Day differences in the cortisol awakening response predict day differences in synaptic plasticity in the brain

The cortisol awakening response (CAR) is the most prominent, dynamic and variable part of the circadian pattern of cortisol secretion. Despite this its precise purpose is unknown. Aberrant patterns of the CAR are associated with impaired physical and mental health and reduced cognitive function, suggesting that it may have a pervasive role or roles. It has been suggested that the CAR primes the brain for the expected demands of the day but the mechanisms underlying this process are unknown. We examined temporal covariation of the CAR and rapid transcranial magnetic stimulation (rTMS)-induced long term depression (LTD)-like responses in the motor cortex. Plasticity was evaluated across 180 measures from 5 time points on 4 sessions across 9 researcher participants, mean age 25 ± 2.5 years. Plasticity estimates were obtained in the afternoon after measurement of the CAR on 4 days, at least 3 days apart. As both CAR magnitude and rTMS-induced responses are variable across days we hypothesised that days with larger than individual average CARs would be associated with a greater than individual average plasticity response. This was confirmed by mixed regression modelling where variation in the CAR predicted variation in rTMS-induced responses (Df: 1, 148.24; F: 10.41; p=0.002). As the magnitude of the CAR is regulated by the ‘master’ circadian CLOCK, and synaptic plasticity is known to be modulated by peripheral ‘slave’ CLOCK genes, we suggest that the CAR may be a mediator between the master and peripheral circadian systems to entrain daily levels of synaptic plasticity

Connectivity between the supplementary motor area and the primary motor cortex declines with age

Aging is associated with decline in voluntary motor control and decline in the quantity and quality of white matter, which results in impaired functional connectivity. The supplementary motor area (SMA) is densely connected with the primary motor cortex (M1) and, together, these two regions are important for selection, updating, execution of appropriate motor plans. Transcranial magnetic stimulation (TMS) protocols can be used to measure functionally relevant excitatory connections between SMA—M1: when a conditioning TMS pulse to SMA precedes a test TMS pulse to M1 at appropriate intervals, the MEP elicited by the test TMS pulse is facilitated due to activation of excitatory networks acting between SMA and M1. We aimed to determine whether SMA-M1 connectivity is reduced in older adults compared to younger adults. Purdue Pegboard was used to measure manual dexterity, the four square step test was used to measure dynamic balance, and dual-coil TMS was used to measure the excitability of connectivity between SMA—M1 in the hand motor region (and preSMA-M1 as a control). Younger adults performed better on the motor tasks than older adults. In younger adults, the interaction between SMA—M1 (but not PreSMA—M1) was facilitatory, replicating previous research; here, we extend this finding to show SMA—M1 facilitation is reduced in older compared to younger adults. Furthermore, a significant positive correlation was found between SMA—M1 facilitation and performance on the Purdue Pegboard task: greater SMA—M1 facilitation is associated with greater number of pegs placed. Together, these findings suggest that SMA—M1 connectivity is functionally relevant, contributing to manual dexterity performance, and that SMA—M1 connectivity is decreased with age. These data provide a neurophysiological basis on which to test whether strengthening SMA—M1 connectivity can improve voluntary motor control in older adults. Funding NHMRC (1088295), Western Australian Department of Health

Supplementary motor area—primary motor cortex facilitation in younger but not older adults

© 2018 Elsevier Inc. Growing evidence implicates a decline in white matter integrity in the age-related decline in motor control. Functional neuroimaging studies show significant associations between functional connectivity in the cortical motor network, including the supplementary motor area (SMA), and motor performance. Dual-coil transcranial magnetic stimulation studies show facilitatory connections between SMA and the primary motor cortex (M1) in younger adults. Here, we investigated whether SMA-M1 facilitation is affected by age and whether the strength of SMA-M1 facilitation is associated with bilateral motor control. Dual-coil transcranial magnetic stimulation was used to measure SMA-M1 connectivity in younger (N = 20) and older adults (N = 18), and bilateral motor control was measured with the assembly subtest of the Purdue Pegboard and clinical measures of dynamic balance. SMA-M1 facilitation was seen in younger but not older adults, and a significant positive association was found between SMA-M1 facilitation and bimanual performance. These results show that SMA-M1 facilitation is reduced in older adults compared to younger adults and provide evidence of the functional importance of SMA-M1 facilitation

Chronic tension-type headache is associated with impaired motor learning

BackgroundSupraspinal activity-dependent neuroplasticity may be important in the transition from acute to chronic pain. We examined neuroplasticity in a cortical region not considered to be a primary component of the central pain matrix in chronic tension-type headache (CTTH) patients. We hypothesised that neuroplasticity would be exaggerated in CTTH patients compared to healthy controls, which might explain (in part) the development of chronic pain in these individuals.MethodsNeuroplasticity was examined following a ballistic motor training task in CTTH patients and control subjects (CS). Changes in peak acceleration (motor learning) and motor-evoked potential (MEP) amplitude evoked by single-pulse transcranial magnetic stimulation were compared.ResultsCTTH patients showed significantly less motor learning on the training task than CS (mean acceleration increase 87% CTTH, 204% CS, P   .05).ConclusionsThese findings suggest a deficit in use-dependent neuroplasticity within networks responsible for task performance in CTTH patients which might reflect reciprocal influences between primary motor cortex and interconnected pain processing networks. These findings may help explain the positive effects of facilitatory non-invasive brain stimulation targeting motor areas on chronic pain and help elucidate the mechanisms mediating chronic pain.Ann-Maree Vallence, Ashleigh Smith, Abby Tabor, Paul E Rolan and Michael C Riddin

Early Career Researcher (ECR) Workshop

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IL-5 contributes to worm expulsion and muscle hypercontractility in a primary T. spiralis infection

Enteric nematode infections lead to increased interleukin (IL)-5 expression, eosinophilic inflammation, and intestinal smooth muscle hypercontractility. Although eosinophils release inflammatory mediators that cause smooth muscle contraction, the role o