Publications by authors named "Cory S Inman"

21 Publications

  • Page 1 of 1

Boundary-anchored neural mechanisms of location-encoding for self and others.

Nature 2021 01 23;589(7842):420-425. Epub 2020 Dec 23.

Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.

Everyday tasks in social settings require humans to encode neural representations of not only their own spatial location, but also the location of other individuals within an environment. At present, the vast majority of what is known about neural representations of space for self and others stems from research in rodents and other non-human animals. However, it is largely unknown how the human brain represents the location of others, and how aspects of human cognition may affect these location-encoding mechanisms. To address these questions, we examined individuals with chronically implanted electrodes while they carried out real-world spatial navigation and observation tasks. We report boundary-anchored neural representations in the medial temporal lobe that are modulated by one's own as well as another individual's spatial location. These representations depend on one's momentary cognitive state, and are strengthened when encoding of location is of higher behavioural relevance. Together, these results provide evidence for a common encoding mechanism in the human brain that represents the location of oneself and others in shared environments, and shed new light on the neural mechanisms that underlie spatial navigation and awareness of others in real-world scenarios.
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http://dx.doi.org/10.1038/s41586-020-03073-yDOI Listing
January 2021

Amygdala Stimulation Leads to Functional Network Connectivity State Transitions in the Hippocampus.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:3625-3628

Several studies have shown that direct brain stimulation can enhance memory in humans and animal models. Investigating the neurophysiological changes induced by brain stimulation is an important step towards understanding the neural processes underlying memory function. Furthermore, it paves the way for developing more efficient neuromodulation approaches for memory enhancement. In this study, we utilized a combination of unsupervised and supervised machine learning approaches to investigate how amygdala stimulation modulated hippocampal network activities during the encoding phase. Using a sliding window in time, we estimated the hippocampal dynamic functional network connectivity (dFNC) after stimulation and during sham trials, based on the covariance of local field potential recordings in 4 subregions of the hippocampus. We extracted different network states by combining the dFNC samples from 5 subjects and applying k-means clustering. Next, we used the between-state transition numbers as the latent features to classify between amygdala stimulation and sham trials across all subjects. By training a logistic regression model, we could differentiate stimulated from sham trials with 67% accuracy across all subjects. Using elastic net regularization as a feature selection method, we identified specific patterns of hippocampal network state transition in response to amygdala stimulation. These results offer a new approach to better understanding of the causal relationship between hippocampal network dynamics and memory-enhancing amygdala stimulation.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176742DOI Listing
July 2020

Wireless Programmable Recording and Stimulation of Deep Brain Activity in Freely Moving Humans.

Neuron 2020 10 17;108(2):322-334.e9. Epub 2020 Sep 17.

Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Uncovering the neural mechanisms underlying human natural ambulatory behavior is a major challenge for neuroscience. Current commercially available implantable devices that allow for recording and stimulation of deep brain activity in humans can provide invaluable intrinsic brain signals but are not inherently designed for research and thus lack flexible control and integration with wearable sensors. We developed a mobile deep brain recording and stimulation (Mo-DBRS) platform that enables wireless and programmable intracranial electroencephalographic recording and electrical stimulation integrated and synchronized with virtual reality/augmented reality (VR/AR) and wearables capable of external measurements (e.g., motion capture, heart rate, skin conductance, respiration, eye tracking, and scalp EEG). When used in freely moving humans with implanted neural devices, this platform is adaptable to ecologically valid environments conducive to elucidating the neural mechanisms underlying naturalistic behaviors and to the development of viable therapies for neurologic and psychiatric disorders.
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http://dx.doi.org/10.1016/j.neuron.2020.08.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785319PMC
October 2020

Functionally distinct high and low theta oscillations in the human hippocampus.

Nat Commun 2020 05 18;11(1):2469. Epub 2020 May 18.

Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4-10 Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta's function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior-posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.
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http://dx.doi.org/10.1038/s41467-020-15670-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235253PMC
May 2020

Case Series: Unilateral Amygdala Ablation Ameliorates Post-Traumatic Stress Disorder Symptoms and Biomarkers.

Neurosurgery 2020 09;87(4):796-802

Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia.

Background: Post-traumatic stress disorder is a severe psychobiological disorder associated with hyperactivity of the amygdala, particularly on the right side. Highly selective laser ablation of the amygdalohippocampal complex is an effective neurosurgical treatment for medically refractory medial temporal lobe epilepsy that minimizes neurocognitive deficits relative to traditional open surgery.

Objective: To examine the impact of amygdalohippocampotomy upon symptoms and biomarkers of post-traumatic stress disorder.

Methods: Two patients with well-documented chronic post-traumatic stress disorder who subsequently developed late-onset epilepsy underwent unilateral laser amygdalohippocampotomy. Prospective clinical and neuropsychological measurements were collected in patient 1. Additional prospective measurements of symptoms and biomarkers were collected pre- and post-surgery in patient 2.

Results: After laser ablation targeting the nondominant (right) amygdala, both patients experienced not only reduced seizures, but also profoundly abated post-traumatic stress symptoms. Prospective evaluation of biomarkers in patient 2 showed robust improvements in hyperarousal symptoms, fear potentiation of the startle reflex, brain functional magnetic resonance imaging responses to fear-inducing stimuli, and emotional declarative memory.

Conclusion: These observations support the emerging hypothesis that the right amygdala particularly perpetuates the signs and symptoms of post-traumatic stress disorder and suggests that focal unilateral amydalohippocampotomy can provide therapeutic benefit.
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http://dx.doi.org/10.1093/neuros/nyaa051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593359PMC
September 2020

Single-Neuron Representations of Spatial Targets in Humans.

Curr Biol 2020 01 2;30(2):245-253.e4. Epub 2020 Jan 2.

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

The hippocampus and surrounding medial-temporal-lobe (MTL) structures are critical for both memory and spatial navigation, but we do not fully understand the neuronal representations used to support these behaviors. Much research has examined how the MTL neurally represents spatial information, such as with "place cells" that represent an animal's current location or "head-direction cells" that code for an animal's current heading. In addition to behaviors that require an animal to attend to the current spatial location, navigating to remote destinations is a common part of daily life. To examine the neural basis of these behaviors, we recorded single-neuron activity from neurosurgical patients playing Treasure Hunt, a virtual-reality spatial-memory task. By analyzing how the activity of these neurons related to behavior in Treasure Hunt, we found that the firing rates of many MTL neurons during navigation significantly changed depending on the position of the current spatial target. In addition, we observed neurons whose firing rates during navigation were tuned to specific heading directions in the environment, and others whose activity changed depending on the timing within the trial. By showing that neurons in our task represent remote locations rather than the subject's own position, our results suggest that the human MTL can represent remote spatial information according to task demands.
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http://dx.doi.org/10.1016/j.cub.2019.11.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981010PMC
January 2020

Memory retrieval modulates spatial tuning of single neurons in the human entorhinal cortex.

Nat Neurosci 2019 12 11;22(12):2078-2086. Epub 2019 Nov 11.

Department of Biomedical Engineering, Columbia University, New York, NY, USA.

The medial temporal lobe is critical for both spatial navigation and memory. Although single neurons in the medial temporal lobe activate to represent locations in the environment during navigation, how this spatial tuning relates to memory for events involving those locations remains unclear. We examined memory-related changes in spatial tuning by recording single-neuron activity from neurosurgical patients performing a virtual-reality object-location memory task. We identified 'memory-trace cells' with activity that was spatially tuned to the retrieved location of the specific object that participants were cued to remember. Memory-trace cells in the entorhinal cortex, in particular, encoded discriminable representations of different memories through a memory-specific rate code. These findings indicate that single neurons in the human entorhinal cortex change their spatial tuning to target relevant memories for retrieval.
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http://dx.doi.org/10.1038/s41593-019-0523-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897360PMC
December 2019

Modulating Human Memory via Entrainment of Brain Oscillations.

Trends Neurosci 2019 07 6;42(7):485-499. Epub 2019 Jun 6.

Department of Neurosurgery, Emory University, 1365 Clifton Road North East, Atlanta, GA 30322, USA.

In the human brain, oscillations occur during neural processes that are relevant for memory. This has been demonstrated by a plethora of studies relating memory processes to specific oscillatory signatures. Several recent studies have gone beyond such correlative approaches and provided evidence supporting the idea that modulating oscillations via frequency-specific entrainment can alter memory functions. Such causal evidence is important because it allows distinguishing mechanisms directly related to memory from mere epiphenomenal oscillatory signatures of memory. This review provides an overview of stimulation studies using different approaches to entrain brain oscillations for modulating human memory. We argue that these studies demonstrate a causal link between brain oscillations and memory, speaking against an epiphenomenal perspective of brain oscillations.
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http://dx.doi.org/10.1016/j.tins.2019.04.004DOI Listing
July 2019

Dynamic Theta Networks in the Human Medial Temporal Lobe Support Episodic Memory.

Curr Biol 2019 04 21;29(7):1100-1111.e4. Epub 2019 Mar 21.

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

The medial temporal lobe (MTL) is a locus of episodic memory in the human brain. It is comprised of cytologically distinct subregions that, in concert, give rise to successful encoding and retrieval of context-dependent memories. However, the functional connections between these subregions are poorly understood. To determine functional connectivity among MTL subregions, we had 131 subjects fitted with indwelling electrodes perform a verbal memory task and asked how encoding or retrieval correlated with inter-regional synchronization. Using phase-based measures of connectivity, we found that synchronous theta (4-8 Hz) activity underlies successful episodic memory. During encoding, we observed a dynamic pattern of connections converging on the left entorhinal cortex, beginning with the perirhinal cortex and shifting through hippocampal subfields. Retrieval-associated networks demonstrated enhanced involvement of the subiculum and CA1, reflecting a substantial reorganization of the encoding network. We posit that coherent theta activity within the MTL marks periods of successful memory, but distinct patterns of connectivity dissociate key stages of memory processing.
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http://dx.doi.org/10.1016/j.cub.2019.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445741PMC
April 2019

Human Verbal Memory Encoding Is Hierarchically Distributed in a Continuous Processing Stream.

eNeuro 2019 Jan-Feb;6(1). Epub 2019 Mar 4.

Department of Neurology, Mayo Clinic, Rochester, MN 55905.

Processing of memory is supported by coordinated activity in a network of sensory, association, and motor brain regions. It remains a major challenge to determine where memory is encoded for later retrieval. Here, we used direct intracranial brain recordings from epilepsy patients performing free recall tasks to determine the temporal pattern and anatomical distribution of verbal memory encoding across the entire human cortex. High γ frequency activity (65-115 Hz) showed consistent power responses during encoding of subsequently recalled and forgotten words on a subset of electrodes localized in 16 distinct cortical areas activated in the tasks. More of the high γ power during word encoding, and less power before and after the word presentation, was characteristic of successful recall and observed across multiple brain regions. Latencies of the induced power changes and this subsequent memory effect (SME) between the recalled and forgotten words followed an anatomical sequence from visual to prefrontal cortical areas. Finally, the magnitude of the memory effect was unexpectedly found to be the largest in selected brain regions both at the top and at the bottom of the processing stream. These included the language processing areas of the prefrontal cortex and the early visual areas at the junction of the occipital and temporal lobes. Our results provide evidence for distributed encoding of verbal memory organized along a hierarchical posterior-to-anterior processing stream.
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http://dx.doi.org/10.1523/ENEURO.0214-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402539PMC
May 2019

Autonomic arousal elicited by subcallosal cingulate stimulation is explained by white matter connectivity.

Brain Stimul 2019 May - Jun;12(3):743-751. Epub 2019 Jan 26.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, 30322, GA, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, 10029, NY, USA.

Background: Subcallosal cingulate deep brain stimulation (SCC DBS) is an experimental treatment for severe depression. Surgery is performed with awake patients and intraoperative stimulation produces acute behavioral responses in select contacts. While there have been reports on the relationship between acute intraoperative behaviors and their relation to the location of the contacts, there are no descriptions of the physiological changes that accompany them.

Objective: The present study sought to examine these physiological readouts, and their association with the anatomical substrates that generated them.

Methods: Nine patients with severe, treatment-resistant depression were tested intraoperatively. The stimulation protocol consisted of 12 three-minute, sham-controlled, double-blind trials. Changes in heart rate and skin conductance were recorded during each stimulation cycle. Probabilistic tractography between the stimulated contacts and predefined regions of the mood regulation network was performed.

Results: Acute intraoperative SCC stimulation produced increases in autonomic sympathetic response that correlated with the salience of the behavioral responses. The autonomic changes were observed within seconds of initiating acute stimulation and prior to verbalization of subjective experiences. The probabilistic tractography analysis suggested that structural connectivity between the stimulated area and the midcingulate cortex is the primary pathway that mediates autonomic responsivity to SCC DBS.

Conclusions: These findings demonstrate that acute SCC stimulation produces autonomic and behavioral changes in the operating room that are explained by the modulation of networks associated with long term antidepressant response. Intraoperative autonomic recordings paired with careful behavioral observations and precise anatomical mapping aid in the identification and classification of the intraoperative phenomena.
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http://dx.doi.org/10.1016/j.brs.2019.01.015DOI Listing
July 2019

Cingulum stimulation enhances positive affect and anxiolysis to facilitate awake craniotomy.

J Clin Invest 2019 03 11;129(3):1152-1166. Epub 2019 Feb 11.

Department of Neurosurgery, and.

Background: Awake neurosurgery requires patients to converse and respond to visual or verbal prompts to identify and protect brain tissue supporting essential functions such as language, primary sensory modalities, and motor function. These procedures can be poorly tolerated because of patient anxiety, yet acute anxiolytic medications typically cause sedation and impair cortical function.

Methods: In this study, direct electrical stimulation of the left dorsal anterior cingulum bundle was discovered to reliably evoke positive affect and anxiolysis without sedation in a patient with epilepsy undergoing research testing during standard inpatient intracranial electrode monitoring. These effects were quantified using subjective and objective behavioral measures, and stimulation was found to evoke robust changes in local and distant neural activity.

Results: The index patient ultimately required an awake craniotomy procedure to confirm safe resection margins in the treatment of her epilepsy. During the procedure, cingulum bundle stimulation enhanced positive affect and reduced the patient's anxiety to the point that intravenous anesthetic/anxiolytic medications were discontinued and cognitive testing was completed. Behavioral responses were subsequently replicated in 2 patients with anatomically similar electrode placements localized to an approximately 1-cm span along the anterior dorsal cingulum bundle above genu of the corpus callosum.

Conclusions: The current study demonstrates a robust anxiolytic response to cingulum bundle stimulation in 3 patients with epilepsy.

Trial Registration: The current study was not affiliated with any formal clinical trial.

Funding: This project was supported by the American Foundation for Suicide Prevention and the NIH.
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http://dx.doi.org/10.1172/JCI120110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391096PMC
March 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.
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http://dx.doi.org/10.1016/j.yebeh.2018.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240385PMC
November 2018

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

Human amygdala stimulation effects on emotion physiology and emotional experience.

Neuropsychologia 2020 08 15;145:106722. Epub 2018 Mar 15.

Department of Neurosurgery, Emory University School of Medicine, 1365 Clifton Road, Atlanta, GA 30322, USA; Emory University School of Medicine, 1760 Haygood Dr., Atlanta, GA 30322, USA. Electronic address:

The amygdala is a key structure mediating emotional processing. Few studies have used direct electrical stimulation of the amygdala in humans to examine stimulation-elicited physiological and emotional responses, and the nature of such effects remains unclear. Determining the effects of electrical stimulation of the amygdala has important theoretical implications for current discrete and dimensional neurobiological theories of emotion, which differ substantially in their predictions about the emotional effects of such stimulation. To examine the effects of amygdala stimulation on physiological and subjective emotional responses we examined epilepsy patients undergoing intracranial EEG monitoring in which depth electrodes were implanted unilaterally or bilaterally in the amygdala. Nine subjects underwent both sham and acute monopolar electrical stimulation at various parameters in electrode contacts located in amygdala and within lateral temporal cortex control locations. Stimulation was applied at either 50 Hz or 130 Hz, while amplitudes were increased stepwise from 1 to 12 V, with subjects blinded to stimulation condition. Electrodermal activity (EDA), heart rate (HR), and respiratory rate (RR) were simultaneously recorded and subjective emotional response was probed after each stimulation period. Amygdala stimulation (but not lateral control or sham stimulation) elicited immediate and substantial dose-dependent increases in EDA and decelerations of HR, generally without affecting RR. Stimulation elicited subjective emotional responses only rarely, and did not elicit clinical seizures in any subject. These physiological results parallel stimulation findings with animals and are consistent with orienting/defensive responses observed with aversive visual stimuli in humans. In summary, these findings suggest that acute amygdala stimulation in humans can be safe and can reliably elicit changes in emotion physiology without significantly affecting subjective emotional experience, providing a useful approach for investigation of amygdala-mediated modulatory effects on cognition.
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http://dx.doi.org/10.1016/j.neuropsychologia.2018.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139084PMC
August 2020

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

Direct electrical stimulation of the amygdala enhances declarative memory in humans.

Proc Natl Acad Sci U S A 2018 01 18;115(1):98-103. Epub 2017 Dec 18.

Department of Neurosurgery, Emory University, Atlanta, GA 30322;

Emotional events are often remembered better than neutral events, a benefit that many studies have hypothesized to depend on the amygdala's interactions with memory systems. These studies have indicated that the amygdala can modulate memory-consolidation processes in other brain regions such as the hippocampus and perirhinal cortex. Indeed, rodent studies have demonstrated that direct activation of the amygdala can enhance memory consolidation even during nonemotional events. However, the premise that the amygdala causally enhances declarative memory has not been directly tested in humans. Here we tested whether brief electrical stimulation to the amygdala could enhance declarative memory for specific images of neutral objects without eliciting a subjective emotional response. Fourteen epilepsy patients undergoing monitoring of seizures via intracranial depth electrodes viewed a series of neutral object images, half of which were immediately followed by brief, low-amplitude electrical stimulation to the amygdala. Amygdala stimulation elicited no subjective emotional response but led to reliably improved memory compared with control images when patients were given a recognition-memory test the next day. Neuronal oscillations in the amygdala, hippocampus, and perirhinal cortex during this next-day memory test indicated that a neural correlate of the memory enhancement was increased theta and gamma oscillatory interactions between these regions, consistent with the idea that the amygdala prioritizes consolidation by engaging other memory regions. These results show that the amygdala can initiate endogenous memory prioritization processes in the absence of emotional input, addressing a fundamental question and opening a path to future therapies.
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http://dx.doi.org/10.1073/pnas.1714058114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776809PMC
January 2018

Distributed Neural Processing Predictors of Multi-dimensional Properties of Affect.

Front Hum Neurosci 2017 14;11:459. Epub 2017 Sep 14.

Brain Imaging Research Center, University of Arkansas for Medical Sciences, Little RockAR, United States.

Recent evidence suggests that emotions have a distributed neural representation, which has significant implications for our understanding of the mechanisms underlying emotion regulation and dysregulation as well as the potential targets available for neuromodulation-based emotion therapeutics. This work adds to this evidence by testing the distribution of neural representations underlying the affective dimensions of valence and arousal using representational models that vary in both the degree and the nature of their distribution. We used multi-voxel pattern classification (MVPC) to identify whole-brain patterns of functional magnetic resonance imaging (fMRI)-derived neural activations that reliably predicted dimensional properties of affect (valence and arousal) for visual stimuli viewed by a normative sample ( = 32) of demographically diverse, healthy adults. Inter-subject leave-one-out cross-validation showed whole-brain MVPC significantly predicted ( < 0.001) binarized normative ratings of valence (positive vs. negative, 59% accuracy) and arousal (high vs. low, 56% accuracy). We also conducted group-level univariate general linear modeling (GLM) analyses to identify brain regions whose response significantly differed for the contrasts of positive versus negative valence or high versus low arousal. Multivoxel pattern classifiers using voxels drawn from all identified regions of interest (all-ROIs) exhibited mixed performance; arousal was predicted significantly better than chance but worse than the whole-brain classifier, whereas valence was not predicted significantly better than chance. Multivoxel classifiers derived using individual ROIs generally performed no better than chance. Although performance of the all-ROI classifier improved with larger ROIs (generated by relaxing the clustering threshold), performance was still poorer than the whole-brain classifier. These findings support a highly distributed model of neural processing for the affective dimensions of valence and arousal. Finally, joint error analyses of the MVPC hyperplanes encoding valence and arousal identified regions within the dimensional affect space where multivoxel classifiers exhibited the greatest difficulty encoding brain states - specifically, stimuli of moderate arousal and high or low valence. In conclusion, we highlight new directions for characterizing affective processing for mechanistic and therapeutic applications in affective neuroscience.
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http://dx.doi.org/10.3389/fnhum.2017.00459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603694PMC
September 2017

Dynamic changes in large-scale functional network organization during autobiographical memory retrieval.

Neuropsychologia 2018 02 23;110:208-224. Epub 2017 Sep 23.

Department of Psychology, Emory University, 36 Eagle Row, Atlanta, GA 30322, United States. Electronic address:

Autobiographical memory (AM), episodic memory for life events, involves the orchestration of multiple dynamic cognitive processes, including memory access and subsequent elaboration. Previous neuroimaging studies have contrasted memory access and elaboration processes in terms of regional brain activation and connectivity within large, multi-region networks. Although interactions between key memory-related regions such as the hippocampus and prefrontal cortex (PFC) have been shown to play an important role in AM retrieval, it remains unclear how such connectivity between specific, individual regions involved in AM retrieval changes dynamically across the retrieval process and how these changes relate to broader memory networks throughout the whole brain. The present functional magnetic resonance imaging (fMRI) study sought to assess the specific changes in interregional connectivity patterns across the AM retrieval processes to understand network level mechanisms of AM retrieval and further test current theoretical accounts of dynamic AM retrieval processes. We predicted that dynamic connections would reflect two hypothesized memory processes, with initial processes reflecting memory-access related connections between regions such as the anterior hippocampal and ventrolateral PFC regions, and later processes reflecting elaboration-related connections between dorsolateral frontal working memory regions and parietal-occipital visual imagery regions. One week prior to fMRI scanning, fifteen healthy adult participants generated AMs using personally selected cue words. During scanning, participants were cued to retrieve the AMs. We used a moving-window functional connectivity analysis and graph theoretic measures to examine dynamic changes in the strength and centrality of connectivity among regions involved in AM retrieval. Consistent with predictions, early, access-related processing primarily involved a ventral frontal to temporal-parietal network associated with strategic search and initial reactivation of specific episodic memory traces. In addition, neural network connectivity during later retrieval processes was associated with strong connections between occipital-parietal regions and dorsal fronto-parietal regions associated with mental imagery, reliving, and working memory processes. Taken together, these current findings help refine and extend dynamic neural processing models of AM retrieval by providing evidence of the specific connections throughout the brain that change in their synchrony with one another as processing progresses from access of specific event memories to elaborative reliving of the past event.
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http://dx.doi.org/10.1016/j.neuropsychologia.2017.09.020DOI Listing
February 2018

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

Altered resting-state effective connectivity of fronto-parietal motor control systems on the primary motor network following stroke.

Neuroimage 2012 Jan 2;59(1):227-37. Epub 2011 Aug 2.

Department of Psychology, Emory University, Atlanta, GA 30322, USA.

Previous brain imaging work suggests that stroke alters the effective connectivity (the influence neural regions exert upon each other) of motor execution networks. The present study examines the intrinsic effective connectivity of top-down motor control in stroke survivors (n=13) relative to healthy participants (n=12). Stroke survivors exhibited significant deficits in motor function, as assessed by the Fugl-Meyer Motor Assessment. We used structural equation modeling (SEM) of resting-state fMRI data to investigate the relationship between motor deficits and the intrinsic effective connectivity between brain regions involved in motor control and motor execution. An exploratory adaptation of SEM determined the optimal model of motor execution effective connectivity in healthy participants, and confirmatory SEM assessed stroke survivors' fit to that model. We observed alterations in spontaneous resting-state effective connectivity from fronto-parietal guidance systems to the motor network in stroke survivors. More specifically, diminished connectivity was found in connections from the superior parietal cortex to primary motor cortex and supplementary motor cortex. Furthermore, the paths demonstrated large individual variance in stroke survivors but less variance in healthy participants. These findings suggest that characterizing the deficits in resting-state connectivity of top-down processes in stroke survivors may help optimize cognitive and physical rehabilitation therapies by individually targeting specific neural pathway.
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http://dx.doi.org/10.1016/j.neuroimage.2011.07.083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195990PMC
January 2012