BACKGROUND: Schizophrenia manifests as a constellation of both psychotic symptoms (eg. hallucinations, delusions) and so-called negative symptoms. The latter includes anhedonia, avolition, amotivation and they are the strongest predictors of disability. Resting state fMRI (rsfMRI) has demonstrated that the brain is organized into low-dimensional number (7-17) brain networks and this allowed visualization of the relationship between symptom severity and large-scale brain network organization. Traditional rsfMRI analyses have assumed that the spatial organization of these networks are spatially invariant between individuals. This dogma has recently been overturned with the observation that the spatial organization of these brain networks shows significant variation between individuals. We sought to determine if previously observed relationships between symptom severity and network connectivity are actually due to individual differences in spatial organization. METHODS: 44 participants diagnosed with schizophrenia underwent rsfMRI scans and clinical assessment. A multivariate pattern analysis was used to examine how each participant’s whole brain functional connectivity correlates with ‘negative’ symptom severity. RESULTS: Brain connectivity to a region of the right dorso-lateral pre-frontal cortex (r DLPFC) correlates with symptom severity. The result is explained by the individual differences in the topographic distribution of two brain networks: the default mode network (DMN) and the task positive network (TPN). Both networks demonstrate strong (r~0.49) and significant (p<0.001) relationships between topography and symptom severity. For individuals with low symptom severity, this critical region is a part of the DMN. In highly symptomatic individuals, this region is a part of the TPN. CONCLUSIONS: Previously overlooked individual variation in brain organization is tightly linked to individual variation in schizophrenia symptom severity. The recognition of critical links between network topology and pathological symptomology may serve as a guide for future interventions aimed at establishing causal relationships between certain critical regions of the brain and cognitive and behavioral phenotypes. Thus, fMRI and network topology may be translated to a clinical setting as a viable, individual-centered treatment option. / 2020-06-17T00:00:00Z

Individuals who speak more than one language have been found to enjoy a number of benefits not directly associated with the use of the languages themselves. One of these benefits is that bilingual individuals appear to develop symptoms of dementia 4-5 years later than comparable individuals who speak just one language. Studies on this topic, however, do not consistently account for factors including if the individual learned their second language as a child or later in life, or their language proficiency. In an attempt to more carefully examine these variables, this study looks at structural and resting-state functional MRI scans of the default mode network, English and Spanish (where applicable) proficiency, language background, and demographics of young healthy adults who fall into one of three groups: early bilinguals, late bilinguals, and monolinguals. Of the three groups, late bilinguals were found to have a small but statistically significantly higher level of connectivity compared with early bilinguals in the region of the medial prefrontal cortex; patterns found examining number of languages and language proficiency in relation to functional connectivity and research group also supported this finding. These results indicate studying a language after adolescence could provide neuroprotective benefits of a nature that could potentially help delay symptoms of dementia. Age, gender, ethnicity, level of education, English language proficiency, and Spanish language use did not result in statistically significant findings, the latter of which challenges using frequency of language use to define bilingualism.

Previous work has linked the onset and progression of Alzheimer’s Disease (AD) to changes in the Default Mode Network (DMN), including greater atrophy within the hippocampus (HC) as well as diminished functional connectivity and effective connectivity between anatomical DMN structures. Animal models have described the HC as a primary region of interest in studying the effects of exercise on adult neurogenesis and memory performance. Human studies have demonstrated that aerobic exercise leads to greater cardiorespiratory fitness and improved functional connectivity in the DMN for healthy adults. The goal of this study is to go beyond the predictions of human and animal studies to investigate how cardiorespiratory fitness may be used to estimate effective connectivity between the HC and the other DMN structures for young adults using resting state fMRI. Due to the data driven nature of this study, no hypothesis has been formulated. To investigate, data from 25 sedentary young adults was analyzed. Data included a resting state fMRI procedure and a cardiorespiratory fitness test, each taken from part of a larger ongoing clinical trial in the Brain Plasticity and Neuroimaging (BPN) Lab at Boston University (BU). We utilized group independent component analysis (GICA) to identify the regions that define the DMN and Conditional Granger Causality Analysis (CGCA) to determine effective connectivity between these regions. GICA indicated 9 structural regions in the DMN, consistent with previous work. This resulted in 72 possible instances of effective connectivity. The difference of causal influence between regions was calculated for each pair of DMN regions for CGCA, resulting in 36 possible instances of causal connectivity. Linear regression models were created to analyze the effect of cardiorespiratory fitness on effective connectivity between DMN regions and found 11 linear models which exhibited a significant (p > 0.05) relationship. Eight of eleven models involved the left or right hippocampus, showing that greater cardiorespiratory fitness is correlated with changes effective connectivity between the HC and the PCC, MPFC, or LTC. These results provide proof of concept that cardiorespiratory fitness in young adults is associated with changes DMN effective connectivity, particularly involving the hippocampus. This adds to the literature suggesting extended aerobic exercise, which is known to increase cardiorespiratory fitness and has been shown to increase the volume of the HC in older adults, may be neuroprotective of the HC across the lifespan. Further investigation is required to explore how effective connectivity in the DMN changes following an aerobic exercise intervention.

This essay investigates the relationship between a malfunctioning Default Mode Network (DMN) and the diagnosis of Major Depressive Disorder (MDD). A deeper understanding of how the DMN affects those brain processes which are implicated in MDD may offer new approaches to reduce the suffering of the very large number of MDD-afflicted patients. The MDD-DMN relationship has been investigated by studying scientific articles within the field of cognitive neuroscience and searching the articles for clues on how a malfunctioning DMN might correlate with the diagnosis of MDD. The essay concludes that there is much experimental evidence in support of there being a strong coupling between a malfunctioning DMN and the diagnosis of MDD.

The default mode network (DMN) consists of a set of interconnected brain regions supporting autobiographical memory, our concept of the self, and the internal monologue. These processes must be maintained at all times and consume the highest amount of the brain’s energy during its baseline state. However, when faced with an active, externally-directed cognitive task, the DMN shows a small, but significant, decrease in activity. The reduction in DMN activity during the performance of an active, externally-directed task compared to a baseline state is termed task-induced deactivation (TID), which is thought to ‘free-up’ resources required to respond to external demands. However, older adults show a reduced level of TID in the DMN. Recently, it has begun to be appreciated that this decrease in TID may be associated with poorer cognitive performance, especially during tasks placing high demands on executive function (EF). Diminished DMN TID has not only been associated with increasing age but also with multiple age-related neurobiological correlates such as accumulating Alzheimer’s disease (AD) pathology and reductions in white matter (WM) connectivity. However, these biological factors—age, WM connectivity reductions and increasing AD pathology—are themselves related. Based on the literature, we hypothesized that declining WM connectivity may represent a common pathway by which both age and AD pathology contribute to diminished DMN TID. Further, we hypothesized that declines in DMN function and WM connectivity would predict poorer in EF. Three experiments were carried out to test these hypotheses. Experiment 1 tested whether WM connectivity predicted the level of DMN TID during a task requiring a high level of EF. Results from 117 adults (ages 25-83) showed that WM connectivity declined with increasing age, and that this decline in WM connectivity was directly associated with reduced DMN TID during the task. Experiment 2 tested whether declines in WM connectivity explained both age-related and AD pathology-related declines in DMN TID. Results from 29 younger adults and 35 older adults showed that declining WM connectivity was associated with increasing age and AD pathology, and that this decline in WM connectivity was a common pathway for diminished DMN TID associated with either aging or AD pathology. Experiment 3 investigated whether measures of WM connectivity and DMN TID at baseline could predict EF measured using clinically-used tests. Results from 29 older adults from Experiment 2 showed that less DMN TID predicted poorer EF at baseline and diminished WM connectivity at baseline predicted a greater decline in EF after 3 years. Further, WM connectivity explained reductions in EF predicted by baseline AD pathology, as well as further reductions in EF not predicted by baseline AD pathology. Together the results of these studies suggest that WM connectivity is a key pathway for age-related and AD pathology-related patterns of diminished DMN TID associated with poorer EF. Further, WM connectivity may represent a potential therapeutic target for interventions attempting to prevent future declines in EF occurring in aging and AD.

Abstract In the 1990s researchers discovered task-deactivated regions in the human brain. Together, these areas make up the default mode network (DMN). It was originally proposed to act as a balancing mechanism between different brain systems, explaining the deactivations, but is now mostly studied with regards to internal awareness, such as daydreaming and mental imagery. The purpose of this thesis is to present a summary of DMN research, focusing on the network’s suggested role in internal awareness. This will be done by reviewing a wide variety of research that either explicitly or indirectly correlate default mode network features with aspects of consciousness and internal awareness. The subjective experience of being conscious have been a source of argument primarily among philosophers, but the qualities we feel are intimately linked to cognitive functions that are supported by the regions found in the DMN. Cognitive neuroscience may therefore be able to contribute to the concept of internal awareness and consciousness.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23069号 / 医博第4696号 / 新制||医||1049(附属図書館) / 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 林 康紀, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

In addition to mood symptoms, major depressive disorder (MDD) is characterized by cognitive impairments that can have detrimental impacts on quality of life and daily function, and have been found to persist into remission. In particular, altered affective cognition (e.g. biased attention to negative stimuli) has been reported in MDD, and may continue into remission. Unfortunately, current pharmacotherapies do not adequately address cognitive dysfunction in acute or remitted MDD. Understanding the neurobiological underpinnings of affective cognitive dysfunction in remitted MDD may help inform the development of new interventions to address this lingering problem and the associated poorer functional outcomes. The triple network model posits that altered functioning of three key networks implicated in normal cognitive function – the default mode network (DMN), central executive network (CEN) and salience network (SN) – underlies cognitive dysfunction in a variety of psychiatric illnesses, including MDD. Though notable exceptions exist, work in acutely depressed MDD patients has found evidence of DMN hyperconnectivity, CEN hypoconnectivity and abberant SN connectivity both at rest and during the completion of various cognitive tasks. The evidence for triple network connectivity alterations persisting into remission is less robust, and warrants further investigation. Furthermore, there is a paucity of studies examining remitted MDD connectivity during affective tasks. As such, the primary objectives of this thesis were to: 1) compare resting-state and task triple network connectivity profiles in remitted MDD patients (rMDDs) and healthy volunteers (HVs) at rest, during an affective (emotional Stroop [eStroop]) task, and during rest vs. the task and, 2) assess the relationship between DMN and CEN connectivity and measures of daily functioning, quality of life and/or negative, self-relational rumination in the rMDD cohort. Behaviourally, there were findings of an affective attentional bias and impaired processing speed in the rMDD vs. HVs, as revealed by a computerized cognitive test battery. However, we found no evidence of DMN hyperconnectivity or CEN hyperconnectivity in the rMDD study sample. We did find evidence of altered intrinsic CEN and CEN-SN connectivity between the rest and task conditions that seemed driven by the rMDD sample, as well as positive CEN-DMN correlations across the entire sample both at rest and during the eStroop task. Suprisingly, we also found higher intrinsic DMN connectivity during the eStroop task vs. at rest across the whole sample. Finally, we found a positive relationship between task-based CEN connectivity and hopeless rumination, and a significant negative relationship between resting state and task-based DMN connectivity and psychosocial dysfunction in the rMDD sample. These findings contribute to our understanding of large-scale intrinsic network connectivity alterations during remitted depression, and their relationship to functional outcomes.

Title: Measuring electrical brain activity during stimulation of trigger zones from concept of Vojta principle Objectives: The aim of this study is to clarify whether there is a change in the electrical brain activity evaluated by the sLORETA program during the stimulation of trigger zones according to the Vojta concept. The source activity during stimulation of trigger zones was scanned from the scalp EEG and compared with the sLORETA program with the source activity measured at rest, before and after the stimulation of the trigger zones. Methods: The research was conducted on 11 healthy adult subjects. The entire research group is consisted of women aged in range 19-32. The data was obtained from the scalp EEG before, during and after stimulation of trigger zones according to Vojta concept. For each proband the measurement of resting EEG with both open and closed eyes (2 x 10 minutes) was first performed, then the measurements were taken during the stimulation of trigger zones with open and closed eyes (2 x 15 minutes). Finally, a resting EEG was measured, alternating open and closed eyes after five minutes (4 x 5 minutes). There was a pause of at least 15 minutes between each stimulation of trigger zones. The order of open and closed eyes during resting EEG and during stimulation of trigger...

This literature review examines the default mode network (DMN) and how its role in self related processing and narrative selfhood relates to well-being. The essay explores the DMN in three levels of activity: Firstly in normal function, where mind-wandering is positively correlated with dissatisfaction; Secondly its abnormal function in depression, characterized by excessive activity and rumination; Thirdly in its arguably improved function during mindfulness and meditation, where lower activity is associated with higher well-being, decreased mind-wandering and altered sense of self. The essay shows a relationship between the DMN and well-being, where higher activity correlates with lower well-being.