Functional and Biochemical Alterations of the Medial Frontal Cortex in Obsessive-Compulsive Disorder

Context: The medial frontal cortex (MFC), including the dorsal anterior cingulate (dAC) and supplementary motor area (SMA), is critical for adaptive and inhibitory control of behaviour. Abnormally high MFC activity has been a consistent finding in functional neuroimaging studies of obsessive-compulsive disorder (OCD). However, the precise regions and the neural alterations associated with this abnormality remain unclear. Objective: To examine the functional and biochemical properties of the MFC in patients with OCD. Design: Cross-sectional design combining volume localized proton magnetic resonance spectroscopy (1H-MRS) and functional MRI (fMRI) with an inhibitory control paradigm (the Multi-Source Interference Task; MSIT) designed to activate the MFC. Setting: Healthy control participants and OCD patients recruited from the general community. Participants: Nineteen OCD patients (10 male, and 9 female) and nineteen age, gender, education and intelligence-matched healthy control participants. Main Outcome Measures: Psychometric measures of symptom severity, MSIT behavioural performance, blood-oxygen-level-dependent (BOLD) activation and 1H-MRS brain metabolite concentrations. Results: MSIT behavioural performance did not differ between OCD patients and control subjects. Reaction-time interference and response errors were correlated with BOLD activation in the dAC region in both groups. Relative to control subjects, OCD patients showed hyper- activation of the SMA during high response-conflict (incongruent > congruent) trials and hyper-activation of the rostral anterior cingulate (rAC) region during low response- conflict (incongruent < congruent) trials. OCD patients also showed reduced levels of neuronal N-acetylaspartate in the dAC region, which was negatively correlated with their BOLD activation of the region. Conclusions: Our findings suggest that hyper-activation of the medial frontal cortex in OCD patients may be a compensatory response to neural pathology in the region. This relationship may partly explain the nature of inhibitory control deficits that are frequently seen in this group and may serve as a focus of future treatment studies

Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11DS) is a recurrent genetic mutation that is highly penetrant for psychosis. Behavioral research suggests that 22q11DS patients exhibit a characteristic neurocognitive phenotype that includes differential impairment in spatial working memory (WM). Notably, spatial WM has also been proposed as an endophenotype for idiopathic psychotic disorder, yet little is known about the neurobiological substrates of WM in 22q11DS. In order to investigate the neural systems engaged during spatial WM in 22q11DS patients, we collected functional magnetic resonance imaging (fMRI) data while 41 participants (16 22q11DS patients, 25 demographically matched controls) performed a spatial capacity WM task that included manipulations of delay length and load level. Relative to controls, 22q11DS patients showed reduced neural activation during task performance in the intraparietal sulcus (IPS) and superior frontal sulcus (SFS). In addition, the typical increases in neural activity within spatial WM-relevant regions with greater memory load were not observed in 22q11DS. We further investigated whether neural dysfunction during WM was associated with behavioral WM performance, assessed via the University of Maryland letter-number sequencing (LNS) task, and positive psychotic symptoms, assessed via the Structured Interview for Prodromal Syndromes (SIPS), in 22q11DS patients. WM load activity within IPS and SFS was positively correlated with LNS task performance; moreover, WM load activity within IPS was inversely correlated with the severity of unusual thought content and delusional ideas, indicating that decreased recruitment of working memory-associated neural circuitry is associated with more severe positive symptoms. These results suggest that 22q11DS patients show reduced neural recruitment of brain regions critical for spatial WM function, which may be related to characteristic behavioral manifestations of the disorder

Development of quality standards for multi-center, longitudinal magnetic resonance imaging studies in clinical neuroscience

Magnetic resonance imaging (MRI) data is generated by a complex procedure. Many possible sources of error exist which can lead to a worse signal. For example, hidden defective components of a MRI-scanner, changes in the static magnetic field caused by a person simply moving in the MRI scanner room as well as changes in the measurement sequences can negatively affect the signal-to-noise ratio (SNR). A comprehensive, reproducible, quality assurance (QA) procedure is necessary, to ensure reproducible results both from the MRI equipment and the human operator of the equipment. To examine the quality of the MRI data, there are two possibilities. On the one hand, water or gel-filled objects, so-called "phantoms", are regularly measured. Based on this signal, which in the best case should always be stable, the general performance of the MRI scanner can be tested. On the other hand, the actually interesting data, mostly human data, are checked directly for certain signal parameters (e.g., SNR, motion parameters). This thesis consists of two parts. In the first part a study-specific QA-protocol was developed for a large multicenter MRI-study, FOR2107. The aim of FOR2107 is to investigate the causes and course of affective disorders, unipolar depression and bipolar disorders, taking clinical and neurobiological effects into account. The main aspect of FOR2107 is the MRI-measurement of more than 2000 subjects in a longitudinal design (currently repeated measurements after 2 years, further measurements planned after 5 years). To bring MRI-data and disease history together, MRI-data must provide stable results over the course of the study. Ensuring this stability is dealt with in this part of the work. An extensive QA, based on phantom measurements, human data analysis, protocol compliance testing, etc., was set up. In addition to the development of parameters for the characterization of MRI-data, the used QA-protocols were improved during the study. The differences between sites and the impact of these differences on human data analysis were analyzed. The comprehensive quality assurance for the FOR2107 study showed significant differences in MRI-signal (for human and phantom data) between the centers. Occurring problems could easily be recognized in time and be corrected, and must be included for current and future analyses of human data. For the second part of this thesis, a QA-protocol (and the freely available associated software "LAB-QA2GO") has been developed and tested, and can be used for individual studies or to control the quality of an MRI-scanner. This routine was developed because at many sites and in many studies, no explicit QA is performed nevertheless suitable, freely available QA-software for MRI-measurements is available. With LAB-QA2GO, it is possible to set up a QA-protocol for an MRI-scanner or a study without much effort and IT knowledge. Both parts of the thesis deal with the implementation of QA-procedures. High quality data and study results can be achieved only by the usage of appropriate QA-procedures, as presented in this work. Therefore, QA-measures should be implemented at all levels of a project and should be implemented permanently in project and evaluation routines

TEAMwork: Testing Emotional Attunement and Mutuality During Parent-Adolescent fMRI.

The parent-child relationship and family context influence the development of emotion regulation (ER) brain circuitry and related skills in children and adolescents. Although both parents' and children's ER neurocircuitry simultaneously affect how they interact with one another, neuroimaging studies of parent-child relationships typically include only one member of the dyad in brain imaging procedures. The current study examined brain activation related to parenting and ER in parent-adolescent dyads during concurrent fMRI scanning with a novel task - the Testing Emotional Attunement and Mutuality (TEAM) task. The TEAM task includes feedback trials indicating the other dyad member made an error, resulting in a monetary loss for both participants. Results indicate that positive parenting practices as reported by the adolescent were positively correlated with parents' hemodynamic activation of the ventromedial prefrontal cortex, a region related to empathy, during these error trials. Additionally, during feedback conditions both parents and adolescents exhibited fMRI activation in ER-related regions, including the dorsolateral prefrontal cortex, anterior insula, fusiform gyrus, thalamus, caudate, precuneus, and superior parietal lobule. Adolescents had higher left amygdala activation than parents during the feedback condition. These findings demonstrate the utility of dyadic fMRI scanning for investigating relational processes, particularly in the parent-child relationship

Attribution of intentional causation influences the perception of observed movements: behavioral evidence and neural correlates

Recent research on human agency suggests that intentional causation is associated with a subjective compression in the temporal interval between actions and their effects. That is, intentional movements and their causal effects are perceived as closer together in time than equivalent unintentional movements and their causal effects. This so-called intentional binding effect is consistently found for one's own self-generated actions. It has also been suggested that intentional binding occurs when observing intentional movements of others. However, this evidence is undermined by limitations of the paradigm used. In the current study we aimed to overcome these limitations using a more rigorous design in combination with functional Magnetic Resonance Imaging (fMRI) to explore the neural underpinnings of intentional binding of observed movements. In particular, we aimed to identify brain areas sensitive to the interaction between intentionality and causality attributed to the observed action. Our behavioral results confirmed the occurrence of intentional binding for observed movements using this more rigorous paradigm. Our fMRI results highlighted a collection of brain regions whose activity was sensitive to the interaction between intentionality and causation. Intriguingly, these brain regions have previously been implicated in the sense of agency over one's own movements. We discuss the implications of these results for intentional binding specifically, and the sense of agency more generally

Individual differences in pain sensitivity are associated with cognitive network functional connectivity following one night of experimental sleep disruption.

Previous work suggests that sleep disruption can contribute to poor pain modulation. Here, we used experimental sleep disruption to examine the relationship between sleep disruption-induced pain sensitivity and functional connectivity (FC) of cognitive networks contributing to pain modulation. Nineteen healthy individuals underwent two counterbalanced experimental sleep conditions for one night each: uninterrupted sleep versus sleep disruption. Following each condition, participants completed functional MRI including a simple motor task and a noxious thermal stimulation task. Pain ratings and stimulus temperatures from the latter task were combined to calculate a pain sensitivity change score following sleep disruption. This change score was used as a predictor of simple motor task FC changes using bilateral executive control networks (RECN, LECN) and the default mode network (DMN) masks as seed regions of interest (ROIs). Increased pain sensitivity after sleep disruption was positively associated with increased RECN FC to ROIs within the DMN and LECN (F(4,14) = 25.28, pFDR = 0.05). However, this pain sensitivity change score did not predict FC changes using LECN and DMN masks as seeds (pFDR &gt; 0.05). Given that only RECN FC was associated with sleep loss-induced hyperalgesia, findings suggest that cognitive networks only partially contribute to the sleep-pain dyad

Internet and gaming addiction: a systematic literature review of neuroimaging studies

In the past decade, research has accumulated suggesting that excessive Internet use can lead to the development of a behavioral addiction. Internet addiction has been considered as a serious threat to mental health and the excessive use of the Internet has been linked to a variety of negative psychosocial consequences. The aim of this review is to identify all empirical studies to date that used neuroimaging techniques to shed light upon the emerging mental health problem of Internet and gaming addiction from a neuroscientific perspective. Neuroimaging studies offer an advantage over traditional survey and behavioral research because with this method, it is possible to distinguish particular brain areas that are involved in the development and maintenance of addiction. A systematic literature search was conducted, identifying 18 studies. These studies provide compelling evidence for the similarities between different types of addictions, notably substance-related addictions and Internet and gaming addiction, on a variety of levels. On the molecular level, Internet addiction is characterized by an overall reward deficiency that entails decreased dopaminergic activity. On the level of neural circuitry, Internet and gaming addiction led to neuroadaptation and structural changes that occur as a consequence of prolonged increased activity in brain areas associated with addiction. On a behavioral level, Internet and gaming addicts appear to be constricted with regards to their cognitive functioning in various domains. The paper shows that understanding the neuronal correlates associated with the development of Internet and gaming addiction will promote future research and will pave the way for the development of addiction treatment approaches

Domain-general and Domain-specific Patterns of Activity Support Metacognition in Human Prefrontal Cortex

Metacognition is the capacity to evaluate the success of one's own cognitive processes in various domains; for example, memory and perception. It remains controversial whether metacognition relies on a domain-general resource that is applied to different tasks or if self-evaluative processes are domain specific. Here, we investigated this issue directly by examining the neural substrates engaged when metacognitive judgments were made by human participants of both sexes during perceptual and memory tasks matched for stimulus and performance characteristics. By comparing patterns of fMRI activity while subjects evaluated their performance, we revealed both domain-specific and domain-general metacognitive representations. Multivoxel activity patterns in anterior prefrontal cortex predicted levels of confidence in a domain-specific fashion, whereas domain-general signals predicting confidence and accuracy were found in a widespread network in the frontal and posterior midline. The demonstration of domain-specific metacognitive representations suggests the presence of a content-rich mechanism available to introspection and cognitive control

3D body scanning and healthcare applications

Developed largely for the clothing industry, 3D body-surface scanners are transforming our ability to accurately measure and visualize a person's body size, shape, and skin-surface area. Advancements in 3D whole-body scanning seem to offer even greater potential for healthcare applications