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1.  Transcallosal sensorimotor fiber tract structure-function relationships 
Human brain mapping  2011;34(2):384-395.
Recent studies have demonstrated neuroanatomically selective relationships between white matter tract microstructure, physiological function and task performance. Such findings suggest that the microstructure of transcallosal motor fibers may reflect the capacity for interhemispheric inhibition between the primary motor cortices, although full characterization of the transcallosal inhibitory sensorimotor network is lacking. Thus, the goal of the current study was to provide a comprehensive description of transcallosal fibers connecting homologous sensorimotor cortical regions and to identify the relationship(s) between fiber tract microstructure and interhemispheric inhibition during voluntary cortical activity. To this end, we assessed microstructure of fiber tracts connecting homologous sensorimotor regions of the cortex with diffusion tensor imaging. We also assessed interhemispheric inhibition by eliciting the ipsilateral silent period (iSP) within the same participants. We mapped mutually exclusive transcallosal connections between homologous sensorimotor regions and computed quantitative metrics of each fiber tract. Paralleling work in non-human primates we found the densest interhemispheric sensorimotor connections to be between the medial motor areas. Additionally, we provide a mid-sagittal callosal atlas in normalized MNI space for future studies to use when investigating callosal fiber tracts connecting primary and secondary sensorimotor cortices. Finally, we report a strong, positive relationship (r = 0.76) between strength of interhemispheric inhibition (iSP) and microstructure of interhemispheric fibers that is specific to tracts connecting the primary motor cortices. Thus, increased fiber microstructure in young adults predicts interhemispheric inhibitory capacity.
doi:10.1002/hbm.21437
PMCID: PMC3271163  PMID: 22042512
Corpus Callosum; Diffusion Tensor Imaging; Ipsilateral Silent Period; Interhemispheric Inhibition; Tractography
2.  Neurocognitive Contributions to Motor Skill Learning: The Role of Working Memory 
Journal of motor behavior  2012;44(6):445-453.
Researchers have begun to delineate the precise nature and neural correlates of the cognitive processes that contribute to motor skill learning. Here, we review recent work from our laboratory designed to further understand the neurocognitive mechanisms of skill acquisition. We have demonstrated an important role for spatial working memory in two different types of motor skill learning, sensorimotor adaptation and motor sequence learning. We have shown that individual differences in spatial working memory capacity predict the rate of motor learning for both sensorimotor adaptation and motor sequence learning. We have also reported neural overlap between a spatial working memory task and the early, but not late, stages of adaptation, particularly in the right dorsolateral prefrontal cortex and bilateral inferior parietal lobules. We propose that spatial working memory is relied upon for processing motor error information to update motor control for subsequent actions. Further, we suggest that working memory is relied upon during learning new action sequences for chunking individual action elements together.
doi:10.1080/00222895.2012.672348
PMCID: PMC3534841  PMID: 23237467
sequence learning; sensorimotor adaptation; working memory
3.  Differential Callosal Contributions to Bimanual Control in Young and Older Adults 
Journal of cognitive neuroscience  2010;23(9):10.1162/jocn.2010.21600.
Our recent work has shown that older adults are disproportionately impaired at bimanual tasks when the two hands are moving out of phase with each other [Bangert, A. S., Reuter-Lorenz, P. A., Walsh, C. M., Schachter, A. B., & Seidler, R. D. Bimanual coordination and aging: Neurobehavioral implications. Neuropsychologia, 48, 1165–1170, 2010]. Interhemispheric interactions play a key role during such bimanual movements to prevent interference from the opposite hemisphere. Declines in corpus callosum (CC) size and microstructure with advancing age have been well documented, but their contributions to age deficits in bimanual function have not been identified. In the current study, we used structural magnetic resonance and diffusion tensor imaging to investigate age-related changes in the relationships between callosal macrostructure, microstructure, and motor performance on tapping tasks requiring differing degrees of interhemispheric interaction. We found that older adults demonstrated disproportionately poorer performance on out-of-phase bimanual control, replicating our previous results. In addition, older adults had smaller anterior CC size and poorer white matter integrity in the callosal midbody than their younger counterparts. Surprisingly, larger CC size and better integrity of callosal microstructure in regions connecting sensorimotor cortices were associated with poorer motor performance on tasks requiring high levels of interhemispheric interaction in young adults. Conversely, in older adults, better performance on these tasks was associated with larger size and better CC microstructure integrity within the same callosal regions. These findings implicate age-related declines in callosal size and integrity as a key contributor to bimanual control deficits. Further, the differential age-related involvement of transcallosal pathways reported here raises new questions about the role of the CC in bimanual control.
doi:10.1162/jocn.2010.21600
PMCID: PMC3809031  PMID: 20954936
4.  The effects of working memory resource depletion and training on sensorimotor adaptation 
Behavioural Brain Research  2011;228(1):107-115.
We have recently demonstrated that visuospatial working memory performance predicts the rate of motor skill learning, particularly during the early phase of visuomotor adaptation. Here, we follow up these correlational findings with direct manipulations of working memory resources to determine the impact on visuomotor adaptation, a form of motor learning. We conducted two separate experiments. In the first one, we used a resource depletion strategy to investigate whether the rate of early visuomotor adaptation would be negatively affected by fatigue of spatial working memory resources. In the second study, we employed a dual n-back task training paradigm that has been shown to result in transfer effects [1] over five weeks to determine whether training-related improvements would boost the rate of early visuomotor adaptation. The depletion of spatial working memory resources negatively affected the rate of early visuomotor adaptation. However, enhancing working memory capacity via training did not lead to improved rates of visuomotor adaptation, suggesting that working memory capacity may not be the factor limiting maximal rate of visuomotor adaptation in young adults. These findings are discussed from a resource limitation / capacity framework with respect to current views of motor learning.
doi:10.1016/j.bbr.2011.11.040
PMCID: PMC3264800  PMID: 22155489
working memory; visuomotor adaptation; resource depletion; cognitive training
5.  Age differences in spatial working memory contributions to visuomotor adaptation and transfer 
Behavioural brain research  2011;225(1):160-168.
Throughout our life span we encounter challenges that require us to adapt to the demands of our changing environment; this entails learning new skills. Two primary components of motor skill learning are motor acquisition, the initial process of learning the skill, and motor transfer, when learning a new skill is benefitted by the overlap with a previously learned one. Older adults typically exhibit declines in motor acquisition compared to young adults, but remarkably, do not demonstrate deficits in motor transfer (Seidler, 2007). Our recent work demonstrates that a failure to engage spatial working memory (SWM) is associated with skill learning deficits in older adults (Anguera et al., 2011). Here, we investigate the role that SWM plays in both motor learning and transfer in young and older adults. Both age groups exhibited performance savings, or positive transfer, at transfer of learning for some performance variables. Measures of spatial working memory performance and reaction time correlated with both motor learning and transfer for young adults. Young adults recruited overlapping brain regions in prefrontal, premotor, parietal and occipital cortex for performance of a SWM and a visuomotor adaptation task, most notably during motor learning, replicating our prior findings (Anguera et al., 2010). Neural overlap between the SWM task and visuomotor adaptation for the older adults was limited to parietal cortex, with minimal changes from motor learning to transfer. Combined, these results suggest that age differences in engagement of cognitive strategies have a differential impact on motor learning and transfer.
doi:10.1016/j.bbr.2011.07.014
PMCID: PMC3170505  PMID: 21784106
Spatial Working Memory; Aging; Visuomotor Adaptation; Skill Acquisition; Transfer
6.  Physical Activity is Related to Timing Performance in Older Adults 
Physical activity has been linked to better cognitive function in older adults, especially for executive control processes. Researchers have suggested that temporal processing of durations less than 1 second is automatic and engages motor processes, while timing of longer durations engages executive processes. The purpose of this study was to determine whether a higher level of physical activity is associated with better reproduction performance in older adults, especially for durations in the “cognitive” range (i.e. longer than 1 s). Older right-handed adults completed a temporal reproduction task with five target durations (300, 650, 1000, 1350, and 1700 ms). Physical activity level was assessed via estimation of VO2 peak using a self-report activity scale. Results indicated that higher physical activity level was associated with better timing accuracy and that this effect was dependent on target duration. Namely, the relationship between physical activity and timing accuracy was strongest at the longest durations. Therefore, greater physical activity in older adults may have specific benefits linked to better executive functions.
doi:10.1080/13825585.2012.715625
PMCID: PMC3528826  PMID: 22917438
Temporal reproduction; Physical Activity; Cognition; Older Adults; Neuro-protection
7.  Neurocognitive Mechanisms of Error-Based Motor Learning 
Advances in experimental medicine and biology  2013;782:10.1007/978-1-4614-5465-6_3.
doi:10.1007/978-1-4614-5465-6_3
PMCID: PMC3817858  PMID: 23296480
8.  The effect of haptic cues on motor and perceptual based implicit sequence learning 
We introduced haptic cues to the serial reaction time (SRT) sequence learning task alongside the standard visual cues to assess the relative contributions of visual and haptic stimuli to the formation of motor and perceptual memories. We used motorized keys to deliver brief pulse-like displacements to the resting fingers, expecting that the proximity and similarity of these cues to the subsequent response motor actions (finger-activated key-presses) would strengthen the motor memory trace in particular. We adopted the experimental protocol developed by Willingham (1999) to explore whether haptic cues contribute differently than visual cues to the balance of motor and perceptual learning. We found that sequence learning occurs with haptic stimuli as well as with visual stimuli and we found that irrespective of the stimuli (visual or haptic) the SRT task leads to a greater amount of motor learning than perceptual learning.
doi:10.3389/fnhum.2014.00130
PMCID: PMC3975096  PMID: 24734013
sequence learning; haptic cue; motor memory; serial reaction time task
9.  Older Adults can Learn to Learn New Motor Skills 
Behavioural brain research  2007;183(1):118-122.
Many studies have demonstrated that aging is associated with declines in skill acquisition. In the current study, we tested whether older adults could acquire general, transferable knowledge about skill learning processes. Older adult participants learned five different motor tasks. Two older adult control groups performed the same number of trials, but learned only one task. The experimental group exhibited faster learning than that seen in the control groups. These data demonstrate that older adults can learn to learn new motor skills.
doi:10.1016/j.bbr.2007.05.024
PMCID: PMC1995805  PMID: 17602760
10.  Differential relationships between transcallosal structural and functional connectivity in young and older adults 
Neurobiology of aging  2011;33(10):2521-2526.
Numerous studies have identified age differences in brain structure and function that correlate with declines in motor performance. While these investigations have typically focused on activity in isolated regions of the brain, resting state functional connectivity MRI and diffusion tensor imaging allow for more integrative assessments of spatially disparate neural networks. The novel contribution of the current study is to combine both resting state functional connectivity and diffusion tensor imaging to examine motor cortico-cortical circuits in young and older adults. We find that relatively greater functional connectivity between the primary motor cortices was strongly associated with decreased structural connectivity and poorer motor performance solely in older adults. We suggest that greater functional connectivity in older adults may be reflective of a release from the normally predominantly inhibitory interhemispheric communication associated with the primary motor cortices.
doi:10.1016/j.neurobiolaging.2011.11.018
PMCID: PMC3310958  PMID: 22177217
11.  Evidence for Motor Cortex Dedifferentiation in Older Adults 
Neurobiology of Aging  2011;33(9):1890-1899.
Older adults (OA) show more diffuse brain activity than young adults (YA) during the performance of cognitive, motor, and perceptual tasks. It is unclear whether this over-activation reflects compensation or dedifferentiation. Typically, these investigations have not evaluated the organization of the resting brain, which can help to determine whether more diffuse representations reflect physiological or task- dependent effects. In the present study we used transcranial magnetic stimulation (TMS) to determine whether there are differences in motor cortex organization of both brain hemispheres in YA and OA. We measured resting motor threshold, motor evoked potential (MEP) latency and amplitude, and extent of first dorsal interosseous representations, in addition to a computerized measure of reaction time. There was no significant age difference in motor threshold, but we did find that OA had larger contralateral MEP amplitudes and a longer contralateral MEP latency. Furthermore, the spatial extent of motor representations in OA was larger. We found that larger dominant hemisphere motor representations in OA were associated with higher reaction times, suggesting dedifferentiation rather than compensation effects.
doi:10.1016/j.neurobiolaging.2011.06.021
PMCID: PMC3391352  PMID: 21813213
aging; transcranial magnetic stimulation; motor cortex
12.  Task-Dependent Effects of Interhemispheric Inhibition on Motor Control 
Behavioural brain research  2011;226(1):211-217.
Interhemispheric communication consists of a complex balance of facilitation and inhibition that is modulated in a task-dependent manner. However, it remains unclear how individual differences in interhemispheric interactions relate to motor performance. To assess interhemispheric inhibition, we utilized the ipsilateral silent period technique (iSP; evoked by suprathreshold transcranial magnetic stimulation), which elicits inhibition of volitional motor activity. Participants performed three force production tasks: 1) unimanual (right hand) constant force, 2) bimanual constant force, (bimanual simultaneous) and 3) bimanual with right hand constant force and left hand sine wave tracking (bimanual independent). We found that individuals with greater IHI capacity demonstrated reduced mirror EMG activity in the left hand during unimanual right hand contraction. However, these same individuals demonstrated the poorest performance during the bimanual independent force production task. We suggest that a high capacity for IHI from one motor cortex to another can effectively prevent “motor overflow” during unimanual tasks, but it can also limit interhemispheric cooperation during independently controlled bimanual tasks.
doi:10.1016/j.bbr.2011.09.018
PMCID: PMC3208314  PMID: 21944939
ipsilateral silent period; force production; motor overflow
13.  Cerebellar contributions to visuomotor adaptation and motor sequence learning: an ALE meta-analysis 
Cerebellar contributions to motor learning are well-documented. For example, under some conditions, patients with cerebellar damage are impaired at visuomotor adaptation and at acquiring new action sequences. Moreover, cerebellar activation has been observed in functional MRI (fMRI) investigations of various motor learning tasks. The early phases of motor learning are cognitively demanding, relying on processes such as working memory, which have been linked to the cerebellum as well. Here, we investigated cerebellar contributions to motor learning using activation likelihood estimation (ALE) meta-analysis. This allowed us to determine, across studies and tasks, whether or not the location of cerebellar activation is constant across differing motor learning tasks, and whether or not cerebellar activation in early learning overlaps with that observed for working memory. We found that different regions of the anterior cerebellum are engaged for implicit and explicit sequence learning and visuomotor adaptation, providing additional evidence for the modularity of cerebellar function. Furthermore, we found that lobule VI of the cerebellum, which has been implicated in working memory, is activated during the early stages of explicit motor sequence learning. This provides evidence for a potential role for the cerebellum in the cognitive processing associated with motor learning. However, though lobule VI was activated across both early explicit sequence learning and working memory studies, there was no spatial overlap between these two regions. Together, our results support the idea of modularity in the formation of internal representations of new motor tasks in the cerebellum, and highlight the cognitive processing relied upon during the early phases of motor skill learning.
doi:10.3389/fnhum.2013.00027
PMCID: PMC3566602  PMID: 23403800
cerebellum; sequence learning; visuomotor adaptation; working memory; meta-analysis
14.  A simple solution for model comparison in bold imaging: the special case of reward prediction error and reward outcomes 
Conventional neuroimaging techniques provide information about condition-related changes of the BOLD (blood-oxygen-level dependent) signal, indicating only where and when the underlying cognitive processes occur. Recently, with the help of a new approach called “model-based” functional neuroimaging (fMRI), researchers are able to visualize changes in the internal variables of a time varying learning process, such as the reward prediction error or the predicted reward value of a conditional stimulus. However, despite being extremely beneficial to the imaging community in understanding the neural correlates of decision variables, a model-based approach to brain imaging data is also methodologically challenging due to the multicollinearity problem in statistical analysis. There are multiple sources of multicollinearity in functional neuroimaging including investigations of closely related variables and/or experimental designs that do not account for this. The source of multicollinearity discussed in this paper occurs due to correlation between different subjective variables that are calculated very close in time. Here, we review methodological approaches to analyzing such data by discussing the special case of separating the reward prediction error signal from reward outcomes.
doi:10.3389/fnins.2013.00116
PMCID: PMC3715737  PMID: 23882174
prediction error; model comparison; dopamine; predicted value; fMRI
15.  Introduction to the special topic: a multidisciplinary approach to motor learning and sensorimotor adaptation 
doi:10.3389/fnhum.2013.00543
PMCID: PMC3766816  PMID: 24058338
motor learning; sensorimotor adaptation; sequence learning; motor cortex; consolidation
16.  Hand Dominance and Age Have Interactive Effects on Motor Cortical Representations 
PLoS ONE  2012;7(9):e45443.
Older adults exhibit more bilateral motor cortical activity during unimanual task performance than young adults. Interestingly, a similar pattern is seen in young adults with reduced hand dominance. However, older adults report stronger hand dominance than young adults, making it unclear how handedness is manifested in the aging motor cortex. Here, we investigated age differences in the relationships between handedness, motor cortical organization, and interhemispheric communication speed. We hypothesized that relationships between these variables would differ for young and older adults, consistent with our recent proposal of an age-related shift in interhemispheric interactions. We mapped motor cortical representations of the right and left first dorsal interosseous muscles using transcranial magnetic stimulation (TMS) in young and older adults recruited to represent a broad range of the handedness spectrum. We also measured interhemispheric communication speed and bimanual coordination. We observed that more strongly handed older adults exhibited more ipsilateral motor activity in response to TMS; this effect was not present in young adults. Furthermore, we found opposing relationships between interhemispheric communication speed and bimanual performance in the two age groups. Thus, handedness manifests itself differently in the motor cortices of young and older adults and has interactive effects with age.
doi:10.1371/journal.pone.0045443
PMCID: PMC3458089  PMID: 23049800
17.  Age differences in callosal contributions to cognitive processes 
Neuropsychologia  2011;49(9):2564-2569.
In many cases bilateral cortical activation in older adults has been associated with better task performance, suggesting that a greater reliance on interhemispheric interactions aids performance. Interhemispheric communication is primarily mediated via the corpus callosum (CC), however with advancing age the anterior half of the CC undergoes significant atrophy. Here we determine whether there are age differences in the relationship between cross-sectional area of the CC and performance on cognitive tests of psychomotor processing speed and working memory. We found that older adults had significantly smaller callosal area in the anterior and mid-body of the CC than young adults. Furthermore, older adults with larger size in these callosal areas performed better on assessments of working memory and processing speed. Our results indicate that older adults with larger size of the anterior half of the CC exhibit better cognitive function, although their performance was still poorer than young adults with similar CC size. Thus, while the capability for interhemispheric interactions, as inferred from callosal size, may provide performance benefits for older adults, this capacity alone does not assure protection from general performance decline.
doi:10.1016/j.neuropsychologia.2011.05.004
PMCID: PMC3137668  PMID: 21601582
Corpus callosum; aging; working memory; processing speed
18.  Dissecting the Clock: Understanding the mechanisms of timing across tasks and temporal intervals 
Acta psychologica  2010;136(1):20-34.
Currently, it is unclear what model of timing best describes temporal processing across millisecond and second timescales in tasks with different response requirements. In the present set of experiments, we assessed whether the popular dedicated scalar model of timing accounts for performance across a restricted timescale surrounding the 1 second duration for different tasks. The first two experiments evaluate whether temporal variability scales proportionally with the timed duration within temporal reproduction. The third experiment compares timing across millisecond and second timescales using temporal reproduction and discrimination tasks designed with parallel structures. The data exhibit violations of the assumptions of a single scalar timekeeper across millisecond and second timescales within temporal reproduction; these violations are less apparent for temporal discrimination. The finding of differences across tasks suggests that task demands influence the mechanisms that are engaged for keeping time.
doi:10.1016/j.actpsy.2010.09.006
PMCID: PMC3019300  PMID: 20955998
Time; Time perception; Time estimation; Prospective timing; Scalar timing PsycINFO classification: 2340
19.  Resting state cortico-cerebellar functional connectivity networks: a comparison of anatomical and self-organizing map approaches 
The cerebellum plays a role in a wide variety of complex behaviors. In order to better understand the role of the cerebellum in human behavior, it is important to know how this structure interacts with cortical and other subcortical regions of the brain. To date, several studies have investigated the cerebellum using resting-state functional connectivity magnetic resonance imaging (fcMRI; Krienen and Buckner, 2009; O'Reilly et al., 2010; Buckner et al., 2011). However, none of this work has taken an anatomically-driven lobular approach. Furthermore, though detailed maps of cerebral cortex and cerebellum networks have been proposed using different network solutions based on the cerebral cortex (Buckner et al., 2011), it remains unknown whether or not an anatomical lobular breakdown best encompasses the networks of the cerebellum. Here, we used fcMRI to create an anatomically-driven connectivity atlas of the cerebellar lobules. Timecourses were extracted from the lobules of the right hemisphere and vermis. We found distinct networks for the individual lobules with a clear division into “motor” and “non-motor” regions. We also used a self-organizing map (SOM) algorithm to parcellate the cerebellum. This allowed us to investigate redundancy and independence of the anatomically identified cerebellar networks. We found that while anatomical boundaries in the anterior cerebellum provide functional subdivisions of a larger motor grouping defined using our SOM algorithm, in the posterior cerebellum, the lobules were made up of sub-regions associated with distinct functional networks. Together, our results indicate that the lobular boundaries of the human cerebellum are not necessarily indicative of functional boundaries, though anatomical divisions can be useful. Additionally, driving the analyses from the cerebellum is key to determining the complete picture of functional connectivity within the structure.
doi:10.3389/fnana.2012.00031
PMCID: PMC3415673  PMID: 22907994
cerebellum; resting state functional connectivity; self-organizing map
20.  Neuroplasticity in middle age: an ecologically valid approach 
doi:10.3389/fnhum.2012.00324
PMCID: PMC3509353  PMID: 23226125
21.  Motor Control and Aging: Links to Age-Related Brain Structural, Functional, and Biochemical Effects 
Although connections between cognitive deficits and age-associated brain differences have been elucidated, relationships with motor performance are less well understood. Here, we broadly review age-related brain differences and motor deficits in older adults in addition to cognition-action theories. Age-related atrophy of the motor cortical regions and corpus callosum may precipitate or coincide with motor declines such as balance and gait deficits, coordination deficits, and movement slowing. Correspondingly, degeneration of neurotransmitter systems—primarily the dopaminergic system—may contribute to age-related gross and fine motor declines, as well as to higher cognitive deficits. In general, older adults exhibit involvement of more widespread brain regions for motor control than young adults, particularly the prefrontal cortex and basal ganglia networks. Unfortunately these same regions are the most vulnerable to age-related effects, resulting in an imbalance of “supply and demand”. Existing exercise, pharmaceutical, and motor training interventions may ameliorate motor deficits in older adults.
doi:10.1016/j.neubiorev.2009.10.005
PMCID: PMC2838968  PMID: 19850077
Aging; Motor Performance; fMRI; Dopamine; Cognition; Plasticity; Exercise; Rehabilitation
22.  Bimanual Coordination and Aging: Neurobehavioral Implications 
Neuropsychologia  2009;48(4):1165-1170.
We investigate whether aging leads to global declines in discrete and continuous bimanual coordination tasks thought to rely on different control mechanisms for temporal coupling of the limbs. All conditions of continuous bimanual circle drawing were associated with age-equivalent temporal control. This was also true for discrete simultaneous tapping. Older adults’ between-hand coordination deficits were specific to discrete tapping conditions requiring asynchronous intermanual timing and were associated with self-reported executive dysfunction on the Dysexecutive (DEX) questionnaire. Also, older adults exclusively showed a relationship between the most difficult bimanual circling condition and a measure of working memory. Thus, age-related changes in bimanual coordination are specific to task conditions that place complex timing demands on left and right hand movements and are, therefore, likely to require executive control.
doi:10.1016/j.neuropsychologia.2009.11.013
PMCID: PMC2828502  PMID: 19941878
Executive Control; Motor Control; Bimanual Coordination; Aging
23.  Neural Correlates of Motor Learning, Transfer of Learning, and Learning to Learn 
Recent studies on the neural bases of sensorimotor adaptation demonstrate that the cerebellar and striatal thalamocortical pathways contribute to early learning. Transfer of learning involves a reduction in the contribution of early learning networks, and increased reliance on the cerebellum. The neural correlates of learning to learn remain to be determined, but likely involve enhanced functioning of general aspects of early learning.
doi:10.1097/JES.0b013e3181c5cce7
PMCID: PMC2796204  PMID: 20016293
sensorimotor adaptation; cerebellum; basal ganglia; skill learning; rehabilitation
24.  Age Differences in Interhemispheric Interactions: Callosal Structure, Physiological Function, and Behavior 
There is a fundamental gap in understanding how brain structural and functional network connectivity are interrelated, how they change with age, and how such changes contribute to older adults’ sensorimotor deficits. Recent neuroimaging approaches including resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) have been used to assess brain functional (fcMRI) and structural (DTI) network connectivity, allowing for more integrative assessments of distributed neural systems than in the past. Declines in corpus callosum size and microstructure with advancing age have been well documented, but their contributions to age deficits in unimanual and bimanual function are not well defined. Our recent work implicates age-related declines in callosal size and integrity as a key contributor to unimanual and bimanual control deficits. Moreover, our data provide evidence for a fundamental shift in the balance of excitatory and inhibitory interhemispheric processes that occurs with age, resulting in age differences in the relationship between functional and structural network connectivity. Training studies suggest that the balance of interhemispheric interactions can be shifted with experience, making this a viable target for future interventions.
doi:10.3389/fnins.2011.00038
PMCID: PMC3077973  PMID: 21519384
interhemispheric; inhibition; aging; motor control
25.  Functional Implications of Age Differences in Motor System Connectivity 
Older adults show less lateralized task-related brain activity than young adults. One potential mechanism of this increased activation is that age-related degeneration of the corpus callosum (CC) may alter the balance of inhibition between the two hemispheres. To determine whether age differences in interhemispheric connectivity affect functional brain activity in older adults, we used magnetic resonance imaging (MRI) to assess resting functional connectivity and functional activation during a simple motor task. We found that older adults had smaller CC area compared to young adults. Older adults exhibited greater recruitment of ipsilateral primary motor cortex (M1), which was associated with longer reaction times. Additionally, recruitment of ipsilateral M1 in older adults was correlated with reduced resting interhemispheric connectivity and a larger CC. We suggest that reduced interhemispheric connectivity reflects a loss of the ability to inhibit the non-dominant hemisphere during motor task performance for older adults, which has a negative impact on performance.
doi:10.3389/fnsys.2010.00017
PMCID: PMC2893009  PMID: 20589101
aging; corpus callosum; fMRI; functional connectivity; motor cortex

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