Denna studie vill besvara tre frågeställningar och hypotesen; man presterar bättre i aritmetiska test efter fysisk aktivitet i jämförelse med före. Hypotesen testas genom en kvantitativ metod med ett bekvämlighetsurval bestående av fyra deltagare. Datainsamlingen genomfördes vid ett tillfälle med mätinstrumentet fNIRS, där varje deltagares insats beräknades ta minst 60 minuter. Resultatet i de aritmetiska testen visar att samtliga deltagare i studien presterar bättre i testet efter fysisk aktivitet i jämförelse med testen före och under fysisk aktivitet. Resultatet visar även att det går att se skillnader i hjärnaktivitet hos en person som besvarar aritmetiska uppgifter före, under och efter fysisk aktivitet. Resultatet har tolkats utifrån att vänstra och högra hjärnhalvorna i den prefrontala delen av hjärnan kan delas upp i kognitiva förmågor respektive rörelser. / This study seeks to answer three questions and the hypothesis; one performs better in arithmetic tests after physical activity compared to before. The hypothesis is tested through a quantitative method with a convenience sample consisting of four participants. The data collection was carried out on one occasion with the measuring instrument fNIRS, where each participant's contribution was estimated to take at least 60 minutes. The results of the arithmetic tests show that all participants in the study perform better in the test after physical activity in comparison with the tests before and during physical activity. The results also show that it is possible to see differences in brain activity in a person who answers arithmetic tasks before, during and after physical activity. The result has been interpreted on the basis that the left and right hemispheres of the brain in the prefrontal part of the brain can be divided into cognitive abilities and movements.

Brain computer interfaces (BCIs) are devices capable of relaying information directly from the brain to a digital device. BCIs have been proposed for a diverse range of clinical and commercial applications; for example, to allow paralyzed subjects to communicate, or to improve machine human interactions. At their core, BCIs need to predict the current state of the brain from variables measuring functional physiology. Functional near infrared spectroscopy (fNIRS) is a non-invasive optical technology able to measure hemodynamic changes in the brain. Along with electroencephalography (EEG), fNIRS is the only technique that allows non-invasive and portable sensing of brain signals. Portability and wearability are very desirable characteristics for BCIs, as they allow them to be used in contexts beyond the laboratory, extending their usability for clinical and commercial applications, as well as for ecologically valid research. Unfortunately, due to limited access to the brain, non-invasive BCIs tend to suffer from low accuracy in their estimation of the brain state. It has been suggested that feedback could increase BCI accuracy as the brain normally relies on sensory feedback to adjust its strategies. Despite this, presenting relevant and accurate feedback in a timely manner can be challenging when processing fNIRS signals, as they tend to be contaminated by physiological and motion artifacts. In this dissertation, I present the hardware and software solutions we proposed and developed to deal with these challenges. First, I will talk about ninjaNIRS, the wearable open source fNIRS device we developed in our laboratory, which could help fNIRS neuroscience and BCIs to become more accessible. Next, I will present an adaptive filter strategy to recover the neural responses from fNIRS signals in real-time, which could be used for feedback and classification in a BCI paradigm. We showed that our wearable fNIRS device can operate autonomously for up to three hours and can be easily carried in a backpack, while offering noise equivalent power comparable to commercial devices. Our adaptive multimodal Kalman filter strategy provided a six-fold increase in contrast to noise ratio of the brain signals compared to standard filtering while being able to process at least 24 channels at 400 samples per second using a standard computer. This filtering strategy, along with visual feedback during a left vs right motion imagery task, showed a relative increase of accuracy of 37.5% compared to not using feedback. With this, we show that it is possible to present relevant feedback for fNIRS BCI in real-time. The findings on this dissertation might help improve the design of future fNIRS BCIs, and thus increase the usability and reliability of this technology.

To understand pain processing requires the assessment of an individual’s perception of pain with temporal stimulation over different periods. Offset analgesia (OA), a phenomenon widely studied, refers to a disproportionate decrease in pain experience following a small reduction in temperature during noxious thermal stimulation. OA leads to skin desensitization, causing brief pain inhibition at the stimulation site and leading to adaptation and a decrease in pain scores. To avoid sensitization and habituation during thermal pain procedures, previous studies have utilized protocols in which the thermal stimulation is applied to different areas of the skin (e.g., upper forearm versus lower forearm). The reliability of this thermal pain calibration procedure in producing a nonadaptive effect has been previously tested using pain rating scales. The utilization of neuroimaging to further elucidate these relationships has not been widely studied, but it is likely an important tool to investigate these constructs. Functional near-infrared spectroscopy (fNIRS) is a noninvasive optical imaging technique that measures changes in hemoglobin (Hb) concentrations within the brain using the characteristic absorption spectra of Hb in the near-infrared range. This thesis investigated whether adaptation exists across four conditions of the OA paradigm using fNIRS. Introducing fNIRS to define significant differences in brain metrics (e.g., activated regions of interest) in participants who have undergone surgery and are experiencing chronic pain as well as healthy, pain-free controls could have implications for more accurate measures of OA and more reliable pain treatment options. In this study, noxious thermal stimulation was given to 19 participants on the forearm of the nondominant hand through a commonly used three-temperature OA paradigm with offset, constant, and control trials. Each OA paradigm consisted of four conditions (A, B, C, and D) with a pseudorandom sequence design of three trials. OA was implemented with the participant while real-time fNIRS data were obtained on the subject’s prefrontal and somatosensory cortices, regions known to be involved in pain processing. Hemoglobin responses during the four OA trials were evaluated and compared within experimental conditions. Repeated measures ANOVA was used to analyze the significant differences among conditions. Results showed no significant differences among the four OA trials. The findings of this thesis study indicated that brain response from the prefrontal and somatosensory cortices is not affected within the four OA trials. The consistent brain activation across multiple trials of stimulation suggests an absence of adaptive responses. In line with previous findings, these results imply the reliability of such thermal pain calibration procedures by fNIRS brain imaging. Further investigation with a larger sample size is likely for the verification of the findings from this study. / 2026-02-14T00:00:00Z

The present study empirically examined the effects of four fatiguing task domains on executive function through participants' reaction time, accuracy, and brain activity in prefrontal cortex (PFC). Forty college-age participants were collected (16 males and 24 females), of which eleven were examined using a functional near-infrared spectroscopy (fNIRS) imaging system. The present study used a 4×2 mixed factorial design consisting of fatiguing task (arm contractions task, vigilance task, distance-manipulated Fitts' task, size-manipulated Fitts' task) as a between-participant variable and n-back testing period (pre-test versus post-test 3-back task) as a within-participant variable. Results indicated significant increases in 3-back performance after the fatiguing tasks, and significant increases in 3-back compensatory brain activity in dorsomedial and dorsolateral prefrontal cortex (dmPFC and dlPFC) after the fatiguing tasks. Furthermore, results showed an interaction between 3-back target type and fatiguing task on standardized changes in reaction time, and an interaction between fatiguing task and testing period on brain activity in dmPFC. Theoretical and practical implications are discussed. Findings from this study may be used to help draw the boundaries on different domains of fatigue and their effects on the brain and body.

"Nature-based solutions", such as green stormwater infrastructure, take advantage of natural systems to tackle the increasing challenges facing the built environment. Green infrastructure is effective in reducing stormwater runoff for urban stormwater management using connected green space. Green infrastructure also delivers multiple benefits to the community (e.g., increased quality of life and public health) and environment (e.g., enhanced biodiversity, less energy use, and reduced urban heat island effect), which is adaptive to the changing climate. However, the pace and the scale of green infrastructure implementation are still not on track with the much-needed change in the urban built environment. Policy barriers, resources barriers, governance barriers, and cognitive barriers are limiting the practice. Cognitive barriers are cited as the most critical barrier because most of the barriers limiting green infrastructure stem from and are intensified by human cognition during the design and decision-making process for infrastructure. Stakeholders involved in the decision-making process for green infrastructure must weigh the perceived risks and benefits that green infrastructure provides. This dissertation aims to better understand how stakeholders perceive green infrastructure, how much they weigh risks and benefits, and test interventions to aid the decision-making process to promote more green infrastructure design. Both a stated preference survey with discrete choice modeling and two sets of experiments using neuroimaging to measure the change in neurocognition were used to explore preference construction and decision-making about green infrastructure. A sample of the public (N=946) across the U.S. participated in the survey and reported their perceptions of risk and benefit about green infrastructure. The result highlights that perceived higher risk of green infrastructure reduced people's preference for green infrastructure. In contrast, perceived higher benefit, age, education, and the use of a rating system to measure sustainability outcomes firstly contribute to people's preference construction for green infrastructure. Engineering students who were trained in stormwater infrastructure design (N=60) participated in a stormwater infrastructure design scenario. Change in students' neurocognition was measured when students made judgments and decisions between a green infrastructure design option and a conventional stormwater infrastructure design option. Two interventions, (1) telling students about a municipal resolution in support of green infrastructure and (2) priming students to think about sustainable design before evaluating design options, were tested to change perceptions about risk and benefit of stormwater design options. The results found that telling decision-makers about a green infrastructure resolution changed their neurocognition when processing perceived risk and reduced the perceived risk they associated with green infrastructure. The results also found that priming decision-makers to think about sustainable design with a rating system for sustainability significantly decreased their cognitive load when evaluating the benefits of green infrastructure and increased their stated benefits associated with green infrastructure. These findings demonstrate the effects of relatively simple choice modifications to promote more green infrastructure. The results provide insights for policy-makers, engineers, and other stakeholders involved in the early-phase decisions on effective practice to modify human choice when facing challenges with sustainable and resilient design. / Doctor of Philosophy / Green stormwater infrastructure uses connected green space to absorb and filter excessive stormwater runoff in the environment where humans live. Green infrastructure also brings multiple benefits, such as increased quality of life and public health, habitats to more creatures, and less energy use. However, the pace and the scale of green infrastructure implementation are still limited. Barriers in policy, resources, governance, and human cognition are preventing the implementation of green infrastructure. Cognitive barriers are believed to be the most critical barrier because they intensify all other barriers during the design and decision-making process for infrastructure. Stakeholders involved in the decision-making process for green infrastructure must weigh the perceived risks and benefits that green infrastructure provides. This dissertation aims to better understand how stakeholders perceive green infrastructure, how much they weigh risks and benefits, and test interventions to aid the decision-making process to promote more green infrastructure design. Both a survey with choice modeling and experiments using neuroimaging to measure the change in brain activity were used to explore preference construction and decision-making about green infrastructure. 946 people across the U.S. participated in the survey and reported their perceptions of risk and benefit about green infrastructure. The result highlights that perceived higher risk of green infrastructure reduced people's preference for green infrastructure. In contrast, perceived higher benefit, age, education, and the use of a rating system to measure sustainability outcomes positively contribute to their preference construction for green infrastructure. 60 Engineering students who were trained in stormwater infrastructure design participated in a stormwater infrastructure design scenario. Change in students' brain activity was measured when they made judgments and decisions between a green infrastructure design option and a conventional stormwater infrastructure design option. Two interventions, (1) telling students about a municipal resolution in support of green infrastructure and (2) priming students to think about the sustainable design before evaluating design options, were tested to change perceptions about the risk and benefit of stormwater design options. The results found that telling decision-makers about a green infrastructure resolution changed their brain activity when evaluating risk and reduced the perceived risk they associated with green infrastructure. The results also found that priming decision-makers to think about sustainable design with a rating system for sustainability significantly decreased their cognitive efforts when evaluating the benefits of green infrastructure and increased their stated benefits associated with green infrastructure. These findings demonstrate such relatively simple choice modifications are effective to promote more green infrastructure. Stakeholders who are involved in the early-phase decisions can take advantage of the findings about the effective practice to modify human choice when facing sustainable design challenges.

Anxiety is characterized by apprehensive expectation regarding the forecasted outcomes of choice. Decision science and in particular reinforcement learning models provide a quantitative framework to explain how the likelihood and value of such outcomes are estimated, thus allowing the measurement of parameters of decision-making that may differ between high- and low- anxiety groups. However, the role of anxiety in choice allocation is not sufficiently understood, particularly regarding the influence of transient threat on current decisions. The presence of threat appears to alter choice behavior and may differentially influence quantitatively derived parameters of learning among anxious individuals. Regarding the neurobiology of reinforcement learning, the dorsolateral prefrontal cortex (dlPFC) has been suggested to play a role in temporally integrating experienced outcomes, as well as in coordinating an overall choice action plan, both of which can be described computationally by learning rate and exploration, respectively. Accordingly, it was hypothesized that high trait anxiety would be associated with a lower reward learning rate, a higher loss learning rate, and diminished exploration of available options, and furthermore that threat would increase the magnitude of these parameters in the high anxiety group. We also hypothesized that the magnitude of neural activation (measured by functional near-infrared spectroscopy; FNIRS) across dissociable regions of the left and right dlPFC would be associated with model parameters, and that threat would further increase the magnitude of activation to model parameters. Finally, it was hypothesized that reward and loss outcomes could be differentiated based on FNIRS channel activation, and that a distinct set of channels would differentiate outcomes in high relative to low anxiety groups. To test these hypotheses, a temporal difference learning model was applied to a decision-making (bandit) task to establish differences in learning parameter magnitudes among individuals high (N=26) and low (N=20) in trait anxiety, as well as the impact of threat on learning parameters. Results indicated a positive association between anxiety and both the reward and loss learning rate parameters. However, threat was not found to impact model parameters. Imaging results indicated a positive association between exploration and the left dlPFC. Reward and loss outcomes were successfully differentiated in the high, but not low anxiety group. Results add to a growing literature suggesting anxiety is characterized by differential sensitivity to both losses and rewards in reinforcement learning contexts, and further suggests that the dlPFC plays a role in modulating exploration-based choice strategies. / Doctor of Philosophy / Anxiety is characterized by worry about possible future negative outcomes. Mathematical models in the area of learning theory allow the representation and measurement of individual differences in decision-making tendencies that contribute to negative future apprehension. Currently, the role of anxiety in the allocation of choices, and particularly the influence of threat on decision-making is poorly understood. Threat may influence learning and alter choice behavior, collectively causing negative future apprehension. With regards to how related decision-making is computed in the brain, the dorsolateral prefrontal cortex (dlPFC) has been suggested to play a role tracking and integrating current and past experienced outcomes, in order to coordinate an overall action plan. Outcome tracking and action plan coordination can be represented mathematically within a learning theory framework by learning rate and exploration parameters, respectively. It was hypothesized that high anxiety would be associated with a lower reward learning rate, a higher loss learning rate, and diminished exploration, and furthermore that threat would increase the magnitude of these tendencies in anxious individuals. We also hypothesized that brain activation in the dlPFC would be associated with these tendencies, and that threat would further increase activation in these brain areas. It was also hypothesized that reward and loss outcomes could be differentiated based on brain activation in the dlPFC. To test these hypotheses, a mathematical model was applied to establish differences in learning within high and low anxiety individuals, as well as to test the impact of threat on these learning tendencies. Results indicated a positive association between anxiety and the rate of learning to reward and loss outcomes. Threat was not found to impact these learning rates. A positive association was found between activation in the dlPFC and the tendency to explore. Reward and loss outcomes were successfully differentiated based on brain activation in high, but not low anxiety individuals. Results add to a growing literature suggesting that anxiety is characterized by differential sensitivity to both losses and rewards, and further adds to our understanding of how the brain computes exploration-based choice strategies.

Il tema delle emozioni è sempre stato considerato marginale rispetto allo studio della cognizione umana, nonostante la ricerca sull’argomento sia sempre stata circondata da grande interesse. Tuttavia negli ultimi 30 anni si è affacciata una nuova prospettiva che descrive le emozioni come cause, mediatori o conseguenze di altri processi psicologici, ma soprattutto delle relazioni interpersonali. Il primo studio della presente Tesi di Dottorato è stato concepito come un paradigma di induzione emotiva allo scopo di individuare alcuni marcatori biologici legati all’esperienza soggettiva, all’interno di una prospettiva multimetodologica. In seguito, nel tentativo di considerare anche una dimensione sociale della condivisione emotiva, è stato condotto il secondo studio proponendo stimoli che rappresentassero interazioni reali tra due soggetti interagenti. Questi potevano variare anche in base alla vicinanza filogenetica, ipotizzando che, grazie a meccanismi di mirroring e simulazione, la percezione delle emozioni altrui possa essere più immediata quando l’altro soggetto viene percepito come simile. Infine, l’idea che alcune variabili legate all’interlocutore sociale siano in grado di modulare la capacità di entrare in risonanza con le emozioni altrui è stata approfondita con il terzo studio: un compito sociale reale con pradigma hyperscanning. L’obiettivo era quello di esplorare la presenza di pattern di sincronizzazione durante il compito eseguito in modo cooperativo. In conclusione, i tre studi sono stati condotti seguendo un livello di complessità crescente, da una prospettiva su singolo soggetto ad un approccio diadico, tramite l’utilizzo di stimoli emotivi standard, interattivi e dinamici applicati a contesti semplici, complessi e iper-complessi. / Despite the great interest addressed to the topic of emotions, it has always been treated as a marginal issue if compared to cognition. Nonetheless in the last 30 years a new perspective suggested that emotions are effectively the causes, mediators, or consequences of other psychological processes, and, above all, of interpersonal relations. The first study of the present Doctoral Thesis was conceived as an emotion induction paradigm in the attempt to identify some biological markers of the subjective emotional experience within a multi-method perspective. Then, in the attempt to move a step forward in describing the social dimension of the emotional sharing, the second study was designed by creating emotional stimuli that represented real interactions between two inter-agents. They could also vary for phylogenetic closeness following the hypothesis that, thanks to mirroring and simulation processes, emotion perception is easier when the other agent is perceived as similar. Finally, the idea that some variables related to the social encounter are able to modulate the capacity to resonate with others’ emotions was better explored in the last study: a real social cooperative task in the form of a hyperscanning paradigm. The aim was to explore the presence of synchronized patterns during the joint action. To conclude, the three studies have been designed according to an increased level of complexity, from a single-subject perspective towards a two-person approach, with simple, interactive, and dynamic emotional cues during simple, complex, and hyper-complex emotional contexts.

Der aufrechte, bipedale Gang ist eine wesentliche Voraussetzung für ein unabhängiges Leben mit gesellschaftlicher Teilhabe. Das sichere Gehen in einer variablen Umwelt kann im Laufe des Lebens durch verschiedene Faktoren beeinträchtigt werden. Neben altersbedingten, degenerativen Prozessen sind häufig auch erworbene, neurologische Defizite ursächlich für eine gestörte Lokomotorik. Der Schlaganfall stellt dabei die häufigste Ursache einer alltagsrelevanten Einschränkung der Mobilität dar. Es resultieren regelmäßig Einschränkungen, am gesellschaftlichen Leben teilzuhaben, psychosoziale Probleme der Vereinsamung, Depression und eine phobische Komponente der Mobilitätseinschränkung. Ein zentrales Ziel der Rehabilitation nach einem Schlaganfall ist es daher, die Gehfähigkeit und damit eine Unabhängigkeit im Alltag wiederzuerlangen. Grundlegend für die Entwicklung evidenzbasierter Therapieansätze ist das Wissen um neurophysiologische Grundlagen menschlicher Lokomotion sowie kortikaler Reorganisationsprozesse. Dazu bedarf es der Entwicklung von Methoden, die eine Bewertung der kortikalen Bewegungskontrolle in einem möglichst realitätsnahen Kontext ermöglichen. Die funktionelle Nahinfrarotspektroskopie (fNIRS) ist insbesondere bei der Untersuchung des freien Gehens anderen bildgebenden Verfahren aufgrund der Portabilität überlegen. Sie wurde in den letzten zwei Jahrzehnten für die Erforschung neuronaler Korrelate des Ganges zunehmend eingesetzt. Die fNIRS basiert auf der Messung kortikaler Oxygenierungsänderungen bei funktioneller Stimulation. Der spektroskopische Ansatz erlaubt eine grobe Kartierung funktioneller Aktivierung bei einem weiten Spektrum motorischer, aber auch kognitiver Paradigmen. Die vorliegende Arbeit gibt zu Beginn einen ausführlichen Überblick über bisherige fNIRS-Studien, die sich dem kortikalen Beitrag zur menschlichen Lokomotion widmeten. Von den 55 berücksichtigten Arbeiten nutzten bis dato nur 4 Studien portable Geräte. In zwei experimentellen Studien wurde im Rahmen der vorliegenden Arbeit daher untersucht, ob mit Hilfe eines portablen fNIRS-Aufbaus die hämodynamische Reaktion primärer und sekundärer motorischer Areale auf unterschiedliche lokomotorische Aufgaben aufgezeichnet werden können. In der ersten Studie absolvierten 23 gesunde, junge Erwachsene ein Paradigma, das synchron zu einem auditorisch vorgegebenen Rhythmus (RAC= rhythmic auditory cueing) vier Bewegungsbedingungen erforderte: Die Bedingungen unterschieden sich hinsichtlich Lokomotion (auf der Stelle: TRETEN vs. raumgreifend: GEHEN) sowie Regelmäßigkeit (regelmäßig: REG vs. unregelmäßig: UNREG. Durch zusätzlich eingefügte Phasen ruhigen Stehens (PAUSE) ergaben sich für die Analyse der Hirnaktivierung insgesamt 5 Bedingungen. Um den Transfer in den neurorehabilitativen Kontext zu ermöglichen, wurde dieses Paradigma in der zweiten Studie bei 21 Schlaganfallpatienten mit leichter bis moderater Gangstörung angewandt. Die Auswertung erfolgte gruppenspezifisch nach dominant paretischer Seite (LP: dominant linksparetisch; RP: dominant rechtsparetisch). Mit diesen zwei Kohorten galt unser Interesse neben der grundsätzlichen Frage nach der Anwendbarkeit der fNIRS beim freien Gehen vor allem dem differenziellen Einfluss der Lokomotion beziehungsweise der Regelmäßigkeit auf die kortikale Aktivierung. In beiden Studien konnten wir durch signifikante Unterschiede zwischen den gemittelten Bewegungsbedingungen und der Ruhebedingung zeigen, dass es mit beschriebenem Paradigma möglich ist, Aktivierungsänderungen in prämotorischen und motorischen Hirnarealen darzustellen. Für eine zerebrale Genese der gemessenen Änderungen sprechen: die Fokalität, die Richtung der Oxygenierungsänderung (oxy-Hb↑ und deoxy-Hb↓), der Zeitverlauf und auch die relative Größe (oxy-Hb>>deoxy-Hb) der ermittelten Änderungen. Unsere Ergebnisse deuten in Übereinstimmung mit früheren Studien auf eine führende Rolle von SMA, PMC und SMC in der Bewegungssteuerung hin (Harada et al., 2009; Kim et al., 2016; Kurz et al., 2012; Lu et al., 2015; Miyai et al., 2001; Okamoto et al., 2004). Der differenzielle Einfluss der Lokomotion zeigte sich in beiden Studien. Spricht das Ergebnis bei den neurotypischen Probanden für eine höhere kortikale Kontrolle beim ungewohnteren, weniger automatisierten Treten, ist für die Patienten anzunehmen, dass läsionsbedingte Kompensationsmechanismen zu Beeinträchtigungen der Bewegungs-automatisation und damit zu erhöhten kortikalen Aktivierungen führen. Dies ist insbesondere für den sensomotorischen Kortex (SMC) beschrieben (Harada et al., 2009; Stuart et al., 2018). Ungeachtet dessen zeigten sich im Vergleich der mittleren Steigung über die Stimulationsdauer bei beiden Kohorten ähnliche Habituationseffekte während des Gehens. Die Konzentrationsabnahme des oxygenierten Hämoglobins über den Verlauf der Bewegung spricht dafür, dass über den Stimulationszeitraum zunehmend automatisiert ist und anzunehmend stärker subkortikal gesteuert wird. Ferner deuten die Patientenergebnisse daraufhin, dass es trotz der oben genannten Beeinträchtigung grundlegender Automatisationsprozesse zu einer teilweisen Restitution in der chronischen Phase nach Schlaganfall kommen kann. Auch bezüglich des Einflusses des Bewegungsrhythmus unterschieden sich die Patienten von den neurotypischen Probanden. Bei Letzteren ergaben sich für die unrhythmischen Bewegungen hypothesenkonform signifikant größere oxy-Hb Antworten als für die rhythmisch ausgeführten Bewegungen. Wie schon in früheren Studien beschrieben, korrelierte die Aktivitätssteigerung mit dem höheren Anspruch vor allem über den prämotorischen Arealen (d.h. pre-SMA, SMA und den PMC). Bei hoher Heterogenität ergab sich bei den Schlaganfallpatienten ein umgekehrter Effekt. Explorative Analysen der rechtsparetischen Gruppe zeigten eine höhere kortikale Beteiligung bei den rhythmischen Bewegungen. Ein in der Literatur als „CRUNCH-Modell“ beschriebener Mechanismus, der bei einer motorisch induzierten Erschöpfung neuronaler Ressourcen eine Verschiebung der Bewegungskontrolle von kortikal nach subkortikal postuliert, könnte hierfür verantwortlich sein. Diese These wird auch durch die Habituationseffekte, die gleichermaßen bei den Probanden wie auch bei den Patienten während der regelmäßigen Bewegungen gefunden wurden, unterstützt. Um dies datenbasiert zu untersuchen, sind in zukünftigen Studien kinematische Daten zur Korrelation mit den kortikalen Aktivierungsmaßen sinnvoll. Frühere Studien konnten die besondere Rolle prä- und supplementär-motorischer Areale bei der Initiierung lokomotorischer Bewegungen zeigen (Chang et al., 2010; MacKinnon et al., 2007; Varghese, Merino, Beyer, & McIlroy, 2016; Yakovenko & Drew, 2009). Die angestrebte Beurteilung des kortikalen Beitrags bei der Initiierung und Beendigung lokomotorischer Aufgaben bei jungen, gesunden Erwachsenen sowie bei Schlaganfallpatienten gestaltete sich mit unserem methodischen Zugang schwierig. Zukünftige Arbeiten könnten für diese Fragestellung einerseits die Startbewegung isoliert betrachten (Varghese et al., 2016; Watanabe, Ishida, Tanabe & Nojima, 2016) andererseits wäre im Rahmen der Datenaufbereitung die Modellierung der hämodynamischen Antwortfunktion auf diese Fragestellung auszurichten. Mit vorliegenden Studien ist es uns erstmalig gelungen, die Anwendbarkeit der fNIRS beim freien Gehen und den differenziellen Einfluss der Lokomotion (Gehen vs. Treten) und der Regelmäßigkeit (rhythmisch vs. unrhythmisch) sowohl bei jungen, gesunden Probanden als auch bei chronischen Schlaganfallpatienten mit leichter bis moderater Gangstörung darzustellen.:INHALTSVERZEICHNIS 1 BIBLIOGRAFISCHE ZUSAMMENFASSUNG 2 ABKÜRZUNGSVERZEICHNIS 3 EINLEITUNG 4 AUFGABENSTELLUNG 5 MATERIALIEN UND METHODEN 5.1 STUDIENDESIGN 5.2 VERSUCHSTEILNEHMER 5.2.1 Probandenstudie 5.2.2 Patientenstudie 5.3. MESSTECHNIK 5.4. DATENVERARBEITUNG UND STATISTISCHE ANALYSEN 6 ERGEBNISSE 6.1 STUDIE 1: PROBANDEN 6.1.1 Zerebrale Oxygenierung bei uneingeschränkter, rhythmisierter Lokomotion bei jungen Erwachsenen 6.1.2 Einfluss von LOKOMOTION und REGULARITÄT auf die kortikale Oxygenierung 6.1.3 Unterschiede zwischen GEHEN und TRETEN (Faktor LOKO) 6.1.3.1 Einfluss von LOKO auf die tonische Antwort 6.1.3.2 Einfluss von LOKO während der Startsequenzen 6.1.3.3 Einfluss von LOKO während der Stoppsequenzen 6.1.3.4 Mittlere Steigung der Oxygenierungsantwort beim GEHEN und TRETEN 6.1.4 Unterschiede zwischen regelmäßigen und unregelmäßigen Bewegungen Faktor REG) 6.1.4.1 Einfluss von REG auf die tonische Antwort 6.1.4.2 Einfluss von REG während der Startsequenzen 6.1.4.3 Einfluss von REG während der Stoppsequenzen 6.1.4.4 Mittlere Steigung der Oxygenierungsantwort bei unterschiedlich rhythmisierten Bewegungen 6.1.5 Interaktion von LOKOMOTION und REGULARITÄT 6.1.5.1 Die Interaktion von LOKOMOTION und REGULARITÄT bezogen auf die gesamte Stimulusdauer (Prädiktor TONISCH) 6.1.5.2 Die Interaktion von LOKOMOTION und REGULARITÄT während der Startsequenz (Prädiktor START) 6.1.5.3 Die Interaktion von LOKOMOTION und REGULARITÄT während der Stoppsequenz (Prädiktor STOP) 6.2 STUDIE 2: PATIENTEN 6.2.1 Zerebrale Oxygenierung bei uneingeschränkter, rhythmisierter Lokomotion von Schlaganfallpatienten 6.2.2 Einfluss von LOKOMOTION und REGULARITÄT auf die kortikale Oxygenierung 6.2.3 Unterschiede zwischen GEHEN und TRETEN (Faktor LOKO) 6.2.3.1 Einfluss von LOKO auf die tonische Antwort 6.2.3.2 Einfluss von LOKO während der Startsequenzen 6.2.3.3 Mittlere Steigung der Oxygenierungsantwort beim Gehen und Treten 6.2.4 Unterschiede zwischen regelmäßigen und unregelmäßigen Bewegungen (Faktor REG) 6.2.4.1 Einfluss von REG auf die tonische Antwort 6.2.4.2 Einfluss von REG während der Startsequenzen 6.2.4.3 Einfluss von REG während der Stoppsequenzen 6.2.4.4 Mittlere Steigung der Oxygenierungsantwort bei unterschiedlich rhythmisierter Lokomotion 6.2.5 Interaktion von LOKOMOTION und REGULARITÄT 6.2.5.1 Die Interaktion von LOKOMOTION und REGULARITÄT bezogen auf die gesamte Stimulusdauer (Prädiktor TONISCH) 6.2.5.2 Die Interaktion von LOKOMOTION und REGULARITÄT während der Startsequenz (Prädiktor START) 7 DISKUSSION 7.1 ANWENDBARKEIT DER FUNKTIONELLEN NIRS ZUR UNTERSUCHUNG KORTIKALER AKTIVIERUNGSMUSTER BEIM FREIEN GEHEN 7.2 UNTERSCHIEDE DER KORTIKALEN HÄMODYNAMIK BEI GEWOHNTER UND UNGEWOHNTER LOKOMOTION 7.2.1 Kortikale Kontrolle der Lokomotion bei jungen, gesunden Erwachsenen 7.2.2 Kortikale Kontrolle der Lokomotion bei Schlaganfallpatienten 7.3 EINFLUSS UNTERSCHIEDLICHER BEWEGUNGSRHYTHMIK AUF DIE KORTIKALE AKTIVITÄT 7.3.1 Kortikale Aktivität bei regelmäßigen und unregelmäßigen Bewegungen bei jungen, gesunden Erwachsenen 7.3.2 Kortikale Aktivität bei regelmäßigen und unregelmäßigen Bewegungen bei Schlaganfallpatienten 7.4 PRÄ- UND SUPPLEMENTÄR-MOTORISCHE AKTIVITÄT BEIM INITIIEREN UND BEENDEN UNGEWOHNTER LOKOMOTORISCHER AUFGABEN 7.4.1 Kortikale Aktivität beim Starten und Stoppen der Lokomotion bei jungen, gesunden Erwachsenen 7.4.2 Kortikale Aktivität beim Starten und Stoppen der Lokomotion bei Schlaganfallpatienten 8 ZUSAMMENFASSUNG 9 LITERATURVERZEICHNIS 10 APPENDIX

The present study compared lateralization of cortical activation patterns in the prefrontal cortex (PFC) of adults who stutter (AWS) and typical speakers (TS) as measured with functional near infrared spectroscopy (fNIRS) in habitual and fluency-enhanced speaking conditions. Participants were AWS (n = 11) and gender- and age-matched TS (n = 11) who completed speaking tasks in three condition blocks: (1) habitual speech using no speaking strategy (2) prolonged speech after receiving short-term training in fluency-shaping strategy-use (3) syllable-timed speech after being trained to speak in rhythm with a metronome at 92 beats per minute. The three primary dependent variables were mean change in HbO (oxygenation) relative to resting baseline in the right and left PFC hemispheres and a Laterality Index (L-R)/(L+R) calculated from these values. Two primary hypotheses were tested: (1) AWS will present with greater right-hemisphere PFC oxygenation relative to TS in a habitual or everyday speaking task (2) AWS will present with reduced right-hemisphere PFC activation (leftward shift in laterality more similar to TS) during fluency-enhanced speech strategy tasks relative to a habitual speech task. Real-time stuttered speech measures using fNIRS indicated greater effortfulness of speech production in AWS when speaking fluently and disfluently as measured by greater bilateral change in PFC HbO relative to TS. AWS laterality did not differ from TS during everyday conversation and did not significantly change when using fluency-enhancing strategies, which was counter to the hypotheses. The TS group presented with significantly greater leftward PFC HbO in the metronome condition compared to AWS. Prolonged speech and metronome-timed speech seem to be associated with different activation patterns in the PFC for AWS and for TS. Results suggest an alternative explanation for compensatory activation in AWS during speech production, such that AWS present with greater overall activation in both PFC hemispheres relative to TS which results in greater right-sided laterality than TS. Future long-term studies on adults receiving prolonged speech treatment and examination of similar measures in young children who stutter may reveal more about the compensatory versus causal nature of stuttering.

A Fibromialgia (FM) é uma síndrome que se caracteriza por dor crônica difusa, fadiga, transtornos do sono e alterações de humor. Embora sua fisiopatologia não esteja totalmente elucidada, o processo neurobiológico parece envolver alterações do córtex sensitivo e motor e de suas conexões com estruturas subcorticais que constituem a neuromatriz da dor, assim como alterações neuropáticas periféricas. Sabe-se que o aumento do cálcio intracelular acima de certo limiar, pode ser parte do processo dependente de atividade que leva à sensibilização central, por aumento do influxo de cálcio por meio de canais NMDA, AMPA, canais dependentes de voltagem, e por liberação de reservas intracelular microssomais. A sensibilização central pode ser também interpretada como um processo de plasticidade mal-adaptativa que sustenta circuitos da dor e de seus correlatos. Por tanto, o córtex sensitivo e motor tem sido alvo diagnóstico e terapêutico para o estudo e tratamento da dor crônica. Dentre as múltiplas estratégias farmacológicas tem sido preconizado o uso da pregabalina, aprovado pela Food and Drug Administration (FDA) dos EUA para uso no tratamento de fibromialgia em 2007. A pregabalina age inibindo os canais de cálcio pré sinápticos dependentes de voltagem por se ligar à proteína auxiliar alfa-2-delta. In vitro, este fármaco reduz a liberação de neurotransmissores cálcio-dependentes incluindo glutamato, norepinefrina, calcitonina e substância P, estes neurotransmissores têm sido associados à sensibilização do sistema nervoso. Portanto, considerando o potencial neuromodulador da pregabalina baseado no seu mecanismo de ação, é um fármaco atrativo para avaliar o papel da modulação do córtex sensitivo e motor na fisiopatolgia da FM. No entanto, para que se avance no conhecimento do efeito dos fármacos na função encefálica, necessitamos utilizar recursos de neuroimagem que sejam exequíveis em contextos diversos, e que permitam mensurar o efeito dos fármacos dinamicamente. Dentre os recursos de imagem existe a Functional Near Infrared Spectroscopy (fNIRS) que permite avaliar ativação cortical por meio da mudança no consumo local de oxigênio que acompanha o disparo neuronal regional, mensurado pelas mudanças na concetração da oxi- e desoxi-hemoglobina. Com estas considerações, hipotetizamos que a modulação farmacológica induzida pela pregabalina poderia ser mensurada, clinicamente por meio de testes psicofísicos da dor (que avaliam vias nociceptivas associadas a termoreceptores e barorreceptores) e à nível de neuroimagem por meio do fNIRS. Por se tratar de um mesmo sistema com potencial de ser avaliado de forma virtualmente simultânea, hipotetizamos também que existirá uma associação entre as modulações clínicas (testes psicofísicos) e neurológicas (fNIRS do córtex sensitivo e motor primários). Desta forma, neste estudo avaliou-se o efeito de pregabalina (150 mg) em dose única em fibromiálgicas e controles saudáveis. Em ambos os grupos a pregabalina foi comparada ao placebo, num desenho de estudo randomizado, duplo-cego, cruzado. Avaliou-se o efeito das intervenções, intra e inter-grupos, na ativação cortical de maneira indireta, pela concetração da oxi-hemoglobina durante testes psicofísicos da dor por meio meio do Quantitative Sensory Testing (QST) e algometria de pressão, que foram comparados com a ativação cortical durante uma tarefa motora de percussão dos dedos da mão (left hand finger tapping). Foram estudadas mulheres com idade entre 18 e 65 anos, 17 fibromiálgicas e 10 controles saudáveis. Os parâmetros do QST foram avaliados uma hora após dose única de 150 mg de pregabalina. Resultados: Na linha de base, as fibromiálgicas apresentaram alterações no QST sugestivas de lesão de fibras finas: o limiar de detecção de calor (HDT, do inglês Heat Detection Threshold) foi maior que nas controles (35,53 ºC ± 3,22 vs. 33,33 ºC ± 0,85; p<0,05), enquanto o limiar de dor por pressão (PPT, do inglês Pain Pressure Threshold) foi menor (2,44 kg/cm2 ± 1,08 vs. 4,32 kg/cm2 ± 1,45; P<0,01). Não foram observadas diferenças nos outros componentes do QST, nem mudanças com a pregabalina. Quando comparados com as saudáveis, nas fibromiálgicas o HDT, limiar de dor por calor (HPT) e a tolerância ao calor (HT) evocaram activação nos giros frontal médio, precentral e póscentral, porém, de menor amplitude do que as controles. Depois da administração da pregabalina, aumentou a ativação em responsta ao HDT, mas não teve correlação com o valor do limiar. Já o HPT mostrou se correlacionar de forma inversa com a ativação nos giros frontal superior (rs=-0,552, p=0,033) e precentral (rs=-0,545, p=0,036) na linha de base e após pregabalina (rs=-0,52, p=0,047). A HT também apresentou uma correlação inversa com os giros frontal superior (rs=-0,645, p=0,032) e precentral (rs=-0,655, p=0,029), mas neste caso, esta correlação desapareceu após ter recebido pregabalina. A ativação cortical pelo PPT não detectou diferenças entre fibromiálgicas e controles. Conclusões: O perfil nos testes psicofísicos nas pacientes apresenta correlação com sua ativação cortical. As alterações nos testes sugerem alterações de fibras finas nociceptivas, o que é explicado por um componente de neuropatia periférica, que na fibromialgia é acompanhado por diminuição da ativação em áreas sensitivas e motoras, e aumento da ativação em áreas associadas com processamento cognitivo da dor, cuja atividade foi elevada com a pregabalina. Quando comparadas às controles, nas fibromiálgicas a HT recrutou mais áreas associada ao processamento cognitivo da dor, o que fortalece a hipótese a favor da existência do componente de sensibilização central na fibromialgia. Desta forma, estes achados reforçam a provável coexistência de alterações periféricas e centrais na fisiopatologia da fibromialgia. / Fibromyalgia is a syndrome characterized by presenting chronic diffuse pain, fatigue, mood and sleep disturbances. Although its pathophysiology has not been totally elucidated yet, the neurobiological processes seems to involve funciontal alterations of the sensorimotor cortex and its conections with subcortical structures (related to the pain neuronal matrix), and also, with quantitative and qualitative alterations in fine sensitive fibers from the peripheral nervous system. It is known that increased intracellular calcium above certain threshold might be part of a process activity-dependant that leads to central sensitization, due to elevated calcium influx through NMDA and AMPA channels, as well as voltage-dependent channels, and also due to relase of intracellular microsomal reserves. Central sensitization can also be interpreted as a maladaptive plasticity that sustains pain circuits and its correlated. Thus, the sensorimotor cortex has been a diagnostic and therapeutic target for the study and treatment of chronic pain. Among the multiple pharmacological strategies, the use of pregabalin has been recommended and approved by the Food and Drug Administration (FDA) of the United States of America for treatment of patients with fibromyalgia since 2007. Pregabalin acts by inhibiting voltage-dependant pre-synaptic calcium channels by binding to the auxiliary protein alfa-2-delta. In vitro, this drug reduces the liberation of neurottransmissors that depend on calcium, and that include glutamate, norepinephrine, calcitonin and P-substance. All the latter mentioned neurotransmitters are associated with the central nervou system sensitization. Thus, considering its potential as neuronal modulation, taking into accout tis mechanisms of action, the pregabalin is an appealing drug to study the role of the modulation fo the sensorimotor cortex in the pathophysiology of fibromyalgia. Nevertheless, to incrase the knowledge about the effect of drugs on the cortical function, we need to use feasible neuroimaging resources able to be applied in diverse contexts, and that allow to measure the effect of the drugs in real time. Among the neuroimaging resources, there is the Functional Near Infrared Spectroscopy (fNIRS), which allows to assess cortical activation estimating the uptake of regional oxygen, that accompanies local neuronal firing. The fNIRS measures changes in the concentration of oxy and desoxy hemoglobin. Given these considerations, we hypothezise that the pharmacological modulation induced by pregabalin could be measured, clinically through psychophysical pain testing, and at the neuroimaging level using fNIRS. Given that it is about the same system with the potential to be assessed in complementary and virtually simultaneous ways, we also hypothesize that there still could exist an association between the clinical modulation (psychophysical tests) and cortical sensorimotor activation (assessed by fNIRS). In this way, this study appraised the effect of a single dose of pregabalin (150 mg) in the cortical activation and psicophysical pain testing in fibromyalgic and in healthy subjects. In both groups, pregabalin was compared to placebo, in a randomized, double-blinded, cross-over trial design. We assessed the effect of pregabalin, within and between-groups, on the cortical activity in an indirect way via the changes in oxy-hemoglobin upon heat and pressure stimuliation inside a protocol of QST, and also compared the psychophysical pain tests results with the performance during a Left Hand Fingertapping Task. We studied women aging 18 to 65, 17 of them with fibromyalgia and 10 healthy controls. QST parameters were assessed one hour after a single dose of 150 mg of pregabalin. Results: At baseline, patients with fibromyalgia presented QST alterations suggestive of fine nerve fibers lesion: baseline HDT was higher in fibromyalgia (35.53±3.22 vs. 33.33±0.85, P<0.05), while PPT was lower (2.44±1.08 vs. 4.32±1.45, P<0.01) than healthy volunteers, but did not change with pregabalin. When compared to healthy subjects, HDT, HPT, and HT evoked smaller activation in the middle frontal, pre- and post-central gyri in fibromyalgia, that increased after pregabalin (only for HDT-induced activation), but that was not correlated to the HDT. HPT was inversely correlated to the activation in the superior frontal (rs=-0.552, p=0.033) and precentral gyri (rs=-0.545, p=0.036), remaining unchanged after pregabalin (rs=-0.52, p=0.047). HT was inversely correlated to the middle frontal (rs=-0.645, p=0.032) and precentral gyri activation (rs=-0.655, p=0.029), but was no longer correlated after pregabalin. PPT cortical activation did not differ between fibromyalgia and healthy volunteers. Conclusions: The psychophysical pain testing profile in fibromyalgia has a cortical correlate. Alterations in tests for small fibers support its probable peripheral neuropathic component, and was accompanied by decreased activation in sensorimotor areas but increased in pain-related cognitive processing cortexes, and whose activity is increased by pregabalin. Also, upon HT fibromyalgia patients recruited more areas related to pain cognitive processing, which could favor the hypothesis of a component of central sensitization in fibromyalgia, and which was poorly modulated by pregabalin. Taken together, these findings support the co-existence of both, peripheral and central alterations in fibromyalgia.