Stimulating Multiple-Demand Cortex Enhances Vocabulary Learning

It is well established that networks within multiple-demand cortex (MDC) become active when diverse skills and behaviors are being learnt. However, their causal role in learning remains to be established. In the present study, we first performed functional magnetic resonance imaging on healthy female and male human participants to confirm that MDC was most active in the initial stages of learning a novel vocabulary, consisting of pronounceable nonwords (pseudowords), each associated with a picture of a real object. We then examined, in healthy female and male human participants, whether repetitive transcranial magnetic stimulation of a frontal midline node of the cingulo-opercular MDC affected learning rates specifically during the initial stages of learning. We report that stimulation of this node, but not a control brain region, substantially improved both accuracy and response times during the earliest stage of learning pseudoword– object associations. This stimulation had no effect on the processing of established vocabulary, tested by the accuracy and response times when participants decided whether a real word was accurately paired with a picture of an object. These results provide evidence that noninvasive stimulation to MDC nodes can enhance learning rates, thereby demonstrating their causal role in the learning process. We propose that this causal role makes MDC candidate target for exper- imental therapeutics; for example, in stroke patients with aphasia attempting to reacquire a vocabulary

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis

Background. Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results. Cross‐sectional T1‐weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta‐Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA‐UE (Fugl‐Meyer Assessment of Upper Extremity). Robust mixed‐effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni‐corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; β=0.16) but not contralesional (P=0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; β=−0.26) and contralesional (P=0.006; β=−0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; β=−0.21) and extent of sensorimotor damage (P=0.003; β=−0.15). Conclusions. The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.S.-L.L. is supported by NIH K01 HD091283; NIH R01 NS115845. A.B. and M.S.K. are supported by National Health and Medical Research Council (NHMRC) GNT1020526, GNT1045617 (A.B.), GNT1094974, and Heart Foundation Future Leader Fellowship 100784 (A.B.). P.M.T. is supported by NIH U54 EB020403. L.A.B. is supported by the Canadian Institutes of Health Research (CIHR). C.M.B. is supported by NIH R21 HD067906. W.D.B. is supported by the Heath Research Council of New Zealand. J.M.C. is supported by NIH R00HD091375. A.B.C. is supported by NIH R01NS076348-01, Hospital Israelita Albert Einstein 2250-14, CNPq/305568/2016-7. A.N.D. is supported by funding provided by the Texas Legislature to the Lone Star Stroke Clinical Trial Network. Its contents are solely the responsibility of the authors and do not necessarily represent the of ficial views of the Government of the United States or the State of Texas. N.E.-B. is supported by Australian Research Council NIH DE180100893. W.F. is sup ported by NIH P20 GM109040. F.G. is supported by Wellcome Trust (093957). B.H. is funded by and NHMRC fellowship (1125054). S.A.K is supported by NIH P20 HD109040. F.B. is supported by Italian Ministry of Health, RC 20, 21. N.S. is supported by NIH R21NS120274. N.J.S. is supported by NIH/National Institute of General Medical Sciences (NIGMS) 2P20GM109040-06, U54-GM104941. S.R.S. is supported by European Research Council (ERC) (NGBMI, 759370). G.S. is supported by Italian Ministry of Health RC 18-19-20-21A. M.T. is sup ported by National Institute of Neurological Disorders and Stroke (NINDS) R01 NS110696. G.T.T. is supported by Temple University sub-award of NIH R24 –NHLBI (Dr Mickey Selzer) Center for Experimental Neurorehabilitation Training. N.J.S. is funded by NIH/National Institute of Child Health and Human Development (NICHD) 1R01HD094731-01A1

Enhancing Europe’s global power: a scenario exercise with eight proposals

In the present context of intensifying competition between the major trading economies and potentially game-changing technological developments, the European Union is generally seen as the weaker party. Lacking the ‘hard power’ derived from military capabilities, it has laid claim to a ‘soft power’ of normative influence externally, yet even that is only partially utilised. Nor has Europe been able to exercise the power to coerce – ‘sharp power’ – commensurate with its economic weight as a trading bloc equivalent in size and reach to the US or China, its most prominent global competitors. How can Europe strengthen its position, and in what fields? Through a scenario exercise, we develop eight policy proposals aimed at countering Europe´s vulnerabilities and enabling it to assert its sharp and soft power more effectively. Specifically, we consider the feasibility, means and scope for their realisation. Together, they provide a transformative agenda for the EU’s position in the world

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (β = 0.21; 95% CI 0.04-0.38, DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets

Biomarkers of stroke recovery: consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable

The most difficult clinical questions in stroke rehabilitation are ‘‘What is this patient’s potential for recovery?’’ and ‘‘What is the best rehabilitation strategy for this person, given her/his clinical profile?’’ Without answers to these questions, clinicians struggle to make decisions regarding the content and focus of therapy, and researchers design studies that inadvertently mix participants who have a high likelihood of responding with those who do not. Developing and implementing biomarkers that distinguish patient subgroups will help address these issues and unravel the factors important to the recovery process. The goal of the present paper is to provide a consensus statement regarding the current state of the evidence for stroke recovery biomarkers. Biomarkers of motor, somatosensory, cognitive and language domains across the recovery timeline post-stroke are considered; with focus on brain structure and function, and exclusion of blood markers and genetics. We provide evidence for biomarkers that are considered ready to be included in clinical trials, as well as others that are promising but not ready and so represent a developmental priority. We conclude with an example that illustrates the utility of biomarkers in recovery and rehabilitation research, demonstrating how the inclusion of a biomarker may enhance future clinical trials. In this way, we propose a way forward for when and where we can include biomarkers to advance the efficacy of the practice of, and research into, rehabilitation and recovery after stroke

Enhancing the creep resistance of a cast AZ91 alloy via minor Sc addition

The influence of 0.2 wt% Sc addition on the microstructure and creep characteristics of a cast AZ91 magnesium alloy was studied by impression creep tests under the constant punch stresses ranging from 175 to 700 MPa in the temperature range 425–525 K. The findings indicated that creep rates decreased at all stress levels and temperatures after Sc addition. This was ascribed to the formation of the thermally stable Al3Sc and Mg5Al4Sc particles, reduction in the quantity of the unstable β-Mg17Al12 phase, and solid solution strengthening of Al in the Mg matrix. The creep stress exponent and activation energy values obtained from the studied alloys ranged from 5–6 and 95–117 kJ/mol, respectively. The detected drop in creep activation energy with increasing stress implies that two concurrent mechanisms of dislocation climb controlled by lattice and pipe-diffusion are competing with each other. The former one was the governing mechanism at low stress levels, while the latter one was the prevailing mechanism in the high stress regimes

Cerebrovascular reactivity has negligible contribution to haemodynamic lag after stroke: implications for fMRI studies.

Background: Functional MRI is ubiquitously used to study post-stroke recovery. However, the fMRI-derived haemodynamic responses are vulnerable to vascular insult which can result in reduced magnitude and temporal delays (lag) in the haemodynamic response function (HRF). The aetiology of HRF lag remains controversial, and a better understanding of it is required to ensure accurate interpretation of post-stroke fMRI studies. In this longitudinal study, we investigate the relationship between haemodynamic lag and cerebrovascular reactivity (CVR) following stroke. Methods: Voxelwise lag maps were calculated relative to a mean grey matter reference signal for 27 healthy controls and 59 patients with stroke across two timepoints (~2 weeks and ~4 months post-stroke), and two conditions: resting-state and breath-holding. The breath-holding condition was additionally used to calculate CVR in response to hypercapnia. HRF lag was computed for both conditions across tissue compartments: lesion, perilesional tissue, unaffected tissue of the lesioned hemisphere, and their homologue regions in the unaffected hemisphere. CVR and lag maps were correlated. Group, condition, and time effects were assessed using ANOVA analyses. Results: Compared with the average grey matter signal, a relative haemodynamic lead was observed in the primary sensorimotor cortices in resting-state and bilateral inferior parietal cortices in breath-holding condition. Whole-brain haemodynamic lag was significantly correlated across conditions irrespective of group, with regional differences across conditions suggestive of a neural network pattern. Patients showed relative lag in the lesioned hemisphere which significantly reduced over time. Breath-hold derived lag and CVR had no significant voxel-wise correlation in controls, or patients within the lesioned hemisphere or the homologous regions of the lesion and perilesional tissue in the right hemisphere (mean r<0.1). Conclusion: The contribution of altered CVR to HRF lag was negligible. We suggest that HRF lag is largely independent of CVR, and could partly reflect intrinsic neural network dynamics amongst other factors

Semantic memory: Which side are you on?

We present two patients in whom the combination of lesion site and cognitive performance was uniquely informative about the organisation and functional anatomy of semantic memory. One had had a single lobar stroke with an unusual distribution, largely destroying the whole of the left temporal lobe ventral to the superior temporal sulcus. The other patient had had herpes simplex encephalitis with destruction that was confined to the left cerebral hemisphere. The lesion again mainly encompassed the left temporal lobe, but also extended to the left inferior frontal gyrus. Cognitive outcomes in the two patients were compared with each other and with published results from patients with semantic dementia. This is because, whereas the majority of semantic dementia patients present with more prominent atrophy of the left rostroventral temporal lobe, they invariably have a degree of atrophy in the mirror region on the right that progresses. Semantic dementia therefore provides no clear evidence about the specific role of the left rostroventral temporal lobe. The two patients showed a highly consistent cognitive profile. Their deficits were also similar in many respects to that observed in patients with mild-moderate semantic dementia, including severe anomia that was not resolved by phonological cues and impairment on non-verbal as well as verbal semantic tasks. Certain key features of the semantic dementia profile, however-including sensitivity to the familiarity and typicality of the stimulus materials-appeared only in tasks requiring verbal output in these two patients with unilateral left temporal lesions. Results in these cases provide some of the first definitive evidence regarding the specific functions of the left anterior temporal lobe