campus Box 1097, St. Louis, MO 63130, USA.

We have exposed human participants to both full-movement and pulsatile viscous force perturbations to study the effect of force duration on the incremental transformation of sensation into adaptation. Traditional views of movement biomechanics could suggest that pulsatile forces would largely be attenuated as stiffness and viscosity act as a natural low-pass filter. Sensory transduction, however, tends to react to changes in stimuli and therefore could underlie heightened sensitivity to briefer, pulsatile forces. Here, participants adapted within perturbation duration conditions in a manner proportionate to sensed force and positional errors. Across perturbation conditions, we found participants had greater adaptive sensitivity when experiencing pulsatile forces rather than full-movement forces. In a follow-up experiment, we employed error-clamped, force channel trials to determine changes in predictive force generation. We found that while participants learned to closely compensate for the amplitude and breadth of full-movement forces, they exhibited a persistent mismatch in amplitude and breadth between adapted motor output and experienced pulsatile forces. This mismatch could generate higher salience of error signals that contribute to heightened sensitivity to pulsatile forces.
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http://dx.doi.org/10.1007/s00221-013-3450-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646637PMC
May 2013