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

Highlights

• There is substantial variability between subjects in response to tDCS.

• Both anodal and cathodal tDCS can affect performance.

• We assessed variability & the effect of tDCS on latent decision processes.

• Anodal and cathodal tDCS modulated performance via different latent processes.

• Stimulation efficacy related to neurochemical concentrations and cortical thickness.

Abstract

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.

Introduction

Transcranial direct current stimulation (tDCS) involves running a small electrical current between two or more electrodes placed on the scalp. The current is directional, flowing between positive (anodal) and negative (cathodal) terminals. The technique is particularly useful for determining the causal role of local cortical regions and their associated perceptual, cognitive or motor functions (for a review, see Filmer et al., 2014). In the context of the present study, tDCS of the prefrontal cortex – implicated in a range of executive processes (Roberts et al., 1998) – has shown promise for the treatment of depression (Brunoni et al., 2017; Nord et al., 2019), attenuating cognitive decline in older adults (Stephens and Berryhill, 2016), and enhancing the benefits of cognitive training in healthy young adults (Filmer et al., 2017a, 2017b; Filmer et al., 2017a, 2017b).

Distinct cortical effects have been associated with each stimulation polarity. Specifically, cortex proximal to the anodal electrode shows increased excitability (Nitsche and Paulus, 2000a) and decreased concentrations of the inhibitory neurochemical gamma-aminobutyric acid (GABA; Bachtiar et al., 2018; Bachtiar et al., 2015; Stagg et al., 2009; Stagg et al., 2011). In contrast, cortex proximal to the cathodal electrode shows decreased excitability (Nitsche and Paulus, 2000a; though this varies with stimulation intensity/duration, Samani, et al., 2019) and reduced concentrations of the excitatory neurochemical glutamate (Stagg et al., 2009). The issue of stimulation polarity is likely to be more nuanced, and dependent on factors such as the orientations of the affected neurons (Liu et al., 2018). Moreover, the effects of tDCS are variable across subjects (Wiethoff et al., 2014), potentially limiting applications (Parkin et al., 2015). However, such individual variability can be harnessed to help relate brain function (Drew and Vogel, 2008; Garner and Dux, 2015), structure (Frank et al., 2016; Kanai et al., 2010; Verghese et al., 2016), and neurochemical concentration (Terhune et al., 2014; Yoon et al., 2016) to behaviour. In addition, baseline neural activity can predict patient response to tDCS treatment for depression (Nord et al., 2019). If the sources of variability in tDCS outcomes are characterised, interventions may be tailored to maximise benefits.

We have previously shown that both anodal and cathodal stimulation with tDCS can disrupt learning in a decision-making task when applied offline over the left prefrontal cortex (Filmer et al., 2013a, 2013b; Filmer et al., 2013a, 2013b), suggesting that tDCS may have similar behavioural effects regardless of stimulation polarity (see also Stagg et al., 2011). It remains unclear, however, whether the two polarities might differentially modulate latent components of the decision-making process which cannot be accessed using response time and accuracy measures alone. Computational models of choice and response time, such as the linear ballistic accumulator framework (LBA; Brown and Heathcote, 2008), can quantify these latent components – specifically, the drift rate (the rate at which evidence is accumulated for response options), the response threshold (the amount of evidence required for a decision to be reached), and non-decision time (a combination of sensory and motor processes). By quantifying latent components, it is possible to obtain a more mechanistic characterisation of how stimulation modulates behavioural outcomes.

Here, we employed our previously replicated decision-making paradigm (Filmer et al., 2013a, 2013b) to ascertain the effect of stimulation on latent decision processes. The effects of stimulation were modelled for each subject, and related to baseline measures of local neurochemical concentrations (using magnetic resonance spectroscopy; MRS) and cortical morphology (using magnetic resonance imaging; MRI). We expected both anodal and cathodal tDCS to disrupt training related gains in reaction times, and for this to be reflected in modulations of latent decision processes (thresholds and/or drift rates). Using an individual differences approach, stimulation effects on decision processes were expected to relate to both cortical thickness and neurochemical concentrations in the left prefrontal cortex. The specific nature of these relationships were not predicted in advance, and hence this element of the study was exploratory. To preview the results, we replicated our finding of polarity non-specific disruption of training benefits on the decision-making task, but also revealed distinct effects of stimulation polarity on latent decision components: whereas anodal stimulation predominantly affected subjects’ response thresholds, cathodal stimulation affected the rate of evidence accumulation. Moreover, we found that variability in the effect of tDCS on decision-making was associated with individual differences in both cortical thickness and local neurochemical concentrations in the prefrontal cortex.