abstract: Transcranial focused ultrasound (tFUS) is a unique neurostimulation modality with potential to develop into a highly sophisticated and effective tool. Unlike any other noninvasive neurostimulation technique, tFUS has a high spatial resolution (on the order of millimeters) and can penetrate across the skull, deep into the brain. Sub-thermal tFUS has been shown to induce changes in EEG and fMRI, as well as perception and mood. This study investigates the possibility of using tFUS to modulate brain networks involved in attention and cognitive control.Three different brain areas linked to saliency, cognitive control, and emotion within the cingulo-opercular network were stimulated with tFUS while subjects performed behavioral paradigms. The first study targeted the dorsal anterior cingulate cortex (dACC), which is associated with performance on cognitive attention tasks, conflict, error, and, emotion. Subjects performed a variant of the Erikson Flanker task in which emotional faces (fear, neutral or scrambled) were displayed in the background as distractors. tFUS significantly reduced the reaction time (RT) delay induced by faces; there were significant differences between tFUS and Sham groups in event related potentials (ERP), event related spectral perturbation (ERSP), conflict and error processing, and heart rate variability (HRV). The second study used the same behavioral paradigm, but targeted tFUS to the right anterior insula/frontal operculum (aIns/fO). The aIns/fO is implicated in saliency, cognitive control, interoceptive awareness, autonomic function, and emotion. tFUS was found to significantly alter ERP, ERSP, conflict and error processing, and HRV responses. The third study targeted tFUS to the right inferior frontal gyrus (rIFG), employing the Stop Signal task to study inhibition. tFUS affected ERPs and improved stopping speed. Using network modeling, causal evidence is presented for rIFG influence on subcortical nodes in stopping. This work provides preliminarily evidence that tFUS can be used to modulate broader network function through a single node, affecting neurophysiological processing, physiologic responses, and behavioral performance. Additionally it can be used as a tool to elucidate network function. These studies suggest tFUS has the potential to affect cognitive function as a clinical tool, and perhaps even enhance wellbeing and expand conscious awareness. / Dissertation/Thesis / Doctoral Dissertation Bioengineering 2020

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Au quotidien, nos ressources attentionnelles sont sollicitées de part et d’autre et la capacité à diriger notre attention sur une tâche et ignorer les distractions (le contrôle attentionnel) est cruciale. Pour mieux comprendre cette influence, les facteurs émotionnels pouvant moduler l’attention sont étudiés. L’omniprésence de la musique, et des émotions qu’elle induit, dans les activités quotidiennes soulève des questions quant à son effet sur cette capacité. Les résultats des études explorant l’effet de la musique de fond sur le contrôle attentionnel sont divergents, ils sont parfois nuisibles ou nuls, mais généralement bénéfiques. Il est possible que cette divergence s’explique par la diversité des caractéristiques émotionnelles (p.ex. le caractère relaxant ou stimulant) de la musique de fond utilisée dans les études. Le contrôle attentionnel peut également être modulé par les variations individuelles de l’anxiété (p.ex. des niveaux faible ou élevé de l’état et du trait d’anxiété). Considérer (a) les niveaux d’activation de la musique de fond et (b) des variations individuelles d’anxiété pourrait clarifier comment le contrôle attentionnel est influencé dans la vie quotidienne. Pour cela, deux groupes tirés d’une population adulte non-clinique ont été testés, un ayant un niveau d’état et de trait d’anxiété faible et un autre ayant un niveau d’état et de trait d’anxiété plus élevé. Tous les participants ont réalisé la tâche Flanker dans trois conditions : avec la présentation de musiques stimulantes et relaxantes, ainsi qu’en silence. Les résultats indiquent que l’effet Flanker est similaire entre les trois conditions pour le groupe à anxiété faible. En revanche, pour le groupe à anxiété plus élevée, l’effet Flanker est significativement augmenté avec la musique relaxante comparativement au silence. Ces résultats suggèrent que l’effet de l’activation de la musique de fond sur le contrôle attentionnel varie selon le niveau d’anxiété. / Daily, attentional control is solicited to maintain attention on a desired task and inhibit distractions. Knowingly, emotional factors are studied to further understand attentional modulation. With the omnipresence of music, and the emotions it induces, in daily activities, its impact on attentional control arises questioning. Studies exploring the effect of background music on attentional control have shown inconsistent results, supporting its effect is sometimes detrimental or null, but mostly beneficial. Differences in the emotional characteristics of music could possibly explain the inconsistent results shown in studies exploring the effect of emotions on attentional control. Additionally, individual variations in emotional states have been shown to impact attentional control capacities, namely variations in anxiety (low/high trait and state anxiety). Considering activation levels of music (stimulating/relaxing) and individual levels of anxiety (low/high) could clarify how attentional control is impacted in the daily life. This study aims explored the effect of (a) the activation levels of background music and (b) individual differences in anxiety on attentional control capacities using the Flanker task. To this aim, a low state-and-trait anxiety group and a high state-and-trait anxiety groups drawn form a non-clinical population were tested under three conditions: with presentation of stimulating and relaxing music, and in silence. For the low-anxiety group, the Flanker effect was similar between the three conditions. On the other hand, for the high-anxiety group, the Flanker effect was significantly increased with the relaxing background music compared to silence. These results suggest that the effect of background music activation levels on attentional control varies as a function of anxiety levels.

I den föreliggande studien undersöktes effekten av en kort mindfulnessövning på inhiberingsförmågan hos ett urval av media-multitaskare, något som definieras som att typiskt sett använda sig av fler än en media samtidigt. Studien var ett internetbaserat experiment där deltagarna delades randomiserat in till antingen en mindfulnessbetingelse (n = 18) eller en kontrollbetingelse bestående av klassisk musik (n = 22). Deltagarna (ålder 20–60 år) rekryterades via facebook, universitet samt posters därmed enligt ett bekvämlighetsurval. De hade ingen tidigare erfarenhet av mindfulnessmeditation och hade inga psykiatriska diagnoser. Det primära utfallsmåttet var inhiberingsförmåga mätt med Eriksen flanker task. Det gjordes även mätningar av mindfulnesstillstånd samt av upplevd stress. Studiens resultat visade att båda grupperna förbättrade sin inhiberingsförmåga, men påvisade ingen skillnad mellan grupperna. Det fanns heller ingen skillnad i skattat mindfulnesstillstånd mellan grupperna. Resultatet indikerar att effekten på inhiberingsförmåga inte var beroende av nivå på självskattad stress men bör tolkas med försiktighet på grund av möjliga svagheter i metoden. Då en focused attention (FA) mindfulnessövning kontra klassisk musik inte skilde sig signifikant i mindfulnesstillstånd bör framtida forskning undersöka validiteten av konstruktet mindfulness. Nyckelord: Inhibering, mindfulness, Eriksen flanker task, exekutiva funktioner. / The present study examined the connection between inhibition and a short mindfulness exercise on a sample of media-multitaskers, defined as a person using more than one media at the same time. The study was an internet-based experiment in which the partcipants were randomly assigned to a mindfulness condition (n = 18) or a control condition (n = 22) in which listened to classical music. Participants (20–60 years) were recruited through facebook, university and posters, the selection was a convenience sample. They had no former experience of mindfulness meditation and had no psychiatric diagnosis. The primary measure was the ability of inhibition measured with the Eriksen flanker task. Additional measures were state mindfulness and self-perceived stress. Both groups improved their inhibition-ability with no significant difference between groups. There was no additional difference in self-assessed mindfulnessstate between groups. Results indicate that the inhibition-ability does not depend on the level of self-assessed stress but this should in addition be interpreted with caution because of methodological shortcomings. As a focused attention (FA) mindfulness exercise to classical music didn’t significantly differ in mindfulness state future research should examinethe validity of the construct mindfulness.

One means by which inhibitory control in selective attention may be studied is with the negative priming (NP) procedure. It is widely assumed that children are characterised by reduced capacity for inhibition (Diamond, 2002) and that inhibitory dysfunction is a key characteristic of children and adolescents with ADHD (Barkley, 1997). This should translate into reduced NP effects for these populations. In this dissertation, four studies using the NP procedure find no evidence for reduced inhibitory function in typical children or in adolescents with ADHD. Study 1 examined the magnitude of NP in children compared with adults. An important line of support for the idea that children suffer an inhibitory decrement has been based an empirical report suggesting that conceptual (identity or semantic) NP effects, assumed to reflect the by-product of distractor inhibition, while consistently found in adults are lacking in children (Tipper, Bourque, Anderson, & Brehaut, 1989). In Study 1, the opposite result was found. Study 2 compared NP effects between 7-year-old children and adults while replicating the respective methodologies of the only two studies to explore conceptual NP effects in developmental populations to date (Pritchard & Neumann, 2004, vs. Tipper et al., 1989) to determine the nature of the divergent results between these studies. In Study 2, it was found that distractor inhibition effects are comparable between children and adults when a NP task contains trials in which the distractor stimulus is consistently incongruent with the target stimulus, but that children may be more susceptible than adults to divide attention between target and distractor when a NP task contains a number of trials in which target selection difficulty is reduced. These are critical new findings, highlighting that reduced NP may often relate to methodological artifacts, and when considered in the light of current theories of NP, are also problematic for anti-inhibitory accounts of NP. Having distinguished more definitively the role of inhibition in developmental NP effects, Studies 3 and 4 explored whether the inhibitory process underpinning NP was implicated in young persons with ADHD. To date, evidence for NP in ADHD populations is equivocal. Study 3 found no evidence for a reduced NP effect in ADHD devoid of a corresponding diagnosis. Study 4 found that conduct and oppositional defiant disorders had the potential to confound the evaluation of NP in ADHD. Taken together, results in Studies 1 - 4 parallel very recent results in the literature on NP in older adults and adult psychopathology where presumed reductions of NP in these populations may also be accounted for by methodological artifacts (Buchner & Mayr, in press). It is concluded that NP may reflect a primitive and robust form of inhibitory processing, one that develops early and one that is often the last to deteriorate.

Wie bereits mehrfach in anderen Studien beschrieben (Falkenstein et al., 1991; Gehring et al., 1993; Holroyd & Coles, 2002) konnte ein signifikanter Unterschied im EEG nach richtigen Antworten im Vergleich zu Fehlern in einem Zeitfenster von -35 bis 108 ms und von 110 bis 450 ms gezeigt werden. Die als Differenz aus den negativsten beziehungsweise positivsten Peaks nach falschen und richtigen Antworten berechnete „error-related negativity“ (ERN) und „error positivity“ (Pe) als wichtigste Komponenten der Fehlerverarbeitung zeigten im Vergleich zu anderen Studien zwar geringere, aber trotzdem vergleichbare Werte. Um den Einfluss von genetischen Unterschieden auf die Fehlerverarbeitung deutlich zu machen, wurde in dieser Studie untersucht, inwieweit Polymorphismen des Dopamintransporters (DAT), der Catechol-O-Methyl-Transferase (COMT) und des Phosphoproteins Stathmin Einfluss auf die Ausprägung der ERN und der Pe nehmen. Bezüglich des DAT-Polymorphismus konnte ein signifikanter Einfluss weder auf die ERN noch auf die Pe nachgewiesen werden. Hier ist zu vermuten, dass der Polymorphismus den Dopaminhaushalt der Basalganglien nicht nennenswert beeinträchtigt und demnach keinen Einfluss auf die Fehlerverarbeitung hat. Im Hinblick auf den COMT – Polymorphismus zeigte sich zwar kein Effekt auf die ERN, bei der Pe konnte man allerdings signifikante Unterschiede zwischen den Gruppen feststellen. Hier zeigten die homozygoten Träger des „val“ – Allels signifikant höhere Pe – Amplituden als die homozygoten Träger des „met“ – Allels. Heterozygote Personen lagen hinsichtlich der Pe – Amplitude zwischen den beiden anderen Gruppen. Dieser Effekt entspricht zwar nicht den Ergebnissen von anderen Studien (Egan et al., 2005; Frank et al., 2007), sollte aber dennoch Gegenstand weiterführender Forschung sein. Der Polymorphismus im Gen des Phosphoproteins Stathmin beeinflusste zwar die Amplitude der Pe nicht, zeigte aber signifikante Auswirkungen auf die ERN, wobei hier Träger des T-Allels signifikant kleinere ERN-Amplituden aufwiesen als Probanden, die dieses Allel nicht trugen. Allerdings wurde deutlich, dass dieser Effekt nach genauerer Analyse nicht stabil gegenüber Veränderungen war. Trotzdem ist davon auszugehen, dass dieser Polymorphismus die Funktion des ACC und damit auch die Fehlerverarbeitung beeinflusst, wodurch die Notwendigkeit weiterer Untersuchungen auf dem Gebiet des Phosphoproteins Stathmin gegeben ist. / As already published in several studies (Falkenstein et al., 1991; Gehring et al., 1993; Holroyd & Coles, 2002) a significant difference after correct answers compared to errors could be shown in EEG in a time window of -35 to 108ms and 110 to 450ms. The error related negativity (ERN) and error positivity (Pe) showed comparable values to other studies. To demonstrate the influence of genetic difference to the error processing, this study researched the influence of dopamine transporter (DAT), catechol-o-methyl transferase (COMT) and Stathmine to ERN and Pe. The DAT polymorphism does not have any significant influence to ERN and Pe. The COMT polymorphism shows no significant influence to ERN, but there is a significant influence to Pe. The genetic polymorphism of Stathmine does not have any impact on the amplitude of Pe but shows significant influence to ERN.

Mental disorders present difficulties in the research of their mechanisms, considering the high levels of comorbidity and the lack of specific neuroscience data to evaluate them. Estipulating deficit circuits in the disorders and the best treatment is a complex task, given the limited comprehension of the factors that correlate to the disorders. The utilization of biomarkers has proved an efficient and reliable alternative to provide precise diagnosis. Among the biomarkers, the Error-Related Negativity component, an event-related cortical potential, has presented high indexes of stability and validity in correlating to anxiety, obsessive, and mood-related mental disorders. The present dissertation evaluated irritability traits in a community sample, using a Flanker task, that has consistently elicited Error-Related Negativity according to the literature. Our results corroborate literature and found a frontocentral negativity, that peaked around 100ms after the commission of an error in the Flanker Task. However, our manipulation of negative feedback did not support literature, and ERN amplitudes were less enhanced post negative feedback. The relationship between irritability and ERN remains unclear. Future studies should, therefore, address these questionings.

Recent computational models and physiological studies suggest that simple, two-alternative forced-choice decision making can be conceptualized as the gradual accumulation of sensory evidence. Accordingly, information is sampled over time from a sensory stimulus, giving rise to an activation function. A response is emitted when this function reaches a criterion level of activity. Critically, the phenomenon known as speed-accuracy tradeoff (SAT) is modeled as a shift in the response boundaries (criterion). As speed stress increases and criterion is lowered, the information function travels less distance before reaching threshold. This leads to faster overall responses, but also an increase in error rate, given that less information is accumulated. Psychophysiological data using EEG and single-unit recordings from monkey cortex suggest that these accumulator models are biologically plausible. The present work is an effort to strengthen this position. Specifically, it seeks to demonstrate a neural correlate of criterion and demonstrate its relationship to behavior. To do so, subjects performed a letter discrimination paradigm under three levels of speed stress. At the same time, electroencephalogram (EEG) was used to derive a measure known as the lateralized readiness potential, which is known to reflect ongoing motor preparation in motor cortex. In Experiment 1, the amplitude of the LRP was related to speed stress: as subjects were forced to respond more quickly, less information was accumulated before making a response. In other words, criterion lowered. These data are complicated by Experiment 2, which found that there are boundary conditions for this effect to obtain.

The current study sought to test the existence of a phenomenon known as sensory-specific satiety, in which attentional bias for food cues is specifically diminished for a consumed food, and the role of gender in such biases. In order to do so, the experiment used a version of the Flanker Task in which participants were shown image groups containing a target image and congruent or incongruent distracting flanker images. Participants (17 males, 22 females) were randomly assigned to consume one of two foods depicted in the flanker task (Ritz Bitz sandwiches or miniature Golden Oreos). Results did not support the idea of sensory-specific satiety, as we found a general reduction in reaction time rather than interactions in target/flanker congruency, suggesting that task performance was not driven by attentional bias to the food cues. However, there was an interesting interaction effect for session, consumption, and gender, such that women were faster than men for the consumed food post-satiety. Results may be explained by differences in motivation potentially caused by dissimilarities in dopamine levels. Additionally, results of the current experiment in combination with previous research could provide insight on gender differences in obesity.