Investigating transcranial direct current stimulation and its therapeutic potential

Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique, which has the potential to modulate cortical excitability. The effects of tDCS are known to outlast the stimulation period, and in some cases, repeated applications have been found to produce long lasting clinically relevant effects. The primary aim of this thesis was to explore the reliability and therapeutic potential of this technique. In Chapters 3 and 4 transcranial magnetic stimulation (TMS) was used to measure tDCS effects. These experiments revealed substantial variability regarding the way in which healthy adults responded to stimulation. Notably, there were differences between participants regarding the direction and magnitude of change in cortical excitability. Furthermore, even when group level effects were found reliably, there was substantial intra-subject variability across repeated testing sessions. Subsequent experiments in Chapters 5 and 6, explored the biological and behavioural effects of tDCS in individuals with Gille de la Tourette’s syndrome (GTS). GTS is a neurodevelopmental disorder characterised by motor and phonic tics which have been linked to hyper excitability within motor-cortical regions. Therefore, these experiments aimed to reduce cortical excitability of targeted regions in the hope that this would impact on tics. Disappointingly, no such effects were found immediately after a single session of tDCS (Chapter 5). Consequently, it was hypothesised that repeated applications may be necessary for significant reductions in tics to occur. This was investigated in Chapter 6 using an in-depth case study. The results were encouraging, in particular there was a substantial drop in tics following 10 days of tDCS at 1.5mA intensity. The stimulation was well tolerated and the treatment regimens were closely adhered to, despite tDCS being delivered in the participants own home with remote supervision. A weaker stimulation intensity was not as effective. The findings of Chapters 3-6 highlight that the optimal stimulation parameters may vary from person to person, and that exploration of individual data is critical in therapeutic contexts. The results also suggest that tDCS may be helpful as a treatment for GTS and furthermore highlight the feasibility of home use stimulation

Investigating transcranial direct current stimulation and its therapeutic potential

Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique, which has the potential to modulate cortical excitability. The effects of tDCS are known to outlast the stimulation period, and in some cases, repeated applications have been found to produce long lasting clinically relevant effects. The primary aim of this thesis was to explore the reliability and therapeutic potential of this technique. In Chapters 3 and 4 transcranial magnetic stimulation (TMS) was used to measure tDCS effects. These experiments revealed substantial variability regarding the way in which healthy adults responded to stimulation. Notably, there were differences between participants regarding the direction and magnitude of change in cortical excitability. Furthermore, even when group level effects were found reliably, there was substantial intra-subject variability across repeated testing sessions. Subsequent experiments in Chapters 5 and 6, explored the biological and behavioural effects of tDCS in individuals with Gille de la Tourette’s syndrome (GTS). GTS is a neurodevelopmental disorder characterised by motor and phonic tics which have been linked to hyper excitability within motor-cortical regions. Therefore, these experiments aimed to reduce cortical excitability of targeted regions in the hope that this would impact on tics. Disappointingly, no such effects were found immediately after a single session of tDCS (Chapter 5). Consequently, it was hypothesised that repeated applications may be necessary for significant reductions in tics to occur. This was investigated in Chapter 6 using an in-depth case study. The results were encouraging, in particular there was a substantial drop in tics following 10 days of tDCS at 1.5mA intensity. The stimulation was well tolerated and the treatment regimens were closely adhered to, despite tDCS being delivered in the participants own home with remote supervision. A weaker stimulation intensity was not as effective. The findings of Chapters 3-6 highlight that the optimal stimulation parameters may vary from person to person, and that exploration of individual data is critical in therapeutic contexts. The results also suggest that tDCS may be helpful as a treatment for GTS and furthermore highlight the feasibility of home use stimulation

Intra-subject consistency and reliability of response following 2mA transcranial direct current stimulation

Background Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique that has been shown to influence cortical excitability. While polarity specific effects have often been reported, this is not always the case, and variability in both the magnitude and direction of the effects have been observed. Objective/ hypothesis We aimed to explore the consistency and reliability of the effects of tDCS by investigating changes in cortical excitability across multiple testing sessions in the same individuals. A within subjects design was used to investigate the effects of anodal and cathodal tDCS applied to the motor cortex. Four experimental sessions were tested for each polarity in addition to two sham sessions. Methods Transcranial Magnetic Stimulation (TMS) was used to measure cortical excitability (TMS recruitment curves). Changes in excitability were measured by comparing baseline measures and those taken immediately following 20minutes of 2mA stimulation or sham stimulation. Results Anodal tDCS significantly increased cortical excitability at a group level, whereas cathodal tDCS failed to have any significant effects. The sham condition also failed to show any significant changes. Analysis of intra-subject responses to anodal stimulation across four sessions suggest that the amount of change in excitability across sessions was only weakly associated, and was found to have poor reliability across sessions (ICC=0.276). The effects of cathodal stimulation show even poorer reliability across sessions (ICC=0.137). In contrast ICC analysis for the two sessions of sham stimulation reflect a moderate level of reliability (ICC=.424). Conclusions Our findings indicate that although 2mA anodal tDCS is effective at increasing cortical excitability at group level, the effects are unreliable across repeated testing sessions within individual participants. Our results suggest that 2mA cathodal tDCS does not significantly alter cortical excitability immediately following stimulation and that there is poor reliability of the effect within the same individual across different testing sessions

Impaired forward model updating in young adults with Tourette syndrome

Current theories of motor control emphasise how the brain may use internal models of the body to ensure accurate planning and control of movements. One such internal model - a forward model - is thought to generate an estimate of the next motor state and/or the sensory consequences of an upcoming movement, thereby allowing movement errors to be monitored. In addition, forward models may provide a means by which to determine a sense of agency, i.e., the (conscious) sense of authorship and control over our actions. Tourette syndrome is a developmental neurological condition characterised by the occurrence of motor and phonic tics. The involuntary (or voluntary) nature of tics has been the subject of considerable debate, and it was recently argued that the presence of tics in Tourette syndrome could result in a blurring of any subjective boundary between voluntary and involuntary movements. In particular, it was proposed that the level of sensorimotor noise that accompanies tics may be particularly high in Tourette syndrome, and this may contribute to less efficient forward models used to determine agency. We investigated whether the internal monitoring of movements is impaired in individuals with Tourette syndrome, relative to a matched group of typically-developing individuals, using a task that involved executing double-step aiming movements using a hand-held robot manipulandum. Participants were required on each trial to execute two movements in turn, each directed to a remembered target location without visual feedback. Importantly, we assumed that to perform accurately on the second (return) movement it would be necessary to update any forward model to take account errors made during the first (outward) movement. Here we demonstrate that while the Tourette syndrome group were equally accurate, and no more variable, than the matched control group in executing aiming movements to the first (outward) target location. They were significantly less accurate, and exhibited greater movement variability, than controls when executing the second (return) movement. Furthermore, we show that for the return movement only, movement accuracy and movement variability were significantly predicted by the Tourette syndrome group’s clinical severity scores. We interpret these findings as consistent with the view that individuals with Tourette syndrome may experience a reduction in the precision of the forward model estimates thought necessary for the accurate planning and control of movements

2020 Kentucky Transportation Cabinet Maintenance Customer Survey

The Kentucky Transportation Cabinet (KYTC) periodically surveys drivers to understand their perceptions of the agency’s maintenance activities. In 2020, Quadratics in conjunction with the Kentucky Transportation Center surveyed 2,400 licensed drivers throughout the state to gauge their perceptions of highway maintenance, identify areas of strength and weakness, and discern how drivers obtain information on traffic and weather conditions. Survey participants answered questions about five areas of highway maintenance — roadside features, pavement surfaces, shoulders, drainage, and signs/markings. Drivers reported being most satisfied with the maintenance of signs, guardrail, and striping. Pavement surfaces, potholes, and overall appearance garnered the lowest ratings. When queried about investment priorities, respondents said the most important areas for KYTC to focus on are pavement surfaces, signs, and markings. A comparison of the 2010, 2016, and 2020 customer maintenance surveys found that responses and reported levels of satisfaction have remained largely consistent. Questions about traffic and weather information revealed that drivers are increasingly reliant on smartphone apps while traditional media (e.g., television, radio) have diminished in importance

Non-invasive brain stimulation as therapy: systematic review and recommendations with a focus on the treatment of Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental condition characterised by tics, which are stereotyped movements and/or vocalisations. Tics often cause difficulties in daily life and many with TS express a desire to reduce and/or gain control over them. No singular effective treatment exists for TS, and while pharmacological and behavioural interventions can be effective, the results are variable, and issues relating to access, availability and side effects can be barriers to treatment. Consequently, over the past decade, there has been increasing interest into the potential benefits of non-invasive brain stimulation (NIBS) approaches. This systematic review highlights work exploring NIBS as a potential treatment for TS. On balance, the results tentatively suggest that multiple sessions of stimulation applied over the supplementary motor area (SMA) may help to reduce tics. However, a number of methodological and theoretical issues limit the strength of this conclusion, with the most problematic being the lack of large-scale sham-controlled studies. In this review, methodological and theoretical issues are discussed, unanswered questions highlighted and suggestions for future work put forward

Carbon-Carbon Single Bond Activation Used for Coupling with Michael Acceptors

Carbon-carbon single bond activation and functionalization occurs in a quinolinyl ketone structure through rhodium catalyzed bond activation and subsequent insertion of a Michael acceptor, primarily methyl acrylate and N,N-dimethylacrylamide. A variety of quinolinyl ketones and Michael acceptors are observed to react catalytically, forming a disubstituted alkene coupling product. A broad scope of quinolinyl ketones and Michael acceptors have been used to investigate the mechanism for the reaction