Lena Ulm

Electrical Brain Stimulation Improves Cognitive Performance by Modulating Functional Connectivity and Task-Specific Activation

Excitatory anodal transcranial direct current stimulation (atDCS) can improve human cognitive functions, but neural underpinnings of its mode of action remain elusive. In a cross-over placebo (“sham”) controlled study we used functional magnetic resonance imaging (fMRI) to investigate neurofunctional correlates of improved language functions induced by atDCS over a core language area, the left inferior frontal gyrus (IFG). Intrascanner transcranial direct current stimulation-induced changes in overt semantic word generation assessed behavioral modulation; task-related and task-independent (resting-state) fMRI characterized language network changes. Improved word-retrieval during atDCS was paralleled by selectively reduced task-related activation in the left ventral IFG, an area specifically implicated in semantic retrieval processes. Under atDCS, resting-state fMRI revealed increased connectivity of the left IFG and additional major hubs overlapping with the language network. In conclusion, atDCS modulates endogenous low-frequency oscillations in a distributed set of functionally connected brain areas, possibly inducing more efficient processing in critical task-relevant areas and improved behavioral performance.

Transcranial direct current stimulation in mild cognitive impairment: behavioral effects and neural mechanisms

The long preclinical phase of Alzheimers disease provides opportunities for potential disease‐modifying interventions in prodromal stages such as mild cognitive impairment (MCI). Anodal transcranial direct current stimulation (anodal‐tDCS), with its potential to enhance neuroplasticity, may allow improving cognition in MCI.

Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults

Language facilitation by transcranial direct current stimulation (tDCS) in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia). However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI), which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1) can enhance language functions. This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal) and bihemispheric (dual) tDCS in 18 healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects. Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions. Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. Functional magnetic resonance imaging revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in improved performance.

Predicting Post-Stroke Infections and Outcome with Blood-Based Immune and Stress Markers

About one third of early deaths and poor outcomes after acute stroke are caused by potentially preventable stroke-associated complications, especially infections. Early identification of patients at high risk of infections and poor prognosis with biomarkers might help to initiate adequate therapies and guide treatment decisions. Acute injury of the central nervous system, including stroke, disturbs the normally well-balanced interplay between the sympathetic nervous system and the immune system, thereby impairing the antibacterial immune response in stroke patients. Changes in immune and stress markers, for example a reduction in HLA-DR expression on monocytes or an increase in serum catecholamine levels, occur very early after stroke onset, explain the high susceptibility of stroke patients to bacterial infections, and are predictive of infectious complications occurring up to 2 weeks after stroke. Outcome prediction is of utmost importance for decision-making in stroke units as well as in neurological intensive care units. However, to date the accuracy of outcome prediction by physicians and clinical scoring systems is only moderate. So far, only two blood-based biomarkers have been identified as independent predictors of outcome and mortality after stroke: the stress marker copeptin and midregional pro-atrial natriuretic peptide. Careful evaluation of prognostic markers is needed to prevent the occurrence of self-fulfilling prophecy.

The Randomized Controlled STRAWINSKI Trial: Procalcitonin-Guided Antibiotic Therapy after Stroke

Background Pneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment. Aims This trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke. Methods In this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with http://ClinicalTrials.gov (Identifier NCT01264549). Results In the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45–1.35, p = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower (p = 0.055), whereas total number of days treated with antibiotics were higher (p = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections (p < 0.0001). Conclusion PCTus-guided antibiotic therapy did not improve functional outcome at 3 months after severe ischemic stroke. PCT is a promising biomarker for early detection of pneumonia and sepsis in acute stroke patients.

Neural Mechanisms Underlying Perilesional Transcranial Direct Current Stimulation in Aphasia: A Feasibility Study.

Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS) impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI). We employed a single subject, cross-over, sham-tDCS controlled design, and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI, which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioral stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS effects on brain functions in aphasia.

A new era of systems neuroscience in aphasia

ABSTRACT Background: Systems neuroscience acknowledges that human brain function relies on complex interactions between specialised brain regions that are organised in widely distributed functional brain networks. This approach provides a powerful framework to investigate how local structural damage such as a stroke impacts language network reorganisation in aphasia patients and its relation to recovery. Aims: In this paper we aim to familiarise the readers with the concept of systems neuroscience and its application in aphasia imaging. Main Contribution: We briefly describe common analytic methods used in systems neuroscience with a focus on magnetic resonance imaging (MRI) based connectivity analyses. We describe task-based and resting-state functional MRI and diffusion weighted imaging based approaches that allow assessing functional and structural network characteristics in the human brain. Subsequently, we discuss recent studies that have used different network-level approaches to investigate recovery and treatment-induced neural reorganisation in aphasia. Conclusions: This illustrative review highlights the potential of the novel systems neuroscience approach to improve our understanding of the neural mechanisms underlying recovery and treatment response in aphasia. We also discuss a number of key issues that need to be addressed in this emerging field before it can effectively contribute to clinical decision-making.

Changes in Chronotype after Stroke: A Pilot Study

This study aimed to elucidate associations between stroke onset and severity as well as chronotype (phase of entrainment) and internal time of stroke. Fifty-six first-ever ischemic stroke patients participated in a cross-sectional study assessing chronotype (mid-sleep on work-free days corrected for sleep deficit on workdays; MSFsc) by applying the Munich ChronoType Questionnaire (MCTQ). The MCTQ was completed twice, on average 68 ± 24 (SD) days post stroke and retrospectively for the time before stroke. To assess the impact of stroke in relation to internal time, InTstroke was calculated as MSFsc minus local time of stroke. Stroke severity was assessed via the standard clinical National Institute Health Stroke Scale (NIHSS) and modified Ranking Scale (mRS), both at hospital admission and discharge. Overall, most strokes occurred between noon and midnight. There was no significant association between MSFsc and stroke onset. MSFsc changed significantly after stroke, especially in patients with more severe strokes. Changes in MSFsc varied with InTstroke - the earlier the internal time of a stroke relative to MSFsc-before-stroke, the more MSFsc advanced after stroke. In addition, we provide first evidence that MSFsc changes varied between stroke locations. Larger trials are needed to confirm these findings.