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.

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.

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.

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.

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.

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.

Understanding bimanual coordination across small time scales from an electrophysiological perspective.

Bimanual movement involves a variety of coordinated functions, ranging from elementary patterns that are performed automatically to complex patterns that require practice to be performed skillfully. The neural dynamics accompanying these coordination patterns are complex and rapid. By means of electro- and magneto-encephalographic approaches, it has been possible to examine these dynamics during bimanual coordination with excellent temporal resolution, which complements other neuroimaging modalities with superb spatial resolution. This review focuses on EEG/MEG studies that unravel the processes involved in movement planning and execution, motor learning, and executive functions involved in task switching and dual tasking. Evidence is presented for a spatio-temporal reorganization of the neural networks within and between hemispheres to meet increased task difficulty demands, induced or spontaneous switches in coordination mode, or training-induced neuroplastic modulation in coordination dynamics. Future theoretical developments will benefit from the integration of research techniques unraveling neural activity at different time scales. Ultimately this work will contribute to a better understanding of how the human brain orchestrates complex behavior via the implementation of inter- and intra-hemispheric coordination networks.

Interactions between brain structure and behavior: the corpus callosum and bimanual coordination.

Bimanual coordination skills are required for countless everyday activities, such as typing, preparing food, and driving. The corpus callosum (CC) is the major collection of white matter bundles connecting both hemispheres that enables the coordination between the two sides of the body. Principal evidence for this brain-behavior relationship in humans was first provided by research on callosotomy patients, showing that sectioning (parts of) the CC affected interactions between both hands directly. Later, new noninvasive in vivo imaging techniques, such as diffusion tensor imaging, have energized the study of the link between microstructural properties of the CC and bimanual performance in normal volunteers. Here we discuss the principal factors (such as age, pathology and training) that mediate the relationship between specific bimanual functions and distinct anatomical CC subdivisions. More specifically, the question is whether different bimanual task characteristics can be mapped onto functionally distinct CC subregions. We review the current status of this mapping endeavor, and propose future perspectives to inspire research on this unique link between brain structure and behavior.

The effects of dual tasking on handwriting in patients with Parkinson's disease.

Previous studies have shown that patients with Parkinson's disease (PD) experience extensive problems during dual tasking. Up to now, dual-task interference in PD has mainly been investigated in the context of gait research. However, the simultaneous performance of two different tasks is also a prerequisite to efficiently perform many other tasks in daily life, including upper limb tasks. To address this issue, this study investigated the effect of a secondary cognitive task on the performance of handwriting in patients with PD. Eighteen PD patients and 11 age-matched controls performed a writing task involving the production of repetitive loops under single- and dual-task conditions. The secondary task consisted of counting high and low tones during writing. The writing tests were performed with two amplitudes (0.6 and 1.0cm) using a writing tablet. Results showed that dual-task performance was affected in PD patients versus controls. Dual tasking reduced writing amplitude in PD patients, but not in healthy controls (p=0.046). Patients' writing size was mainly reduced during the small-amplitude condition (small amplitude p=0.017; large amplitude p=0.310). This suggests that the control of writing at small amplitudes requires more compensational brain-processing recourses in PD and is as such less automatic than writing at large amplitudes. In addition, there was a larger dual-task effect on the secondary task in PD patients than controls (p=0.025). The writing tests on the writing tablet proved highly correlated to daily life writing as measured by the 'Systematic Screening of Handwriting Difficulties' test (SOS-test) and other manual dexterity tasks, particularly during dual-task conditions. Taken together, these results provide additional insights into the motor control of handwriting and the effects of dual tasking during upper limb movements in patients with PD.

Arm sway holds sway: locomotor-like modulation of leg reflexes when arms swing in alternation.

It has been argued that arm movements are important during human gait because they affect leg activity due to neural coupling between arms and legs. Consequently, one would expect that locomotor-like alternating arm swing is more effective than in-phase swing in affecting the legs' motor output. Other alternating movements such as trunk rotation associated to arm swing could also affect leg reflexes. Here, we assessed how locomotor-like movement patterns would affect soleus H-reflexes in 13 subjects performing arm swing in the sagittal plane (ipsilateral, contralateral and bilateral in-phase versus locomotor-like anti-phase arm movements) and trunk rotation with the legs stationary, and leg stepping with the arms stationary. Findings revealed that soleus H-reflexes were suppressed for all arm, trunk or leg movements. However, a marked reflex modulation occurred during locomotor-like anti-phase arm swing, as was also the case during leg stepping, and this modulation flattened out during in-phase arm swing. This modulation had a peculiar bell shape and showed maximum suppression at a moment where the heel-strike would occur during a normal walking cycle. Furthermore, this modulation was independent from electromyographic activity, suggesting a spinal processing at premotoneuronal level. Therefore, trunk movement can affect legs' output, and a special neural coupling occurs between arms and legs when arms move in alternation. This may have implications for gait rehabilitation.

Altered structural networks and executive deficits in traumatic brain injury patients.

Recent research on traumatic brain injury (TBI) has shown that impairments in cognitive and executive control functions are accompanied by a disrupted neural connectivity characterized by white matter damage. We constructed binary and weighted brain structural networks in 21 patients with chronic TBI and 17 healthy young adults utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. Executive function was assessed with the local global task and the trail making task, requiring inhibition, updating, and switching. The results revealed that TBI patients were less successful than controls on the executive tasks, as shown by the higher reaction times, higher switch costs, and lower accuracy rates. Moreover, both TBI patients and controls exhibited a small world topology in their white matter networks. More importantly, the TBI patients demonstrated increased shortest path length and decreased global efficiency of the structural network. These findings suggest that TBI patients have a weaker globally integrated structural brain network, resulting in a limited capacity to integrate information across brain regions. Furthermore, we showed that the white matter networks of both groups contained highly connected hub regions that were predominately located in the parietal cortex, frontal cortex, and basal ganglia. Finally, we showed significant correlations between switching performance and network property metrics within the TBI group. Specifically, lower scores on the switching tasks corresponded to a lower global efficiency. We conclude that analyzing the structural brain network connectivity provides new insights into understanding cognitive control changes following brain injury.

White matter organization in relation to upper limb motor control in healthy subjects: exploring the added value of diffusion kurtosis imaging.

Diffusion tensor imaging (DTI) characterizes white matter (WM) microstructure. In many brain regions, however, the assumption that the diffusion probability distribution is Gaussian may be invalid, even at low b values. Recently, diffusion kurtosis imaging (DKI) was suggested to more accurately estimate this distribution. We explored the added value of DKI in studying the relation between WM microstructure and upper limb coordination in healthy controls (N = 24). Performance on a complex bimanual tracking task was studied with respect to the conventional DTI measures (DKI or DTI derived) and kurtosis metrics of WM tracts/regions carrying efferent (motor) output from the brain, corpus callosum (CC) substructures and whole brain WM. For both estimation models, motor performance was associated with fractional anisotropy (FA) of the CC-genu, CC-body, the anterior limb of the internal capsule, and whole brain WM (r s range 0.42-0.63). Although DKI revealed higher mean, radial and axial diffusivity and lower FA than DTI (p < 0.001), the correlation coefficients were comparable. Finally, better motor performance was associated with increased mean and radial kurtosis and kurtosis anisotropy (r s range 0.43-0.55). In conclusion, DKI provided additional information, but did not show increased sensitivity to detect relations between WM microstructure and bimanual performance in healthy controls.

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.

Long-term TENS treatment decreases cortical motor representation in multiple sclerosis.

This study investigated the effects of a long-term transcutaneous electrical nerve stimulation (TENS) treatment on cortical motor representation in patients with multiple sclerosis (MS). In this double-blind crossover design, patients received either TENS or sham stimulation for 3 weeks (1h per day) on the median nerve region of the most impaired hand, followed by the other stimulation condition after a washout period of 6 months. Cortical motor representation was mapped using transcranial magnetic stimulation (TMS) at the baseline and after the 3-week stimulation protocol. Our results revealed that 3 weeks of daily stimulation with TENS significantly decreased the cortical motor representation of the stimulated muscle in MS patients. Although the mechanisms underlying this decrease remain unclear, our findings indicate that TENS has the ability to induce long-term reorganization in the motor cortex of MS patients.

Age-related neural correlates of cognitive task performance under increased postural load.

Behavioral studies suggest that postural control requires increased cognitive control and visuospatial processing with aging. Consequently, performance can decline when concurrently performing a postural and a demanding cognitive task. We aimed to identify the neural substrate underlying this effect. A demanding cognitive task, requiring visuospatial transformations, was performed with varying postural loads. More specifically, old and young subjects performed mental rotations of abstract figures in a seated position and when standing on a force platform. Additionally, functional magnetic resonance imaging (fMRI) was used to identify brain regions associated with mental rotation performance. Old as compared to young subjects showed increased blood oxygenation level-dependent (BOLD) responses in a frontoparietal network as well as activations in additional areas. Despite this overall increased activation, they could still modulate BOLD responses with increasing task complexity. Importantly, activity in left lingual gyrus was highly predictive (r = -0.83, adjusted R(2) = 0.65) of the older subjects' degree of success in mental rotation performance when shifting from a sitting to a standing position. More specifically, increased activation in this area was associated with better performance, once postural load increased.

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.