Interactions between the aging brain and motor task complexity across the lifespan: balancing brain activity resource demand and supply.

The Compensation Related Utilization of Neural Circuits Hypothesis (CRUNCH) proposes a framework for understanding task-related brain activity changes as a function of healthy aging and task complexity. Specifically, it affords the following predictions: (i) all adult age groups display more brain activation with increases in task complexity, (ii) older adults show more brain activation compared with younger adults at low task complexity levels, and (iii) disproportionately increase brain activation with increased task complexity, but (iv) show smaller (or no) increases in brain activation at the highest complexity levels. To test these hypotheses, performance on a bimanual tracking task at 4 complexity levels and associated brain activation were assessed in 3 age groups (20-40, 40-60, and 60-80 years, n = 99). All age groups showed decreased tracking accuracy and increased brain activation with increased task complexity, with larger performance decrements and activation increases in the older age groups. Older adults exhibited increased brain activation at a lower complexity level, but not the predicted failure to further increase brain activity at the highest complexity level. We conclude that older adults show more brain activation than younger adults and preserve the capacity to deploy increased neural resources as a function of task demand.

Representational similarity scores of digits in the sensorimotor cortex are associated with behavioral performance.

Previous studies aimed to unravel a digit-specific somatotopy in the primary sensorimotor (SM1) cortex. However, it remains unknown whether digit somatotopy is associated with motor preparation and/or motor execution during different types of tasks. We adopted multivariate representational similarity analysis to explore digit activation patterns in response to a finger tapping task (FTT). Sixteen healthy young adults underwent magnetic resonance imaging, and additionally performed an out-of-scanner choice reaction time task (CRTT) to assess digit selection performance. During both the FTT and CRTT, force data of all digits were acquired using force transducers. This allowed us to assess execution-related interference (i.e., digit enslavement; obtained from FTT & CRTT), as well as planning-related interference (i.e., digit selection deficit; obtained from CRTT) and determine their correlation with digit representational similarity scores of SM1. Findings revealed that digit enslavement during FTT was associated with contralateral SM1 representational similarity scores. During the CRTT, digit enslavement of both hands was also associated with representational similarity scores of the contralateral SM1. In addition, right hand digit selection performance was associated with representational similarity scores of left S1. In conclusion, we demonstrate a cortical origin of digit enslavement, and uniquely reveal that digit selection is associated with digit representations in primary somatosensory cortex (S1). Significance statement In current systems neuroscience, it is of critical importance to understand the relationship between brain function and behavioral outcome. With the present work, we contribute significantly to this understanding by uniquely assessing how digit representations in the sensorimotor cortex are associated with planning- and execution-related digit interference during a continuous finger tapping and a choice reaction time task. We observe that digit enslavement (i.e., execution-related interference) finds its origin in contralateral digit representations of SM1, and that deficits in digit selection (i.e., planning-related interference) in the right hand during a choice reaction time task are associated with more overlapping digit representations in left S1. This knowledge sheds new light on the functional contribution of the sensorimotor cortex to everyday motor skills.

Network-specific differences in transient brain activity at rest are associated with age-related reductions in motor performance.

Multiple functional changes occur in the brain with increasing age. Among those, older adults typically display more restricted fluctuations of brain activity, both during resting-state and task execution. These altered dynamic patterns have been linked to reduced task performance across multiple behavioral domains. Windowed functional connectivity, which is typically employed in the study of connectivity dynamics, however, might not be able to properly characterize moment-to-moment variations of individual networks. In the present study, we used innovation-driven co-activation patterns (ICAP) to overcome this limitation and investigate the length (duration) and frequency (innovation) in which various brain networks emerged across the adult lifespan (N= 92) during a resting-state period. We identified a link between increasing age and a tendency to engage brain areas with distinct functional associations simultaneously as a single network. The emergence of isolated and spatially well-defined visual, motor, frontoparietal, and posterior networks decreased with increased age. This reduction in dynamics of specialized networks mediated age-related performance decreases (i.e., increases in interlimb interference) in a bimanual motor task. Altogether, our findings demonstrated that older compared to younger adults tend to activate fewer network configurations, which include multiple functionally distinct brain areas. The reduction in independent emergence of functionally well-defined and task-relevant networks may reflect an expression of brain dedifferentiation and is likely associated with functional modulatory deficits, negatively impacting motor behavior.

Stress Modulates the Balance between Hippocampal and Motor Networks during Motor Memory Processing.

The functional interaction between hippocampo- and striato-cortical regions during motor sequence learning is essential to trigger optimal memory consolidation. Based on previous evidence from other memory domains that stress alters the balance between these systems, we investigated whether exposure to stress prior to motor learning modulates motor memory processes. Seventy-two healthy young individuals were exposed to a stressful or nonstressful control intervention prior to training on a motor sequence learning task in a magnetic resonance imaging (MRI) scanner. Consolidation was assessed with an MRI retest after a sleep episode. Behavioral results indicate that stress prior to learning did not influence motor performance. At the neural level, stress induced both a larger recruitment of sensorimotor regions and a greater disengagement of hippocampo-cortical networks during training. Brain-behavior regression analyses showed that while this stress-induced shift from (hippocampo-)fronto-parietal to motor networks was beneficial for initial performance, it was detrimental for consolidation. Our results provide the first experimental evidence that stress modulates the neural networks recruited during motor memory processing and therefore effectively unify concepts and mechanisms from diverse memory fields. Critically, our findings suggest that intersubject variability in brain responses to stress determines the impact of stress on motor learning and subsequent consolidation.

Indices of callosal axonal density and radius from diffusion MRI relate to upper and lower limb motor performance.

Understanding the relationship between human brain structure and functional outcome is of critical importance in systems neuroscience. Diffusion MRI (dMRI) studies show that fractional anisotropy (FA) is predictive of motor control, underscoring the importance of white matter (WM). However, as FA is a surrogate marker of WM, we aim to shed new light on the structural underpinnings of this relationship by applying a multi-compartment microstructure model providing axonal density/radius indices. Sixteen young adults (7 males / 9 females), performed a hand/foot tapping task and a Multi Limb Reaction Time task. Furthermore, diffusion (STEAM &HARDI) and fMRI (localizer hand/foot activations) data were obtained. Sphere ROIs were placed on activation clusters with highest t value to guide interhemispheric WM tractography. Axonal radius/density indices of callosal parts intersecting with tractography were calculated from STEAM, using the diffusion-time dependent AxCaliber model, and correlated with behavior. Results indicated a possible association between larger apparent axonal radii of callosal motor fibers of the hand and higher tapping scores of both hands, and faster selection-related processing (normalized reaction) times (RTs) on diagonal limb combinations. Additionally, a trend was present for faster selection-related processing (normalized reaction) times for lower limbs being related with higher axonal density of callosal foot motor fibers, and for higher FA values of callosal motor fibers in general being related with better tapping and faster selection-related processing (normalized reaction) times. Whereas FA is sensitive in demonstrating associations with motor behavior, axon radius/density (i.e., fiber geometry) measures are promising to explain the physiological source behind the observed FA changes, contributing to deeper insights into brain-behavior interactions.

Task-related measures of short-interval intracortical inhibition and GABA levels in healthy young and older adults: A multimodal TMS-MRS study.

Establishing the associations between magnetic resonance spectroscopy (MRS)-assessed gamma-aminobutyric acid (GABA) levels and transcranial magnetic stimulation (TMS)-derived 'task-related' modulations in GABAA receptor-mediated inhibition and how these associations change with advancing age is a topic of interest in the field of human neuroscience. In this study, we identified the relationship between GABA levels and task-related modulations in GABAA receptor-mediated inhibition in the dominant (left) and non-dominant (right) sensorimotor (SM) cortices. GABA levels were measured using edited MRS and task-related GABAA receptor-mediated inhibition was measured using a short-interval intracortical inhibition (SICI) TMS protocol during the preparation and premotor period of a choice reaction time (CRT) task in 25 young (aged 18-33 years) and 25 older (aged 60-74 years) adults. Our results demonstrated that GABA levels in both SM voxels were lower in older adults as compared to younger adults; and higher SM GABA levels in the dominant as compared to the non-dominant SM voxel pointed to a lateralization effect, irrespective of age group. Furthermore, older adults showed decreased GABAA receptor-mediated inhibition in the preparation phase of the CRT task within the dominant primary motor cortex (M1), as compared to young adults. Finally, results from an exploratory correlation analysis pointed towards positive relationships between MRS-assessed GABA levels and TMS-derived task-related SICI measures. However, after correction for multiple comparisons none of the correlations remained significant.

Age-related differences in network flexibility and segregation at rest and during motor performance.

Brain networks undergo widespread changes in older age. A large body of knowledge gathered about those changes evidenced an increase of functional connectivity between brain networks. Previous work focused mainly on cortical networks during the resting state. Subcortical structures, however, are of critical importance during the performance of motor tasks. In this study, we investigated age-related changes in cortical, striatal and cerebellar functional connectivity at rest and its modulation by motor task execution. To that end, functional MRI from twenty-five young (mean age 21.5 years) and eighteen older adults (mean age 68.6 years) were analysed during rest and while performing a bimanual tracking task practiced over a two-week period. We found that inter-network connectivity among cortical structures was more positive in older adults both during rest and task performance. Functional connectivity within striatal structures decreased with age during rest and task execution. Network flexibility, the changes in network composition from rest to task, was also reduced in older adults, but only in networks with an age-related increase in connectivity. Finally, flexibility of areas in the prefrontal cortex were associated with lower error scores during task execution, especially in older adults. In conclusion, our findings indicate an age-related reduction in the ability to suppress irrelevant network communication, leading to less segregated and less flexible cortical networks. At the same time, striatal connectivity is impaired in older adults, while cerebellar connectivity shows heterogeneous age-related effects during rest and task execution. Future research is needed to clarify how cortical and subcortical connectivity changes relate to one another.

Age-Related Declines in Motor Performance are Associated With Decreased Segregation of Large-Scale Resting State Brain Networks.

Aging is typically associated with substantial declines in motor functioning as well as robust changes in the functional organization of brain networks. Previous research has investigated the link between these 2 age-varying factors but examinations were predominantly limited to the functional organization within motor-related brain networks. Little is known about the relationship between age-related behavioral impairments and changes in functional organization at the whole brain (i.e., multiple network) level. This knowledge gap is surprising given that the decreased segregation of brain networks (i.e., increased internetwork connectivity) can be considered a hallmark of the aging process. Accordingly, we investigated the association between declines in motor performance across the adult lifespan (20-75 years) and age-related modulations of functional connectivity within and between resting state networks. Results indicated that stronger internetwork resting state connectivity observed as a function of age was significantly related to worse motor performance. Moreover, performance had a significantly stronger association with the strength of internetwork as compared with intranetwork connectivity, including connectivity within motor networks. These findings suggest that age-related declines in motor performance may be attributed to a breakdown in the functional organization of large-scale brain networks rather than simply age-related connectivity changes within motor-related networks.

Coordinative task difficulty and behavioural errors are associated with increased long-range beta band synchronization.

The neural network and the task-dependence of (local) activity changes involved in bimanual coordination are well documented. However, much less is known about the functional connectivity within this neural network and its modulation according to manipulations of task complexity. Here, we assessed neural activity via high-density electroencephalography, focussing on changes of activity in the beta frequency band (~15-30Hz) across the motor network in 26 young adult participants (19-29 years old). We investigated how network connectivity was modulated with task difficulty and errors of performance during a bimanual visuomotor movement consisting of dial rotation according to three different ratios of speed: an isofrequency movement (1:1), a non-isofrequency movement with the right hand keeping the fast pace (1:3), and the converse ratio with the left hand keeping the fast pace (3:1). To quantify functional coupling, we determined neural synchronization which might be key for the timing of the activity within brain regions during task execution. Individual source activity with realistic head models was reconstructed at seven regions of interest including frontal and parietal areas, among which we estimated phase-based connectivity. Partial least squares analysis revealed a significant modulation of connectivity with task difficulty, and significant correlations between connectivity and errors in performance, in particular between sensorimotor cortices. Our findings suggest that modulation of long-range synchronization is instrumental for coping with increasing task demands in bimanual coordination.

The neural correlates of upper limb motor blocks in Parkinson's disease and their relation to freezing of gait.

Due to basal ganglia dysfunction, bimanual motor performance in Parkinson patients reportedly relies on compensatory brain activation in premotor-parietal-cerebellar circuitries. A subgroup of Parkinson's disease (PD) patients with freezing of gait (FOG) may exhibit greater bimanual impairments up to the point that motor blocks occur. This study investigated the neural mechanisms of upper limb motor blocks and explored their relation with FOG. Brain activation was measured using functional magnetic resonance imaging during bilateral finger movements in 16 PD with FOG, 16 without FOG (PD + FOG and PD - FOG), and 16 controls. During successful movement, PD + FOG showed decreased activation in right dorsolateral prefrontal cortex (PFC), left dorsal premotor cortex (PMd), as well as left M1 and bilaterally increased activation in dorsal putamen, pallidum, as well as subthalamic nucleus compared with PD - FOG and controls. On the contrary, upper limb motor blocks were associated with increased activation in right M1, PMd, supplementary motor area, and left PFC compared with successful movement, whereas bilateral pallidum and putamen activity was decreased. Complex striatofrontal activation changes may be involved in the difficulties of PD + FOG to perform bimanual movements, or sequential movements in general. These novel results suggest that, whatever the exact underlying cause, PD + FOG seem to have reached a saturation point of normal neural compensation and respond belatedly to actual movement breakdown.

Motor learning-induced changes in functional brain connectivity as revealed by means of graph-theoretical network analysis.

Complex bimanual motor learning causes specific changes in activation across brain regions. However, there is little information on how motor learning changes the functional connectivity between these regions, and whether this is influenced by different sensory feedback modalities. We applied graph-theoretical network analysis (GTNA) to examine functional networks based on motor-task-related fMRI activations. Two groups learned a complex 90° out-of-phase bimanual coordination pattern, receiving either visual or auditory feedback. 3T fMRI scanning occurred before (day 0) and after (day 5) training. In both groups, improved motor performance coincided with increased functional network connectivity (increased clustering coefficients, higher number of network connections and increased connection strength, and shorter communication distances). Day×feedback interactions were absent but, when examining network metrics across all examined brain regions, the visual group had a marginally better connectivity, higher connection strength, and more direct communication pathways. Removal of feedback had no acute effect on the functional connectivity of the trained networks. Hub analyses showed an importance of specific brain regions not apparent in the standard fMRI analyses. These findings indicate that GTNA can make unique contributions to the examination of functional brain connectivity in motor learning.

Specific cerebellar regions are related to force amplitude and rate of force development.

The human cerebellum has been implicated in the control of a wide variety of motor control parameters, such as force amplitude, movement extent, and movement velocity. These parameters often covary in both movement and isometric force production tasks, so it is difficult to resolve whether specific regions of the cerebellum relate to specific parameters. In order to address this issue, the current study used two experiments and SUIT normalization to determine whether BOLD activation in the cerebellum scales with the amplitude or rate of change of isometric force production or both. In the first experiment, subjects produced isometric pinch-grip force over a range of force amplitudes without any constraints on the rate of force development. In the second experiment, subjects varied the rate of force production, but the target force amplitude remained constant. The data demonstrate that BOLD activation in separate sub-areas of cerebellar regions lobule VI and Crus I/II scales with both force amplitude and force rate. In addition, BOLD activation in cerebellar lobule V and vermis VI was specific to force amplitude, whereas BOLD activation in lobule VIIb was specific to force rate. Overall, cerebellar activity related to force amplitude was located superior and medial, whereas activity related to force rate was inferior and lateral. These findings suggest that specific circuitry in the cerebellum may be dedicated to specific motor control parameters such as force amplitude and force rate.

Shared neural resources between left and right interlimb coordination skills: the neural substrate of abstract motor representations.

Functional magnetic resonance imaging was used to reveal the shared neural resources between movements performed with effectors of the left versus right body side. Prior to scanning, subjects extensively practiced a complex coordination pattern involving cyclical motions of the ipsilateral hand and foot according to a 90 degrees out-of-phase coordination mode. Brain activity associated with this (nonpreferred) coordination pattern was contrasted with pre-existing isodirectional (preferred) coordination to extract the learning-related brain networks. To identify the principal candidates for effector-independent movement encoding, the conjunction of training-related activity for left and right limb coordination was determined. A dominantly left-lateralized parietal-to-(pre)motor activation network was identified, with activation in inferior and superior parietal cortex extending into intraparietal sulcus and activation in the premotor areas, including inferior frontal gyrus (pars opercularis). Similar areas were previously identified during observation of complex coordination skills by expert performers. These parietal-premotor areas are principal candidates for abstract (effector-independent) movement encoding, promoting motor equivalence, and they form the highest level in the action representation hierarchy.

Neural correlates of motor dysfunction in children with traumatic brain injury: exploration of compensatory recruitment patterns.

Traumatic brain injury (TBI) is a common form of disability in children. Persistent deficits in motor control have been documented following TBI but there has been less emphasis on changes in functional cerebral activity. In the present study, children with moderate to severe TBI (n = 9) and controls (n = 17) were scanned while performing cyclical movements with their dominant and non-dominant hand and foot according to the easy isodirectional (same direction) and more difficult non-isodirectional (opposite direction) mode. Even though the children with TBI were shown to be less successful on various items of a clinical motor test battery than the control group, performance on the coordination task during scanning was similar between groups, allowing a meaningful interpretation of their brain activation differences. fMRI analysis revealed that the TBI children showed enhanced activity in medial and anterior parietal areas as well as posterior cerebellum as compared with the control group. Brain activation generally increased during the non-isodirectional as compared with the isodirectional mode and additional regions were involved, consistent with their differential degree of difficulty. However, this effect did not interact with group. Overall, the findings indicate that motor impairment in TBI children is associated with changes in functional cerebral activity, i.e. they exhibit compensatory activation reflecting increased recruitment of neural resources for attentional deployment and somatosensory processing.

Deficits in executed and imagined aiming performance in brain-injured children.

Motor disorders are a frequent consequence of acquired brain injury (ABI) in children and much effort is currently invested in alleviating these deficits. The aim of the present study was to test motor imagery (MI) capabilities in children with ABI (n=25) and an age- and gender-matched control group (n=25). A computerized Virtual Radial Fitts Task (VRFT) was used to investigate the speed-accuracy trade-offs (or Fitts' law) that occur as target size is varied for both executed and imagined performance. In the control group, the speed for accuracy trade-off for both executed and imagined performance conformed to Fitts' law. In the ABI group, only executed movements conformed to Fitts' law. These findings suggest that children with ABI show an inferior ability to imagine the time needed to complete goal-directed movements with differential difficulty levels.

Directional constraints during bimanual coordination: the interplay between intrinsic and extrinsic directions as revealed by head motions.

The role of directional compatibility was investigated during the production of in-phase and anti-phase coordination patterns involving both arms as well as the head. Our first aim was to compare the quality of coordination between both arms when symmetrical arm posture manipulations were used to disentangle muscle homology from the mutual direction of limb motions in extrinsic space. Findings revealed that in-phase coordination, characterized by the simultaneous activation of homologous muscle groups, was resistant to posture manipulations. Conversely, during anti-phase coordination, the influence of extrinsic direction became more prevalent whereby isodirectionality in extrinsic space contributed to stabilization of anti-phase coordination patterns. The second aim was to study the effect of periodic head movements upon the assembling of a coordinative synergy among the body segments. The findings demonstrated that the in-phase patterns were hardly affected by directionality of head motion. Conversely, the anti-phase patterns were more vulnerable to the directional influence of head movements, showing less accurate and stable coordination during non-isodirectional than isodirectional head motions. These observations underscore the robust nature of coordination patterns based on muscle homology, even in the absence of symmetric arm positions. Moreover, isodirectional head movements became easily integrated with the overall coordination pattern, whereas head-limb coupling was poor when the head moved anti-directional with the limbs.

Posture control and complex arm coordination: analysis of multijoint coordinative movements and stability of stance.

The authors addressed the interactions between control of bimanual multijoint coordination tasks and posture. Participants (N = 6) performed 8 coordination patterns that differed in degree of complexity by using their bilateral elbows and wrists under 3 scaled motion speeds while standing on 2 force plates. Results indicated that producing complex bimanual multijoint coordinative tasks affected postural sway, thus resulting in an increase of sway activity. Behavioral as well as mechanical factors accounted for the increased disturbance in postural sway. Those findings suggest that performing complex coordination tasks disrupts postural control in normal young adults.

Symmetry constraints mediate the learning and transfer of bimanual coordination patterns across planes of motion.

The authors investigated whether neuromuscular and directional constraints are dissociable limitations that affect learning and transfer of a bimanual coordination pattern. Participants (N = 9) practiced a 45 degrees muscular relative phasing pattern in the transverse plane over 4 days. The corresponding to-be-learned spatial relative phasing was 225 degrees. Before, during, and following practice, the authors administered probe tests in the sagittal plane to assess transfer of learning. In the probe tests, participants performed various patterns characterized by different muscular and spatial relative phasing (45 degrees, 45 degrees, 45 degrees, 225 degrees, 225 degrees, 45 degrees, and 225 degrees, 225 degrees). The acquisition of the to-be-learned pattern in the transverse plane resulted in spontaneous positive transfer of learning only to coordination patterns having 45 degrees of spatial relative phase, irrespective of muscular phasing. Moreover, transfer occurred in the sagittal plane to coordination patterns that had symmetry properties similar to those of the to-be-learned pattern. The authors conclude that learning and transfer of spatial features of coordination patterns from the transverse to the sagittal plane of motion are mediated by mirror-symmetry constraints.

The advantage of cyclic over discrete movements remains evident following changes in load and amplitude.

Previous studies suggested that the advantage in speed accuracy trade-off of cyclic over discrete aiming tasks with the upper limbs may be associated with the operation of spinal neural oscillators, as in locomotion. Similar to the locomotor rhythm that is fairly robust and can accommodate changes in loading or stride length, we predicted that cyclic aiming tasks would be equally resistant to changes in load or amplitude, thereby preserving the advantage over discrete tasks. To test the hypothesis, cyclic and discrete aiming movements were performed with and without loading of the hand. Furthermore a "complex" condition was introduced in which the distance between the targets that the participants moved to alternated between 2.5 and 5 cm. In all cases, two target sizes were used to test spatial accuracy and to be able to calculate the Index of Performance (IP). Findings revealed that even though part of the advantage of the cyclic over the discrete regime was lost during the complex movement pattern and with addition of weight, the former remained superior to the latter. Furthermore, adding weight did not change the oscillation frequency in the cyclic movements. It is concluded that the superiority of cyclic movements over discrete ones is fairly robust, consistent with the high degree of flexibility that is typically observed in neural oscillators.

The role of directional compatibility in assembling coordination patterns involving the upper and lower limb girdles and the head.

The role of directional compatibility was investigated during the production of in-phase and anti-phase coordination patterns involving the four limbs as well as the head. Our first aim was to compare the quality of interlimb coordination between concordant and discordant coordination patterns across girdles at different cycling frequencies. Concordant implied adoption of either the in-phase or anti-phase coordination mode across both girdles whereas discordant implied a combination of both modes. The second aim was to study the effect of periodic head movements upon the assembling of a coordinative synergy among the limbs. Findings revealed that concordant coordination modes were produced with higher accuracy and consistency than discordant coordination modes and this effect was more distinct at higher cycling frequencies. Inclusion of head movements was found to destabilize in-phase coordination but stabilize anti-phase coordination patterns, particularly during discordant conditions at higher cycling frequencies. This observation contrasts with previous findings in which anti-phase modes have invariably been shown to be more vulnerable to experimental perturbations than in-phase modes. The findings are discussed within the context of the coalition of egocentric and allocentric constraints during multilimb coordination and the role of direction as an organizing principle in movement control.