Prefrontal stimulation prior to motor sequence learning alters multivoxel patterns in the striatum and the hippocampus

AbstractMotor sequence learning (MSL) is supported by dynamical interactions between hippocampal and striatal networks that are thought to be orchestrated by the prefrontal cortex. In the present study, we tested whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex (DLPFC) prior to MSL can modulate multivoxel response patterns in the stimulated cortical area, the hippocampus and the striatum. Response patterns were assessed with multivoxel correlation structure analyses of functional magnetic resonance imaging data acquired during task practice and during resting-state scans before and after learning/stimulation. Results revealed that, across stimulation conditions, MSL induced greater modulation of task-related DLPFC multivoxel patterns than random practice. A similar learning-related modulatory effect was observed on sensorimotor putamen patterns under inhibitory stimulation. Furthermore, MSL as well as inhibitory stimulation affected (posterior) hippocampal multivoxel patterns at post-intervention rest. Exploratory analyses showed that MSL-related brain patterns in the posterior hippocampus persisted into post-learning rest preferentially after inhibitory stimulation. These results collectively show that prefrontal stimulation can alter multivoxel brain patterns in deep brain regions that are critical for the MSL process. They also suggest that stimulation influenced early offline consolidation processes as evidenced by a stimulation-induced modulation of the reinstatement of task pattern into post-learning wakeful rest.

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Prefrontal stimulation prior to motor sequence learning alters multivoxel patterns in the striatum and the hippocampus

10.1101/2021.07.01.450671 ◽

2021 ◽

Author(s):

Mareike A. Gann ◽

Bradley R. King ◽

Nina Dolfen ◽

Menno P. Veldman ◽

Marco Davare ◽

...

Keyword(s):

Prefrontal Cortex ◽

Sequence Learning ◽

Brain Regions ◽

Response Patterns ◽

Motor Sequence Learning ◽

Imaging Data ◽

Motor Sequence ◽

Post Intervention ◽

Dorsolateral Prefrontal ◽

Task Practice

Motor sequence learning (MSL) is supported by dynamical interactions between hippocampal and striatal networks that are thought to be orchestrated by the prefrontal cortex. In the present study, we tested whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex (DLPFC) prior to MSL, can modulate multivoxel response patterns in the stimulated cortical area, the hippocampus and the striatum. Response patterns were assessed with multivoxel correlation structure analyses of functional magnetic resonance imaging data acquired during task practice and during resting-state scans before and after learning/stimulation. Results revealed that, across stimulation conditions, MSL induced greater modulation of task-related DLPFC multivoxel patterns than random practice. A similar learning-related modulatory effect was observed on sensorimotor putamen patterns under inhibitory stimulation. Furthermore, MSL as well as inhibitory stimulation affected (posterior) hippocampal multivoxel patterns at post-intervention rest. Exploratory analyses showed that MSL-related brain patterns in the posterior hippocampus persisted into post-learning rest preferentially after inhibitory stimulation. These results collectively show that prefrontal stimulation can alter multivoxel brain patterns in deep brain regions that are critical for the MSL process. They also suggest that stimulation influenced early offline consolidation processes as evidenced by a stimulation-induced modulation of the reinstatement of task pattern into post-learning wakeful rest.

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Persistence of Hippocampal and Striatal Multivoxel Patterns during Awake Rest after Motor Sequence Learning

10.1101/2021.06.29.450290 ◽

2021 ◽

Author(s):

Bradley R. King ◽

Mareike A. Gann ◽

Dante Mantini ◽

Julien Doyon ◽

Genevieve Albouy

Keyword(s):

Motor Learning ◽

Sequence Learning ◽

Memory Consolidation ◽

Primary Motor Cortex ◽

Critical Role ◽

Brain Regions ◽

Response Patterns ◽

Motor Sequence Learning ◽

Motor Sequence ◽

Task Practice

Memory consolidation is thought to be mediated by the offline reactivation of brain regions recruited during initial learning. Evidence for hippocampal reactivation in humans comes from studies showing that hippocampal response patterns elicited during learning can persist into subsequent rest intervals. Such investigations have largely been limited to declarative memory, which is surprising given the critical role of the hippocampus in motor memory processes. The primary goal of this study was therefore to investigate whether motor learning induces persistence of hippocampal patterns into subsequent rest. Based on their critical roles in motor learning and memory consolidation processes, we also assessed persistence in the striatum and primary motor cortex (M1). Functional magnetic resonance imaging (fMRI) data were recorded during motor learning as well as pre- and post-learning resting periods from 55 young healthy adults (males and females). Patterns of brain responses were assessed with intra- and inter-regional multivoxel correlation structure (MVCS). Intra-regional multivoxel patterns during motor sequence learning within the hippocampus and the striatum - but not within M1 - were more similar to post-learning as compared to pre-learning resting epochs, indicating persistence of task-related patterns thought to reflect reactivation processes. Interestingly, the multivoxel pattern of hippocampal connectivity with the striatum (i.e., inter-regional MVCS) was strongly dissimilar between post-learning rest and task practice. Altogether, these results provide evidence for the persistence of learning-related response patterns within the hippocampus and striatum into rest following motor learning. They also suggest that striatal-hippocampal connectivity patterns elicited by task practice are reorganized in post-learning waking rest.

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Using high-definition transcranial direct current stimulation to investigate the role of the dorsolateral prefrontal cortex in explicit sequence learning

PLoS ONE ◽

10.1371/journal.pone.0246849 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0246849

Author(s):

Hannah K. Ballard ◽

Sydney M. Eakin ◽

Ted Maldonado ◽

Jessica A. Bernard

Keyword(s):

Prefrontal Cortex ◽

Skill Acquisition ◽

Direct Current ◽

Sequence Learning ◽

Dorsolateral Prefrontal Cortex ◽

Motor Sequence Learning ◽

Motor Sequence ◽

High Definition ◽

Dorsolateral Prefrontal

Though we have a general understanding of the brain areas involved in motor sequence learning, there is more to discover about the neural mechanisms underlying skill acquisition. Skill acquisition may be subserved, in part, by interactions between the cerebellum and prefrontal cortex through a cerebello-thalamo-prefrontal network. In prior work, we investigated this network by targeting the cerebellum; here, we explored the consequence of stimulating the dorsolateral prefrontal cortex using high-definition transcranial direct current stimulation (HD-tDCS) before administering an explicit motor sequence learning paradigm. Using a mixed within- and between- subjects design, we employed anodal (n = 24) and cathodal (n = 25) HD-tDCS (relative to sham) to temporarily alter brain function and examine effects on skill acquisition. The results indicate that both anodal and cathodal prefrontal stimulation impedes motor sequence learning, relative to sham. These findings suggest an overall negative influence of active prefrontal stimulation on the acquisition of a sequential pattern of finger movements. Collectively, this provides novel insight on the role of the dorsolateral prefrontal cortex in initial skill acquisition, when cognitive processes such as working memory are used. Exploring methods that may improve motor learning is important in developing therapeutic strategies for motor-related diseases and rehabilitation.

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Using high-definition transcranial direct current stimulation to investigate the role of the dorsolateral prefrontal cortex in explicit sequence learning

10.1101/727842 ◽

2019 ◽

Author(s):

Hannah K. Ballard ◽

Sydney M. Eakin ◽

Ted Maldonado ◽

Jessica A. Bernard

Keyword(s):

Prefrontal Cortex ◽

Skill Acquisition ◽

Direct Current ◽

Sequence Learning ◽

Dorsolateral Prefrontal Cortex ◽

Motor Sequence Learning ◽

Motor Sequence ◽

High Definition ◽

Dorsolateral Prefrontal

AbstractThough we have a general understanding of the brain areas involved in motor sequence learning, there is more to discover about the neural mechanisms underlying skill acquisition. Skill acquisition may be subserved, in part, by interactions between the cerebellum and prefrontal cortex through a cerebello-thalamo-prefrontal network. In prior work, we investigated this network by targeting the cerebellum; here, we explored the consequence of stimulating the dorsolateral prefrontal cortex using high-definition transcranial direct current stimulation (HD-tDCS) before administering an explicit motor sequence learning paradigm. Using a mixed within- and between-subjects design, we employed anodal (n = 24) and cathodal (n = 25) HD-tDCS (relative to sham) to temporarily alter brain function and examine effects on skill acquisition. The results indicate that both anodal and cathodal prefrontal stimulation impedes motor sequence learning, relative to sham. These findings suggest an overall negative influence of active prefrontal stimulation on the acquisition of a sequential pattern of finger movements. Collectively, this provides novel insight on the role of the dorsolateral prefrontal cortex in initial skill acquisition, when cognitive processes such as working memory are used. Exploring methods that may improve motor learning is important in developing therapeutic strategies for motor-related diseases and rehabilitation.

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Functional Mapping of Sequence Learning in Normal Humans

Journal of Cognitive Neuroscience ◽

10.1162/jocn.1995.7.4.497 ◽

1995 ◽

Vol 7 (4) ◽

pp. 497-510 ◽

Cited By ~ 469

Author(s):

Scott T. Grafton ◽

Eliot Hazeltine ◽

Richard Ivry

Keyword(s):

Blood Flow ◽

Prefrontal Cortex ◽

Motor Learning ◽

Sequence Learning ◽

Spatial Working Memory ◽

Premotor Cortex ◽

Occipital Cortex ◽

Motor Sequence ◽

Dorsolateral Prefrontal ◽

Attentional Interference

The brain localization of motor sequence learning was studied in normal subjects with positron emission tomography. Subjects performed a serial reaction time (SRT) task by responding to a series of stimuli that occurred at four different spatial positions. The stimulus locations were either determined randomly or according to a 6-element sequence that cycled continuously. The SRT task was performed under two conditions. With attentional interference from a secondary counting task there was no development of awareness of the sequence. Learning-related increases of cerebral blood flow were located in contralateral motor effector areas including motor cortex, supplementary motor area, and putamen, consistent with the hypothesis that nondeclarative motor learning occurs in cerebral areas that control limb movements. Additional cortical sites included the rostral prefrontal cortex and parietal cortex. The SRT learning task was then repeated with a new sequence and no attentional interference. In this condition, 7 of 12 subjects developed awareness of the sequence. Learning-related blood flow increases were present in right dorsolateral prefrontal cortex, right premotor cortex, right ventral putamen, and biparieto-occipital cortex. The right dorsolateral prefrontal and parietal areas have been previously implicated in spatial working memory and right prefrontal cortex is also implicated in retrieval tasks of verbal episodic memory. Awareness of the sequence at the end of learning was associated with greater activity in bilateral parietal, superior temporal, and right premotor cortex. Motor learning can take place in different cerebral areas, contingent on the attentional demands of the task.

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A role for GABA in the modulation of striatal and hippocampal systems under stress

Communications Biology ◽

10.1038/s42003-021-02535-x ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Nina Dolfen ◽

Menno P. Veldman ◽

Mareike A. Gann ◽

Andreas von Leupoldt ◽

Nicolaas A. J. Puts ◽

...

Keyword(s):

Motor Learning ◽

Sequence Learning ◽

Blood Oxygen Level Dependent ◽

Resonance Spectroscopy ◽

Gamma Aminobutyric Acid ◽

Motor Sequence Learning ◽

Motor Sequence ◽

Blood Oxygen Level ◽

Post Intervention

AbstractPrevious research has demonstrated that stress modulates the competitive interaction between the hippocampus and striatum, two structures known to be critically involved in motor sequence learning. These earlier investigations, however, have largely focused on blood oxygen-level dependent (BOLD) responses. No study to date has examined the link between stress, motor learning and levels of striatal and hippocampal gamma-aminobutyric acid (GABA). This knowledge gap is surprising given the known role of GABA in neuroplasticity subserving learning and memory. The current study thus examined: a) the effects of motor learning and stress on striatal and hippocampal GABA levels; and b) how learning- and stress-induced changes in GABA relate to the neural correlates of learning. To do so, fifty-three healthy young adults were exposed to a stressful or non-stressful control intervention before motor sequence learning. Striatal and hippocampal GABA levels were assessed at baseline and post-intervention/learning using magnetic resonance spectroscopy. Regression analyses indicated that stress modulated the link between striatal GABA levels and functional plasticity in both the hippocampus and striatum during learning as measured with fMRI. This study provides evidence for a role of GABA in the stress-induced modulation of striatal and hippocampal systems.

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The Neural Correlates of Speech Motor Sequence Learning

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00737 ◽

2015 ◽

Vol 27 (4) ◽

pp. 819-831 ◽

Cited By ~ 30

Author(s):

Jennifer A. Segawa ◽

Jason A. Tourville ◽

Deryk S. Beal ◽

Frank H. Guenther

Keyword(s):

Motor Learning ◽

Sequence Learning ◽

Neural Correlates ◽

Brain Regions ◽

Motor Sequence Learning ◽

Motor Sequence ◽

Learning Success ◽

Frontal Operculum ◽

Speech Motor Learning ◽

Speech Motor

Speech is perhaps the most sophisticated example of a species-wide movement capability in the animal kingdom, requiring split-second sequencing of approximately 100 muscles in the respiratory, laryngeal, and oral movement systems. Despite the unique role speech plays in human interaction and the debilitating impact of its disruption, little is known about the neural mechanisms underlying speech motor learning. Here, we studied the behavioral and neural correlates of learning new speech motor sequences. Participants repeatedly produced novel, meaningless syllables comprising illegal consonant clusters (e.g., GVAZF) over 2 days of practice. Following practice, participants produced the sequences with fewer errors and shorter durations, indicative of motor learning. Using fMRI, we compared brain activity during production of the learned illegal sequences and novel illegal sequences. Greater activity was noted during production of novel sequences in brain regions linked to non-speech motor sequence learning, including the BG and pre-SMA. Activity during novel sequence production was also greater in brain regions associated with learning and maintaining speech motor programs, including lateral premotor cortex, frontal operculum, and posterior superior temporal cortex. Measures of learning success correlated positively with activity in left frontal operculum and white matter integrity under left posterior superior temporal sulcus. These findings indicate speech motor sequence learning relies not only on brain areas involved generally in motor sequencing learning but also those associated with feedback-based speech motor learning. Furthermore, learning success is modulated by the integrity of structural connectivity between these motor and sensory brain regions.

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