Studies attempting to increase working memory (WM) capacity show promise in enhancing related cognitive functions (see Morrison & Chein, 2011 for a recent review), but have also raised criticism in the broader scientific community given the scattered findings produced by these studies (Morrison & Chein, 2011; Shipstead, Redick, & Engle, 2010, 2012). Non-invasive brain stimulation, in particular transcranial direct current stimulation, has been shown to enhance WM performance in a single session (Fregni, et al., 2005) as well as learning over time in other cognitive domains (Iuculano & Cohen Kadosh, 2013; Reis, et al., 2009). However, the extent to which tDCS might enhance learning on a WM training regime, and the extent to which learning gains might transfer outside of the training task remain unknown. To this end, participants engaged in an adaptive WM training task (previously utilized in Chein & Morrison, 2010; Richmond, Morrison, Chein, & Olson, 2011) for 10 sessions over two weeks, concurrent with either active or sham stimulation of dorsolateral prefrontal cortex. Before and after training, a battery of tests tapping domains known to relate to WM abilities was administered. Results show that tDCS reliably enhanced learning on the training task, particularly in the verbal domain. Furthermore, tDCS was shown to enhance transfer to other untrained WM tasks. These results lend support to the idea that tDCS might bolster training and transfer gains in populations with compromised WM abilities. / Psychology

With increasing life expectancy and global population of older adults, preserving cog- nitive function throughout life represents a growing priority. Numerous approaches to cognitive enhancement exist, but few have scientific merit. Among the most preva- lent – and commercialized – approaches are cognitive training (“brain training”) and non-invasive brain stimulation through electric currents applied at the surface of the scalp. The present dissertation describes a collection of work contextualizing the appeal of these cognitive enhancement methods and addressing some of the most pervasive limitations of research in this field thus far. One largely ignored issue in cognitive intervention research pertains to people’s expectations of programs and their relationship with intervention outcomes. In a series of initial studies, we developed and validated the Expectation Assessment Scale (EAS), a tool created to measure as well as prime expectations of outcomes in the context of cognitive enhancement interventions. In our first two studies, we probed expectations of cognitive training or non-invasive brain stimulation in over 1,000 young, middle-aged, and older adults. Ratings on the EAS suggested that older adults may have particularly high expectations of cognitive training, but that expectations can be primed to increase or decrease – at least in hypothetical scenarios. We used these data to assess the psychometric properties of the EAS with item-response theory, and confirmed its internal consistency. Next, we incorporated the EAS into two cognitive enhancement trials, one in- vestigating a computerized cognitive training intervention in nearly 100 older adults and another examining non-invasive brain stimulation in nearly 100 young adults. Both trials had a double-blind balanced-placebo design in which participants were assigned to the intervention or control condition, and then subdivided to receive ei- ther high or low expectation priming (i.e., primed to have high or low expectations of the program’s effectiveness). Although expectation ratings replicated our previous findings, results from these trials suggest little, if any, effect of either expectations or the intervention on performance outcomes. We nevertheless found that participants enjoyed their assigned program and that those who received high expectation prim- ing tended to report a more positive experience. Our findings put into question the effectiveness of such interventions and support the need for more rigorous trials of cognitive enhancement.

<p>Non-invasive electromagnetic brain stimulation uses electrodes and/or coils to modulate brain activity via the induced E-fields. E-field dosimetry solvers have improved non-invasive electromagnetic brain stimulation protocol and our understanding of neuroscience. However, E-field dosimetry techniques are incomplete in that the contributions of non-linear neuron activity are left unaccounted for. To better understand the neurological effects of non-invasive electromagnetic stimulation, we introduce an integral equation formulation for modeling the non-linear behavior of neurons due to an incident E-field generated by electrode and coil sources. We formulate the new integral equation using a boundary element approach. We compare the boundary element solver accuracy with an established finite element solver and multi-scale cable equation approaches. Unlike previous approaches, this new boundary integral formulation avoids multi-scaling challenges from meshing while retaining the accuracy and the robust spatial support of integral equation-based methods. The memory savings from switching to surface meshes makes simulations with more complex morphologies computationally tractable. Additionally, we examine the ability of neurons to couple to one another via the local extracellular fields. Examples of simulations with both transcranial electric and magnetic stimulation results for simple geometries are used to illustrate the capabilities of a boundary integral approach. This boundary integral method will aid the development of better neurological understanding, delineate the mechanisms by which electromagnetic stimulation engenders neuronal activity, and aid in modeling local E-field coupling.</p>

La stimulation transcrânienne par courant alternatif (tACS) est une technique de stimulation non invasive du cerveau qui est d’un intérêt croissant, entre autres pour ses effets sur les ondes cérébrales intrinsèques. Par opposition à la stimulation transcranienne par courant direct (tDCS), la tACS permet l’administration d’un courant sinusoïdal ajusté à la fréquence endogène individuelle d’un individu. Les oscillations cérébrales constituant la bande de fréquence alpha (8-12 Hz) sont parmi les plus étudiées en raison de leurs associations variées avec les fonctions et états cérébraux. Un nombre important d’études ont montré l’efficacité de la tACS de diverses façons pour augmenter la puissance de l’activité EEG dans la bande de fréquence alphal’onde alpha. Cependant, l’hétérogénéité des paramètres de stimulation, particulièrement l’intensité, rend l’implémentation de nouveaux protocoles ardue. En effet, il n’y a actuellement aucun consensus sur les paramètres optimaux de stimulation pour moduler l’activité EEG dans la bande de fréquence alphal’onde alpha. Ce projet a pour but de documenter l’impact différentiel de contrôler les caractéristiques de stimulation tACS, soit l’intensité, la fréquence et le site (antérieur ou postérieur) de stimulation. À cette fin, 20 participants en santé ont pris part à notre étude, chacun soumis à 4 conditions de stimulation tACS, échelonnées sur 2 jours (2 blocs par jour). Pour chaque condition expérimentale, la stimulation tACS a été administrée de façon continue via 2 électrodes pendant 20 minutes. Deux conditions actives de tACS ont été réalisées aux sites PO7-PO8 (Système International EEG 10-10), l’une à Fréquence Alpha Individuelle (IAF) et l’autre à Fréquence Theta Individuelle (ITF), qui ont été prédéterminées par une session EEG, au repos et les yeux ouverts, de 5 minutes a priori. Deux conditions de stimulation ont été effectuées avec les électrodes de stimulation positionnées aux sites F3F4 (Système International EEG 10-20), à IAF ou à intensité SHAM (montée de courant 15 secondes seulement). L’intensité de stimulation a été ajustée en respectant le degré de confort de chaque participant, selon une échelle standardisée de désagréabilité (≤ 40 sur 100), et ne pouvait excéder 6 mA. La seconde séance journalière était exécutée 180 minutes après la première séance de tACS. Afin d’évaluer les niveaux de fatigue, les participants ont eu à réaliser une tâche psychomotrice de vigilance (PVT) durant la tACS. Toutes les conditions ont été contrebalancées. Les résultats suggèrent que la tACS ajustée à IAF a été plus efficace que les conditions ITF et SHAM afin d’augmenter la puissance alpha. Pour les deux sites de stimulation IAF tACS, l’augmentation de puissance spectrale la plus importante a été obtenue en tACS antérieure; par contre cette augmentation est distale et spécifique aux générateurs alpha, en pariéto-occipital. Pour ce qui est du montage tACS postérieur, l’augmentation alpha est observée pour les deux régions cérébrales, frontale et postérieure, tout en démontrant un effet d’augmentation préférentiel sur la puissance alpha, versus les autres bandes de fréquence theta et beta. Cette étude propose une évidence préliminaire que la tACS ajustée à IAF à plus hautes intensités est bien tolérée et démontre que l’optimisation de la technique peut avoir un impact prometteur dans le domaine. / Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique increasingly used for its modulating effect on intrinsic brain oscillations. In comparison to transcranial direct current stimulation (tDCS), tACS allows the administration of a sinusoidal current adjusted to one’s endogenous measured frequency. Oscillations within the alpha band range (8-12 Hz) are among the most studied, given their various associations with brain functions and states. A number of studies have proven to be effective in increasing alpha power using tACS through diverse methods. However, the heterogeneity of stimulation parameters, notably the intensity, makes it difficult to implement new tACS protocol. Indeed, there is currently no consensus on optimal stimulation parameters to modulate the alpha rhythm. The current project aimed to document the differential impact of controlling for key tACS stimulation characteristics, namely the stimulation intensity, the stimulation frequency and the stimulation site (anterior or posterior). To this end, we conducted a study, in which 20 healthy participants underwent four different tACS conditions conducted over two non-consecutive days (2 blocks per day). In each experimental condition, tACS stimulation was continuously delivered via two electrodes for a total duration of 20 minutes. Two active tACS conditions were administered at electrode sites PO7-PO8 (10-10 International System) at either the Individual’s Alpha Frequency (IAF) or at the Individual’s Theta Frequency (ITF), which were a priori determined via a 5-minute pre-stimulation EEG recording with eyes open at rest. Two stimulation conditions were performed with stimulating electrodes positioned over F3-F4 electrode sites, at IAF or sham intensity (ramp-up of 15 seconds). The stimulation intensity was set according to the participant’s own rating of unpleasantness on a standardized unpleasantness scale (≤ 40 out of 100) and could not exceed 6 mA. The second tACS condition was administered 180 minutes after the first tACS condition. To assess for fatigue levels, participants were asked to perform a psychomotor vigilance task (PVT) during tACS. All conditions were counterbalanced. Results suggest that alpha tACS stimulation adjusted to IAF was effective in increasing alpha power. Of the two stimulating sites, anterior alpha tACS stimulation induced greatest increases in alpha power, maximal when set to IAF, although specific to alpha generators’ site. Posterior alpha tACS stimulation showed overall increase both over frontal and posterior brain areas. These effects persisted at the 60-minute recording for the anterior tACS only. The current pilot study provides preliminary evidence that posterior tACS stimulation adjusted to IAF at higher intensities is well tolerated and shows potential as an effective brain stimulation technique to increase posterior alpha power.

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Spike timing-dependent plasticity (STDP) has been suggested as one of the key mechanism underlying learning and memory. Due to its importance, timing-dependent plasticity studies have been approached in the living human brain by means of non-invasive brain stimulation (NIBS) protocols such as paired associative stimulation (PAS). However, contrary to STDP studies at a cellular level, functional plasticity induction in the human brain implies the interaction among target cortical networks and investigates plasticity mechanisms at a systems level. This thesis comprises of two independent studies that aim at understanding the importance of considering broad cortical networks when predicting the outcome of timing-dependent associative plasticity induction in the human brain. In the first study we developed a new protocol (ipsilateral PAS (ipsiPAS)) that required timing- and regional-specific information transfer across hemispheres for the induction of timing-dependent plasticity within M1 (see chapter 3). In the second study, we tested the influence of individual brain structure, as measured with voxel-based cortical thickness, on a standard PAS protocol (see chapter 4). In summary, we observed that the near-synchronous associativity taking place within M1 is not the only determinant influencing the outcome of PAS protocols. Rather, the online interaction of the cortical networks integrating information during a PAS intervention determines the outcome of the pairing of inputs in M1.

Numerical cognition has been shown to share many aspects of spatial cognition, both behavioural and neurological. However, it is unclear whether a particular type of spatial cognition, visuospatial mental imagery (VSMI), may play a role in symbolic numerical representation. In this thesis, I first show that mental rotation, a form of VSMI, is related to two measures of basic numerical representation. I then show that number-space synaesthesia (NSS), a rare type of VSMI involving visualised spatial layouts for numbers, does not show an advantage in mental rotation, but shows interference in number line mapping. I next present a study investigating links between NSS and the ability to learn novel numerical symbols. I demonstrate that NSS shows an advantage at learning novel numerals, and that transcranial random noise stimulation, which increases cortical excitability, confers broadly similar advantages that nonetheless differ in subtle ways. I present a study of transcranial alternating current stimulation on the same symbol learning paradigm, which fails to demonstrate effects. Lastly, I present data showing that strength of numerical representation in these newly-learnt symbols is correlated with a measure of mental rotation, and also with visual recognition ability for the symbols after, but not before, training. All together, these findings suggest that VSMI does indeed play a role in numerical cognition, and that it may do so from an early stage of learning symbolic numbers.

Spike timing-dependent plasticity (STDP) has been suggested as one of the key mechanism underlying learning and memory. Due to its importance, timing-dependent plasticity studies have been approached in the living human brain by means of non-invasive brain stimulation (NIBS) protocols such as paired associative stimulation (PAS). However, contrary to STDP studies at a cellular level, functional plasticity induction in the human brain implies the interaction among target cortical networks and investigates plasticity mechanisms at a systems level. This thesis comprises of two independent studies that aim at understanding the importance of considering broad cortical networks when predicting the outcome of timing-dependent associative plasticity induction in the human brain. In the first study we developed a new protocol (ipsilateral PAS (ipsiPAS)) that required timing- and regional-specific information transfer across hemispheres for the induction of timing-dependent plasticity within M1 (see chapter 3). In the second study, we tested the influence of individual brain structure, as measured with voxel-based cortical thickness, on a standard PAS protocol (see chapter 4). In summary, we observed that the near-synchronous associativity taking place within M1 is not the only determinant influencing the outcome of PAS protocols. Rather, the online interaction of the cortical networks integrating information during a PAS intervention determines the outcome of the pairing of inputs in M1.

Alcohol use disorder (AUD) is characterized by excessive habitual drinking and loss of control over alcohol intake despite negative consequences. Both of these aspects foster uncontrolled drinking and high relapse rates in AUD patients. Yet, common interventions mostly focus on the phenomenological level, and prioritize the reduction of craving and withdrawal symptoms. Our review provides a mechanistic understanding of AUD and suggests alternative therapeutic approaches targeting the mechanisms underlying dysfunctional alcohol-related behaviours. Specifically, we explain how repeated drinking fosters the development of rigid drinking habits and is associated with diminished cognitive control. These behavioural and cognitive effects are then functionally related to the neurobiochemical effects of alcohol abuse. We further explain how alterations in fronto-striatal network activity may constitute the neurobiological correlates of these alcohol-related dysfunctions. Finally, we discuss limitations in current pharmacological AUD therapies and suggest non-invasive brain stimulation (like TMS and tDCS interventions) as a potential addition/alternative for modulating the activation of both cortical and subcortical areas to help re-establish the functional balance between controlled and automatic behaviour.