Neuromodulation of executive vigilance via transcranial direct current stimulation

Abstract

Many everyday tasks and working environments rely on our ability to keep our attention focused for prolonged periods of time. However, as we have all experienced, this ability is effortful and cannot be sustained indefinitely. Inevitably, as time goes by, our performance becomes less sharp and more error-prone, as our mind either falters in the face of demands it cannot sustain, or it slowly disengages from the task at hand, wandering elsewhere. This phenomenon is known as vigilance decrement. This thesis begins by disentangling a working definition of the concept of vigilance, as its use across different disciplines, and its fuzzy description within cognitive psychology render it hard to grasp. By distinguishing vigilance from other processes such as arousal, alertness, and sustained attention, we land on the following working definition: “the ability to monitor the environment and detect rare but critical stimuli”. Further refining this definition, the present thesis accounts for a recent conceptualization of vigilance as a two-component process: (i) executive vigilance (EV), defined as the ability to monitor the environment to detect specific infrequent but critical signals, requiring the exertion of control to decide whether a response has to be emitted or not (Luna et al., 2018a); (ii) arousal vigilance (AV), on the other hand, defined as the general maintenance of a basic state of activation to emit fast and relatively automatic responses to those rare but critical stimuli requiring minimal topdown control (Luna et al., 2018a). A further aspect of relevance for the present thesis is the specific sensitivity of the EV decrement to the cognitive demands required by the task (Luna, Barttfeld, et al., 2022). The inevitable decrement of vigilance over time will lead to consequences that can range from the trivial, such as missing the right exit on the motorway while driving, to the catastrophic, such as a fatal accident (Wundersitz, 2019). In addition to these everyday or work-related consequences, lesions or alterations in the development of the brain can reduce the capacity for exerting vigilance. This motivates the main aim of the present thesis: to study the potential of transcranial direct current stimulation (tDCS) in mitigating this vigilance decrement. By applying a constant electrical current across the scalp, tDCS can influence the excitability of underlying neuronal populations. This modulation of neuronal activity, in turn, can modulate cognitive functions, including attention and vigilance (Coffman et al., 2014a). A review of the existing literature on the application of tDCS to attention deficits in clinical populations with attention deficit hyperactivity disorder (ADHD) or acquired brain injury (ABI), and to vigilance in healthy populations, shows that the large heterogeneity of tDCS parameters and outcome measures does not yet provide a clear picture of the efficacy of tDCS in mitigating vigilance decrements. The present thesis aims to further explore the potential of applying anodal high-definition tDCS (HD-tDCS) over the right posterior parietal cortex (rPPC) to mitigate the EV decrement (Luna et al., 2020), by exploring the impact of differing cognitive demands as well as underlying neuroimaging data as outcome predictors. In a first study, participants (N = 60) completed the ANTI-Vea task while receiving either anodal or sham HD-tDCS over the rPPC. Electrophysiological (EEG) recordings were completed before and after stimulation. Anodal HD-tDCS specifically mitigated executive vigilance (EV) and reduced the increment of alpha power with time-on-task, while further increasing the increment of gamma power. Through a new proposed index of Alphaparietal/Gammafrontal a further dissociation is observed. The increment of this Alphaparietal/Gammafrontal Index with time-on-task was associated with a steeper EV decrement in the sham group, which was abolished by anodal HD-tDCS. In a second study, participants (N = 120) completed a modified ANTI-Vea task (single or dual task) while receiving either anodal or sham HD-tDCS over the rPPC. Joint analyses of this data and data from prior studies performing a triple task (combined N = 240, Study I and Luna et al. 2020) were completed. We observed that against the mitigated vigilance decrement observed in the triple task condition (standard ANTI-Vea) with anodal HD-tDCS, both the single and dual load conditions showed significant EV decrements that were not affected by the application of HDtDCS. In a third study, EEG data collected in Studies I and II (N = 180) was analysed more in-depth, by parametrizing the EEG power spectra to disentangle periodic (oscillatory) from aperiodic (non-oscillatory, namely aperiodic exponent and offset) components. HD-tDCS led to a decrement of the aperiodic exponent extracted from the 30-45 Hz frequency range, suggesting an increased excitation/inhibition (E/I) balance with active stimulation. This increment of the E/I balance was associated with a mitigated EV decrement in the high-demand (triple) task and an exacerbated EV decrement in the low-demand (single) task. While these results require further research as the results were only observed considering a directional hypothesis and other interactions may obscure the effect, they illustrate a potential mechanistic explanation of the cognitiveload dependent effect. A last empirical chapter contains a report with an initial exploration of the potential influence of microstructural white matter connectivity on the effect of the HD-tDCS protocol on the EV decrement. We analysed diffusion-weighted imaging (DWI) data collected from participants (N = 172) in Studies I and II (triple, dual, or single tasks combined with either anodal or sham HD-tDCS over the rPPC). The preliminary findings suggest the right third branch of the superior longitudinal fasciculus (SLF), the left second branch of the SLF, the Cingulum, and the Splenium of the Corpus Callosum as potentially relevant structures for future causal analyses, such as moderation analyses. This thesis contributes to the understanding of the vigilance decrement and the potential of tDCS to mitigate it, highlighting the importance of considering cognitive load and individual differences in neurophysiological responses for a more nuanced understanding of its effects. Specifically, the results from this thesis highlight: (i) the need for replication studies and the integration of neurophysiological measures as a means to potentially predict stimulation outcomes, (ii) the need to consider the task used as an outcome measure due to the different brain states it will induce, (iii) the importance of considering the underlying brain state in interaction with the effects of tDCS to better understand its mechanisms of action, and whilst no definitive predictions can be made yet, (iv) it offers a promising first look at the potential of predicting tDCS outcomes from pre-intervention structural neuroimaging data. With future research, the results of this thesis can aid in further exploring this interesting intersection of neuromodulation, vigilance, and neurophysiology, which may help design more precise future interventions to mitigate the inevitable decrement of vigilance over time.