Aberrations of anterior insular cortex functional connectivity in nontreatment-seeking alcoholics

An emergent literature suggests that resting state functional magnetic resonance imaging (rsfMRI) functional connectivity (FC) patterns are aberrant in alcohol use disorder (AUD) populations. The salience network (SAL) is an established set of brain regions prominent in salience attribution and valuation, and includes the anterior insular cortex (AIC). The SAL is thought to play a role in AUD through directing increased attention to interoceptive cues of intoxication. There is very little information on the salience network (SAL) in AUD, and, in particular, there are no data on SAL FC in currently drinking, nontreatment seeking individuals with AUD (NTS). rsfMRI data from 16 NTS and 21 social drinkers (SD) were compared using FC correlation maps from ten seed regions of interest in the bilateral AIC. As anticipated, SD subjects demonstrated greater insular FC with frontal and parietal regions. We also found that, compared to SD, NTS had higher insular FC with hippocampal and medial orbitofrontal regions. The apparent overactivity in brain networks involved in salience, learning, and behavioral control in NTS suggests possible mechanisms in the development and maintenance of AUD

3D Deep Learning on Medical Images: A Review

The rapid advancements in machine learning, graphics processing technologies and availability of medical imaging data has led to a rapid increase in use of deep learning models in the medical domain. This was exacerbated by the rapid advancements in convolutional neural network (CNN) based architectures, which were adopted by the medical imaging community to assist clinicians in disease diagnosis. Since the grand success of AlexNet in 2012, CNNs have been increasingly used in medical image analysis to improve the efficiency of human clinicians. In recent years, three-dimensional (3D) CNNs have been employed for analysis of medical images. In this paper, we trace the history of how the 3D CNN was developed from its machine learning roots, give a brief mathematical description of 3D CNN and the preprocessing steps required for medical images before feeding them to 3D CNNs. We review the significant research in the field of 3D medical imaging analysis using 3D CNNs (and its variants) in different medical areas such as classification, segmentation, detection, and localization. We conclude by discussing the challenges associated with the use of 3D CNNs in the medical imaging domain (and the use of deep learning models, in general) and possible future trends in the field.Comment: 13 pages, 4 figures, 2 table

The YOUth cohort study: MRI protocol and test-retest reliability in adults

The YOUth cohort study is a unique longitudinal study on brain development in the general population. As part of the YOUth study, 2000 children will be included at 8, 9 or 10 years of age and planned to return every three years during adolescence. Magnetic resonance imaging (MRI) brain scans are collected, including structural T1-weighted imaging, diffusion-weighted imaging (DWI), resting-state functional MRI and task-based functional MRI. Here, we provide a comprehensive report of the MR acquisition in YOUth Child & Adolescent including the test-retest reliability of brain measures derived from each type of scan. To measure test-retest reliability, 17 adults were scanned twice with a week between sessions using the full YOUth MRI protocol. Intraclass correlation coefficients were calculated to quantify reliability. Global brain measures derived from structural T1-weighted and DWI scans were reliable. Resting-state functional connectivity was moderately reliable, as well as functional brain measures for both the inhibition task (stop versus go) and the emotion task (face versus house). Our results complement previous studies by presenting reliability results of regional brain measures collected with different MRI modalities. YOUth facilitates data sharing and aims for reliable and high-quality data. Here we show that using the state-of-the art YOUth MRI protocol brain measures can be estimated reliably

Artificial Intelligence for Detection, Characterization, and Classification of Complex Visual Patterns in Medical Imaging; Applications in Pulmonary and Neuro-imaging

Medical imaging is widely used in current healthcare and research settings for various purposes such as diagnosis, treatment options, patient monitoring, longitudinal studies, etc. The two most commonly used imaging modalities in the United States are Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Raw images acquired via CT or MRI need to undergo a variety of processing steps prior to being used for the purposes explained above. These processing steps include quality control, noise reduction, anatomical segmentation, tissue classification, etc. However, since medical images often include millions of voxels (smallest 3D units in the image containing information) it is extremely challenging to process them manually by relying on visual inspection and the experience of trained clinicians. In light of this, the field of medical imaging is seeking ways to automate data processing. With the impressive performance of Artificial Intelligence (AI) in the field of Computer Vision, researchers in the medical imaging community have shown increasing interest in utilizing this powerful tool to automate the task of processing medical imaging data. Despite AI’s significant contributions to the medical imaging field, large cohorts of data still remain without optimized and robust AI-based tools to process images efficiently and accurately. This thesis focuses on exploiting large cohorts of CT and MRI data to design AI-based methods for processing medical images using weakly-supervised and supervised learning strategies, as well as mathematical (and/or statistical) modeling and signal processing methods. In particular, we address four image processing problems in this thesis. Namely: 1) We propose a weakly-supervised deep learning method to automate binary quality control of diffusion MRI scans into ‘poor’ and ‘good’ quality classes; 2) We design a weakly-supervised deep learning framework to learn and detect visual patterns related to a set of different artifact categories considered in this work, in order to identify major artifact types present in dMRI volumes; 3) We develop a supervised deep learning method to classify multiple lung texture patterns with association to Emphysema disease on human lung CT scans; 4) We investigate and characterize the properties of two types of negative BOLD response elicited in human brain fMRI scans during visual stimulation using mathematical modeling and signal processing tools. Our results demonstrate that through the use of artificial intelligence and signal processing algorithms: 1) dMRI scans can be automatically categorized into two quality groups (i.e., ‘poor’ vs ‘good’) with a high classification accuracy, enabling rapid sifting of large cohorts of dMRI scans to be utilized in research or clinical settings; 2) Type of the major artifact present in ‘poor’ quality dMRI volumes can be identified robustly and automatically with high precision enabling exclusion/correction of corrupt volumes according to the artifact type contaminating them; 3) Multiple lung texture patterns related to Emphysema disease can be automatically and robustly classified across various large cohorts of CT scans enabling investigation of the disease through longitudinal studies on multiple cohorts; 4) Negative BOLD responses of different categories can be fully characterized on fMRI data collected from visual stimulation of human brain enabling researchers to better understand the human brain functionality through studying cohorts of fMRI scans

Pharmaco-fMRI Challenges before and after short-term Treatment of Major Depression with Escitalopram, Mirtazapine, Agomelatine or Placebo and the Relation to the Hypothalamus-Pituitary-Adrenal-Axis Activity

Background: Major Depressive Disorder (MDD) is a chronic stress related disorder characterized by depressed mood, by vegetative and cognitive symptoms. Imaging biomarkers may help to predict the impaired processing and regulation of emotions related to MDD and to antidepressant treatment response. Pharmaco neuroimaging and behavioral studies have shown that antidepressants can affect emotional processing very early after starting the treatment and independently from changes in subjective mood. Moreover, normalization of hypothalamus-pituitary-adrenal (HPA) axis regulation, which is usually disturbed in MDD, is often associated with successful recovery from depression. Therefore, we investigated the relationship between neural activation before and after short term treatment with antidepressants and HPA axis activity in relation to clinical outcome in MDD patients. Methods: We investigated 33 in-patients admitted to the Department of Psychiatry and Psychotherapy, University of Regensburg, for the treatment of MDD. Firstly, we considered the evidence for a cognitive neuropsychological model of antidepressant drug action by employing pharmaco-fMRI (3T) in a double-blind randomized placebo-controlled design to investigate the effect of short-term treatment with escitalopram, mirtazapine, agomelatine or placebo on the BOLD signal change in predefined brain regions associated with a visual facial emotional and neutral stimulation task. Additionally, all patients received the same amount of psychotherapeutic support. Results: After one week of short-term treatment we detected a statistically significant reduction in the BOLD % signal change in the bilateral amygdala, right dorsolateral prefrontal cortex and the right fusiform gyrus during the presentation of facial emotional and neutral expressions. In a second evaluation, we compared medicated patients with unmedicated (placebo treated) patients. Here we could see significant effects in the described regions but could not detect significant differences between verum and placebo groups. After that, each treatment group was investigated separately and compared together. The results showed again statistically significant effects in the above described regions, but no significant differences between the treatment groups. The clinical outcome after one week of treatment showed a partial recovery of the patients with reduced scores in the Hamilton rating scale for depression together with and correlated with BOLD % signal change in some specific regions. Moreover, the activity of the HPA axis was reduced slightly. In addition, this reduction showed significant correlations with the BOLD % signal change in some of the regions of interest. Discussion: The purpose of this study was to provide a better understanding of the interface between neural systems during antidepressant treatment, the short term effects of antidepressants on emotional processing, to bridge the gap between defined brain regions (amygdala, DLPFC, fusiform gyrus, hippocampus and insula) the fMRI BOLD signal, HPA axis hyperactivity, and the clinical status of major depressed patients. We could show that bilateral amygdala hyperactivities in depressed patients were reduced even after short term treatment. A trend to reduce and normalize also the activity in the right dorsolateral prefrontal cortex and in the right fusiform gyrus was consistent also with other fMRI studies. In addition, we could demonstrate a probable association between the HPA axis regulation and the activity in the brain regions of interest investigated in our study. We could demonstrate the onset of a normalization of the HPA axis activity, as well as the onset of clinical improvement after one week of treatment, but our study lacked statistic power to differentiate between our four treatment groups. In addition, it is possible that unspecific effects of counseling and the in-patient treatment regimen outweigh any specific pharmacological treatment effects after only one week of antidepressant treatment

The cognitive and neural mechanisms involved in motor imagery of speech

Inner speech is a common phenomenon that influences motivation, problem-solving and self-awareness. Motor imagery of speech refers to the simulation of speech that gives rise to the experience of inner speech. Substantial evidence exists that several cortical areas are recruited in general motor imagery processes, including visual and speech motor imagery, but the evidence for primary motor cortex involvement is less clear. One influential model proposes that motor cortex is recruited during speech motor imagery, while another prominent model suggests motor cortex is bypassed. This thesis presents six experiments that explore the role of motor cortex in speech motor imagery. Experiments 1-3 build on established visual motor imagery tasks and expand these tasks to the speech motor imagery domain for the first time, using behavioural (experiments 1 and 2) and neuroimaging methods (experiment 3). Experiment 4 uses transcranial magnetic stimulation to explore motor cortex recruitment during a speech imagery condition, relative to a motor execution and baseline condition in hand and lip muscles. Experiments 5 and 6 use transcranial magnetic stimulation to explore speech motor imagery in tongue muscles relative to a hearing and a baseline condition. The results show that recruitment of motor cortex during speech motor imagery is modulated depending on task demands: simple speech stimuli do not recruit motor cortex, while complex speech stimuli are more likely to do so. The results have consequences specifically for models that always or never implicate motor cortex: it appears that complex stimuli require more active simulation than simple stimuli. In turn, the results suggest that complex inner speech experiences are linked to motor cortex recruitment. These findings have important ramifications for atypical populations whose inner speech experience may be impaired, such as those who experience auditory verbal hallucinations, or those with autism spectrum disorder

Multimodal Investigation of Brain Network Systems: From Brain Structure and Function to Connectivity and Neuromodulation

The field of cognitive neuroscience has benefited greatly from multimodal investigations of the human brain, which integrate various tools and neuroimaging data to understand brain functions and guide treatments for brain disorders. In this dissertation, we present a series of studies that illustrate the use of multimodal approaches to investigate brain structure and function, brain connectivity, and neuromodulation effects. Firstly, we propose a novel landmark-guided region-based spatial normalization technique to accurately quantify brain morphology, which can improve the sensitivity and specificity of functional imaging studies. Subsequently, we shift the investigation to the characteristics of functional brain activity due to visual stimulations. Our findings reveal that the task-evoked positive blood-oxygen-level dependent (BOLD) response is accompanied by sustained negative BOLD responses in the visual cortex. These negative BOLD responses are likely generated through subcortical neuromodulatory systems with distributed ascending projections to the cortex. To further explore the cortico-subcortical relationship, we conduct a multimodal investigation that involves simultaneous data acquisition of pupillometry, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). This investigation aims to examine the connectivity of brain circuits involved in the cognitive processes of salient stimuli. Using pupillary response as a surrogate measure of activity in the locus coeruleus-norepinephrine system, we find that the pupillary response is associated with the reorganization of functional brain networks during salience processing. In addition, we propose a cortico-subcortical integrated network reorganization model with potential implications for understanding attentional processing and network switching. Lastly, we employ a multimodal investigation that involves concurrent transcranial magnetic stimulation (TMS), EEG, and fMRI to explore network perturbations and measurements of the propagation effects. In a preliminary exploration on brain-state dependency of TMS-induced effects, we find that the propagation of left dorsolateral prefrontal cortex TMS to regions in the lateral frontoparietal network might depend on the brain-state, as indexed by the EEG prefrontal alpha phase. Overall, the studies in this dissertation contribute to the understanding of the structural and functional characteristics of brain network systems, and may inform future investigations that use multimodal methodological approaches, such as pupillometry, brain connectivity, and neuromodulation tools. The work presented in this dissertation has potential implications for the development of efficient and personalized treatments for major depressive disorder, attention deficit hyperactivity disorder, and Alzheimer's disease

Neuroimaging of endogenous lapses of responsiveness,

Attention lapses (ALs) and microsleeps (MSs) are complete lapses of responsiveness in which performance is completely disrupted for a short period of time, but consciousness is retained in the case of ALs. ALs are behaviourally different from MSs, as in an AL the eyes remain open whereas in a MS eyes are partially or completely closed. Both ALs and MSs can result in catastrophic consequences, especially in the transportation sector. Research over the past two decades has investigated the AL and MS phenomena using behavioural and physiological means. However, both ALs and MSs need further investigation to separate the different types of ALs physiologically, and to explore the neural signature of MSs in relation to normal sleep and drowsiness. Hence, the objective of this project was to understand the underlying physiological substrates of endogenous (internal) ALs and MSs which could potentially result in differentiating types of ALs and provide more understanding of MSs. Data from two previous Christchurch Neurotechnology Research Programme (NeuroTech™) studies (C and D) were combined resulting in a total of 40 subjects. During each session, subjects performed a 2-D continuous visuomotor tracking (CVT) task for 50 min (Study C) and 20 min (Study D). For each participant, tracking performance, eye-video, EEG, and fMRI were simultaneously collected. A human expert visually inspected the tracking performance and eye-video recordings to identify and categorize lapses of responsiveness for each participant. Participants performed the 2-D CVT task without interruptions. The repetitive nature of the task and the lack of a motivational factor made the task monotonous and fatiguing. As a result, it was more likely to introduce boredom leading to task-unrelated thoughts (TUTs), which divides attention between the task and the internal thoughts unrelated to the task, also fatigue which will introduce a trend of vigilance decrement over time. The project had hypotheses focusing on the changes in the brain’s activity compared to the baseline of good responsiveness tracking. We expected a decrease in dorsal attention network (DAN) activity during ALs due to a decoupling of attention from the external environment. Furthermore, we hypothesized that the ALs were due to involuntary mind-blanks. As such, we expected no change in default mode network (DMN) activity, as would have otherwise been expected if the ALs were due to mind-wandering. Functional connectivity (FC) of the brain was also investigated between the networks of interest which were the DMN, DAN, frontoparietal network (FPN), sensorimotor network (SMN), visual network (VSN), salience network (SN), eye-movement network (EMN), and working memory network (WMN), by analysing data from fMRI. EEG data were also used to perform analysis on ALs and MSs, by analysing changes in power in the delta, theta, alpha, beta, and gamma bands. Voxel-wise fMRI throughout the whole brain, group-ICA, haemodynamic response (HR) over the regions of interest (ROIs), and FC analyses were performed to reveal the neural signature during ALs. In voxel-wise analysis, a significant increase in activity was found in two regions: the dorsal anterior cingulate cortex (dACC) and the supplementary motor area (SMA). The group-ICA analysis did not show any significant results but did show a trend of increased activity in an independent component (IC) that was spatially correlated with SMN. Dynamic HR analysis was performed to further investigate findings from the voxel-wise analysis. Our results were not significant but there were strong trends of change. There was a trend of increased HR 7.5 s after the onset of the AL in the left intraparietal sulcus (IPS) of the DAN. There was also a decrease of 2.5 s before the onset of the AL in the right posterior parietal cortex (PPC) of the FPN. There was also an increase in the HR 5 s after the onset of the AL in the dACC of the SN. Finally, an increase in the HR 15 s before the onset of ALs in the left inferior parietal lobule (IPL) of the DMN is a major finding, as it is an indication that a lapse is about to happen. The HR analysis provided consistent findings with the voxel-wise analysis. FC analysis showed increases in FC within all networks of interest during the ALs. On looking at FC between networks, there was an increase in FC between the DMN and the FPN, no change between the DAN and the FPN, a decrease in FC between the SMN and the FPN, and an increase in FC between the FPN and the VSN. The EMN had an increased FC with the DMN, while it had both increases and decreases in FC with the DAN. There was also an increase in FC between the SN and the DAN, and no change between the SN and the DMN. Finally, a decrease in FC was found between the WMN and the DMN. These findings indicate an overlap between decoupling due to ALs and the process of recovery from ALs. The EEG analysis showed no significant change in the relative difference between average spectral power during ALs and their average baselines for any band of interest for ALs. During MSs, there was a significant increase in power relative to responsive baselines in the delta, theta, alpha, beta, and gamma bands. However, we could not be completely sure that all motion-related artefacts had been removed. Hence, we investigated this further by removing the effect of the global signal, which left only an increase in gamma activity, in addition to a trend of decreased activity in the alpha band. The significant increase in BOLD seen in the voxel-wise analysis is considered to represent the recovery of responsiveness following ALs. This was also seen in trends in group ICA and HR analyses. Overall, findings from the FC analysis show that, in addition to decoupling during ALs, and recovery from ALs, it is highly likely that the ALs during the 2-D CVT task were due to involuntary mind-blanks. This is supported by three major findings: (1) no significant increase in DMN activity in both voxel-wise and HR analyses, (2) the decrease in the HR in the FPN prior to the onset of the AL, and (3) the decrease in FC between the DMN and the WMN. This is further supported behaviourally by the short average duration of ALs (~ 1.7 s), in contrast to what would be likely during mind-wandering. Finally, the significant results from the EEG analysis of MSs, agreed with the literature in delta, theta, and alpha bands. However, increased power in beta and gamma bands was an important finding. We consider this increased high-frequency activity reflects unconscious ‘cognitive’ activity during a MS aimed at restoring consciousness after having fallen asleep during an active task. This highlights a key behavioural and physiological difference between MSs and sleep. Even after removing the effect of the global signal, we still believe that MSs and sleep are physiologically different in the recovery process. To summarize our key findings: (1) this is the first study to demonstrate that ALs during a continuous task are likely to be due to involuntary mind-blanks, (2) the increase in the HR in the DMN 15 s before the onset of AL could be a predictive signature of these lapses, and finally (3) MSs are physiologically different from sleep in terms of the recovery process. This project has improved our understanding of endogenous ALs and MSs and taken us a step closer to accurate detection/prediction systems which can increase prevention of fatal accidents