Periodic Reporting for period 1 - Stim-Plast-O (Effects of non-invasive brain stimulation on motor learning-related neuroplasticity in healthy older adults)
Periodo di rendicontazione: 2016-04-01 al 2018-03-31
Research on the aging brain and its effect on behaviour have considerably increased during the past decade, significantly boosted by the emergence of brain imaging technologies. Although imaging research on cognitive functioning and aging has been abundant, less is known about neural changes in relation to motor functioning. As life expectancy continues to increase and the ability to learn and maintain motor functions is critical for everyday activities, investigations into the interaction between the aging brain and motor behaviour are of the utmost importance and are consistent with the European Commission's initiative to increase the healthy lifespan by 2 years prior to 2020.
Aging has traditionally been associated with a multitude of movement-related impairments, including decreased speed, increased movement variability, impaired coordination as well as decreased postural stability. There is also accumulating evidence over the last several years that older adults exhibit deficits in the neuroplastic processes underlying the learning, consolidation and retention of motor skills. One potential promising avenue to boost motor learning-related neuroplasticity in older adults is non-invasive brain stimulation (NIBS), and transcranial direct current stimulation (tDCS) in particular. However, remarkably little is known with respect to the neural correlates of such interventions.
Accordingly, this research programme had two overarching objectives: 1) to examine the neural processes - via multiple magnetic resonance imaging (MRI) acquisition sequences and analytic techniques - underlying age-related deficits in motor behaviour; and, 2) to investigate the effects of NIBS on the neuroplasticity underlying motor learning and subsequent memory consolidation in healthy older adults (STIM-PLAST-O; STIMulation-induced neuroPLASTicity in Older adults).
Aging has traditionally been associated with a multitude of movement-related impairments, including decreased speed, increased movement variability, impaired coordination as well as decreased postural stability. There is also accumulating evidence over the last several years that older adults exhibit deficits in the neuroplastic processes underlying the learning, consolidation and retention of motor skills. One potential promising avenue to boost motor learning-related neuroplasticity in older adults is non-invasive brain stimulation (NIBS), and transcranial direct current stimulation (tDCS) in particular. However, remarkably little is known with respect to the neural correlates of such interventions.
Accordingly, this research programme had two overarching objectives: 1) to examine the neural processes - via multiple magnetic resonance imaging (MRI) acquisition sequences and analytic techniques - underlying age-related deficits in motor behaviour; and, 2) to investigate the effects of NIBS on the neuroplasticity underlying motor learning and subsequent memory consolidation in healthy older adults (STIM-PLAST-O; STIMulation-induced neuroPLASTicity in Older adults).
We conducted a multi-experiment research programme to investigate learning- and brain stimulation-dependent changes in brain structure and function in healthy older adults.
We first examined the hypothesis that age-related declines in motor behaviour may be the by-product of a breakdown in the functional organization of brain networks, as assessed by fMRI resting state connectivity. Ninety-six participants between 20 and 75 years of age completed a bimanual coordination task and a resting state fMRI scan in experimental sessions separated by approximately one week. Our results demonstrated that the stronger connectivity between large-scale resting state networks (that subserve various cognitive, motor and sensory functions) observed in older adults was significantly related to worse motor performance. Moreover, these age-related declines in motor performance had a significantly stronger association with connectivity between these networks rather than connectivity within networks, including within 2 motor networks. These findings indicated that age-related declines in motor performance can be attributed to changes in the functional organization of large-scale brain networks, rather than simply age-related connectivity changes within task-relevant, motor networks. These findings were accepted to be published in Cerebral Cortex and were also presented at the 2017 Society for Neuroscience meeting in Washington, DC (US).
The second goal of this research programme was to examine the potential of NIBS to facilitate motor learning-related neuroplasticity and ultimately enhance motor behaviour in older adults. Eighty-three healthy older adults completed a motor learning task before and 6 hours after receiving either anodal or sham (i.e. placebo) stimulation to the contralateral primary motor cortex as well as an extensive magnetic resonance imaging (MRI) protocol assessing learning- and stimulation-induced changes in brain activity, task-related functional connectivity and neurometabolite concentrations and how these effects are modulated by individual variations in brain structure. A subset of the brain imaging analyses is currently in progress but our findings to date have led to the following novel conclusions:
a) The application of tDCS after learning a motor skill differentially influences subsequent memory consolidation processes in healthy older adults depending on which brain hemisphere received stimulation. However, and contrary to previous research, post-learning brain stimulation did not significantly enhance motor learning and memory consolidation in older adults.
b) Post-learning tDCS altered the recruitment of task-relevant brain regions such as bilateral caudate nuclei during task performance in older adults. This stimulation-induced neuroplasticity, however, was maladaptive, as it was associated with worse performance.
c) Learning a motor task resulted in a significant, transient decrease in the concentration of gamma-Aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system, in the sensorimotor cortices of healthy older adults. Post-learning anodal tDCS did not result in a further decrease in GABA concentration.
These results have been presented at the 2017 North American Society for the Psychology of Sport and Physical Activity (NASPSPA) conference in San Diego, California (US) as well as the 2018 Neural Control of Movement (NCM) conference in Santa Fe, New Mexico (US).
We first examined the hypothesis that age-related declines in motor behaviour may be the by-product of a breakdown in the functional organization of brain networks, as assessed by fMRI resting state connectivity. Ninety-six participants between 20 and 75 years of age completed a bimanual coordination task and a resting state fMRI scan in experimental sessions separated by approximately one week. Our results demonstrated that the stronger connectivity between large-scale resting state networks (that subserve various cognitive, motor and sensory functions) observed in older adults was significantly related to worse motor performance. Moreover, these age-related declines in motor performance had a significantly stronger association with connectivity between these networks rather than connectivity within networks, including within 2 motor networks. These findings indicated that age-related declines in motor performance can be attributed to changes in the functional organization of large-scale brain networks, rather than simply age-related connectivity changes within task-relevant, motor networks. These findings were accepted to be published in Cerebral Cortex and were also presented at the 2017 Society for Neuroscience meeting in Washington, DC (US).
The second goal of this research programme was to examine the potential of NIBS to facilitate motor learning-related neuroplasticity and ultimately enhance motor behaviour in older adults. Eighty-three healthy older adults completed a motor learning task before and 6 hours after receiving either anodal or sham (i.e. placebo) stimulation to the contralateral primary motor cortex as well as an extensive magnetic resonance imaging (MRI) protocol assessing learning- and stimulation-induced changes in brain activity, task-related functional connectivity and neurometabolite concentrations and how these effects are modulated by individual variations in brain structure. A subset of the brain imaging analyses is currently in progress but our findings to date have led to the following novel conclusions:
a) The application of tDCS after learning a motor skill differentially influences subsequent memory consolidation processes in healthy older adults depending on which brain hemisphere received stimulation. However, and contrary to previous research, post-learning brain stimulation did not significantly enhance motor learning and memory consolidation in older adults.
b) Post-learning tDCS altered the recruitment of task-relevant brain regions such as bilateral caudate nuclei during task performance in older adults. This stimulation-induced neuroplasticity, however, was maladaptive, as it was associated with worse performance.
c) Learning a motor task resulted in a significant, transient decrease in the concentration of gamma-Aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system, in the sensorimotor cortices of healthy older adults. Post-learning anodal tDCS did not result in a further decrease in GABA concentration.
These results have been presented at the 2017 North American Society for the Psychology of Sport and Physical Activity (NASPSPA) conference in San Diego, California (US) as well as the 2018 Neural Control of Movement (NCM) conference in Santa Fe, New Mexico (US).
Results of this research program represent progress beyond the state of the art on two fronts. First, our findings indicate that age-related impairments in motor functioning are related to a breakdown in the functional organization of large-scale brain networks and not necessarily the result of age-related changes within motor-related networks. Future research should thus adopt a more whole-brain approach to deepen our understanding of the neural underpinning of age-related declines in motor behaviour. Second, our results revealed that, contrary to previous research, tDCS protocols do not appear to be a viable avenue to enhance motor learning and memory consolidation-related plasticity in older adults. Moreover, our findings revealed that the effect of tDCS on motor behaviour in healthy older adults is dependent on which brain hemisphere received stimulation. Both of these results have widespread implications for the use of stimulation approaches as a neurorehabilitative tool following a neurological injury such as stroke, a potential application that has received considerable attention over the last several years.