Biology subjects

Stagg, C. J.

Publications and source records attributed to Stagg, C. J..

33 records · Page 2Linked to original sources

bioRxiv2023

The effect of pulse shape in theta-burst stimulation: monophasic vs biphasic TBS

BackgroundIntermittent theta-burst stimulation (i)(TBS) is a transcranial magnetic stimulation (TMS) plasticity protocol. Conventionally, TBS is applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to recruit cortical neurons more selectively than biphasic pulses, thus yielding stronger plasticity effects. Monophasic and biphasic TBS can be generated using a custom-made pulse-width modulation-based TMS device (pTMS). ObjectiveUsing pTMS, we tested the hypothesis that monophasic iTBS would induce greater plasticity effects than biphasic, measured as induced changes in motor corticospinal excitability. MethodsIn a repeated-measures design, thirty healthy volunteers participated in three separate sessions, where monophasic and biphasic iTBS was applied to the primary motor cortex (M1 condition) or the vertex (control condition). Plasticity was quantified as changes in motor corticospinal excitability after versus before iTBS, by comparing peak-to-peak amplitudes of motor evoked potentials (MEP) measured at baseline and over 60 minutes after iTBS. ResultsBoth monophasic and biphasic M1 iTBS led to significant increases in MEP amplitude. As predicted, monophasic iTBS induced a significantly larger effect than biphasic iTBS (linear mixed effect model analysis: ({chi}2(1) = 7.48, p = 0.006), which persisted even after subtracting each individuals control (vertex) condition data from the M1 conditions ({chi}2(1) = 5.48, p = 0.019). ConclusionsIn this study, monophasic iTBS induced a stronger motor corticospinal excitability increase than biphasic within participants. This greater physiological effect suggests that monophasic iTBS may also have potential for greater functional impact, of interest for future fundamental and clinical applications of TBS.

neuroscience↗

bioRxiv2023

Ramped V1 transcranial ultrasonic stimulation modulates but does not evoke visual evoked potentials

Transcranial ultrasonic stimulation (TUS), has been shown to evoke visual evoked potential (VEP)-like potentials on EEG recordings, and also to modulate sensory evoked potentials. However, pulsed TUS is accompanied by an auditory confound, and it is possible that any observed effects were, in-part, evoked by this confound. Therefore, we used ramped TUS pulses, which are not as easily audible, to examine whether primary visual cortex (V1) TUS evokes VEP-like potentials, and modulates VEPs elicited using a checkerboard stimulus. MethodsWe tested 14 healthy participants (31 {+/-} 4.3 yrs, 4 F and 10 M). TUS was applied to the left V1 using a 270 kHz transducer (H115-2AA, Sonic Concepts). Ramped pulses (1 ms ramp, 3.25 ms total pulse duration) were repeated at 250 Hz, with a pulse train duration of 300 ms, an effective duty cycle of 50%, and Isppa without ramping of 16 W/cm2 in water. EEG was recorded from 16 channels using the g.USBamp amplifier (g.tec medical engineering GmbH). In two blocks (TUS-only), real and sham (100 each) TUS trials were repeated every 2 s. In another two blocks (TUS+checkerboard), a checkerboard stimulus was flipped every 0.5 s, and every fourth stimulus was associated with either a real or sham (100 each) TUS trial. The TUS trial started approx. 130 ms (0-5 ms jitter) before the checkerboard flip. All EEG data were analysed using Fieldtrip, and cluster-based permutation tests were used to test for differences between conditions. Results and discussionIn the TUS-only condition, in contrast to a previous study, we found no evoked potentials using ramped pulses which minimised the auditory artifact. In the TUS+checkerboard condition, we observed a modulation of the early-component of the VEP in real TUS, relative to no TUS trials. This suggests that, in line with in-vitro and animal data, there is a direct neuromodulatory effect of ultrasound, in addition to any confounding effects. Moving forward, ramping offers a relatively easy approach to minimise the auditory confound.

neuroscience↗

bioRxiv2023

Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans

Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show for the first time in humans that theta-burst TUS selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition, that changes in TUS-mediated neuroplasticity last at least 50 minutes after stimulation, and that these effects may be state-dependent - a mechanism increasingly recognized to influence the brains response to neuromodulation.

neuroscience↗

bioRxiv2022

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

Background and ObjectiveTranscranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. MethodsData from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual MPRAGE images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. ResultsIn M1, higher mean E-field magnitude was associated with greater tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = -3.55, p =0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. ConclusionsOur data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects. HighlightsO_LIWe study the link between individually simulated electric field dose and tDCS-induced change in GABA in the cortex. C_LIO_LIThe electric field strength in the brain correlates with a decrease in GABA in the motor cortex. C_LIO_LIThe correlation between the electric field and GABA change is modulated by the amount of grey matter in the MRS voxel. C_LIO_LIWe find no association between the electric field and GABA in the temporal cortex. C_LI

neuroscience↗

bioRxiv2021

Cerebellar GABA change during visuomotor adaptation relates to adaptation performance and cerebellar network connectivity: A Magnetic Resonance Spectroscopic Imaging study.

Motor adaptation is crucial for performing accurate movements in a changing environment and relies on the cerebellum. Although cerebellar involvement has been well characterized, the neurochemical changes in the cerebellum underpinning human motor adaptation remain unknown. We used a novel Magnetic Resonance Spectroscopic Imaging (MRSI) technique to measure changes in the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA) in the human cerebellum during visuomotor adaptation. Participants used their right hand to adapt to a rotated cursor in the scanner, compared with a control task requiring no adaptation. We spatially resolved adaptation-driven GABA changes at the cerebellar nuclei and cerebellar cortex in the left and the right cerebellar hemisphere independently and found that simple right-hand movements increase GABA in the right cerebellar nuclei and decreases GABA in the left. When isolating adaptation-driven GABA changes, we found an increase in GABA in the left cerebellar nuclei and decrease in GABA in the right cerebellar nuclei. Early adaptation-driven GABA change in the right cerebellar nuclei correlated with adaptation performance: Participants showing greater GABA decrease adapted better, suggesting early GABA change is behaviourally relevant. Early GABA change also correlated with functional connectivity change in a cerebellar network: Participants showing greater decreases in GABA showed greater strength increases in cerebellar network connectivity. Results were specific to GABA, to adaptation and to the cerebellar network. This study provides first evidence for plastic changes in cerebellar neurochemistry during motor adaptation. Characterising these naturally occurring neurochemical changes may provide a basis for developing therapeutic interventions to facilitate human motor adaptation. Significance StatementDespite motor adaptation being fundamental to maintaining accurate movements, its neurochemical basis remains poorly understood, perhaps because measuring neurochemicals in the human cerebellum is technically challenging. Using a novel magnetic resonance spectroscopic imaging method, this study provides evidence for GABA changes in the left and right cerebellar nuclei driven by both simple movement and motor adaptation. The adaptation-driven GABA change in the right cerebellar nuclei correlated with adaptation performance, and with functional connectivity change in a cerebellar network. These results show the first evidence for plastic changes in cerebellar neurochemistry during a cerebellar learning task. This provides the basis for developing therapeutic interventions that facilitate these naturally occurring changes to amplify cerebellar-dependent learning.

neuroscience↗

bioRxiv2021

Fatigue induces behavioural improvements in the unfatigued hand via altered functional connectivity and neurochemicals in cortical motor areas

In humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising approach to augment motor performance in the contralateral hand. In a within-participant, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional-MRI and MR-Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands. Nine minutes of 50% MVC contractions resulted in decreased handgrip force in the contracting hand, and decreased RTs in the contralateral hand. This improved motor performance in the contralateral hand was supported by significant neural changes: increased FC between SMA-SMA and increased FC between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of GABA decline in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support the use of repeated handgrip contractions as a potential modality for improving motor performance in the contralateral hand. Significance StatementEnhanced functional connectivity and decreased inhibition in sensorimotor areas of the brain underpin enhancements in motor performance and learning. In this study we investigated the impact of repeated right handgrip contractions at 50% MVC to improve behaviour, enhance functional connectivity and alter sensorimotor inhibition. We found that after nine minutes of repeated 50% MVC handgrip contractions with the right-hand, left-hand response times were significantly improved. This behavioural improvement was accompanied by altered interhemispheric functional connectivity and neurochemical changes across sensorimotor areas. Repeated unilateral handgrip contractions may be an effective method for enhancing contralateral limb motor performance in rehabilitation settings.

neuroscience↗

bioRxiv2021

Brain stimulation boosts perceptual learning by altering sensory GABAergic plasticity and functional connectivity

Interpreting cluttered scenes --a key skill for successfully interacting with our environment-- relies on our ability to select relevant sensory signals while filtering out noise. Training is known to improve our ability to make these perceptual judgements by altering local processing in sensory brain areas. Yet, the brain-wide network mechanisms that mediate our ability for perceptual learning remain largely unknown. Here, we combine transcranial direct current stimulation (tDCS) with multi-modal brain measures to modulate cortical excitability during training on a signal-in-noise task (i.e. detection of visual patterns in noise) and test directly the link between processing in visual cortex and its interactions with decision-related areas (i.e. posterior parietal cortex). We test whether brain stimulation alters inhibitory processing in visual cortex, as measured by magnetic resonance spectroscopy (MRS) of GABA and functional connectivity between visual and posterior parietal cortex, as measured by resting state functional magnetic resonance imaging (rs-fMRI). We show that anodal tDCS during training results in faster learning and decreased GABA+ during training, before these changes occur for training without stimulation (i.e. sham). Further, anodal tDCS decreases occipito-parietal interactions and time-varying connectivity across the visual cortex. Our findings demonstrate that tDCS boosts learning by accelerating visual GABAergic plasticity and altering interactions between visual and decision-related areas, suggesting that training optimises gain control mechanisms (i.e. GABAergic inhibition) and functional inter-areal interactions to support perceptual learning.

neuroscience↗

bioRxiv2021

Human motor cortical gamma activity relates to GABAergic signalling and to behaviour

Gamma activity ({gamma}, >30 Hz) is universally demonstrated across brain regions and species. However, the physiological basis and functional role of {gamma} sub-bands (slow-{gamma}, mid-{gamma}, fast-{gamma}) have been predominantly studied in rodent hippocampus; {gamma} activity in the human neocortex is much less well understood. Here we combined neuroimaging and non-invasive brain stimulation to examine the properties of {gamma} activity sub-bands in the primary motor cortex (M1), and their relationship to both local GABAergic activity and to motor learning. In 33 healthy individuals, we quantified movement-related {gamma} activity in M1 using magnetoencephalography, assessed GABAergic signaling using transcranial magnetic stimulation (TMS), and estimated motor learning via a serial reaction time task. We characterised two distinct {gamma} sub-bands (slow-{gamma}, mid-{gamma}) which show movement-related increase in activity during unilateral index finger movements and are characterised by distinct temporal-spectral-spatial profiles. Bayesian correlation analysis revealed strong evidence for a positive relationship between slow-{gamma} ([~]30-60Hz) peak frequency and endogenous GABA signalling during movement preparation (as assessed using the TMS-metric short interval intracortical inhibition). There was also moderate evidence for a relationship between power of the movement-related mid-{gamma} activity (60-90Hz) and motor learning. These relationships were neurochemically- and frequency-specific. These data provide new insights into the neurophysiological basis and functional roles of {gamma} activity in human M1 and allow the development of a new theoretical framework for {gamma} activity in the human neocortex. Significance StatementGamma ({gamma}) activity is ubiquitous in the brain, yet our understanding of the mechanisms and function of {gamma} activity in the human neocortex, and particularly in the human motor cortex, is limited. Using a multimodal approach, we characterised two patterns of movement-related {gamma} activity in the human motor cortex (slow-{gamma} and mid-{gamma}), with different spatial, temporal and spectral properties. Slow-{gamma} peak frequency was correlated to local GABA-A activity, whereas mid-gamma power predicted performance in a subsequent motor learning task. Based on these findings and previous research, we propose a theoretical framework to explain how human motor cortical {gamma} activities may arise and their potential role in plasticity and motor learning, providing new hypotheses to be tested in future studies. Key PointsO_LIWe combined neuroimaging (i.e. MEG) and non-invasive brain stimulation (i.e. TMS) to examine the properties of {gamma} activity sub-bands in the primary motor cortex. C_LIO_LITwo distinct {gamma} sub-bands (slow-{gamma}, mid-{gamma}) show a movement-related increase in activity during finger movements and are characterised by distinct temporal-spectral-spatial profiles. C_LIO_LIWe found strong evidence for a positive relationship between slow-{gamma} ([~]30-60Hz) peak frequency and endogenous GABA signalling during movement preparation (as assessed using the TMS-metric short interval intracortical inhibition). C_LI

neuroscience↗

bioRxiv2021

From synaptic activity to human in vivo quantification of neurotransmitter dynamics: a neural modelling approach

Understanding the role of neurotransmitters glutamate and GABA during normal and abnormal brain function and under external stimulation in humans are critical neuroscientific and clinical goals. The recent development of functional 1H-Magnetic resonance spectroscopy (fMRS) has allowed us to study neuro-transmitter activity in vivo for the first time. However, the physiological basis of the observed fMRS signal remains unclear. It has been proposed that fMRS detects shifts in metabolite concentrations as they move from presynaptic vesicles, where they are largely invisible, to extracellular and cytosolic pools, where they are visible. Here we bridge the gap between neural dynamics and fMRS by developing a mean-field model to link the neurotransmitter dynamics at the microscopic-level to the macroscopic-level imaging measurements. GABA and glutamate are described as cycling between three metabolic pools: in the vesicles; active in the cleft; or undergoing recycling in the astrocytic or neuronal cytosol. We interrogate the model by applying a current to manipulate the mean membrane potential and firing rate of the neural populations. We find that by disregarding the contribution from the vesicular pool, our model predicts activity-dependent changes in the MRS signal, which are consistent with reported empirical findings. Further, we show that current magnitude and direction has a selective effect on the GABA/glutamate-MRS signal: inhibitory stimulation leads to reduction of both metabolites, whereas excitatory stimulation leads to increased glutamate and decreased GABA. In doing so, we link neural dynamics and fMRS and provide a mechanistic account for the activity-dependent change in the observed MRS signal. Key Points SummaryO_LIThe recent development of functional 1H-Magnetic resonance spectroscopy (fMRS) has allowed us to study neurotransmitter activity in vivo for the first time in humans. However, the physiological basis of the observed fMRS signal is unclear. C_LIO_LIIt has been proposed that fMRS detects shifts in metabolite concentrations as they move from presynaptic vesicles, where they are largely invisible to MRS, to extracellular and cytosolic pools, where they are visible to MRS. C_LIO_LIWe test this hypothesis using a mean field model which links the neural dynamics of neurotransmitters at the microscopic-level to the macroscopic-level imaging measurements obtained in experimental studies. C_LIO_LIBy disregarding activity in the vesicular pool, our model can generate activity-dependent changes in the MRS signal in response to stimulation which are consistent with experimental findings in the literature. C_LIO_LIWe provide a mechanistic account for the activity-dependent change in observed neurotransmitter concentrations using MRS. C_LI

neuroscience↗

bioRxiv2020

Heterogeneous relationships between white matter and behaviour

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2*). Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone. To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40 to 200 may be required to detect such joint multimodal effects, depending on the task being considered. These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WMs relationship with behaviour, suggesting that variable biological effects may be shaping their interaction. HighlightsO_LIPre-registered testing of microstructural imaging across modalities (FA, MT, R1, R2*) to test WM-behaviour relationships. C_LIO_LIPartial support for FA-behaviour relationships hypothesised based on previous literature. C_LIO_LIMultimodal approaches can help detect WM-behaviour relationships that are not detected with FA alone. C_LIO_LISample sizes of 40 to 200 may be needed to detect myelin-behaviour relationships in joint multimodal analyses. C_LIO_LIVariable biological effects may be shaping WM-behaviour relationships. C_LI

neuroscience↗

bioRxiv2019

Increasing motor skill acquisition by driving theta-gamma coupling

Skill learning is a fundamental adaptive process, but the mechanisms remain poorly understood. Hippocampal learning is closely associated with gamma activity, which is amplitude-modulated by the phase of underlying theta activity. Whether such nested activity patterns also underpin skill acquisition in non-hippocampal tasks is unknown. Here we addressed this question by using transcranial alternating current stimulation (tACS) over sensorimotor cortex to modulate theta-gamma activity during motor skill acquisition, as an exemplar of a non-hippocampal-dependent task. We demonstrated, and then replicated, a significant improvement in skill acquisition with theta-gamma tACS, which outlasted the stimulation by an hour. Our results suggest that theta-gamma activity may be a common mechanism for learning across the brain and provides a putative novel intervention for optimising functional improvements in response to training or therapy.

neuroscience↗

bioRxiv2019

Intention to learn modulates the impact of reward and punishment on sequence learning

In real-world settings, learning is often characterised as intentional: learners are aware of the goal during the learning process, and the goal of learning is readily dissociable from the awareness of what is learned. Recent evidence has shown that reward and punishment (collectively referred to as valenced feedback) are important factors that influence performance during learning. Presently, however, studies investigating the impact of valenced feedback on skill learning have only considered unintentional learning, and therefore the interaction between intentionality and valenced feedback has not been systematically examined. The present study investigated how reward and punishment impact behavioural performance when participants are instructed to learn in a goal-directed fashion (i.e. intentionally) rather than unintentionally. In Experiment 1, participants performed the serial response time task with reward, punishment, or control feedback and were instructed to ignore the presence of the sequence, i.e., learn unintentionally. Experiment 2 followed the same design, but participants were instructed to intentionally learn the sequence. We found that punishment was significantly beneficial to performance during learning only when participants learned unintentionally, and we observed no effect of punishment when participants learned intentionally. Thus, the impact of feedback on performance may be influenced by goal of the learner.

neuroscience↗

bioRxiv2018

Motor learning shapes temporal activity in human sensorimotor cortex

Although neuroimaging techniques have provided vital insights into the anatomical regions involved in motor learning, the underlying changes in temporal dynamics are not well understood. Using magnetoencephalography and Hidden Markov Modelling to model the dynamics of neural oscillations on data-adaptive time-scales, we detected specific changes in movement-related sensorimotor {beta}-activity during practice of a self-paced sequential visuo-motor task. The behaviourally-relevant neural signature generalised to another motor task, emphasising the centrality of {beta}-activity in motor plasticity.

neuroscience↗

bioRxiv2018

The dynamics of cortical GABA in human motor learning

The ability to learn novel motor skills is both a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7T MR Spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, baseline M1 GABA was strongly predictive of the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain.\n\nFunding informationJ.K.:Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship (204696/Z/16/Z). C.J.S.: Wellcome Trust/Royal Society Henry Dale Fellowships (102584/Z/13/Z).

neuroscience↗

bioRxiv2018

Reward and punishment differentially recruit cerebellum and medial temporal lobe to facilitate skill memory retention

Reward and punishment shape behavior, but the mechanisms underlying their effect on skill learning are not well understood. Here, we tested whether the functional connectivity of premotor cortex (PMC), a region known to be critical for learning of sequencing skills, is altered after training by reward or punishment given during training. Resting-state fMRI was collected in two experiments before and after participants trained on either a serial reaction time task (SRTT; n = 36) or force-tracking task (FTT; n = 36) with reward, punishment, or control feedback. In each experiment, training-related change in PMC functional connectivity was compared across feedback groups. In both tasks, reward and punishment differentially affected PMC functional connectivity. On the SRTT, participants trained with reward showed an increase in functional connectivity between PMC and cerebellum as well as PMC and striatum, while participants trained with punishment showed an increase in functional connectivity between PMC and medial temporal lobe connectivity. After training on the FTT, subjects trained with control and reward showed increases in PMC connectivity with parietal and temporal cortices after training, while subjects trained with punishment showed increased PMC connectivity with ventral striatum. While the results from the two experiments overlapped in some areas, including ventral pallidum, temporal lobe, and cerebellum, these regions showed diverging patterns of results across the two tasks for the different feedback conditions. These findings suggest that reward and punishment strongly influence spontaneous brain activity after training, and that the regions implicated depend on the task learned.

neuroscience↗