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Hendrikse, J. J.

Publications and source records attributed to Hendrikse, J. J..

11 recordsLinked to original sources

Beta power modulation supports micro-consolidation of implicit motor sequences

The consolidation of novel motor skills has traditionally been investigated over the timescale of hours-days following practice. However, a growing body of evidence has demonstrated that consolidation of skills occurs more rapidly across a scale of seconds - a process termed micro-consolidation. Micro-consolidation of explicitly cued motor sequences is supported by frontoparietal beta oscillations. Whether beta power modulation is a common mechanism supporting rapid consolidation of other forms of skill learning, such as implicit sequence learning, is yet to be elucidated. 72 healthy adults aged 18-35 (55% female) completed a serial reaction time task with concurrent electroencephalography recording. In line with our previous work, we show that the early fast learning on an implicit sequence task is primarily expressed as micro-offline gains during brief rest periods between periods of practice. Beta power was modulated as a function of active practice vs rest epochs (i.e., event-related synchronisation/desynchronisation), and here we demonstrate that micro-offline gains are associated with this modulation of beta power during the rest epochs. This relationship was specific to the beta frequency, and was not observed across either mu or gamma bands. Overall, in line with seminal work implicating beta in early explicit motor learning, our results indicate that beta is a shared neurophysiological signature of micro-consolidation of implicit sequences. Key points summary- Recent evidence demonstrates rapid consolidation of motor skills over seconds, termed micro-consolidation. - Seminal work has implicated beta oscillations in early explicit motor learning, though whether beta supports rapid consolidation of other forms of skill learning is unclear. - Using electroencephalography, we demonstrate that beta modulation is a neurophysiological signature of micro-consolidation of implicitly learnt motor sequences. - Lower beta at rest is associated with a higher degree of micro-consolidation. - Our findings shed critical new insight into the neurophysiological mechanisms mediating rapid consolidation of implicit motor skills during early fast learning.

neuroscience↗

Non-invasive Neuromodulation Targeting Approach by Mapping Stimulations and Lesions That Modify Visual Memory

Therapeutic brain stimulation is believed to target specific networks, but targeting approaches for memory remain debated. For other symptoms, neuromodulation targets have been localized by mapping connectivity of lesions and stimulation sites to specific symptoms. This approach has yielded networks for global memory, but it remains unclear whether it applies to specific types of memory. Here, we mapped connectivity of stimulation sites, lesions, and atrophy patterns associated with different memory types. We included 544 individuals across three datasets: transcranial magnetic stimulation (N=262), penetrating head trauma (N=169), and ischemic stroke (N=113). We identified a network preferentially connected to lesions and stimulation sites specifically associated with changes in visual memory. Of note, the direction of this effect was inverted depending on whether lesions or stimulation occurred at younger age or an older age, consistent with prior results. This age effect was replicated in an independent dataset of patients with preclinical Alzheimers disease (N=1240). To examine neuromodulation targets, we computed electrical field models for potential TMS sites that overlap with the networks derived from each stimulation or lesion dataset; the resulting targets intersected with established targets that demonstrated efficacy for treating memory impairment - precuneus, cortical-hippocampal network, and dorsolateral prefrontal cortex - with peak intersection at medial posterior parietal lobe, angular gyrus, and left anterior middle frontal gyrus, respectively. Future head-to-head clinical trials are needed to systematically compare these proposed neuromodulation targets against each other. One Sentence SummaryNeuromodulation targets for visual memory diverge by age at the time of injury or stimulation.

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Investigating cross-memory interactions of timing structures

Motor and episodic memories are classically conceptualised as distinct memory domains. However, both memory sequences are characterised by order and timing of their elements. Generalisation has been previously documented between these different memories, with a shared ordinal structure facilitating learning. However, it is unclear whether this generalisation also applies to the timing structure of a sequence. In a between-subject design, healthy adults (N = 143) learned and reproduced motor and episodic memory sequences with either the same or different timing structures. Contrary to expectations, recall of an episodic timeline was poorer when preceded by learning a motor sequence with the same timing structure. Motor sequence reproduction was not affected by prior episodic encoding. The findings do not support the hypothesis of cross-domain generalisation of timing structure between episodic and motor memories. However, the observed interference may suggest some overlap in the mechanism encoding timing information between memory systems.

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Transcranial ultrasound stimulation induces white matter plasticity in the human corticospinal tract

Non-invasive methods to causally modulate human white matter tracts have proved elusive. In vitro and in vivo studies indicate that myelinated axons are sensitive to mechanical perturbations from ultrasound, providing a mechanistic rationale for targeting white matter tracts with ultrasound neuromodulation. Here, we demonstrate that transcranial ultrasound stimulation (TUS) targeted at the human corticospinal tract induces site-specific changes in motor neurophysiology. In a within-subject study, 15 healthy adults received 5 Hz repetitive TUS targeted at the left corticospinal tract at the level of the superior internal capsule. The homologous tract in the opposite hemisphere and the ipsilateral motor cortex were targeted as comparison conditions to confirm site specificity. Left corticospinal tract TUS increased corticomotor excitability and intracortical facilitation, whereas left motor cortex TUS reduced intracortical inhibition. Supporting analysis using diffusion tractography indicated that the magnitude of these changes depended jointly on ultrasound pressure and white matter microstructure (fractional anisotropy). These findings provide causal evidence that ultrasound can modulate white matter neurophysiology and establish TUS as a tool for non-invasive neuromodulation of white matter tracts in health and disorders of white matter. Significance statementWhite matter pathways are central to brain function and disease, yet causal tools to modulate these tracts in humans are lacking. We show that neuronavigated, low-intensity transcranial ultrasound targeted to the corticospinal white matter tract induces site-specific changes in motor neurophysiology. Supporting analyses using diffusion MRI tractography indicated that individual responses depended jointly on ultrasound pressure and local tissue properties, supporting an anatomy-informed, precision approach. These findings establish tract-targeted ultrasound as a non-invasive way to modulate human white matter neurophysiology, opening new opportunities for mechanistic tests of brain circuits and for developing circuit-guided interventions in neurological and psychiatric disorders.

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High frequency oscillations and the 1/f slope vary across a spectrum of depression severity

Depression is a highly prevalent mental disorder that impacts an individuals functioning, societal productivity, and quality of life. It is associated with disrupted neural activity (e.g., balance of excitation-inhibition) across networks implicated in emotional processing, such as between prefrontal and limbic regions. High frequency oscillations measured with electroencephalography (i.e., beta and gamma rhythms) differ between healthy individuals and those with depression, and predict treatment outcomes following pharmacological intervention. However, to date research has focussed on binary comparisons between individuals with a clinical depression diagnosis relative to healthy control populations, providing limited insight into how these measures may shift as a function of illness severity. To establish the utility of EEG measures as potential biomarkers for depression, an improved understanding across the spectrum of symptom profiles is required. Here, we aimed to bridge this gap and investigate changes in high frequency beta and gamma oscillations and the 1/f slope in resting-state EEG across a spectrum of mild to severe depression symptom presentations. In line with expectations, we demonstrate graded alterations to gamma and beta power and the 1/f slope across a spectrum of depression severity. Our findings provide critical new insights into the neurophysiological signature of depression symptoms, and highlight the utility of EEG markers to inform future precision psychiatry approaches to more effectively assess and treat depression. HighlightsO_LIHigh frequency brain oscillations are associated with depression severity C_LIO_LIExcitation-inhibition balance is altered in depression C_LIO_LIThese neural markers could inform precision psychiatry approaches C_LI

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High-intensity cardiovascular exercise facilitates online motor skill learning, with no effect of BDNF genotype

Previous studies have demonstrated that exercise can influence motor skill learning. However, the specific components of learning primed by exercise remain unclear. This study examined the effect of a preceding bout of high intensity interval training (HIIT) on the acquisition of a novel motor skill. The investigation focused on whether improvement in skill across the session was attributable to online gains during active practice or offline rest periods between practice blocks. There was also exploration as to whether common polymorphisms of the BDNF and DRD2/ANKK1 genes that regulate plasticity, learning, and memory, influenced the relationship between exercise and motor learning. It was demonstrated that HIIT enhanced skill acquisition, but that the effects of HIIT priming were not specifically attributable to within-session online or offline learning processes. Contrary to research on overnight consolidation, there was no interaction between BDNF, nor DRD2/ANKK1 genotype, with exercise primed skill learning.

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Default mode and motor networks facilitate early learning of implicit motor sequences: a multimodal MR spectroscopy and fMRI study

Learning new motor skills is a fundamental process that involves the sequencing of actions. Skill develops with practice and time, and manifests as performance that is fast and accurate. Although we know that learning can occur through an implicit process in the absence of conscious awareness, and across multiple temporal scales, the precise neural mechanisms mediating implicit motor sequence learning remain poorly understood. Similarly, the capacity for interventions with known influence on learning and memory, such as cardiovascular exercise, to facilitate implicit learning is yet to be clearly established. Here, we investigated the neuroplasticity of implicit motor sequence learning and the effect of acute exercise priming. Healthy adults (39.5% female) aged 22.55 {+/-} 2.69 years were allocated to either a high-intensity exercise (HIIT) group (n = 16) or to a very low-intensity control group (n = 17). Following exercise, participants performed a serial reaction time task. MR spectroscopy estimates of sensorimotor gamma-aminobutyric acid (GABA) were acquired before and after exercise, and during task performance, and resting-state fMRI was acquired at the end of the protocol. We show that early stages of learning are linked to default mode network connectivity, while the overall degree of learning following sustained practice is associated with motor network connectivity. Sensorimotor GABA concentration was linked to the early stages of learning, and GABA concentration was modulated following HIIT, although the two were not related. Overall, via integration of multiple neuroimaging modalities we demonstrate that interactions between hippocampal and motor networks underlie implicit motor sequence learning. Key points summary- Motor learning occurs across different temporal scales and can arise implicitly in the absence of conscious awareness. - Explicit motor learning is linked to the brains primary inhibitory neurotransmitter, GABA, and interactions across motor and hippocampal networks. - Whether these same neural mechanisms are implicated in implicit learning is unclear. Similarly, the capacity to influence learning via priming with cardiovascular exercise is yet to be clearly established. - We show that early implicit learning is underpinned by default mode network connectivity and sensorimotor GABA concentration, while total learning following sustained practice is linked to motor network connectivity. We also found that HIIT exercise elevated sensorimotor GABA concentration, but not the magnitude of implicit learning. - Overall, our results highlight shared involvement of default mode and motor networks in implicit motor sequence learning.

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Ageing attenuates exercise-enhanced motor cortical plasticity

Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (M {+/-} s.d. = 25.30 {+/-} 4.00 years) and 20 older (M {+/-} s.d. = 64.10 {+/-} 6.50 years) healthy adults. Single and paired pulse TMS measures were collected before and after a 20-minute bout of high-intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in gamma-aminobutyric acid (GABA) inhibition. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise. These results demonstrate an age-dependent decline in cortical plasticity and indicate that a preceding bout of high-intensity interval exercise may be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. Key pointsO_LIExercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown. C_LIO_LIHere, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high-intensity interval exercise, and again after a plasticity-inducing protocol - intermittent theta burst stimulation. C_LIO_LIIn both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in gamma-aminobutyric acid (GABAergic) inhibition. C_LIO_LIOur key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults. C_LIO_LIOur findings demonstrate an age-dependent decline in exercise-enhanced cortical plasticity and indicate that a preceding bout of high-intensity interval exercise may be less effective for enhancing primary motor cortex plasticity in older adults. C_LI

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The effects of multi-day rTMS and cardiorespiratory fitness on working memory and local GABA concentration

Working memory (WM) refers to the capacity to temporarily retain and manipulate finite amounts of information; a critical process in complex behaviours such as reasoning, comprehension, and learning. This cognitive function is supported by a parietal-prefrontal network and linked to the activity of key neurotransmitters, such as gamma-aminobutyric acid (GABA). Impairments in WM are seen in a range of psychiatric and neurological disorders, and there are currently no effective treatments. In this study, we analysed secondary outcome measures from a trial investigating the effects of multi-day rTMS on cognition. Participants received four days of 20 Hz rTMS to an individualised region of left parietal cortex in one week, and an individualised region of pre-supplementary motor area (pre-SMA) in a separate week. We assessed changes to WM function before and after each week of stimulation (N = 39), and changes to GABA concentration before and after stimulation in week one using MR spectroscopy (N = 18 per stimulation condition). We hypothesised that parietal rTMS would enhance WM and alter GABA concentration at the site of stimulation, but this was not observed. Instead, we report some evidence of improved WM function following the first week of pre-SMA rTMS stimulation, and a generalised increase in GABA concentration across both parietal and pre-SMA voxels following pre-SMA rTMS. Additionally, we found that higher cardiorespiratory fitness was associated with greater WM improvement following pre-SMA stimulation. This study does not support the use of parietal multi-day rTMS for the enhancement of working memory. In contrast, the results suggest that increasing cardiorespiratory fitness may provide a novel approach to enhance the effects of pre-SMA rTMS on cognition.

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The effects of regular aerobic exercise on hippocampal structure and function

Regular exercise has numerous benefits for brain health, including the structure and function of the hippocampus. The hippocampus plays a critical role in memory function, and is altered in a number of psychiatric disorders associated with memory impairments (e.g. depression and schizophrenia), as well as healthy ageing. While many studies have focussed on how regular exercise may improve hippocampal integrity in older individuals, less is known about these effects in young to middle-aged adults. Therefore, we assessed the associations of regular exercise and cardiorespiratory fitness with hippocampal structure and function in these age groups. We recruited 40 healthy young to middle-aged adults, comprised of two groups (n = 20) who self-reported either high or low levels of exercise, according to World Health Organisation guidelines. We assessed cardiorespiratory fitness using a graded exercise test (VO2max) and hippocampal structure via manual tracing of T1-weighted magnetic resonance images. We also assessed hippocampal function using magnetic resonance spectroscopy to derive estimates of NAA concentration and hippocampal-dependent associative memory and pattern separation tasks. We observed evidence of increased N-acetyl-aspartate concentration and associative memory performance in individuals engaging in high levels of exercise. However, no differences in hippocampal volume or pattern separation capacity were observed between groups. Cardiorespiratory fitness was positively associated with hippocampal volume (left, right, and bilateral), N-acetyl-aspartate concentration, and pattern separation. However, no association was observed between cardiorespiratory fitness and associative memory. Therefore, we provide evidence that higher levels of exercise and cardiorespiratory fitness are associated with improved hippocampal structure and function. Exercise may provide a low-risk, effective method of improving hippocampal integrity in an early-to-mid-life stage.

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Multi-day rTMS exerts site-specific effects on functional connectivity but does not influence associative memory performance

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique with the capacity to modulate brain network connectivity and cognitive function. Recent studies have demonstrated long-lasting improvements in associative memory and resting-state connectivity following multi-day repetitive TMS (rTMS) to individualised parietal-hippocampal networks. We aimed to assess the reproducibility and network- and cognitive-specificity of these effects following multi-day rTMS. Participants received four days of 20 Hz rTMS to a subject-specific region of left lateral parietal cortex exhibiting peak functional connectivity to the left hippocampus. In a separate week, the same stimulation protocol was applied to a subject-specific region of pre-supplementary motor area (pre-SMA) exhibiting peak functional connectivity to the left putamen. We assessed changes to associative memory before and after each week of stimulation (N = 39), and changes to resting-state functional connectivity before and after stimulation in week one (N = 36). We found no evidence of long-lasting enhancement of associative memory or increased parieto-hippocampal connectivity following multi-day rTMS to the parietal cortex, nor increased pre-SMA-putamen connectivity following multi-day rTMS to pre-SMA. Instead, we observed some evidence of site-specific modulations of functional connectivity lasting [~]24 hours, with reduced connectivity within targeted networks and increased connectivity across distinct non-targeted networks. Our findings suggest a complex interplay between multi-day rTMS and network connectivity. Further work is required to develop reliable rTMS paradigms for driving changes in functional connectivity between cortical and subcortical regions.

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