Transcranial random noise stimulation does not enhance the effects of working memory training

Transcranial random noise stimulation (tRNS), a noninvasive brain stimulation technique, enhances the generalization and sustainability of gains following mathematical training. Here it is combined for the first time with working memory training in a double-blind randomized controlled trial. Adults completed 10 sessions of Cogmed Working Memory Training with either active tRNS or sham stimulation applied bilaterally to dorsolateral pFC. Training was associated with gains on both the training tasks and on untrained tests of working memory that shared overlapping processes with the training tasks, but not with improvements on working memory tasks with distinct processing demands or tests of other cognitive abilities (e.g., IQ, maths). There was no evidence that tRNS increased the magnitude or transfer of these gains. Thus, combining tRNS with Cogmed Working Memory Training provides no additional therapeutic value

Neurostimulator with Waveforms Inspired by Nature for Wearable Electro-Acupuncture

The work presented here has 3 goals: establish the need for novel neurostimulation waveform solutions through a literature review, develop a neurostimulation pulse generator, and verify the operation of the device for neurostimulation applications. The literature review discusses the importance of stimulation waveforms on the outcomes of neurostimulation, and proposes new directions for neurostimulation research that would help in improving the reproducibility and comparability between studies. The pulse generator circuit is then described that generates signals inspired by the shape of excitatory or inhibitory post-synaptic potentials (EPSP, IPSP). The circuit analytical equations are presented, and the effects of the circuit design components are discussed. The circuit is also analyzed with a capacitive load using a simplified Randles model to represent the electrode-electrolyte interface, and the output is measured in phosphate-buffered saline (PBS) solution as the load with acupuncture needles as electrodes. The circuit is designed to be used in different types of neurostimulators depending on the needs of the application, and to study the effects of varying neurostimulation waveforms. The circuit is used to develop a remote-controlled wearable veterinary electro-acupuncture machine. The device has a small form-factor and 3D printed enclosure, and has a weight of 75 g with leads attached. The device is powered by a 500 mAh lithium polymer battery, and was tested to last 6 hours. The device is tested in an electro-acupuncture animal study on cats performed at the Louisiana State University School of Veterinary Medicine, where it showed expected electro-acupuncture effects. Then, a 2-channel implementation of the device is presented, and tested to show independent output amplitude, frequency, and stimulation duration per channel. Finally, the software and hardware requirements for control of the wearable veterinary electro-acupuncture machine are detailed. The number of output channels is limited to the number of hardware PWM timers available for use. The Arduino software implements PWM control for the output amplitude and frequency. The stimulation duration control is provided using software timers. The communications protocol between the microcontroller board and Android App are described, and communications are performed via Bluetooth

Kurzzeiteffekte der transkraniellen Elektrostimulation (tES) in der Behandlung von Narkolepsie und Idiopathischer Hypersomnie

Die zentralen Störungen mit Tagesschläfrigkeit stellen einen neuen, bislang wenig erforschten Anwendungsbereich der transkraniellen Elektrostimulation (tES) des Gehirns dar. In dem Fallbericht von Frase et al. (Brain Stimul 8(4), 844-6, 2015) wurde eine objektive und subjektive vigilanzsteigernde Wirkung der anodalen transkraniellen Gleichstromstimulation (tDCS) in der Behandlung eines Patienten mit organischer Hypersomnie beschrieben. In der vorliegenden Pilotstudie wurden die Kurzzeiteffekte von tDCS und transkranieller Rauschstromstimulation (tRNS) auf die Wachheit von Patienten mit Hypersomnien zentralnervösen Ursprungs analysiert (α=10%). Die Studie wurde von März bis November 2016 an der Klinik und Poliklinik für Psychiatrie und Psychotherapie der Universität Regensburg am Bezirksklinikum durchgeführt. Bei 29 Patienten (27 Narkolepsie (14 Typ 1; 13 Typ 2); 2 idiopathische Hypersomnie) wurden tES-Behandlungen an drei aufeinanderfolgenden Tagen in einem doppel-verblindeten placebokontrollierten pseudorandomisierten balancierten Cross-over-Design durchgeführt. Stimulationsmodi waren die bifrontale anodale tDCS (FP1/FP2; je 1 mA; Referenzelektroden: P3/P4; 2x13 Minuten; 20 Minuten Stimulationspause); die tRNS (Setup identisch; 100–640Hz) und eine Placebo-Stimulation (30-sekündiges Fade-in-/Fade-out-Design). Als primärer Studienendpunkt wurde die inverse mittlere Reaktionszeit (iRT) in der Psychomotor Vigilance Task (PVT) definiert, sekundäre Endpunkte waren subjektive Parameter (u.a. Epworth Sleepiness Scale (ESS)) und weitere objektive PVT-Parameter (u.a. Standardabweichung der iRT (SD iRT); Fehleranfälligkeit (Falsch-positive Reaktionen)). Der Vorher-Nachher-Vergleich der iRT ergab keine signifikanten Unterschiede zwischen den Behandlungen mit Verum und Placebo im Gesamtkollektiv (p=0.49) sowie in den Subgruppen. Die anodale tDCS erhöhte die Fehleranfälligkeit in der PVT (1.15 (±1.16) vs. 2.35 (±2.30); p=0.02) bei unveränderter Aufmerksamkeitsleistung. Bei der Stimulation mit tRNS zeigte sich eine Abnahme der SD iRT (0.68 (±0.14) vs. 0.63 (±0.10); p=0.06) ohne signifikante Überlegenheit gegenüber tDCS und Placebo (p=0.21). Die Verringerung der ESS-Werte nach der Behandlungsserie (15.8 (±3.7) vs. 14.2 (±3.8); p=0.03) kann nicht sicher von einem Placebo-Effekt abgegrenzt werden. Bei ausreichender Power (0.8) konnten keine klinisch relevanten (Cohen’s d>0.5) objektivierbaren Kurzzeiteffekte der tES auf die Wachheit von 29 Patienten mit Hypersomnien nachgewiesen werden

Working memory training and transcranial electrical brain stimulation

Working memory training improves performance on trained and untrained working memory tasks, but there is little consistent evidence that these gains benefit everyday tasks that rely on working memory. Evidence has shown that transcranial electrical stimulation (tES) may be an effective tool for enhancing cognitive training and promoting transfer. In the first study, participants completed Cogmed working memory training with either active or sham transcranial random noise stimulation (tRNS). Training was associated with substantial gains on the training activities and on transfer measures of working memory with common processing and storage demands to the training tasks. tRNS did not enhance gains on trained or untrained activities. The second study systematically investigated the boundary conditions to training transfer by testing whether gains following backward digit recall (BDR) training transferred within- and across-paradigm to untrained backward recall and n-back tasks with varying degrees of overlap with the training activity. A further aim was to test whether transcranial direct current stimulation (tDCS) enhanced training and transfer. Participants were allocated to one of three conditions: (i) BDR training with active tDCS, (ii) BDR training with sham tDCS, or (iii) visual search control training with sham tDCS. The results indicated that training transfer is constrained by paradigm, but not by stimuli domain or stimuli materials. There was no evidence that tDCS enhanced performance on the training or transfer tasks. The results of Study 1 and Study 2 provide no evidence that tES enhances the benefits of working memory training. The absence of transfer between backward recall training and n-back in Study 2 suggested the tasks might tap into distinct aspects of working memory. Consequently, the final study used a latent variable approach to explore the degree of overlap between different forms of backward recall and n-back tasks containing digits, letters, or spatial locations as stimuli. The best-fitting factor model included two distinct but related (r = .68) constructs corresponding to backward recall and n-back. Both categories of task were linked to a separate fluid reasoning construct, providing evidence that both are valid measures of higher-order complex cognition. Overall, the experiments in this thesis suggest that working memory tasks tap into separate processes and that training may be targeting and improving these distinct processes, explaining the absence of cross-paradigm transfer.Medical Research Council PhD Studentshi

Investigation of Methodological and Physiological Factors Influencing Non-Invasive Transcranial Electrical Brain Stimulation

Non-invasive transcranial electrical brain stimulation (tES) techniques, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS), can alter neuronal activity and related brain functions. However, tES effects seem to be modulated by various influencing factors, leading to high inter-individual variability in tES effects and often only low effect sizes, or even no effects. The present thesis therefore aimed to investigate methodological and physiological influencing factors of tDCS, tACS and tRNS that have not been sufficiently examined so far. A first study investigated the influence of montage and individual functional performance level on the effects of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) in healthy adults. Compared with sham stimulation, a multichannel montage led to stronger effects than a bipolar montage. For both montages the effects of stimulation were dependent on the functional performance level of participants. A second study investigated the effects of multichannel tDCS over the left DLPFC in healthy children and adolescents, considering the influence of concurrent target task performance during stimulation and individual head anatomy. tDCS did not influence the target outcome but led to transfer effects on non-target task performance and neurophysiological activity, that were only partly influenced by task performance during stimulation. The individual head anatomy had no influence on stimulation effects. A third study investigated tACS and tRNS effects on motor cortex excitability in healthy children and adolescents in comparison to adults. The individual response to sham stimulation was investigated as marker for the individual physiological brain state. Motor cortex excitability was not modulated by age but by individual response to sham stimulation. All studies provide important insights into the modulatory factors of stimulation effects. Based on these results, future studies should aim at individualising tES application

Neuromodulation of Spatial Associations: Evidence from Choice Reaction Tasks During Transcranial Direct Current Stimulation

Various portions of human behavior and cognition are influenced by covert implicit processes without being necessarily available to intentional planning. Implicit cognitive biases can be measured in behavioral tasks yielding SNARC effects for spatial associations of numerical and non-numerical sequences, or yielding the implicit association test effect for associations between insect-flower and negative-positive categories. By using concurrent neuromodulation with transcranial direct current stimulation (tDCS), subthreshold activity patterns in prefrontal cortical regions can be experimentally manipulated to reduce implicit processing. Thus, the application of tDCS can test neurocognitive hypotheses on a unique neurocognitive origin of implicit cognitive biases in different spatial-numerical and non-numerical domains. However, the effects of tDCS are not only determined by superimposed electric fields, but also by task characteristics. To outline the possibilities of task-specific targeting of tDCS, task characteristics and instructions can be varied systematically when combined with neuromodulation. In the present thesis, implicit cognitive processes are assessed in different paradigms concurrent to left-hemispheric prefrontal tDCS to investigate a verbal processing hypothesis for implicit associations in general. In psychological experiments, simple choice reaction tasks measure implicit SNARC and SNARC-like effects as relative left-hand vs. right-hand latency advantages for responding to smaller number or ordinal sequence targets. However, different combinations of polarity-dependent tDCS with stimuli and task procedures also reveal domain-specific involvements and dissociations. Discounting previous unified theories on the SNARC effect, polarity-specific neuromodulation effects dissociate numbers and weekday or month ordinal sequences. By considering also previous results and patient studies, I present a hybrid and augmented working memory account and elaborate the linguistic markedness correspondence principle as one critical verbal mechanism among competing covert coding mechanisms. Finally, a general stimulation rationale based on verbal working memory is tested in separate experiments extending also to non-spatial implicit association test effects. Regarding cognitive tDCS effects, the present studies show polarity asymmetry and task-induced activity dependence of state-dependent neuromodulation. At large, distinct combinations of the identical tDCS electrode configuration with different tasks influences behavioral outcomes tremendously, which will allow for improved task- and domain-specific targeting

Évaluation et modulation des fonctions exécutives en neuroergonomie - Continuums cognitifs et expérimentaux

Des études en neuroergonomie ont montré que le pilote d’avion pouvait commettre des erreurs en raison d’une incapacité transitoire à faire preuve de flexibilité mentale. Il apparait que certains facteurs, tels qu’une forte charge mentale ou une pression temporelle importante, un niveau de stress trop élevé, la survenue de conflits, ou une perte de conscience de la situation, peuvent altérer temporairement l’efficience des fonctions exécutives permettant cette flexibilité. Depuis mes travaux initiaux, dans lesquels je me suis intéressé aux conditions qui conduisent à une négligence auditive, j’ai souhaité développer une approche scientifique visant à quantifier et limiter les effets délétères de ces différents facteurs. Ceci a été fait à travers l’étude des fonctions exécutives chez l’être humain selon le continuum cognitif (du cerveau lésé au cerveau en parfait état de fonctionnement) et le continuum expérimental (de l’ordinateur au monde réel). L’approche fondamentale de l’étude des fonctions exécutives en neurosciences combinée à l’approche neuroergonomique graduelle avec des pilotes et des patients cérébro-lésés, a permis de mieux comprendre la manière dont ces fonctions sont mises en jeu et altérées. Cette connaissance à contribuer par la suite à la mise en place de solutions pour préserver leur efficacité en situation complexe. Après avoir rappelé mon parcours académique, je présente dans ce manuscrit une sélection de travaux répartis sur trois thématiques de recherche. La première concerne l’étude des fonctions exécutives impliquées dans l’attention et en particulier la façon dont la charge perceptive et la charge mentale peuvent altérer ces fonctions. La deuxième correspond à un aspect plus appliqué de ces travaux avec l’évaluation de l’état du pilote. Il a été question d’analyser cet état selon l’activité de pilotage elle-même ou à travers la gestion et la supervision d’un système en particulier. La troisième et dernière thématique concerne la recherche de marqueurs prédictifs de la performance cognitive et l’élaboration d’entraînements cognitifs pour limiter les troubles dysexécutifs, qu’ils soient d’origine contextuelle ou lésionnelle. Ces travaux ont contribué à une meilleure compréhension des troubles cognitifs transitoires ou chroniques, mais ils ont aussi soulevé des questions auxquelles je souhaite répondre aujourd’hui. Pour illustrer cette réflexion, je présente en dernière partie de ce document mon projet de recherche qui vise à développer une approche multifactorielle de l’efficience cognitive, éthique et en science ouverte