Biology subjects

Diedrichsen, J.

Publications and source records attributed to Diedrichsen, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

A paradigm to study the learning of muscle activity patterns outside of the natural repertoire

The acquisition of novel muscle activity patterns is a key aspect of motor skill learning which can be seen at play, for example, when beginner musicians learn new guitar or piano chords. To study this process, here we introduce a new paradigm that requires quick and synchronous flexion and extension of multiple fingers. First, participants practiced all the 242 possible combinations of isometric finger flexion and extension around the metacarpophalangeal joint (i.e., chords). We found that some chords were initially extremely challenging, but participants could eventually achieve them with practice, showing that the initial difficulty did not reflect hard biomechanical constraints imposed by the interaction of tendons and ligaments. In a second experiment we found that chord learning was largely chord-specific and did not generalize to untrained chords. Finally, we explored which factors make some chords more difficult than others. Difficulty was well predicted by the muscle activity pattern required by that chord. Interestingly, difficulty related to how similar chords muscle activity patterns are to the muscle activity patterns required by everyday hand use, and to the overall size of the muscle activity. Together, our results suggest that the new paradigm introduced in this work may provide a valuable tool to study the neural processes underlying the acquisition of novel muscle activity patterns in the human motor system.

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bioRxiv2024

Motor sequence learning involves better prediction of the next action andoptimization of movement trajectories

Learning new sequential movements is a fundamental skill for many animals. Although the behavioral manifestations of sequence learning are clear, the underlying mechanisms remain poorly understood. Motor sequence learning may arise from three distinct processes: (1) improved execution of individual movements independent of their sequential context; (2) enhanced anticipation of "what" movement should be executed next, enabling faster initiation; and (3) the development of motoric sequence-specific representations that encode "how" movements should be optimally performed within a sequence. However, many existing paradigms conflate the "what" and "how" components of learning, as participants often acquire both the sequence content (what to do) and its execution (how to do it). This overlap obscures the distinct contributions of each mechanism to motor sequence learning. In this study, we disentangled these mechanisms using a continuous reaching task. Performance in trained sequences was compared to random sequences to rule out improvements attributable solely to isolated movement execution. By also varying how many upcoming targets were visible we assessed the role of anticipation in learning. When participants could only see one future target, improvements were mostly due to them learning which target would come next. When they could see four future targets, participants immediately demonstrated fast movement times and increased movement smoothness, surpassing late-stage performance in the one target condition. Crucially, even with full visibility of future targets, participants showed further sequence-specific learning caused by a continuous optimization of movement trajectories. Follow-up experiments revealed that the learned sequence representations were effector-specific and encoded contextual information of four movements or longer. Our paradigm enables a clear dissociation between the "what" and "how" components of motor sequence learning and provides compelling evidence for the development of effector-specific sequence representations that guide optimal movement execution.

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bioRxiv2024

Sensory expectations shape neural population dynamics in motor circuits

The neural basis of movement preparation has been extensively studied during self-initiated actions where motor cortical activity during preparation shows a lawful relationship to the parameters of the subsequent action1,2. However, movements are regularly triggered and constantly corrected based on sensory inputs caused by disturbances to the body or environment. Since such disturbances are often predictable and since preparing for disturbances would make movements better, we hypothesized that expectations about sensory inputs also influence preparatory activity in motor circuits. Here we show that when humans and monkeys are probabilistically cued about the direction of a future mechanical perturbation, they incorporate sensory expectations into their movement preparation and improve their corrective responses. Using high-density neural recordings, we establish that sensory expectations are widespread across the brain, including the motor cortical areas involved in preparing self-initiated actions. The geometry of these preparatory signals in the neural population state is simple, scaling directly with the probability of each perturbation direction. After perturbation onset, a condition-independent perturbation signal shifts the neural state leading to rapid responses that initially reflect sensory expectations. Based on neural networks coupled to a biomechanical model of the arm3, we show that this neural geometry emerges through training, but only when the incoming sensory information indicating perturbation direction coincides with - or is preceded by - a condition-independent signal indicating that a perturbation has occurred. Thus, motor circuit dynamics are shaped by future sensory inputs, providing clear empirical support for the idea that movement is governed by the sophisticated manipulation of sensory feedback4.

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bioRxiv2024

Repetition effects reveal the sub-sequence representation of actions

When a movement sequence is repeated, the second execution is faster than the first. This demonstrates that the brain retains some trace of the just-executed sequence, the earliest form of sequence memory. Currently, it is unclear whether this memory trace is represented at the level of (a) transitions between movements, (b) chunks of multiple movements, or (c) the entire sequence. To answer this question, we instructed human participants to generate sequences of 11 finger presses in a delayed response paradigm. From one trial to the next, segments of variable length (1, 2, 4, 6, 11) could be repeated from the previous trial. We observed that repetition benefits appeared when a segment of 4 consecutive finger presses or longer was repeated from the previous trial. This suggests that the benefit of repetition is not merely the sum of improvements in individual transitions, nor does it require the entire sequence to be repeated. The repetition benefit was small for the first transition of a repeated segment and increased with additional repetitions. This suggests that the memory supporting the repetition effect is mainly activated when a series of past movements matches the memory trace. Planned future movements had less of an effect on the repetition effect. Our results provide insight into the structure of the earliest memory traces for motor sequences. Significance StatementMany motor skills involve concatenating single movements into complex sequences. Already after a single execution of a sequence, humans retain a memory trace that accelerates the execution of the sequence if it is repeated in the next trial. Our results show a repetition benefit even when only a small portion of movements from the previous trial is repeated, suggesting that full sequence repetition is not necessary. Detailed analyses indicate that the memory trace is activated when the last 2-3 movements match the current execution. Our work, therefore, sheds light on the structure of the earliest sequence memory and will interest researchers studying motor skill learning and the neural basis of movement control.

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bioRxiv2024

"Micro-offline gains" convey no benefit for motor skill learning

While practising a new motor skill, resting for a few seconds can improve performance immediately after the rest. This improvement has been interpreted as rapid offline learning1,2 ("micro-offline gains", MOG), supported by neural replay of the trained movement sequence during rest3. Here, we provide evidence that MOG reflect transient performance benefits, partially mediated by motor planning, and not replay-mediated offline learning. In five experiments, participants trained to produce a sequence of finger movements as many times as possible during fixed-duration practice periods. When participants trained during 10-second practice periods, each followed by a 10-second rest period, they produced more correct keypresses during training than participants who trained without taking breaks. However, this benefit vanished within seconds after the end of training, when both groups performed under comparable conditions, revealing similar levels of skill acquisition. This challenges the idea that MOG reflect offline learning, which, if present, should result in sustained performance benefits, compared to training without breaks. Furthermore, sequence-specific replay was not necessary for MOG, given that we observed persistent MOG when participants produced random sequences that never repeated, preventing any effect of (sequence-specific) replay on the performance. Importantly, we observed diminished MOG when participants could not pre-plan the first few movements of an upcoming practice period. We conclude that "micro-offline gains" represent short-lived performance benefits that are partially driven by motor pre-planning, rather than replay-mediated offline learning.

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bioRxiv2024

Task-specific topographical maps of neural activity in the primate lateral prefrontal cortex

Neurons in the primate lateral prefrontal cortex (LPFC) flexibly adapt their activity to support a wide range of cognitive tasks. Whether and how the topography of LPFC neural activity changes as a function of task is unclear. In the present study, we address this issue by characterizing the functional topography of LPFC neural activity in awake behaving macaques performing three distinct cognitive tasks. We recorded from chronically implanted multi-electrode arrays and show that the topography of LPFC activity is stable within a task, but adaptive across tasks. The topography of neural activity exhibits a spatial scale compatible with prior anatomical tracing work on a!erent LPFC inputs. Our findings show that LPFC maps of neural population activity are stable for a specific task, providing robust neural codes that support task specialization. Moreover, the variability in functional topographies across tasks indicates activity landscapes can adapt, providing flexibility to LPFC neural codes.

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bioRxiv2024

Intrinsic structural covariation links cerebellum subregions to the cerebral cortex

The human cerebellum is increasingly recognized to be involved in non-motor and higher-order cognitive functions. Yet, its ties with the entire cerebral cortex have not been holistically studied in a whole-brain exploration with a unified analytical framework. Here, we characterized disso-ciable cortical-cerebellar structural covariation patterns across the brain in n=38,527 UK Bio-bank participants. Our results invigorate previous observations in that important shares of corti-cal-cerebellar structural covariation are described as i) a dissociation between the higher-level cognitive system and lower-level sensorimotor system, as well as ii) an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel pattern of ipsilateral, rather than contralateral, cerebral-cerebellar associations. Furthermore, phenome-wide association assays revealed key phenotypes, including cognitive phenotypes, lifestyle, physical properties, and blood assays, associated with each decomposed covariation pattern, helping to understand their real-world implications. This systems neurosci-ence view paves the way for future studies to explore the implications of these structural covaria-tions, potentially illuminating new pathways in our understanding of neurological and cognitive disorders.

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bioRxiv2023

Cortical areas for planning sequences before and during movement

Production of rapid movement sequences relies on preparation before (pre-planning) and during (online planning) movement. Here, we asked how different cortical sensorimotor areas contribute to these processes. Human participants performed three single-finger and three multi-finger sequences in a delayed movement paradigm. During preparation, 7T functional MRI revealed that primary motor (M1) and somatosensory (S1) areas showed pre-activation of the first movement, even though the overall activation level did not change from baseline. During production, the activity in M1 and S1 could be explained by temporal summation of activity patterns corresponding to constituent fingers. In contrast, dorsal premotor (PMd) and anterior superior parietal lobule (aSPL) showed substantial activation during preparation of multi-finger as compared to single-finger sequences. The same regions were also more activated during production of multi-finger sequences, suggesting that the same areas are involved in both pre- and online planning. Nonetheless, we observed small but robust differences between the two contrasts, suggesting preferential involvements of these areas in pre- and online planning. Multivariate analysis revealed sequence-specific representations in both PMd and aSPL, which remained stable across both preparation and production phases. This suggests that these areas maintain a sequence-specific representation before and during sequence production, likely guiding the execution-related areas. Significance StatementUnderstanding how the brain orchestrates complex behavior remains a core challenge in human neuroscience. Here, we combine high-resolution neuroimaging and a carefully crafted design to study the neural control of rapid sequential finger movements, like typing or playing the piano. Advancing prior research, we show that the brain areas involved in planning these movements maintain those representations throughout the execution of the sequence. This representational stability across planning and execution suggests an intricate connection between these processes. Our results shed light on the nuanced contributions of different cortical areas to different aspects of coordinating skilled movement. This work is well placed to inform future research in animal models and the development of targeted interventions against movement disorders.

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bioRxiv2023

A hierarchical atlas of the human cerebellum for functional precision mapping

The human cerebellum is activated by a wide variety of cognitive and motor tasks. Previous functional atlases have relied on single task-based or resting-state fMRI datasets. Here, we present a functional atlas that integrates information from 7 large-scale datasets, outperforming existing group atlasses. The new atlas has three further advantages: First, the atlas allows for precision mapping in individuals: The integration of the probabilistic group atlas with an individual localizer scan results in a marked improvement in prediction of individual boundaries. Second, we provide both asymmetric and symmetric versions of the atlas. The symmetric version, which is obtained by constraining the boundaries to be the same across hemispheres, is especially useful in studying functional lateralization. Finally, the regions are hierarchically organized across 3 levels, allowing analyses at the appropriate level of granularity. Overall, the new atlas is an important resource for the study of the interdigitated functional organization of the human cerebellum in health and disease.

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bioRxiv2023

Neural correlates of online action preparation

When performing movements in rapid succession, the brain needs to coordinate preparation of an upcoming action with ongoing execution. Here we identify the processes and brain areas involved in this ability. Human participants performed pairs of single-finger presses or three-finger chords in settings where they had to prepare the second movement before or after the first response. Despite matched perceptual and movement requirements, 7T functional MRI revealed increased brain activity in regions along the intra-parietal sulcus and ventral visual stream when actions overlapped. Multivariate analyses suggested that these areas were involved in stimulus identification and action selection. In contrast, the dorsal premotor cortex, known to be involved in planning upcoming movements, showed no discernible signs of heightened activity. This observation suggests that the bottleneck during simultaneous action control and preparation arises at the level of stimulus identification and action selection, whereas movement planning in the premotor cortex can unfold concurrently with execution without interference between the two processes. SummaryThe brains ability to prepare for upcoming actions while controlling ongoing movements is a crucial evolutionary adaptation of the action system. However, the neural basis of online action preparation remains largely unknown. We found that superior-parietal and occipito-temporal areas exhibited heightened activation during online preparation. Surprisingly, the dorsal premotor cortex, known to be a crucial structure in motor planning, did not display additional activation for overlapping actions. These findings imply that while motor planning within the premotor cortex can occur in parallel with the execution of ongoing movement, the parallel stimulus identification and action selection in the posterior parietal cortex requires additional neural processes. HighlightsO_LIIndividuals prepare upcoming actions while simultaneously controlling ongoing movement C_LIO_LIWhen these two processes overlap, superior-parietal and occipito-temporal areas show increased activation C_LIO_LIMultivariate analysis suggests that increased activation arises to resolve simultaneous stimulus identification and action selection C_LIO_LIThe premotor cortex, known to be involved in motor planning, coordinates simultaneous planning and execution without extra neural engagement C_LI

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bioRxiv2023

Interaction of multiple future movement plans in sequential reaching

Real world actions often comprise of a series of movements that cannot be entirely planned before initiation. When these actions are executed rapidly, the planning of multiple future movements needs to occur simultaneously with the ongoing action. How the brain solves this task remains unknown. Here we address this question with a new sequential arm reaching paradigm that manipulates how many future reaches are available for planning while controlling execution of the ongoing reach. We show that participants plan at least two future reaches simultaneously with an ongoing reach. Further, the planning processes of the two future reaches are not independent of one another. Evidence that the planning processes interact is two-fold. First, correcting for a visual perturbation of the ongoing reach target is slower when more future reaches are planned. Second, the curvature of the current reach is modified based on the next reach only when their planning processes temporally overlap. These interactions between future planning processes may enable smooth production of sequential actions by linking individual segments of a long sequence at the level of motor planning.

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bioRxiv2023

A hierarchical Bayesian brain parcellation framework for fusion of functional imaging datasets

One important barrier in the development of complex models of human brain organization is the lack of a large and comprehensive task-based neuro-imaging dataset. Therefore, current atlases of functional brain organization are mainly based on single and homogeneous resting-state datasets. Here, we propose a hierarchical Bayesian framework that can learn a probabilistically defined brain parcellation across numerous task-based and resting-state datasets, exploiting their combined strengths. The framework is partitioned into a spatial arrangement model that defines the probability of a specific individual brain parcellation, and a set of dataset-specific emission models that defines the probability of the observed data given the individual brain organization. We show that the framework optimally combines information from different datasets to achieve a new population-based atlas of the human cerebellum. Furthermore, we demonstrate that, using only 10 min of individual data, the framework is able to generate individual brain parcellations that outperform group atlases.

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bioRxiv2023

Large Data on the Small Brain: Population-wide Cerebellar Growth Models of Children and Adolescents

In the past, the cerebellum has been best known for its crucial role in motor function. However, increasingly more findings highlight the importance of cerebellar contributions in cognitive functions and neurodevelopment. Using large scale, population-wide neuroimaging data, we describe and provide detailed, openly available models of cerebellar development in childhood and adolescence, an important time period for brain development and onset of neuropsychiatric disorders. Next to a traditionally used anatomical parcellation of the cerebellum, we generated growth models based on a recently proposed functional parcellation. In both, we find an anterior-posterior growth gradient mirroring the age-related improvements of underlying behavior and function, which is analogous to cerebral maturation patterns and offers new evidence for directly related cerebello-cortical developmental trajectories. Finally, we illustrate how the current approach can be used to detect cerebellar abnormalities in clinical samples.

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bioRxiv2023

Does ipsilateral remapping following hand loss impact motor control of the intact hand?

What happens once a cortical territory becomes functionally redundant? We addressed brain and behavioural adaptations for the intact hand in individuals with a missing hand. Previous studies reported increased ipsilateral activity in the somatosensory territory of the missing hand (i.e., remapping) in acquired amputees, but not in individuals with a congenitally missing hand (one-handers). It is unclear whether remapping in amputees involves recruiting more neural resources to support the intact hand, and whether such activity is increased in tasks that demand greater motor control. We investigated sensorimotor learning and neural representation of the intact hand in one-handers and amputees using a multi-finger configuration task, as well as univariate and multivariate fMRI. We found that ipsilateral activity increased with motor demand - but only in the amputees group. However, these changes did not reflect behavioural differences. The representation of the finger configurations, as revealed by multivariate analysis, was stronger in amputees and closer to the typical representation found in controls contralateral hand territory, compared to one-handers. This collaborative contra-ipsilateral activity may reflect the intact hands efference copy. One-handers struggled to learn difficult finger configurations, but this did not translate to differences in univariate or multivariate activity relative to controls. Together with a supplementary structural white matter analysis, our results suggest that enhanced activity in the missing hand territory may not reflect intact hand function. Instead, we suggest that plasticity is more restricted than generally assumed and may depend on the availability of homologous pathways acquired early in life. Significant StatementWe studied whether brain resources in the missing-hand territory support demanding intact hand motor control in people who were born with one hand or lost a hand later in life. We found that amputees had increased activity in the brain area used for the missing hand, but no improvement in the performance of their intact hand. This collaborative contra-ipsilateral activity may reflect the intact hands efference copy. One-handers showed slight deficits while learning to perform complex motor movements, but no brain activity differences in the missing hand territory, compared to controls. Our results suggest that brain plasticity is limited and may depend on early life experiences.

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bioRxiv2023

Cortical changes during the learning of sequences of simultaneous finger presses

The cortical alterations underpinning the acquisition of motor skills remain debated. In this longitudinal study in younger adults, we acquired performance and neuroimaging (7T MRI) measures weekly over the course of 6 weeks to investigate neural changes associated with learning sequences of simultaneous finger presses executed with the non-dominant hand. Both the intervention group (n = 33) and the control group (n = 30) showed general performance improvements, but performance improved more and became more consistent for sequences that were intensively trained by the intervention group, relative to those that were not. Brain activity for trained sequences decreased compared with untrained sequences in the bilateral parietal and premotor cortices. No training-related changes in the primary sensorimotor areas were detected. The similarity of activation patterns between trained and untrained sequences decreased in secondary, but not primary, sensorimotor areas, while the similarity of the activation patterns between different trained sequences did not show reliable changes. Neither the variability of activation patterns across trials, nor the estimates of brain structure displayed practice-related changes that reached statistical significance. Overall, the main correlate of learning configural sequences was a reduction in brain activity in secondary motor areas.

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bioRxiv2023

Selective recruitment: Evidence for task-dependent gating of inputs to the cerebellum

fMRI studies have documented cerebellar activity across a wide array of tasks. However, the functional contribution of the cerebellum within these task domains remains unclear because cerebellar activity is often studied in isolation. This is problematic, as cerebellar fMRI activity may simply reflect the transmission of neocortical activity through fixed connections. Here we present a new approach that addresses this problem. Rather than focus on task-dependent activity changes in the cerebellum alone, we ask if neocortical inputs to the cerebellum are gated in a task-dependent manner. We hypothesize that input is upregulated when the cerebellum functionally contributes to a task. We first validated this approach using a finger movement task, where the integrity of the cerebellum has been shown to be essential for the coordination of rapid alternating movements but not for force generation. While both neocortical and cerebellar activity increased with increasing speed and force, the speed-related changes in the cerebellum were larger than predicted by an optimized cortico-cerebellar connectivity model. We then applied the same approach in a cognitive domain, assessing how the cerebellum supports working memory. Enhanced gating was associated with the encoding of items in working memory, but not with the manipulation or retrieval of the items. Focusing on task-dependent gating of neocortical inputs to the cerebellum offers a promising approach for using fMRI to understand the specific contributions of the cerebellum to cognitive function.

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bioRxiv2021

Mapping the integration of sensory information across fingers in human sensorimotor cortex

The integration of somatosensory signals across fingers is essential for dexterous object manipulation. Previous experiments suggest that this integration occurs in neural populations in the primary somatosensory cortex (S1). However, the integration process has not been fully characterized, as previous studies have mainly used two-finger stimulation paradigms. Here, we addressed this gap by stimulating all 31 single- and multi-finger combinations. We measured population-wide activity patterns evoked during finger stimulation in human S1 and primary motor cortex (M1) using 7T functional magnetic resonance imaging (fMRI) in female and male participants. Using multivariate fMRI analyses, we found clear evidence of unique non-linear interactions between fingers. In Brodmann area (BA) 3b, interactions predominantly occurred between pairs of neighbouring fingers. In BA 2, however, we found equally strong interactions between spatially distant fingers, as well as interactions between finger triplets and quadruplets. We additionally observed strong interactions in the hand area of M1. In both M1 and S1, these non-linear interactions did not reflect a general suppression of overall activity, suggesting instead that the interactions we observed reflect rich, non-linear integration of sensory inputs from the fingers. We suggest that this non-linear finger integration allows for a highly flexible mapping from finger sensory inputs to motor responses that facilitates dexterous object manipulation.

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bioRxiv2021

The role of feedback in the production of skilled finger sequences

Actions involving fine control of the hand, for example grasping an object, rely heavily on sensory information from the fingertips. While the integration of feedback during execution of individual movements is well understood, less is known about the use of sensory feedback in the control of skilled movement sequences. To address this gap, we trained participants to produce sequences of finger movements on a keyboard-like device over a four-day training period. Participants received haptic, visual, and auditory feedback indicating the occurrence of each finger press. We then either transiently delayed or advanced the feedback for a single press by a small amount of time (30 or 60 ms). We observed that participants rapidly adjusted their ongoing finger press by either accelerating or prolonging the ongoing press, in accordance with the direction of the perturbation. Furthermore, we could show that this rapid behavioural modulation was driven by haptic feedback. While these feedback-driven adjustments reduced in size with practice, they were still clearly present at the end of training. In contrast to the directionally-specific effect we observed on the perturbed press, a feedback perturbation resulted in a delayed onset of the subsequent presses irrespective of perturbation direction or feedback modality. This observation is consistent with a hierarchical organization of skilled movement sequences, with different levels reacting distinctly to sensory perturbations.

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