Biology subjects

King, B. R.

Publications and source records attributed to King, B. R..

At least 19 recordsLinked to original sources

bioRxiv2026

Children exhibit greater persistence of motor learning-related patterns of hippocampal activity into post-task wake epochs

Previous research has demonstrated that children exhibit superior - as compared to adults - consolidation of newly acquired motor sequences across post-learning periods of wakefulness. Given that consolidation is thought to be supported by the reactivation of learning-related patterns of brain activity during the rest periods following active task practice, we hypothesized that the childhood advantage in offline consolidation may be linked to greater reactivation during post-learning wakefulness. Twenty-two children (7-11 years) and 23 adults (18-30 years) completed two sessions of a motor sequence learning task, separated by a 5-hour wake interval. Multivoxel analyses of task-related and resting-state functional magnetic resonance imaging data were employed to assess the persistence of learning-related patterns of neural activity into post-task rest epochs, reflective of reactivation processes. Behavioral results demonstrated the previously reported childhood advantage in offline consolidation over a post-learning wake interval. Imaging results revealed that children exhibited greater persistence of task-related hippocampal - but not putaminal - activity into post-learning rest as compared to adults. These findings suggest that the childhood advantage in awake motor memory consolidation may be supported, at least partially, by enhanced reactivation of task-dependent hippocampal activity patterns during offline epochs.

neuroscience↗

bioRxiv2026

No evidence for an effect of M1 cTBS on schema-mediated motor sequence learning

The availability of a pre-existing cognitive-motor schema accelerates the learning of novel motor information. The encoding of a novel schema-compatible, compared to-incompatible, motor sequence was recently shown to be supported by the left primary motor cortex (M1). However, causal evidence for the role of M1 in schema-mediated motor learning is currently lacking. In the current study, we aimed to address this knowledge gap by transiently disrupting M1 using inhibitory continuous theta burst stimulation (cTBS). Forty-eight young healthy participants learned a bimanual motor sequence task (cognitive-motor schema). Twenty-four hours later, they learned a novel sequence whose ordinal schematic structure was compatible with that learned on the previous day. To provide causal evidence for a role of M1 on such schema-mediated motor learning, we applied either cTBS or sham stimulation to the left M1 immediately prior to encoding the schema-compatible novel sequence. Electromyography results showed no evidence for an effect of left M1 cTBS on corticospinal excitability as measured with motor-evoked potentials. Similarly, behavioral results indicated no significant effect of cTBS on subsequent schema-mediated motor sequence learning. Altogether, the present data do not provide evidence for a causal role of the left M1 in schema-mediated motor sequence learning.

neuroscience↗

bioRxiv2026

The order, but not the structure, of cross-domain learning influences memory consolidation

Everyday activities often require learning sequences that necessitate the involvement of both the declarative and the procedural memory domains. Previous research has shown that a learning structure that is common across tasks from different domains can improve learning and resistance to interference. However, it remains unknown whether such shared learning structure can enhance longer-term memory retention. To address this question, forty-eight healthy adults participated in a pre-registered study in which they learned both an object sequence task (declarative learning) and a motor sequence task (procedural learning) in two separate sessions separated by 4h. Participants were assigned to either an associated group, where the two tasks shared a common learning structure - that consisted of a specific mapping between finger movements and object categories across learning sessions - or an unassociated group with no such cross-domain shared structure. Memory retention was assessed with a 24h retest session on both tasks. Contrary to our predictions, a shared higher-order structure between tasks from different domains did not enhance memory retention. Exploratory follow-up analyses revealed that the order the tasks were learned (i.e., object or motor first), rather than their structural overlap, influenced performance. Specifically, learning the motor task before the object task impaired the consolidation of the object task irrespective of whether the tasks shared a common learning structure or not. This effect was unidirectional as learning the object task before the motor task had no effect on the consolidation of the motor task. Altogether, the current findings suggest that the order of cross-domain learning experiences rather than their structure influences memory consolidation.

neuroscience↗

bioRxiv2025

Neural correlates of motor sequence learning and enhanced offline consolidation in 7- to 11-year-old children

IntroMany daily activities involve series of interrelated movements and thus the capacity to learn new motor sequences is vital for everyday functioning. Although learning new skills is especially prominent throughout childhood, remarkably few studies have examined the neural underpinnings of motor sequence learning (MSL) and memory consolidation in children. MethodsTwenty-two children (7-11 years) and 23 adults (18-30 years) underwent functional magnetic resonance imaging while completing two sessions of a MSL task, separated by a 5-hour offline period of wakefulness. ResultsAnalyses of the behavioral data revealed comparable initial learning in children and adults. However, and consistent with previous research, children exhibited superior motor memory consolidation over the 5-hour offline epoch. Neuroimaging analyses revealed that children exhibited smaller modulations in brain activity between task and rest epochs in a widespread network, including the sensorimotor cortex, supplementary motor area, cerebellum, putamen and regions associated with the default mode network. Similar levels of activity during task and rest epochs in the hippocampus, dorsolateral prefrontal cortex and somatosensory cortex were associated with better motor memory consolidation in children. ConclusionResults potentially suggest that the continued engagement of the developing brain during interleaved rest contributes to the childhood advantage in motor memory consolidation.

neuroscience↗

bioRxiv2025

Motor cortical areas facilitate schema-mediated integration of new motor information into memory

New information is rapidly learned when it is compatible with pre-existing knowledge, i.e. with a previously acquired schematic representation of the learned information. The influence of pre-established schema on learning has been extensively studied in the declarative memory domain, where it was shown that schema-compatible information could be rapidly assimilated into neocortical storage, bypassing the slow hippocampo-neocortical memory transfer process. Schema-mediated learning was recently examined in the motor memory domain; however, its neural substrates remain unknown. The goal of this study was to address this knowledge gap using both univariate and multivariate analyses of functional Magnetic Resonance Imaging (fMRI) data acquired in 60 young healthy participants during the practice of a motor sequence that was either compatible or incompatible with a previously acquired cognitive-motor schema. Consistent with previous literature, our behavioural results suggest that performance of sequential movements was enhanced when practice occurred in a context that was compatible with the previously acquired schema. Brain imaging results show that practice in a schema-compatible context specifically recruited the left primary motor cortex and resulted in a decrease in connectivity between the bilateral motor cortex and a set of task-relevant brain regions including the hippocampus, striatum, and cerebellum. Temporally fine-grained MRI analyses revealed that multivoxel activation patterns in the primary motor and the premotor cortices were modulated by schema-compatibility, with greater pattern similarity detected for sequence elements corresponding to and surrounding novel sequential movements under schema-compatible compared with -incompatible conditions. Altogether, these results suggest that motor cortical regions facilitate schema-mediated integration of novel movements into memory.

neuroscience↗

bioRxiv2024

The capacity of the medial temporal lobe to represent memory items in their ordinal position in a sequence is domain-general

Memory systems in humans are less segregated than initially thought as learning tasks from different memory domains (e.g., declarative vs. procedural) can recruit similar brain areas. However, it remains unclear whether the functional role of these overlapping brain regions - and the hippocampus in particular - is domain-general. Here, we test the hypothesis that the hippocampus encodes and preserves the temporal order of sequential information irrespective of the nature of that information. We used multivariate pattern analyses (MVPA) of functional magnetic resonance imaging (fMRI) data acquired in young healthy individuals during the execution of learned sequences of movements and objects to test whether the hippocampus represents information about the temporal order of items in a learned sequence irrespective of their nature. We also examined such coding in brain regions involved in both motor (primary and premotor cortices) and object (perirhinal cortex and parahippocampus) sequence learning. Our results suggest that hippocampal and perirhinal multivoxel activation patterns do not carry information about specific items or temporal position in a random series of objects or movements. Rather, these regions code for the representation of items in their learned temporal position in sequences irrespective of their nature (i.e., item-position coding). In contrast, although all other ROIs showed evidence of item-position coding, this representation could - at least partially - be attributed to the coding of other information such as position information. Altogether, our findings indicate that the capacity of regions in the medial temporal lobe to represent the temporal order of sequential information is domain-general. Our data suggest that these regions contribute to the development of item-position maps that might provide a cognitive framework to order sequential behaviors irrespective of their nature.

neuroscience↗

bioRxiv2024

Computational stabilization of a non-heme iron enzyme enables efficient evolution of new function

Directed evolution has emerged as a powerful tool for engineering new biocatalysts. However, introducing new catalytic residues can be destabilizing, and it is generally beneficial to start with a stable enzyme parent. Here we show that the deep learning-based tool ProteinMPNN can be used to redesign Fe(II)/KG superfamily enzymes for greater stability, solubility, and expression while retaining both native activity and industrially-relevant non-native functions. For the Fe(II)/KG enzyme tP4H, we performed site-saturation mutagenesis with both the wild-type and stabilized design variant and screened for activity increases in a non-native C-H hydroxylation reaction. We observed substantially larger increases in non-native activity for variants obtained from the stabilized scaffold compared to those from the wild-type enzyme. ProteinMPNN is user-friendly and widely-accessible, and straightforward structural criteria were sufficient to obtain stabilized, catalytically-functional variants of the Fe(II)/KG enzymes tP4H and GriE. Our work suggests that stabilization by computational sequence redesign could be routinely implemented as a first step in directed evolution campaigns for novel biocatalysts.

biochemistry↗

bioRxiv2024

Neurophysiological Correlates of Phase-Specific Enhancement of Motor Memory Consolidation via Slow-Wave Closed-Loop Targeted Memory Reactivation

Memory consolidation can be enhanced during sleep using targeted memory reactivation (TMR) and closed-loop (CL) acoustic stimulation on the up-phase of slow oscillations (SOs). Here, we tested whether applying TMR at specific phases of the SOs (up vs. down vs. no reactivation) could influence the behavioral and neural correlates of motor memory consolidation in healthy young adults. Results showed that up- (as compared to down-) state cueing resulted in greater performance improvement. Sleep electrophysiological data indicated that up-stimulated SOs exhibited higher amplitude and greater peak-nested sigma power. Task-related functional magnetic resonance images revealed that up-state cueing strengthened activity in - and segregation of - striato-motor and hippocampal networks; and that these modulations were related to the beneficial effect of TMR on sleep features and performance. Overall, these findings highlight the potential of CL-TMR to induce phase-specific modulations of motor performance, sleep oscillations and brain responses during motor memory consolidation.

neuroscience↗

bioRxiv2023

Children exhibit a developmental advantage in the offline processing of a learned motor sequence

Research that examines changes in a specific behavior across the lifespan frequently reports an inverted-U trajectory. That is, young adults exhibit optimal performance, children are conceptualized as developing systems progressing towards this ideal state, and older adulthood is characterized by performance decrements. However, not all behaviors follow this trajectory, as there are instances in which children outperform young adults. This study aimed to reveal instances of childhood advantage in the domain of motor learning and memory consolidation. Using a visually cued serial reaction time task, data were acquired from 7-35 and >55-year-old participants (n=238 datasets) across two experiments that assessed initial encoding as well as memory consolidation over 5-hour and 24-hour offline periods. Results revealed comparable initial learning dynamics among age groups, but 7- to 12-year-old children exhibited smaller sequence-specific learning relative to adolescents (13-17 year-olds), young adults (18-35 year-olds) and older adults (> 55 years). Interestingly, children demonstrated the greatest performance gains in the 5-hour and 24-hour delayed retests, reflecting enhanced motor memory consolidation. These results suggest that children exhibit an advantage in the offline processing of recently learned motor sequences.

neuroscience↗

bioRxiv2022

The hippocampus binds movements to their temporal position in a motor sequence

A plethora of daily motor tasks consist of sequences of movements or steps that need to be performed in a specific order. Yet, it remains unclear how the brain represents sequential motor actions in a way that preserves their temporal order. Here, we used multivoxel pattern similarity analysis of functional Magnetic Resonance Imaging (fMRI) data acquired during motor sequence practice to investigate whether the hippocampus, a brain region known to support temporal order in the non-motor memory domain, represents information about the temporal order of sequential motor actions. We also examined such representation in other regions of the motor network (i.e., the premotor cortex (PMC), supplementary motor area (SMA), anterior superior parietal lobule (aSPL) and striatum) known for their critical role in motor sequence learning. Our results show that hippocampal activation patterns carried information about movements in their learned temporal position in the sequence (i.e., movement-position binding), but not about movements or positions in random movement patterns. In contrast, other ROIs showed evidence of binding in the sequence as well as movement (M1, SMA, PMC, putamen and aSPL) and position (aSPL and PMC) coding in random movement patterns. Importantly, movement coding contributed to sequence learning patterns in M1, SMA and PMC but not in the putamen and aSPL, suggesting a specific involvement of these regions in movement-position binding. Altogether, our findings provide novel insight into the role of the hippocampus in the motor memory domain and point to its capacity to bind movements to their temporal position in a motor sequence. Our results also deepen our understanding of how striatal and cortical regions contribute to motor sequence learning via movement coding or movement-position binding. Significance StatementConsistent evidence collected over the last two decades indicates that the hippocampus - a brain structure traditionally associated to declarative memory - is critically involved in motor memory. Yet, the functional role and representational contribution of the hippocampus during motor learning remains to be elucidated. Using a multivariate functional MRI approach, we show here that the hippocampus binds movements to their temporal position in a learned sequence of actions. These results point towards the involvement of the hippocampus in preserving information about temporal order in motor memory - a process well described for declarative memories. We suggest that the ability of the hippocampus to encode temporal order during sequence learning is common across declarative and non-declarative memory systems.

neuroscience↗

bioRxiv2022

Prefrontal stimulation disrupts motor memory consolidation at the micro timescale

Functional brain responses in hippocampo- and striato-cortical networks during initial motor sequence learning (MSL) are critical for memory consolidation. We have recently shown that prefrontal stimulation applied prior to initial MSL can alter these learning-related responses. In the present study, we investigated whether such stimulation-induced modulations of brain responses can influence motor memory consolidation at different timescales. Specifically, we examined the effect of prefrontal stimulation on the behavioral and neural responses associated to (i) fast consolidation processes occurring during short rest episodes interspersed with practice during initial learning (i.e., micro timescale) and (ii) slow consolidation process taking place across practice sessions separated by 24h (i.e., macro timescale). To do so, we applied active (inhibitory or facilitatory) or control theta-burst stimulation to the prefrontal cortex of young healthy participants before they were trained on an MSL task while their brain activity was recorded using functional magnetic resonance imaging (fMRI). Motor performance was retested, in the MRI scanner, after a night of sleep. Both our behavioral and brain imaging results indicate that while stimulation did not modulate consolidation at the macro timescale, it disrupted the micro-offline consolidation process. Specifically, our behavioral data indicate that active - as compared to control - stimulation resulted in a decrease in micro-offline gains in performance over the short rest intervals. At the brain level, stimulation disrupted activity in the caudate nucleus and the hippocampus during the micro-offline intervals. Additionally, multivariate pattern persistence from task into inter-practice rest episodes - which is thought to reflect the reactivation of learning-related patterns - was hindered by active prefrontal stimulation in the hippocampus and caudate nucleus. Importantly, stimulation also altered the link between the brain and the behavioral markers of the micro-offline consolidation process. These results collectively suggest that active prefrontal stimulation prior to MSL disrupted both the behavioral and neural correlates of motor memory consolidation at the micro timescale.

neuroscience↗

bioRxiv2022

Electrophysiological signatures of targeted memory reactivation during sleep are not accompanied by motor performance improvements in older adults

Targeted memory reactivation (TMR) during sleep enhances memory consolidation in young adults by modulating electrophysiological markers of neuroplasticity. Interestingly, older adults exhibit deficits in motor memory consolidation, an impairment that has been linked to age-related degradations in the same sleep features sensitive to TMR. We hypothesized that TMR would enhance consolidation in older adults via the modulation of these markers. Seventeen older participants were trained on a motor task involving two auditory-cued sequences. During a post-learning nap, two auditory cues were played: one associated to a learned (i.e., reactivated) sequence and one control. Performance during two delayed retests did not differ between reactivated and non-reactivated sequences. Moreover, both associated and control sounds modulated brain responses, yet there were no consistent differences between the auditory cue types. Our results collectively demonstrate that older adults do not benefit from specific reactivation of a motor memory trace by an associated auditory cue during post-learning sleep. It is possible, however, that auditory stimulation during post-learning sleep boosts motor memory consolidation in a non-specific manner.

neuroscience↗

bioRxiv2022

Timing of Transcranial Direct Current Stimulation at M1 Does Not Affect Motor Sequence Learning

Administering anodal tDCS at the primary motor cortex (M1) at various temporal loci relative to motor training is reported to affect subsequent performance gains. Stimulation administered in conjunction with motor training appears to offer the most robust benefit that emerges during offline epochs. This conclusion is made, however, based on between-experiment comparisons that involved varied methodologies. The present experiment addressed this shortcoming by administering the same 15-minute dose of anodal tDCS at M1 before, during, or after practice of a serial reaction time task (SRTT). It was anticipated that exogenous stimulation during practice with a novel SRTT would facilitate offline gains. Ninety participants were randomly assigned to one of four groups: tDCS before practice, tDCS during practice, tDCS after practice, or no tDCS. Each participant was exposed to 15 minutes of 2 mA of tDCS and motor training of an eight-element SRTT. The anode was placed at right M1 with the cathode at left M1, and the left hand was used to execute the SRTT. Test blocks were administered 1 and 24 hours after practice concluded. The results revealed significant offline gain for all conditions at the 1-hour and 24-hour test blocks. Importantly, exposure to anodal tDCS at M1 at any point before, during, or after motor training failed to change the trajectory of skill development as compared to the no stimulation control condition. These data add to the growing body of evidence questioning the efficacy of exogenous stimulation as an adjunct to motor training for fostering skill learning. HighlightsO_LITime-dependent consolidation of a novel motor skill occurred within 1 hour after the first practice block C_LIO_LIFurther consolidation of this memory still occurred 24 hours after practice C_LIO_LItDCS at M1 before, during, or after the initial bout of practice did not modify online or offline performance gains C_LI

neuroscience↗

bioRxiv2022

Drug-induced adaptation along a resistance continuum in cancer cells

Advancements in rational drug design over the past decades have consistently produced new cancer therapies, but such treatments are inevitably countered through an adaptive process that fosters therapy resistance. Malignant cells achieve drug resistance through intrinsic and acquired mechanisms, rooted in genetic and non-genetic determinants. In particular, recent work has highlighted the role of intrinsic cellular heterogeneity in the emergence of transient drug-tolerant persister cells that survive drug treatment, as well as non-genetically driven cell plasticity toward stable resistance. However, these models do not account for the role of dose and treatment duration as extrinsic forces in eliciting cancer cell adaptation. Here, we show that these two components together drive the resistance of ovarian cancer cells to targeted therapy along a trajectory of cellular adaptation, that we denote the resistance continuum. We report that gradual dose exposure and prolonged treatment promote a continuous increase in fitness, and show that this process is mediated by evolving transcriptional, epigenetic and genetic changes that promote multiple cell state transitions. The resistance continuum is underpinned by the assembly of gene expression programs and epigenetically reinforced stress response regulation. Using both in vivo and in vitro models, we found that this process involves widespread reprogramming of cell survival pathways, including interferon response, lineage reprogramming, metabolic rewiring and oxidative stress regulation. Together, the resistance continuum reveals the dynamic nature of cellular adaptation, and carries implications for cancer therapies, as initial exposure to lower doses primes cells over time for increased resistance to higher doses. Beyond cancer, such continuous adaptation exposes a basic aspect of cellular plasticity, which may also be deployed in other biological systems such as development, immune response and host-pathogen interactions.

cancer biology↗

bioRxiv2022

Sleep does not influence schema-facilitated motor memory consolidation

Study ObjectivesNovel information is rapidly learned when it is compatible with previous knowledge. This "schema" effect, initially described for declarative memories, was recently extended to the motor memory domain. Importantly, this beneficial effect was only observed 24 hours - but not immediately - following motor schema acquisition. Given the established role of sleep in memory consolidation, we hypothesized that sleep following the initial learning of a schema is necessary for the subsequent rapid integration of novel motor information. MethodsTwo experiments were conducted to investigate the effect of diurnal and nocturnal sleep on schema-mediated motor sequence memory consolidation. In Experiment 1, participants first learned an 8-element motor sequence through repeated practice (Session 1). They were then afforded a 90-minute nap opportunity (N=25) or remained awake (N=25) before learning a second motor sequence (Session 2) which was highly compatible with that learned prior to the sleep/wake interval. Experiment 2 was similar; however, Sessions 1 and 2 were separated by a 12-hour interval that included nocturnal sleep (N=28) or only wakefulness (N=29). ResultsFor both experiments, we found no group differences in motor sequence performance (reaction time and accuracy) following the sleep/wake interval. Furthermore, in Experiment 1, we found no correlation between sleep features (non-REM sleep duration, spindle and slow wave activity) and post-sleep behavioral performance. ConclusionsThe results of this research suggest that integration of novel motor information into a cognitive-motor schema does not specifically benefit from post-learning sleep.

neuroscience↗

bioRxiv2021

Sigma Oscillations Protect or Reinstate Motor Memory Depending on their Temporal Coordination with Slow Waves

Targeted memory reactivation (TMR) during post-learning sleep is known to enhance motor memory consolidation but the underlying neurophysiological processes remain unclear. Here, we confirm the beneficial effect of auditory TMR on motor performance. At the neural level, TMR enhanced slow wave (SW) characteristics. Additionally, greater TMR-related phase-amplitude coupling between slow (0.5-2 Hz) and sigma (12-16 Hz) oscillations after the SW peak was related to higher TMR effect on performance. Importantly, sounds that were not associated to learning strengthened SW-sigma coupling at the SW trough and the increase in sigma power nested in the trough of the potential evoked by these unassociated sounds was related to the TMR benefit. Altogether, our data suggest that, depending on their precise temporal coordination during post learning sleep, slow and sigma oscillations play a crucial role in either memory reinstatement or protection against irrelevant information; two processes that critically contribute to motor memory consolidation.

neuroscience↗

bioRxiv2021

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

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.

neuroscience↗

bioRxiv2021

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

Memory consolidation, the process by which newly encoded and fragile memories become more robust, is thought to be supported by the reactivation of brain regions - including the hippocampus - during post-learning rest. While hippocampal reactivations have been demonstrated in humans in the declarative memory domain, it remains unknown whether such a process takes place after motor learning. Using multivariate analyses of task-related and resting state fMRI data, here we show that patterns of brain activity within both the hippocampus and striatum elicited during motor learning persist into post-learning rest, indicative of reactivation of learning-related neural activity patterns. Moreover, results indicate that hippocampal reactivation reflects the spatial representation of the learned motor sequence. These results thus provide insights into the functional significance of neural reactivation after motor sequence learning.

neuroscience↗