Learning and using an additional language is shown to have an impact on the structure and function of the brain, including in regions involved in cognitive control and the connections between them. ...However, the available evidence remains variable in terms of the localization, extent, and trajectory of these effects. Variability likely stems from the fact that bilingualism has been routinely operationalized as a categorical variable (bilingual/monolingual), whereas it is a complex and dynamic experience with a number of potentially deterministic factors affecting neural plasticity. Here we present a study investigating the combined effects of experience-based factors (EBFs) in bilingual language use on brain structure and functional connectivity. EBFs include an array of measures of everyday usage of a second language in different types of immersive settings (e.g., amount of use in social settings). Analyses reveal specific adaptations in the brain, both structural and functional, correlated to individual EBFs and their combined effects. Taken together, the data show that the brain adapts to be maximally efficient in the processing and control of two languages, although modulated ultimately by individual language experience.
Neuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer's disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD ...continuum, to reveal putative protective or harmful stage-dependent patterns of activation.
We included healthy controls (n = 36) and Aβ-positive (Aβ+) cases (as defined by pathological CSF amyloid beta 1-42 (Aβ42)) with either subjective cognitive decline (SCD, n = 19), mild cognitive impairment (MCI, n = 39), or AD dementia (n = 27). The following CSF markers were measured: a microglial activation marker-soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a marker of microglial inflammatory reaction-monocyte chemoattractant protein-1 (MCP-1), two astroglial activation markers-chitinase-3-like protein 1 (YKL-40) and clusterin, a neuron-microglia communication marker-fractalkine, and the CSF AD biomarkers (Aβ42, phosphorylated tau (P-tau), total tau (T-tau)). Using ANOVA with planned comparisons, or Kruskal-Wallis tests with Dunn's pairwise comparisons, CSF levels were compared between clinical groups and between stages of biomarker severity using CSF biomarkers for classification based on amyloid pathology (A), tau pathology (T), and neurodegeneration (N) giving rise to the A/T/N score.
Compared to healthy controls, sTREM2 was increased in SCD (p < .01), MCI (p < .05), and AD dementia cases (p < .001) and increased in AD dementia compared to MCI cases (p < .05). MCP-1 was increased in MCI (p < .05) and AD dementia compared to both healthy controls (p < .001) and SCD cases (p < .01). YKL-40 was increased in dementia compared to healthy controls (p < .01) and MCI (p < .05). All of the CSF activation markers were increased in subjects with pathological CSF T-tau (A+T-N+ and A+T+N+), compared to subjects without neurodegeneration (A-T-N- and A+T-N-).
Microglial activation as indicated by increased sTREM2 is present already at the preclinical SCD stage; increased MCP-1 and astroglial activation markers (YKL-40 and clusterin) were noted only at the MCI and AD dementia stages, respectively, and in Aβ+ cases (A+) with pathological T-tau (N+). Possible different effects of early and later glial activation need to be explored.
Transcranial direct current stimulation (tDCS) is a non‐invasive brain stimulation method that is frequently used to study cortical excitability changes and their impact on cognitive functions in ...humans. While most stimulators are capable of operating in double‐blind mode, the amount of discomfort experienced during tDCS may break blinding. Therefore, specifically designed sham stimulation protocols are being used. The “fade‐in, short‐stimulation, fade‐out” (FSF) protocol has been used in hundreds of studies and is commonly believed to be indistinguishable from real stimulation applied at 1 mA for 20 min. We analysed subjective reports of 192 volunteers, who either received real tDCS (n = 96) or FSF tDCS (n = 96). Participants reported more discomfort for real tDCS and correctly guessed the condition above chance‐level. These findings indicate that FSF does not ensure complete blinding and that better active sham protocols are needed.
We performed a secondary analysis of our high‐powered (N = 192), pre‐registered, multi‐site replication attempt to study the blinding efficacy of the “fade‐in, short‐stimulation, fade‐out” active sham protocol of transcranial direct current stimulation (tDCS). Bayesian data analysis of subjective ratings revealed that blinding is compromised for 20 min of 1 mA tDCS in healthy, young adults. Our findings emphasize that better active sham protocols are needed for this commonly used protocol.
OBJECTIVE:To evaluate long-term treatment efficacy and safety of one-time telemedicine consultations for nonacute headaches.
METHODS:We randomized, allocated, and consulted nonacute headache patients ...via telemedicine (n = 200) or in a traditional manner (n = 202) in a noninferiority trial. Efficacy endpoints, assessed by questionnaires at 3 and 12 months, included change from baseline in Headache Impact Test–6 (HIT-6) (primary endpoint) and pain intensity (visual analogue scale VAS) (secondary endpoint). The primary safety endpoint, assessed via patient records, was presence of secondary headache within 12 months after consultation.
RESULTS:We found no differences between telemedicine and traditional consultations in HIT-6 (p = 0.84) or VAS (p = 0.64) over 3 periods. The absolute difference in HIT-6 from baseline was 0.3 (95% confidence interval CI −1.26 to 1.82, p = 0.72) at 3 months and 0.2 (95% CI −1.98 to 1.58, p = 0.83) at 12 months. The absolute change in VAS was 0.4 (95% CI −0.93 to 0.22, p = 0.23) after 3 months and 0.3 (95% CI −0.94 to 0.29, p = 0.30) at 12 months. We found one secondary headache in each group at 12 months. The estimated number of consultations needed to miss one secondary headache with the use of telemedicine was 20,200.
CONCLUSION:Telemedicine consultation for nonacute headache is as efficient and safe as a traditional consultation.
CLINICALTRIALS.GOV IDENTIFIER:NCT02270177.
CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that a one-time telemedicine consultation for nonacute headache is noninferior to a one-time traditional consultation regarding long-term treatment outcome and safety.
Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, ...access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT.
TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890).
From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group intention-to-treat population). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 10% patients in the tenecteplase group and 23 8% in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64).
In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT.
Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.