The functional neuroanatomy of language localization in dyslexia has primarily been studied in the context of reading. However, dyslexia is sometimes referred to as a “language-based learning disability,” yet the functional signature of the core language comprehension network in dyslexia is far less understood. This thesis presents a series of studies designed to compare the functionality of the brain regions supporting linguistic processing between typical and impaired readers in order to characterize the cortical language network in dyslexia. First, we investigate the extent to which the efficiency (or quality of data vs. amount of scan time) of a functional language localizer based on passive spoken language comprehension can be maximized in Chapter 2. By demarcating the language network based on smaller amounts of data and testing stability and reliability within this framework, we found that scan time can be substantially reduced without sacrificing functional specialization for language. In Chapter 3, we apply the spoken language localizer to determine differences in functional organization of language in dyslexia and provide evidence that the core spoken language comprehension network is not markedly different between typical readers and those with dyslexia. We compared the individual activations from whole-brain analysis and functional profiles in the canonical language-selective regions and found that the functional response of localized language regions in individuals with dyslexia was as selective as in typically reading adults. Chapter 4 follows up on the functional evidence reported in Chapter 3 to examine the structural connectivity within the same functional language network and additionally found essentially no differences between controls and dyslexia, further supporting the observations made in Chapter 3 that core linguistic processing is intact in dyslexia. All together, these findings converge on the suggestion that individuals with dyslexia do not rely on a separate cognitive architecture for language, potentially revealing important new insight into the dissociation of language specialization abilities and reading difficulty in dyslexia.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18876号 / 医博第3987号 / 新制||医||1008(附属図書館) / 31827 / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 小泉 昭夫, 教授 宮本 享 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Gender differences in emotion regulation (ER) are well documented, but studies have often relied on behavioral and self-report data. Less is known about gender differences in the neural basis of ER. This systematic review aims to fill this gap and investigate gender differences in the neural basis of ER. The systematic search process ended in eight articles, using either structural or functional neuroimaging methods while investigating the neural correlates of ER using either an ER task to manipulate ER or assessed trait ER with questionnaires. The studies either used reappraisal or expressive suppression as ER strategies. The results were partly inconsistent, but most studies demonstrate the involvement of areas within the prefrontal cortex in ER. Males activated areas involved in cognitive control while females activated emotion-focused areas involved in emotional processing. There is disagreements among researchers whether more activity in the prefrontal cortex represent more effort during ER (and how it does so), as well as whetherless activity represent less effort or more efficient regulation. These insights may help us understand each other better. Future research is needed to address if activation within the prefrontal cortex reflects more or less efficiency when regulating emotions.

The purpose of this systematic review was to characterize further the structural differences in the prefrontal cortex, limbic and paralimbic regions and amygdala alone in psychopaths. Psychopathy is a multifaceted personality disorder characterized by interpersonal and affective traits like lack of empathy, guilt or remorse, shallow affect, and carelessness, as well as behavioral traits such as impulsivity, and poor behavioral control. In recent years, the interest in the neuroanatomical differences in psychopaths has grown. This review aims to understand the prefrontal cortex, limbic and paralimbic areas, and how these regions differ between psychopathic patients and healthy controls. By systematically screening articles that used magnetic resonance imaging (MRI) and voxel based morphometry (VBM) the studies in this review examined people with psychopathic traits. To assess for psychopathy, the most used assessment tool, the Psychopathy Checklist-Revised (PCL-R) was used. Results show that the higher the PCL-R scores of the offenders, the less gray matter volume was found in the superior parts of the prefrontal cortex, limbic and paralimbic areas. Additionally, amygdala deficits in individuals with psychopathy were found. This systematic review may benefit in the way that if we increase our understanding of psychopathy and pave the way forthe creation of effective psychopathic treatments it could prevent future acts of violence. The link between a structural brain anomaly and psychopathy may have a profound clinical, legal, and scientific impact. A psychopathy diagnosis may serve as a precursor to severe societal violence.

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Cognitive Science of Religion attempts to explain how humans came to develop belief in the supranatural by exploring the underlying neurocognitive mechanisms of religion. New imaging technologies provide a unique possibility to identify pathways activated during religious practice. Main studies in this field have been reviewed and summarised by Schoejdt, and by Grafman et al. This thesis reviews the imaging-based studies and applies content analysis to investigate whether their design and results are adequate to probe their hypotheses and provide information regarding neural pathways involved in religious practice. A total of eight studies are identified for further analysis. This thesis reviews the studies based on their sample size, subject matter, choice of imaging, psychological tests, hypotheses and outcomes. It identifies small sample size and limited diversity but suggests that with stringent study design imaging can provide important information about neural basis of religion.

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.

Introduction: Through large neuroimaging consortia, researchers have identified a series of neuroanatomical alterations in mood and psychotics disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). However, the mechanism behind these alterations is not well understood. One of the existing hypotheses suggests that the observed brain changes are related to a process of accelerated brain ageing. Studies investigating this hypothesis use a measure called the brain age gap (i.e., the difference between machine learning model predictions of brain age and chronological age). Thus far, there is limited understanding on how mood and psychotic disorders affect model predictions, how can predictions be clinically useful, and what is the biological meaning behind the brain age gap. In this thesis, we investigated accelerated brain ageing in mood and psychotic disorders. We sought to estimate the effect of the brain age gap and propose new ways of modeling brain age. We also explored the clinical utility and meaning of the brain age gap. Results: We confirmed the presence of a brain age gap in MDD, BD, and SCZ through a systematic review and meta-analysis. SCZ presented the highest levels of brain age gap, followed by BD and MDD. We analyzed the clinical utility of brain age for antidepressant treatment response and concluded that the brain age gap is not a predictor of antidepressant treatment response in weeks 8 and 16. We proposed a new method for brain age prediction that is more interpretable than previous approaches while preserving good predictive performance. We have also used model explanation strategies and identified that the brain age gap is largely associated with total gray matter volume reduction and ventricle enlargement in SCZ. Conclusion: The results of this thesis suggest that the brain age gap is present across mood and psychotic disorders. The results have also helped to clarify the meaning behind the brain age gap, a largely used but still poorly understood measure in neuroimaging research. So far, there is no indication that the brain age gap can be a useful tool for treatment response prediction in MDD. / Thesis / Doctor of Philosophy (PhD)

Introduction: The brain can change its structure and functionality as a result ofexternal factors. The working memory (WM) of the brain is where informationcan be held and manipulated during a short period of time, with the purpose ofachieving higher cognitive functions such as reasoning and learning. The WMimproves in capacity during the development from childhood into adulthood,and variation of improvement is possible as an effect of situational factors andstimuli.Goal: The main goal of this project was to examine the effects of a WMtraining program on power distribution, connectivity and synchronicity withinbrain networks, using an intra-individual analysis approach.Method: A series of magnetoencephalography (MEG) measurements wasacquired for four subjects while they were performing WM and control tasks,during a WM training program, along with an MRI image of the brain for eachof the participants. The data was preprocessed for noise and artifact removaland a source reconstruction was performed. Time-frequency representationsof the data were created and the frequencies were categories into alpha,beta and gamma bands. The power difference between the WM and controltask was calculated as a function of cognitive load of each frequency band,and its variation over load was calculated as a constructed metric called’area under power difference curve’ (AUPDC), and visualised using colourscale representation upon the brain MRI of each subject. Brain parcels thatsignificantly deviated from a random distribution of AUPDC values wereidentified using a Gaussian distribution fit.Results and discussion: All subjects showed a clear improvement inperformance accuracy of the tasks, but as the effect on the power distributionsvaried considerably for each subject and frequency band, other aspects besidepower need to be investigated in order to understand the mechanisms behindthe improvement. However, the overall results indicate that many significantAUPDC values seem to have decreased during the WM training, both forthe positive and negative significant AUPDC values, suggesting a strongerdecreasing trend in power difference over cognitive load and a weaker increasingtrend. This could suggest an improved brain activation efficiency as an effectof the WM training.