A1 Functional advantages of cell-type heterogeneity in neural circuits

The potential of non-invasive brain stimulation (NIBS) for both probing human neuroplasticity and the induction of functionally relevant neuroplastic change has received significant interest. However, at present the utility of NIBS is limited due to high response variability. One reason for this response variability is that NIBS targets a diffuse cortical population and the net outcome to stimulation depends on the relative levels of excitability in each population. There is evidence that the relative excitability of complex oligosynaptic circuits (late I-wave circuits) as assessed by transcranial magnetic stimulation (TMS) is useful in predicting NIBS response. Here we examined whether an additional marker of cortical excitability, MEP amplitude variability, could provide additional insights into response variability following application of the continuous theta burst stimulation (cTBS) NIBS protocol. Additionally we investigated whether I-wave recruitment was associated with MEP variability. Thirty-four healthy subjects (15 male, aged 18-35 years) participated in two experiments. Experiment 1 investigated baseline MEP variability and cTBS response. Experiment 2 determined if I-wave recruitment was associated with MEP variability. Data show that both baseline MEP variability and late I-wave recruitment are associated with cTBS response, but were independent of each other; together, these variables predict 31% of the variability in cTBS response. This study provides insight into the physiological mechanisms underpinning NIBS plasticity responses and may facilitate development of more reliable NIBS protocols.

Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging non-invasive neuromodulation therapy. This study aimed to explore the therapeutic use of taVNS, optimal stimulation parameters, effective sham protocols, and safety. A scoping review was conducted. Five databases and grey literature were searched. The data extracted included stimulation parameters, adverse events (AEs), and therapeutic effects on clinical outcomes. 109 studies were included. taVNS was used across 21 different clinical populations, most commonly in psychiatric, cardiac, and neurological disorders. Overall, 2,214 adults received active taVNS and 1,017 received sham taVNS. Reporting of stimulation parameters was limited and inconsistent. taVNS appeared to have a favourable therapeutic effect across a wide range of clinical populations with varied parameters. Three sham protocols were reported but their effectiveness was documented in only two of the 54 sham-controlled studies. Most reported adverse events were localised to stimulation site. There is growing evidence for taVNS therapeutic effect. taVNS appears safe and tolerable. Sham protocols need evaluation. Standardised and comprehensive reporting of both stimulation parameters and adverse events is required. Two different questionnaires have been proposed to evaluate adverse events and the effectiveness of sham methods in blinding participants.

Background: Reduced sensation is experienced by one in two individuals following stroke, impacting both the ability to function independently and overall quality of life. Repetitive activation of sensory input using active and passive sensory-based interventions have been shown to enhance adaptive motor cortical plasticity, indicating a potential mechanism which may mediate recovery. However, rehabilitation specifically focusing on somatosensory function receives little attention. Objectives: To investigate sensory-based interventions reported in the literature and determine the effectiveness to improve sensation and sensorimotor function of individuals following stroke. Methods: Electronic databases and trial registries were searched from inception until November 2018, in addition to hand searching systematic reviews. Study selection included randomized controlled trials for adults of any stroke type with an upper and/or lower limb sensorimotor impairment. Participants all received a sensory-based intervention designed to improve activity levels or impairment, which could be compared with usual care, sham, or another intervention. The primary outcomes were change in activity levels related to sensorimotor function. Secondary outcomes were measures of impairment, participation or quality of life. Results: A total of 38 study trials were included (n = 1,093 participants); 29 explored passive sensory training (somatosensory; peripheral nerve; afferent; thermal; sensory amplitude electrical stimulation), 6 active (sensory discrimination; perceptual learning; sensory retraining) and 3 hybrid (haptic-based augmented reality; sensory-based feedback devices). Meta-analyses (13 comparisons; 385 participants) demonstrated a moderate effect in favor of passive sensory training on improving a range of upper and lower limb activity measures following stroke. Narrative syntheses were completed for studies unable to be pooled due to heterogeneity of measures or insufficient data, evidence for active sensory training is limited however does show promise in improving sensorimotor function following stroke. Conclusions: Findings from the meta-analyses and single studies highlight some support for the effectiveness of passive sensory training in relation to sensory impairment and motor function. However, evidence for active sensory training continues to be limited. Further high-quality research with rigorous methods (adequately powered with consistent outcome measures) is required to determine the effectiveness of sensory retraining in stroke rehabilitation, particularly for active sensory training.