Accounting for individual differences in the response to tDCS with baseline levels of neurochemical excitability

There is now considerable evidence that applying a small electrical current to the cerebral cortex can have wide ranging effects on cognition and performance, and may provide substantial benefit as a treatment for conditions such as depression. However, there is variability across subjects in the extent to which stimulation modulates behaviour, providing a challenge for the development of applications. Here, we employed an individual differences approach to test if baseline concentrations of the neurochemicals GABA and glutamate are associated with an individual's response to transcranial direct current stimulation (tDCS). Using a previously replicated response selection training paradigm, we applied tDCS to the left prefrontal cortex part-way through the learning of a six-alternative-forced-choice task. Across three sessions, subjects received anodal, cathodal, or sham stimulation. Pre-tDCS baseline measures of GABA and glutamate, acquired using magnetic resonance spectroscopy (MRS), correlated with the extent to which stimulation modulated behaviour. Specifically, relative concentrations of GABA and glutamate (used as an index of neurochemical excitability) in the prefrontal cortex were associated with the degree to which active stimulation disrupted response selection training. This work represents an important step forward in developing models to predict stimulation efficacy, and provides a unique insight into how trait-based properties of the targeted cortex interact with stimulation

The efficacy of transcranial direct current stimulation to prefrontal areas is related to underlying cortical morphology

Applying a weak electrical current to the cortex can have effects on a range of behaviours. Techniques such as transcranial direct current stimulation (tDCS) have been widely used in both research and clinical settings. However, there is significant variability across individuals in terms of their responsiveness to stimulation, which poses practical challenges to the application of tDCS, but also provides a unique opportunity to study the link between the brain and behaviour. Here, we assessed the role of individual differences in cortical morphology specifically in prefrontal cortical regions of interest - for determining the influence of tDCS on decision-making performance. Specifically, we employed magnetic resonance imaging (MRI) and a previously replicated paradigm in which we modulated learning in a simple decision-making task by applying tDCS to the left prefrontal cortex in human subjects of both sexes. Cortical thickness of the left (but not right) prefrontal cortex accounted for almost 35% of the variance in stimulation efficacy across subjects. This is the first demonstration that variations in cortical architecture are associated with reliable differences in the effects of tDCS on cognition. Our findings have important implications for predicting the likely efficacy of different non-invasive brain stimulation treatments on a case by case basis

Accounting for variability in the efficacy of tDCS with cortical structure and neurochemicals

MRI, MRS, and behavioural data along with task and data extraction script

Dissociable effects of tDCS polarity on latent decision processes are associated with individual differences in neurochemical concentrations and cortical morphology

Applying a weak electrical current to the cortex has the potential to modulate neural functioning and behaviour. The most common stimulation technique, transcranial direct current stimulation (tDCS), has been used for causal investigations of brain and cognitive functioning, and to treat psychiatric conditions such as depression. However, the efficacy of tDCS in modulating behaviour varies across individuals. Moreover, despite being associated with different neural effects, the two polarities of electrical stimulation – anodal and cathodal – can result in similar behavioural outcomes. Here we employed a previously replicated behavioural paradigm that has been associated with polarity non-specific disruption of training effects in a simple decision-making task. We then used the linear ballistic accumulator model to quantify latent components of the decision-making task. In addition, magnetic resonance imaging measures were acquired prior to tDCS sessions to quantify cortical morphology and local neurochemical concentrations. Both anodal and cathodal stimulation disrupted learning-related task improvement relative to sham (placebo) stimulation, but the two polarities of stimulation had distinct effects on latent task components. Whereas anodal stimulation tended to affect decision thresholds for the behavioural task, cathodal stimulation altered evidence accumulation rates. Moreover, performance variability with anodal stimulation was related to cortical thickness of the inferior frontal gyrus, whereas performance variability with cathodal stimulation was related to cortical thickness in the inferior precentral sulcus, as well as to prefrontal neurochemical excitability. Our findings demonstrate that both cortical morphology and local neurochemical balance are important determinants of individual differences in behavioural responses to electrical brain stimulation

Channel gating regulation by the cystic fibrosis transmembrane conductance regulator (CFTR) first cytosolic loop

Background: Elucidating the mechanochemistry of ABC transporters is essential for understanding several human disease states. Results: We show a novel intermolecular binding step that governs CFTR channel activity. Conclusion: CFTR gating and ATP hydrolysis require a properly configured transmembrane domain interface. Significance: These findings indicate a new approach for discovering therapeutic targets within ABC proteins that modulate function