Anatomical registration of intracranial electrodes. Robust model-based localization and deformable smooth brain-shift compensation methods

Abstract:

Background: Intracranial electrodes are typically localized from post-implantation CT artifacts. Automatic algorithms localizing low signal-to-noise ratio artifacts and high-density electrode arrays are missing. Additionally, implantation of grids/strips introduces brain deformations, resulting in registration errors when fusing post- implantation CT and pre-implantation MR images. Brain-shift compensation methods project electrode coordinates to cortex, but either fail to produce smooth solutions or do not account for brain deformations. New methods: We first introduce GridFit, a model-based fitting approach that simultaneously localizes all electrodes’ CT artifacts in grids, strips, or depth arrays. Second, we present CEPA, a brain-shift compensation algorithm combining orthogonal-based projections, spring-mesh models, and spatial regularization constraints. Results: We tested GridFit on ~6000 simulated scenarios. The localization of CT artifacts showed robust performance under difficult scenarios, such as noise, overlaps, and high-density implants (<1 mm errors). Validation with data from 20 challenging patients showed 99% accurate localization of the electrodes (3160/3192). We tested CEPA brain-shift compensation with data from 15 patients. Projections accounted for simple mechanical deformation principles with <0.4 mm errors. The inter-electrode distances smoothly changed across neighbor electrodes, while changes in inter-electrode distances linearly increased with projection distance. Comparison with existing methods: GridFit succeeded in difficult scenarios that challenged available methods and outperformed visual localization by preserving the inter-electrode distance. CEPA registration errors were smaller than those obtained for well-established alternatives. Additionally, modeling resting-state high-frequency activity in five patients further supported CEPA.

Authors:

• Alejandro Omar Blenkmann

• Sabine Liliana Leske

• Anaïs Llorens

• Jack J. Lin

• Edward F. Chang

• Peter Brunner

• Gerwin Schalk

• Jugoslav Ivanovic

• Pål Gunnar Larsson

• Robert Thomas Knight

• Tor Endestad

• Anne-Kristin Solbakk

Date: 2024

DOI: https://doi.org/10.1016/j.jneumeth.2024.110056

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Altered hierarchical auditory predictive processing after lesions to the orbitofrontal cortex

Abstract:

Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation, and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the role of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a local–global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e., between tones within sequences) and at a global (i.e., between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) and P3a to local prediction violation, as well as a diminished MMN followed by a delayed P3a to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate that the neural correlates of detection of auditory regularity violation are impacted at two hierarchical levels of rule abstraction.

Authors:

• Olgerta Asko

• Alejandro Omar Blenkmann

• Sabine Liliana Leske

• Maja Dyhre Foldal

• Anais Llorens

• Ingrid Funderud

• Torstein R Meling

• Robert T Knight

• Tor Endestad

• Anne-Kristin Solbakk

Date: 2024

DOI: https://doi.org/10.7554/eLife.86386

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Predictable and unpredictable deviance detection in the human hippocampus and amygdala

Abstract:

Our brains extract structure from the environment and form predictions given past experience. Predictive circuits have been identified in wide-spread cortical regions. However, the contribution of medial temporal structures in predictions remains under-explored. The hippocampus underlies sequence detection and is sensitive to novel stimuli, sufficient to gain access to memory, while the amygdala to novelty. Yet, their electrophysiological profiles in detecting predictable and unpredictable deviant auditory events remain unknown. Here, we hypothesized that the hippocampus would be sensitive to predictability, while the amygdala to unexpected deviance. We presented epileptic patients undergoing presurgical monitoring with standard and deviant sounds, in predictable or unpredictable contexts. Onsets of auditory responses and unpredictable deviance effects were detected earlier in the temporal cortex compared with the amygdala and hippocampus. Deviance effects in 1–20 Hz local field potentials were detected in the lateral temporal cortex, irrespective of predictability. The amygdala showed stronger deviance in the unpredictable context. Low-frequency deviance responses in the hippocampus (1–8 Hz) were observed in the predictable but not in the unpredictable context. Our results reveal a distributed network underlying the generation of auditory predictions and suggest that the neural basis of sensory predictions and prediction error signals needs to be extended.

Authors:

• Athina Tzovara

• Tommaso Fedele

• Johannes Sarnthein

• Debora Ledergerber

• Jack J. Lin

• Robert T. Knight

Date: 2024

DOI: https://doi.org/10.1093/cercor/bhad532

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Ramping dynamics and theta oscillations reflect dissociable signatures during rule-guided human behavior

abstract:

Contextual cues and prior evidence guide human goal-directed behavior. The neurophysiological mechanisms that implement contextual priors to guide subsequent actions in the human brain remain unclear. Using intracranial electroencephalography (iEEG), we demonstrate that increasing uncertainty introduces a shift from a purely oscillatory to a mixed processing regime with an additional ramping component. Oscillatory and ramping dynamics reflect dissociable signatures, which likely differentially contribute to the encoding and transfer of different cognitive variables in a cue-guided motor task. The results support the idea that prefrontal activity encodes rules and ensuing actions in distinct coding subspaces, while theta oscillations synchronize the prefrontal-motor network, possibly to guide action execution. Collectively, our results reveal how two key features of large-scale neural population activity, namely continuous ramping dynamics and oscillatory synchrony, jointly support rule-guided human behavior.

Authors:

• Jan Weber

• Anne-Kristin Solbakk

• Alejandro O. Blenkmann

• Anais Llorens

• Ingrid Funderud

• Sabine Leske

• Pål Gunnar Larsson

• Lugoslav Ivanovic

• Robert T. Knight

• Tor Endestad

• Randolph F. Helfrich

Date: 2024

DOI: https://doi.org/10.1038/s41467-023-44571-7

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Awake ripples enhance emotional memory encoding in the human brain

Abstract:

Enhanced memory for emotional experiences is hypothesized to depend on amygdala-hippocampal interactions during memory consolidation. Here we show using intracranial recordings from the human amygdala and the hippocampus during an emotional memory encoding and discrimination task increased awake ripples after encoding of emotional, compared to neutrally-valenced stimuli. Further, post-encoding ripple-locked stimulus similarity is predictive of later memory discrimination. Ripple-locked stimulus similarity appears earlier in the amygdala than in hippocampus and mutual information analysis confirms amygdala influence on hippocampal activity. Finally, the joint ripple-locked stimulus similarity in the amygdala and hippocampus is predictive of correct memory discrimination. These findings provide electrophysiological evidence that post-encoding ripples enhance memory for emotional events.

Authors:

• Haoxin Zhang

• Ivan Skelin

• Shiting Ma

• Michelle Paff

• Lilit Mnatsakanyan

• Michael A. Yassa

• Robert T. Knight

• Jack J. Lin

Date: 2024

DOI: https://doi.org/10.1038/s41467-023-44295-8

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Differential contribution of sensorimotor cortex and subthalamic nucleus to unimanual and bimanual hand movements

Abstract:

Why does unilateral deep brain stimulation improve motor function bilaterally? To address this clinical observation, we collected parallel neural recordings from sensorimotor cortex (SMC) and the subthalamic nucleus (STN) during repetitive ipsilateral, contralateral, and bilateral hand movements in patients with Parkinson’s disease. We used a cross-validated electrode-wise encoding model to map electromyography data to the neural signals. Electrodes in the STN encoded movement at a comparable level for both hands, whereas SMC electrodes displayed a strong contralateral bias. To examine representational overlap across the two hands, we trained the model with data from one condition (contralateral hand) and used the trained weights to predict neural activity for movements produced with the other hand (ipsilateral hand). Overall, between-hand generalization was poor, and this limitation was evident in both regions. A similar method was used to probe representational overlap across different task contexts (unimanual vs. bimanual). Task context was more important for the STN compared to the SMC indicating that neural activity in the STN showed greater divergence between the unimanual and bimanual conditions. These results indicate that SMC activity is strongly lateralized and relatively context-free, whereas the STN integrates contextual information with the ongoing behavior.

Authors:

• Christina M. Merrick

• Owen N. Doyle

• Natali E. Gallegos

• Zachary T. Irwin

• Joseph W. Olson

• Christopher L. Gonzalez

• Robert T. Knight

• Richard B. Ivry

• Harrison C. Walker

Date: 2023

DOI: https://doi.org/10.1093/cercor/bhad492

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Asymmetric coding of reward prediction errors in human insula and dorsomedial prefrontal cortex

Abstract:

The signed value and unsigned salience of reward prediction errors (RPEs) are critical to understanding reinforcement learning (RL) and cognitive control. Dorsomedial prefrontal cortex (dMPFC) and insula (INS) are key regions for integrating reward and surprise information, but conflicting evidence for both signed and unsigned activity has led to multiple proposals for the nature of RPE representations in these brain areas. Recently developed RL models allow neurons to respond differently to positive and negative RPEs. Here, we use intracranially recorded high frequency activity (HFA) to test whether this flexible asymmetric coding strategy captures RPE coding diversity in human INS and dMPFC. At the region level, we found a bias towards positive RPEs in both areas which paralleled behavioral adaptation. At the local level, we found spatially interleaved neural populations responding to unsigned RPE salience and valence-specific positive and negative RPEs. Furthermore, directional connectivity estimates revealed a leading role of INS in communicating positive and unsigned RPEs to dMPFC. These findings support asymmetric coding across distinct but intermingled neural populations as a core principle of RPE processing and inform theories of the role of dMPFC and INS in RL and cognitive control.

Authors:

• Colin W. Hoy

• David R. Quiroga-Martinez

• Eduardo Sandoval

• David King-Stephens

• Kenneth D. Laxer

• Peter Weber

• Jack J. Lin

• Robert T. Knight

Date: 2023

DOI: https://doi.org/10.1038/s41467-023-44248-1

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Periodic attention deficits after frontoparietal lesions provide causal evidence for rhythmic attentional sampling

Abstract:

Contemporary models conceptualize spatial attention as a blinking spotlight that sequentially samples visual space. Hence, behavior fluctuates over time, even in states of presumed ‘‘sustained’’ attention. Recent evidence has suggested that rhythmic neural activity in the frontoparietal network constitutes the functional basis of rhythmic attentional sampling. However, causal evidence to support this notion remains absent. Using a lateralized spatial attention task, we addressed this issue in patients with focal lesions in the frontoparietal attention network. Our results revealed that frontoparietal lesions introduce periodic attention deficits, i.e., temporally specific behavioral deficits that are aligned with the underlying neural oscillations. Attention guided perceptual sensitivity was on par with that of healthy controls during optimal phases but was attenuated during the less excitable sub-cycles. Theta-dependent sampling (3–8 Hz) was causally dependent on the prefrontal cortex, while high-alpha/low-beta sampling (8–14 Hz) emerged from parietal areas. Collectively, our findings reveal that lesion-induced high-amplitude, low-frequency brain activity is not epiphenomenal but has immediate behavioral consequences. More generally, these results provide causal evidence for the hypothesis that the functional architecture of attention is inherently rhythmic.

Authors:

• Isabel Raposo

• Sara M. Szczepanski

• Kathleen Haaland

• Tor Endestad

• Anne-Kristin Solbakk

• Robert T. Knight

• Randolph F. Helfrich

Date: 2023

DOI: https://doi.org/10.1016/j.cub.2023.09.065

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Decision and response monitoring during working memory are sequentially represented in the human insula

Abstract:

Emerging research supports a role of the insula in human cognition. Here, we used intracranial EEG to investigate the spatiotemporal dynamics in the insula during a verbal working memory (vWM) task. We found robust effects for theta, beta, and high frequency activity (HFA) during probe presentation requiring a decision. Theta band activity showed differential involvement across left and right insulae while sequential HFA modulations were observed along the anteroposterior axis. HFA in anterior insula tracked decision making and subsequent HFA was observed in posterior insula after the behavioral response. Our results provide electrophysiological evidence of engagement of different insula subregions in both decision-making and response monitoring during vWM and expand our knowledge of the role of the insula in complex human behavior.

Authors:

• Anaïs Llorens

• Ludovic Bellier

• Alejandro O. Blenkmann

• Jugoslav Ivanovic

• Pål G. Larsson

• Jack J. Lin

• Tor Endestad

• Anne-Kristin Solbakk

• Robert T. Knight

Date: 2023

DOI: https://doi.org/10.1016/j.isci.2023.107653

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Multiple memory systems for efficient temporal order memory

Abstract:

We report distinct contributions of multiple memory systems to the retrieval of the temporal order of events. The neural dynamics related to the retrieval of movie scenes revealed that recalling the temporal order of close events elevates hippocampal theta power, like that observed for recalling close spatial relationships. In contrast, recalling far events increases beta power in the orbitofrontal cortex, reflecting recall based on the overall movie structure.

Authors:

• Anna Jafarpour

• Jack J. Lin

• Robert T. Knight

• Elizabeth A. Buffalo

Date: 2023

DOI: https://doi.org/10.1002/hipo.23550

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Electrophysiological signatures of inequity-dependent reward encoding in the human OFC

Abstract:

Social decision making requires the integration of reward valuation and social cognition systems, both dependent on the orbitofrontal cortex (OFC). How these two OFC functions interact is largely unknown. We recorded intracranial activity from the OFC of ten patients making choices in a social context where reward inequity with a social counterpart varied and could be either advantageous or disadvantageous. We find that OFC high-frequency activity (HFA; 70–150Hz) encodes self-reward, consistent with previous reports. We also observe encoding of the social counterpart’s reward, as well as the type of inequity being experienced. Additionally, we find evidence of inequity-dependent reward encoding: depending on the type of inequity, electrodes rapidly and reversibly switch between different reward-encoding profiles. These results provide direct evidence for encoding of self- and other rewards in the human OFC and highlight the dynamic nature of encoding in the OFC as a function of social context.

Authors:

• Deborah Marciano

• Brooke R. Staveland

• Jack J. Lin

• Ignacio Saez

• Ming Hsu

• Robert T. Knight

Date: 2023

DOI: https://doi.org/10.1016/j.celrep.2023.112865

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Human REM sleep recalibrates neural activity in support of memory formation

Abstract:

The proposed mechanisms of sleep-dependent memory consolidation involve the overnight regulation of neural activity at both synaptic and whole-network levels. Now, there is a lack of in vivo data in humans elucidating if, and how, sleep and its varied stages balance neural activity, and if such recalibration benefits memory. We combined electrophysiology with in vivo two-photon calcium imaging in rodents as well as intracranial and scalp electroencephalography (EEG) in humans to reveal a key role for non-oscillatory brain activity during rapid eye movement (REM) sleep to mediate sleep-dependent recalibration of neural population dynamics. The extent of this REM sleep recalibration predicted the success of overnight memory consolidation, expressly the modulation of hippocampal—neocortical activity, favoring remembering rather than forgetting. The findings describe a non-oscillatory mechanism how human REM sleep modulates neural population activity to enhance long-term memory.

Authors:

• Janna D. Lendner

• Niels Niethard

• Bryce A. Mander

• Frank J. van Schalkwijk

• Sigrid Schuh-Hofer

• Hannah Schmidt

• Robert T. Knight

• Jan Born

• Matthew P. Walker

• Jack J. Lin

• Randolph F. Helfrich

Date: 2023

DOI: DOI: 10.1126/sciadv.adj1895

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Dynamic expectations: Behavioral and electrophysiological evidence of sub-second updates in reward predictions

Abstract:

Expectations are often dynamic: sports fans know that expectations are rapidly updated as games unfold. Yet expectations have traditionally been studied as static. Here we present behavioral and electrophysiological evidence of sub-second changes in expectations using slot machines as a case study. In Study 1, we demonstrate that EEG signal before the slot machine stops varies based on proximity to winning. Study 2 introduces a behavioral paradigm to measure dynamic expectations via betting, and shows that expectation trajectories vary as a function of winning proximity. Notably, these expectation trajectories parallel Study 1’s EEG activity. Studies 3 (EEG) and 4 (behavioral) replicate these findings in the loss domain. These four studies provide compelling evidence that dynamic sub-second updates in expectations can be behaviorally and electrophysiologically measured. Our research opens promising avenues for understanding the dynamic nature of reward expectations and their impact on cognitive processes.

Authors:

• Déborah Marciano

• Ludovic Bellier

• Ida Mayer

• Michael Ruvalcaba

• Sangil Lee

• Ming Hsu

• Robert T. Knight

Date: 2023

DOI: https://doi.org/10.1038/s42003-023-05199-x

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Music can be reconstructed from human auditory cortex activity using nonlinear decoding models

Abstract:

Music is core to human experience, yet the precise neural dynamics underlying music perception remain unknown. We analyzed a unique intracranial electroencephalography (iEEG) dataset of 29 patients who listened to a Pink Floyd song and applied a stimulus reconstruction approach previously used in the speech domain. We successfully reconstructed a recognizable song from direct neural recordings and quantified the impact of different factors on decoding accuracy. Combining encoding and decoding analyses, we found a right-hemisphere dominance for music perception with a primary role of the superior temporal gyrus (STG), evidenced a new STG subregion tuned to musical rhythm, and defined an anterior–posterior STG organization exhibiting sustained and onset responses to musical elements. Our findings show the feasibility of applying predictive modeling on short datasets acquired in single patients, paving the way for adding musical elements to brain–computer interface (BCI) applications.

Authors:

• Ludovic Bellier

• Anaïs Llorens

• Déborah Marciano

• Aysegul Gunduz

• Gwerwin Schalk

• Peter Brunner

• Robert T. Knight

Date: 2023

DOI: https://doi.org/10.1371/journal.pbio.3002176

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Distinct ventral stream and prefrontal cortex representational dynamics during sustained conscious visual perception

Abstract:

Instances of sustained stationary sensory input are ubiquitous. However, previous work focused almost exclusively on transient onset responses. This presents a critical challenge for neural theories of consciousness, which should account for the full temporal extent of experience. To address this question, we use intracranial recordings from ten human patients with epilepsy to view diverse images of multiple durations. We reveal that, in sensory regions, despite dramatic changes in activation magnitude, the distributed representation of categories and exemplars remains sustained and stable. In contrast, in frontoparietal regions, we find transient content representation at stimulus onset. Our results highlight the connection between the anatomical and temporal correlates of experience. To the extent perception is sustained, it may rely on sensory representations and to the extent perception is discrete, centered on perceptual updating, it may rely on frontoparietal representations.

Authors:

• Gal Vishne

• Edden M. Gerber

• Robert T. Knight

• Leon Y. Deouell

Date: 2023

DOI: https://doi.org/10.1016/j.celrep.2023.112752

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Subspace partitioning in the human prefrontal cortex resolves cognitive interference

Abstract:

The human prefrontal cortex (PFC) constitutes the structural basis underlying flexible cognitive control, where mixed-selective neural populations encode multiple task features to guide subsequent behavior. The mechanisms by which the brain simultaneously encodes multiple task–relevant variables while minimizing interference from task-irrelevant features remain unknown. Leveraging intracranial recordings from the human PFC, we first demonstrate that competition between coexisting representations of past and present task variables incurs a behavioral switch cost. Our results reveal that this interference between past and present states in the PFC is resolved through coding partitioning into distinct low-dimensional neural states; thereby strongly attenuating behavioral switch costs. In sum, these findings uncover a fundamental coding mechanism that constitutes a central building block of flexible cognitive control.

Authors:

• Jan Weber

• Gabriela Iwama

• Anne-Kristin Solbakk

• Alejandro O. Blenkmann

• Pal G. Larsson

• Jugoslav Ivanovic

• Robert T. Knight

• Tor Endestad

• Randolph Helfrich

Date: 2023

DOI: https://doi.org/10.1073/pnas.2220523120

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Unexpected sound omissions are signaled in human posterior superior temporal gyrus: an intracranial study

Abstract:

Context modulates sensory neural activations enhancing perceptual and behavioral performance and reducing prediction errors. However, the mechanism of when and where these high-level expectations act on sensory processing is unclear. Here, we isolate the effect of expectation absent of any auditory evoked activity by assessing the response to omitted expected sounds. Electrocorticographic signals were recorded directly from subdural electrode grids placed over the superior temporal gyrus (STG). Subjects listened to a predictable sequence of syllables, with some infrequently omitted. We found high-frequency band activity (HFA, 70–170 Hz) in response to omissions, which overlapped with a posterior subset of auditory-active electrodes in STG. Heard syllables could be distinguishable reliably from STG, but not the identity of the omitted stimulus. Both omission- and target-detection responses were also observed in the prefrontal cortex. We propose that the posterior STG is central for implementing predictions in the auditory environment. HFA omission responses in this region appear to index mismatch-signaling or salience detection processes.

Authors:

• Hohyun Cho

• Yvonne M Fonken

• Markus Adamek

• Richard Jimenez

• Jack J Lin

• Gerwin Schalk

• Robert T Knight

• Peter Brunner

Date: 2023

DOI: https://doi.org/10.1093/cercor/bhad155

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A rapid theta network mechanism for flexible information encoding

Abstract:

Flexible behavior requires gating mechanisms that encode only task-relevant information in working memory. Extant literature supports a theoretical division of labor whereby lateral frontoparietal interactions underlie information maintenance and the striatum enacts the gate. Here, we reveal neocortical gating mechanisms in intracranial EEG patients by identifying rapid, within-trial changes in regional and inter-regional activities that predict subsequent behavioral outputs. Results first demonstrate information accumulation mechanisms that extend prior fMRI (i.e., regional high-frequency activity) and EEG evidence (inter-regional theta synchrony) of distributed neocortical networks in working memory. Second, results demonstrate that rapid changes in theta synchrony, reflected in changing patterns of default mode network connectivity, support filtering. Graph theoretical analyses further linked filtering in task-relevant information and filtering out irrelevant information to dorsal and ventral attention networks, respectively. Results establish a rapid neocortical theta network mechanism for flexible information encoding, a role previously attributed to the striatum.

Authors:

• Elizabeth L. Johnson

• Jack J. Lin

• David King-Stephens

• Peter B. Weber

• Kenneth D. Laxer

• Ignacio Saez

• Fady Girgis

• Mark D’Esposito

• Robert T. Knight

• David Badre

Date: 2023

DOI: https://doi.org/10.1038/s41467-023-38574-7

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Grasp-specific high-frequency broadband mirror neuron activity during reach-and-grasp movements in humans

Abstract:

Broadly congruent mirror neurons, responding to any grasp movement, and strictly congruent mirror neurons, responding only to specific grasp movements, have been reported in single-cell studies with primates. Delineating grasp properties in humans is essential to understand the human mirror neuron system with implications for behavior and social cognition. We analyzed electrocorticography data from a natural reach-and-grasp movement observation and delayed imitation task with 3 different natural grasp types of everyday objects. We focused on the classification of grasp types from high-frequency broadband mirror activation patterns found in classic mirror system areas, including sensorimotor, supplementary motor, inferior frontal, and parietal cortices. Classification of grasp types was successful during movement observation and execution intervals but not during movement retention. Our grasp type classification from combined and single mirror electrodes provides evidence for grasp-congruent activity in the human mirror neuron system potentially arising from strictly congruent mirror neurons.

Authros:

• Alexander M. Dreyer

• Leo Michalke

• Anat Perry

• Edward F. Chang

• Jack J. Lin

• Robert T. Knight

• Jochem W. Rieger

Date: 2022

DOI: https://doi.org/10.1093/cercor/bhac504

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Deep brain stimulation of the ventrointermediate nucleus of the thalamus to treat essential tremor improves motor sequence learning

Abstract:

The network of brain structures engaged in motor sequence learning comprises the same structures as those involved in tremor, including basal ganglia, cerebellum, thalamus, and motor cortex. Deep brain stimulation (DBS) of the ventrointermediate nucleus of the thalamus (VIM) reduces tremor, but the effects on motor sequence learning are unknown. We investigated whether VIM stimulation has an impact on motor sequence learning and hypothesized that stimulation effects depend on the laterality of electrode location. Twenty patients (age: 38–81 years; 12 female) withVIM electrodes implanted to treat essential tremor (ET) successfully performed a serial reaction time task, varying whether the stimuli followed a repeating pattern or were selected at random, during which VIM-DBS was either on or off. Analyses of variance were applied to evaluate motor sequence learning performance according to reaction times (RTs) and accuracy. An interaction was observed between whether the sequence was repeated or random and whether VIM-DBS was on or off (F[1,18]=7.89,p=.012). Motor sequence learning, reflected by reduced RTs for repeated sequences, was greater with DBS on than off (T[19]=2.34,p=.031). Stimulation location correlated with the degree of motor learning, with greater motor learning when stimulation targeted the lateral VIM (n=23,ρ=0.46;p=.027).These results demonstrate the beneficial effects of VIM-DBS on motor sequence learning in ET patients, particularly with lateral VIM electrode location, and provide evidence for a role for the VIM in motor sequence learning.

Authors:

• Laila Terzic

• Angela Voegtle

• Amr Farahat

• Nanna Hartong

• Imke Galazky

• Slawomir J. Nasuto

• Adriano de Oliveira Andrade

• Robert T. Knight

• Richard B. Ivry

• Jürgen Voges

• Lars Buentjen

• Catherine M. Sweeney-Reed

Date: 2022

DOI: 10.1002/hbm.25989

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