Increased adverse events following third dose of BNT162b2/Pfizer vaccine in those with previous COVID-19, but not with concurrent influenza vaccine.

Prior studies suggest that adverse events (AEs) following doses one and two of BNT162b2/Pfizer vaccine are worse in those with a prior history of COVID-19. To establish whether this outcome applies to a third/booster dose, we conducted a survey with 534 healthcare workers (HCW) in Northeast England, who reported AEs following all three doses of BNT162b2/Pfizer vaccine. We also explored AEs associated with concurrent seasonal influenza immunisation, in a subset of 492 HCWs. For all doses of BNT162b2/Pfizer vaccine there was a cluster of systemic AEs that were consistently worse in HCWs with a prior history of COVID-19. AEs were no worse in HCWs who received their third/booster dose within 7 days of the influenza jab, rather than further apart. Gender and the presence of ongoing COVID-19 symptoms (OCS) had no effect on AEs associated with COVID-19 or influenza vaccination, though younger HCWs experienced more AEs overall. Our findings have implications for vaccine hesitancy and immunisation protocols.

Prior COVID-19 infection is associated with increased Adverse Events (AEs) after the first, but not the second, dose of the BNT162b2/Pfizer vaccine.

The BNT162b2/Pfizer SARS-CoV-2 vaccine has been widely used in the UK, particularly amongst healthcare workers (HCWs). To establish whether previous COVID-19 influenced vaccine-associated Adverse Events (AEs), we conducted a survey-based study of HCWs in Northeast England. Out of 1238 HCWs, 32% self-reported prior positive PCR and/or antibody test for SARS-CoV-2. Post-dose AEs were worse in those with prior COVID-19 after the first, but not the second dose of vaccine. Second dose AEs were greater in frequency/severity, regardless of COVID-19 history, and they were more systemic in nature. Women and younger HCW were more likely to report AEs after both doses, while dosing interval had no effect on AEs. Ongoing Symptomatic COVID-19 was associated with greater frequency/severity of AEs after dose 2, but not dose one. Overall, AEs were self-limiting and short-lived (i.e.,<48 h) in nature. These findings have implications for vaccine hesitancy and informing guidelines for recommended dosing protocols.

Noninvasive vagus nerve stimulation in Parkinson's disease: current status and future prospects.

INTRODUCTION: Parkinson's disease (PD) is a common progressive neurodegenerative disorder with multifactorial etiology. While dopaminergic medication is the standard therapy in PD, it provides limited symptomatic treatment and non-pharmacological interventions are currently being trialed. AREAS COVERED: Recent pathophysiological theories of Parkinson's suggest that aggregated α-synuclein form in the gut and spread to nuclei in the brainstem via autonomic connections. In this paper, we review the novel hypothesis that noninvasive vagus nerve stimulation (nVNS), targeting efferent and afferent vagal projections, is a promising therapeutic tool to improve gait and cognitive control and ameliorate non-motor symptoms in people with Parkinson's. We conducted an unstructured search of the literature for any studies employing nVNS in PD as well as for studies examining the efficacy of nVNS on improving cognitive function and where nVNS has been applied to co-occurring conditions in PD. EXPERT OPINION: Evidence of nVNS as a novel therapeutic to improve gait in PD is preliminary, but early signs indicate the possibility that nVNS may be useful to target dopa-resistant gait characteristics in early PD. The evidence for nVNS as a therapeutic tool is, however, limited and further studies are needed in both brain health and disease.

Skill acquisition as a function of age, hand and task difficulty: Interactions between cognition and action.

Some activities can be meaningfully dichotomised as 'cognitive' or 'sensorimotor' in nature-but many cannot. This has radical implications for understanding activity limitation in disability. For example, older adults take longer to learn the serial order of a complex sequence but also exhibit slower, more variable and inaccurate motor performance. So is their impaired skill acquisition a cognitive or motor deficit? We modelled sequence learning as a process involving a limited capacity buffer (working memory), where reduced performance restricts the number of elements that can be stored. To test this model, we examined the relationship between motor performance and sequence learning. Experiment 1 established that older adults were worse at learning the serial order of a complex sequence. Experiment 2 found that participants showed impaired sequence learning when the non-preferred hand was used. Experiment 3 confirmed that serial order learning is impaired when motor demands increase (as the model predicted). These results can be captured by reinforcement learning frameworks which suggest sequence learning will be constrained both by an individual's sensorimotor ability and cognitive capacity.

Kinematic measures provide useful information after intracranial aneurysm treatment.

INTRODUCTION: Current methods of assessing the outcomes of intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage are relatively insensitive, and thus unlikely to detect subtle deficits. Failures to identify cognitive and motor outcomes of intracranial aneurysm treatment might prevent delivery of optimal post-operative care. There are also concerns over risks associated with using intracranial aneurysm treatment as a preventative measure. METHODS: We explored whether our kinematic tool would yield useful information regarding motor/cognitive function in patients who underwent intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage or unruptured aneurysm. Computerised kinematic motor and learning tasks were administered alongside standardised clinical outcome measures of cognition and functional ability, in 10 patients, as a pilot trial. Tests at post-intracranial aneurysm treatment discharge and six-week follow-up were compared to see which measures detected changes. RESULTS: Kinematic tests captured significant improvements from discharge to six-week follow-up, indexed by reduced motor errors and improved learning. Increased Addenbrooke's Cognitive Examination-Revised scores reflected some recovery of memory function for most individuals, but other standardised cognitive measures, functional outcome scores and a psychological questionnaire showed no changes. CONCLUSIONS: Kinematic measures can identify variation in performance in individuals with only slightly improved abilities post-intracranial aneurysm treatment. These measures may provide a sensitive way to explore post-operative outcomes following intracranial aneurysm treatment, or other similar surgical procedures.

Motor Sequence Learning in Healthy Older Adults Is Not Necessarily Facilitated by Transcranial Direct Current Stimulation (tDCS).

BACKGROUND: Transcranial Direct Current Stimulation (tDCS) of the primary motor cortex (M1) can modulate neuronal activity, and improve performance of basic motor tasks. The possibility that tDCS could assist in rehabilitation (e.g., for paresis post-stroke) offers hope but the evidence base is incomplete, with some behavioural studies reporting no effect of tDCS on complex motor learning. Older adults who show age-related decline in movement and learning (skills which tDCS could potentially facilitate), are also under-represented within tDCS literature. To address these issues, we examined whether tDCS would improve motor sequence learning in healthy young and older adults. METHODS: In Experiment One, young participants learned 32 aiming movements using their preferred (right) hand whilst receiving: (i) 30 min Anodal Stimulation of left M1; (ii) 30 min Cathodal Stimulation of right M1; or (iii) 30 min Sham. Experiment Two used a similar task, but with older adults receiving Anodal Stimulation or Sham. RESULTS: Whilst motor learning occurred in all participants, tDCS did not improve the rate or accuracy of motor learning for either age group. CONCLUSION: Our results suggest that the effects of tDCS may be limited to motor performance with no clear beneficial effects for motor learning.

The 'Goldilocks Zone': getting the measure of manual asymmetries.

Some studies have shown that manual asymmetries decrease in older age. These results have often been explained with reference to models of reduced hemispheric specialisation. An alternative explanation, however, is that hand differences are subtle, and capturing them requires tasks that yield optimal performance with both hands. Whereas the hemispheric specialisation account implies that reduced manual asymmetries should be reliably observed in older adults, the 'measurement difficulty' account suggests that manual asymmetries will be hard to detect unless a task has just the right level of difficulty--i.e. within the 'Goldilocks Zone', where it is not too easy or too hard, but just right. Experiment One tested this hypothesis and found that manual asymmetries were only detected when participants performed in this zone; specifically, performance on a tracing task was only superior in the preferred hand when task constraints were high (i.e. fast speed tracing). Experiment Two used three different tasks to examine age differences in manual asymmetries; one task produced no asymmetries, whilst two tasks revealed asymmetries in both younger and older groups (with poorer overall performance in the old group across all tasks). Experiment Three revealed task-dependent asymmetries in both age groups, but highlighted further detection difficulties linked with the metric of performance and compensatory strategies used by participants. Results are discussed with reference to structural learning theory, whereby we suggest that the processes of inter-manual transfer lead to relatively small performance differences between the hands (despite a strong phenomenological sense of performance disparities).

Anodal transcranial direct current stimulation (tDCS) over the motor cortex increases sympathetic nerve activity.

BACKGROUND: Transcranial direct current stimulation (tDCS) is currently being investigated as a non-invasive neuromodulation therapy for a range of conditions including stroke rehabilitation. tDCS affects not only the area underlying the electrodes but also other areas of the cortex and subcortical structures. This could lead to unintended alteration in brain functions such as autonomic control. OBJECTIVE: We investigated the potential effects of tDCS on cardiovascular autonomic function in healthy volunteers. METHODS: Anodal (n = 14) or cathodal (n = 8) tDCS at 1 mA was applied over the primary motor cortex with the second electrode placed on the contralateral supraorbital region. Subjects visited the department twice and received active or sham tDCS for 15 min. Heart rate, blood pressure and respiration were recorded at baseline, during tDCS and after stimulation. Heart rate variability (HRV) was calculated using spectral analysis of beat-to-beat intervals derived from ECG data. Microneurography was also used to record muscle sympathetic nerve activity (MSNA; n = 5). RESULTS: Anodal tDCS caused a significant shift in HRV toward sympathetic predominance (P = 0.017), whereas there was no significant change in the cathodal or sham groups. Microneurography results also showed a significant increase in MSNA during anodal tDCS that continued post-stimulation. CONCLUSIONS: Anodal tDCS of the motor cortex shifts autonomic nervous system balance toward sympathetic dominance due at least in part to an increase in sympathetic output. These results suggest further investigation is warranted on tDCS use in patient groups with potential autonomic dysfunction, such as stroke patients.

Reduced motor asymmetry in older adults when manually tracing paths.

Handedness, a preference towards using the right or left hand, is established in early childhood. Such specialisation allows a higher level of skill to be maintained in the preferred hand on specific tasks through continuous practice and performance. Hand asymmetries might be expected to increase with age because of the time spent practising with the preferred hand. However, neurophysiological work has suggested reduced hemispheric function lateralisation in the ageing brain, and behavioural studies have found reduced motor asymmetries in older adults (Przybyla et al., in Neurosci Lett 489:99-104, 2011). We therefore tested the predictions of behavioural change from reduced hemispheric function by measuring tracing performance (arguably one of the most lateralised of human behaviours) along paths of different thickness in a group of healthy young and older adults. Participants completed the task once with their preferred (right) hand and once with their non-preferred (left) hand. Movement time (MT) and shape accuracy (SA) were dependant variables. A composite measure of MT and SA, the speed accuracy cost function (SACF) provided an overall measure of motor performance. Older participants were slower and less accurate when task demands were high. Combined analyses of both hands revealed reduced asymmetries in MT and SACF in the older group. The young were significantly faster when tracing with their preferred hand, but older participants were equally slow with either hand. Our results are consistent with the growing literature reporting decreased hemispheric function lateralisation in the ageing brain.

Movement control in older adults: does old age mean middle of the road?

Old age is associated with poorer movement skill, as indexed by reduced speed and accuracy. Nevertheless, reductions in speed and accuracy can also reflect compensation as well as deficit. We used a manual tracing and a driving task to identify generalized spatial and temporal compensations and deficits associated with old age. In Experiment 1, participants used a hand-held stylus to trace a path. In Experiment 2, participants steered along paths in a virtual reality driving simulator. In both experiments, participants were required to stay within the boundaries while we manipulated task difficulty by changing path width or movement speed. The older group showed worse performance in the highly constrained conditions. Corner cutting effectively reduces the curvature of bends but yields a greater risk of error (i.e., clipping the path or road edge). Corner cutting is thus less risky on wider paths, and we found that corner cutting increased for both age groups in both tasks when paths were wider. Crucially, we observed a greater degree of corner cutting in the young group compared with the old, suggesting the old group compensated for decreased motor skill with "middle-of-the-road" behavior. Enforcing increased speed caused all participants to increase corner cutting. Thus, older participants showed spatial compensation for decreased skill by biasing their position toward the middle of the path in both a manual and steering task. External constraints (narrow paths and fast speeds) prevented this strategy and revealed age-related declines in skills central to manual control and driving.