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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The role of the anterior nuclei of the thalamus in human memory processing

Abstract:

Extensive neuroanatomical connectivity between the anterior thalamic nuclei (ATN) and hippocampus and neocortex renders them well-placed for a role in memory processing, and animal, lesion, and neuroimaging studies support such a notion. The deep location and small size of the ATN have precluded their real-time electrophysiological investigation during human memory processing. However, ATN electrophysiological recordings from patients receiving electrodes implanted for deep brain stimulation for pharmacoresistant focal epilepsy have enabled high temporal resolution study of ATN activity. Theta frequency synchronization of ATN and neocortical oscillations during successful memory encoding, enhanced phase alignment, and coupling between ATN local gamma frequency activity and frontal neocortical and ATN theta oscillations provide evidence of an active role for the ATN in memory encoding, potentially integrating information from widespread neocortical sources. Greater coupling of a broader gamma frequency range with theta oscillations at rest than during memory encoding provides additional support for the hypothesis that the ATN play a role in selecting local, task-relevant high frequency activity associated with particular features of a memory trace.

Authors:

• Catherine M Sweeney-Reed

• Lars Buentjen

• Jürgen Voges

• Friedhelm C Schmitt

• Tino Zaehle

• Julia WY Kam

• Jörn Kaufmann

• Hans-Jochen Heinze

• Hermann Hinrichs

• Robert T Knight

• Michael D Rugg

Date: 2021

DOI: https://doi.org/10.1016/j.neubiorev.2021.02.046

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Anterior thalamic high frequency band activity is coupled with theta oscillations at rest

ABSTRACT

Cross-frequency coupling (CFC) between slow and fast brain rhythms, in the form of phase–amplitude coupling (PAC), is proposed to enable the coordination of neural oscillatory activity required for cognitive processing. PAC has been identified in the neocortex and mesial temporal regions, varying according to the cognitive task being performed and also at rest. PAC has also been observed in the anterior thalamic nucleus (ATN) during memory processing. The thalamus is active during the resting state and has been proposed to be involved in switching between task-free cognitive states such as rest, in which attention is internally-focused, and externally-focused cognitive states, in which an individual engages with environmental stimuli. It is unknown whether PAC is an ongoing phenomenon during the resting state in the ATN, which is modulated during different cognitive states, or whether it only arises during the performance of specific tasks. We analyzed electrophysiological recordings of ATN activity during rest from seven patients who received thalamic electrodes implanted for treatment of pharmacoresistant focal epilepsy. PAC was identified between theta (4–6 Hz) phase and high frequency band (80–150 Hz) amplitude during rest in all seven patients, which diminished during engagement in tasks involving an external focus of attention. The findings are consistent with the proposal that theta–gamma coupling in the ATN is an ongoing phenomenon, which is modulated by task performance.

AUTHORS

• Catherine M. Sweeney-Reed

• Tino Zauhle

• Jürgen Voges

• Friedhelm Schmitt

• Lars Buentjen

• Viola Borchardt

• Hermann Hinrichs

• Hans-Jochen Heinze

• Michael D. Rugg

• Robert T. Knight

Date: 2017

DOI: 10.3389/fnhum.2017.00358

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Pre-stimulus thalamic theta power predicts human memory formation

ABSTRACT

Pre-stimulus theta (4–8 Hz) power in the hippocampus and neocortex predicts whether a memory for a subsequent event will be formed. Anatomical studies reveal thalamus-hippocampal connectivity, and lesion, neuroimaging, and electrophysiological studies show that memory processing involves the dorsomedial (DMTN) and anterior thalamic nuclei (ATN). The small size and deep location of these nuclei have limited real-time study of their activity, however, and it is unknown whether pre-stimulus theta power predictive of successful memory formation is also found in these subcortical structures. We recorded human electrophysiological data from the DMTN and ATN of 7 patients receiving deep brain stimulation for refractory epilepsy. We found that greater pre-stimulus theta power in the right DMTN was associated with successful memory encoding, predicting both behavioral outcome and post-stimulus correlates of successful memory formation. In particular, significant correlations were observed between right DMTN theta power and both frontal theta and right ATN gamma (32–50 Hz) phase alignment, and frontal-ATN theta-gamma cross-frequency coupling. We draw the following primary conclusions. Our results provide direct electrophysiological evidence in humans of a role for the DMTN as well as the ATN in memory formation. Furthermore, prediction of subsequent memory performance by pre-stimulus thalamic oscillations provides evidence that post-stimulus differences in thalamic activity that index successful and unsuccessful encoding reflect brain processes specifically underpinning memory formation. Finally, the findings broaden the understanding of brain states that facilitate memory encoding to include subcortical as well as cortical structures.

AUTHORS

• Catherine M. Sweeney-Reed

• Tino Zaehle

• Jürgen Voges

• Friedhelm Schmitt

• Lars Buentjen

• Klaus Kopitzki

• Alan Richardson-Klavehn

• Hermann Hinrichs

• Hans-Jochen Heinze

• Robert T. Knight

• Michael D. Rugg

Date: 2016

DOI: 10.1016/j.neuroimage.2016.05.042

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Thalamic theta phase alignment predicts human memory formation and anterior thalamic cross-frequency coupling

Authors:

• Catherine M. Sweeney-Reed

• Tino Zaehle

• Jürgen Voges

• Friedhelm Schmitt

• Lars Buentjen

• Klaus Kopitzki

• Hermann Hinrichs

• Hans-Jochen Heinze

• Michael D. Rugg

• Robert T. Knight

• Alan Richardson-Klavehn

Date: 2015

DOI: 10.7554/eLife.07578

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Abstract:

Previously we reported electrophysiological evidence for a role for the anterior thalamic nucleus (ATN) in human memory formation (Sweeney-Reed et al. 2014). Theta-gamma cross-frequency coupling (CFC) predicted successful memory formation, with the involvement of gamma oscillations suggesting memory-relevant local processing in the ATN. The importance of the theta frequency range in memory processing is well-established, and phase alignment of oscillations is considered to be necessary for synaptic plasticity. We hypothesized that theta phase alignment in the ATN would be necessary for memory encoding. Further analysis of the electrophysiological data reveal that phase alignment in the theta rhythm was greater during successful compared with unsuccessful encoding, and that this alignment was correlated with the CFC. These findings support an active processing role for the ATN during memory formation.

Sensory Deviancy Detection Measured Directly Within the Human Nucleus Accumbens

Authors:

• S. Durschmid

• Tino Zauhle

• Hermann Hinrichs

• Hans-Jochen Heinze

• Jürgen Voges

• Marta Garrido

• Raymond J. Dolan

• Robert T. Knight

Date: 2015

DOI: 10.1093/cercor/bhu304

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Abstract:

Rapid changes in the environment evoke a comparison between expectancy and actual outcome to inform optimal subsequent behavior. The nucleus accumbens (NAcc), a key interface between the hippocampus and neocortical regions, is a candidate region for mediating this comparison. Here, we report event-related potentials obtained from the NAcc using direct intracranial recordings in 5 human participants while they listened to trains of auditory stimuli differing in their degree of deviation from repetitive background stimuli. NAcc recordings revealed an early mismatch signal (50–220 ms) in response to all deviants. NAcc activity in this time window was also sensitive to the statistics of stimulus deviancy, with larger amplitudes as a function of the level of deviancy. Importantly, this NAcc mismatch signal also predicted generation of longer latency scalp potentials (300–400 ms). The results provide direct human evidence that the NAcc is a key component of a network engaged in encoding statistics of the sensory environmental.

Corticothalamic phase synchrony and cross-frequency coupling predict human memory formation

Authors:

• Catherine M. Sweeney-Reed

• Tino Zaehle

• Jürgen Voges

• Friedhelm Schmitt

• Lars Buentjen

• Klaus Kopitzki

• Christine Esslinger

• Hermann Hinrichs

• Hans-Jochen Heinze

• Robert T. Knight

• Alan Richardson-Klavehn

Date: 2014

DOI: 10.7554/eLife.05352.001

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Abstract:

The anterior thalamic nucleus (ATN) is thought to play an important role in a brain network involving the hippocampus and neocortex, which enables human memories to be formed. However, its small size and location deep within the brain have impeded direct investigation in humans with non-invasive techniques. Here we provide direct evidence for a functional role for the ATN in memory formation from rare simultaneous human intrathalamic and scalp electroencephalogram (EEG) recordings from eight volunteering patients receiving intrathalamic electrodes implanted for the treatment of epilepsy, demonstrating real-time communication between neocortex and ATN during successful memory encoding. Neocortical-ATN theta oscillatory phase synchrony of local field potentials and neocortical-theta-to-ATN-gamma cross-frequency coupling during presentation of complex photographic scenes predicted later memory for the scenes, demonstrating a key role for the ATN in human memory encoding.

Phase-amplitude cross-frequency coupling in the human nucleus acumbens tracks action monitoring during cognitive control

Authors:

• S. Durschmid

• Tino Zaehle

• Klaus Kopitzki

• Jürgen Voges

• Friedhelm Schmitt

• Hans-Jochen Heinze

• Robert T. Knight

• Hermann Hinrichs

Date: 2013

DOI: 10.3389/fnhum.2013.00635

PubMed: 24586885

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Abstract:

The Nucleus Accumbens (NAcc) is an important structure for the transfer of information between cortical and subcortical structures, especially the prefrontal cortex and the hippocampus. However, the mechanism that allows the NAcc to achieve this integration is not well understood. Phase-amplitude cross-frequency coupling (PAC) of oscillations in different frequency bands has been proposed as an effective mechanism to form functional networks to optimize transfer and integration of information. Here we assess PAC between theta and high gamma oscillations as a potential mechanism that facilitates motor adaptation. To address this issue we recorded intracranial field potentials directly from the bilateral human NAcc in three patients while they performed a motor learning task that varied in the level of cognitive control needed to perform the task. As in rodents, PAC was observable in the human NAcc, transiently occurring contralateral to a movement following the motor response. Importantly, PAC correlated with the level of cognitive control needed to monitor the action performed. This functional relation indicates that the NAcc is engaged in action monitoring and supports the evaluation of motor programs during adaptive behavior by means of PAC.