Resting-state abnormalities in heroin-dependent individuals

Drug addiction is a major health problem worldwide. Recent neuroimaging studies have shed light into the underlying mechanisms of drug addiction as well as its consequences to the human brain. The most vulnerable, to heroin addiction, brain regions have been reported to be specific prefrontal, parietal, occipital, and temporal regions, as well as, some subcortical regions. The brain regions involved are usually linked with reward, motivation/drive, memory/learning, inhibition as well as emotional control and seem to form circuits that interact with each other. So, along with neuroimaging studies, recent advances in resting-state dynamics might allow further assessments upon the multilayer complexity of addiction. In the current manuscript, we comprehensively review and discuss existing resting-state neuroimaging findings classified into three overlapping and interconnected groups: functional connectivity alterations, structural deficits and abnormal topological properties. Moreover, behavioral traits of heroin-addicted individuals as well as the limitations of the currently available studies are also reviewed. Finally, in need of a contemporary therapy a multimodal therapeutic approach is suggested using classical treatment practices along with current neurotechonologies, such as neurofeedback and goal-oriented video-games

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

The Relation of Impulsivity and Obesity: A Neuroimaging Analysis

The current study examined the relation of impulsivity and obesity in three neuroimaging studies using MRI techniques to test the hypothesis that deficits in brain regions responsible for inhibitory control are associated with obesity. The first study used voxel-based morphometry (VBM) to explore volumetric differences in lean, overweight, and obese women (N=83) and found that BMI was negatively correlated with grey matter (GM) in the insula, frontal operculum, and inferior frontal gyrus. BMI was positively correlated with white matter (WM) in the fusiform gyrus, parahippocampal gyrus, Rolandic operculum, and dorsal striatum. Genetic alleles for dopamine expression moderated these relations. Additionally, less GM in the superior frontal gyrus predicted future increases in BMI. The second study used VBM to examine differences between lean adolescents at risk versus not at risk for obesity (N=54). There were no regional GM or WM differences based on risk status. There were also no regional differences that predicted weight gain over 1-year follow-up. Additionally, genetic alleles for dopamine expression did not moderate any of these regions. These findings suggest that volumetric differences may emerge after excessive weight gain. Finally, the third study used a psychophysiological interaction analysis to test functional connectivity between prefrontal and limbic regions as a function of BMI in lean, overweight, and obese women (N=37) during a go/no-go task. There was no functional connectivity found in seed regions in relation to BMI. Implications for intervention and future research are discussed

Machine learning-based identification of suicidal risk in patients with schizophrenia using multi-level resting-state fMRI features

Background: Some studies suggest that as much as 40% of all causes of death in a group of patients with schizophrenia can be attributed to suicides and compared with the general population, patients with schizophrenia have an 8.5-fold greater suicide risk (SR). There is a vital need for accurate and reliable methods to predict the SR among patients with schizophrenia based on biological measures. However, it is unknown whether the suicidal risk in schizophrenia can be related to alterations in spontaneous brain activity, or if the resting-state functional magnetic resonance imaging (rsfMRI) measures can be used alongside machine learning (ML) algorithms in order to identify patients with SR. Methods: Fifty-nine participants including patients with schizophrenia with and without SR as well as age and gender-matched healthy underwent 13 min resting-state functional magnetic resonance imaging. Both static and dynamic indexes of the amplitude of low-frequency fluctuation (ALFF), the fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity as well as functional connectivity (FC) were calculated and used as an input for five machine learning algorithms: Gradient boosting (GB), LASSO, Logistic Regression (LR), Random Forest and Support Vector Machine. Results: All groups revealed different intra-network functional connectivity in ventral DMN and anterior SN. The best performance was reached for the LASSO applied to FC with an accuracy of 70% and AUROC of 0.76 (p < 0.05). Significant classification ability was also reached for GB and LR using fALFF and ALFF measures. Conclusion Our findings suggest that SR in schizophrenia can be seen on the level of DMN and SN functional connectivity alterations. ML algorithms were able to significantly differentiate SR patients. Our results could be useful in developing neuromarkers of SR in schizophrenia based on non-invasive rsfMRI

BRAIN CONNECTIVITY AND TREATMENT RESPONSE IN ADULT ADHD:understanding the relationship between individual differences in fronto-parietal and fronto-striatal brain networks and response to chronic treatment with methylphenidate

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, characterised by disrupted anatomical and/or functional connectivity, mainly in the fronto-striatal and fronto-parietal networks. Stimulants, such as methylphenidate (MPH), represent a first-line treatment in ADHD, but one third of patients fail to respond, with severe consequences for the individual and the society at large. Hence, a comprehensive understanding of the relationship between individual differences in brain abnormalities and treatment response is needed.This thesis focused on two main brain networks: the fronto-striatal network, a central theme in ADHD research, and the fronto-parietal attentive network, formed by the three branches of the superior longitudinal fasciculus (SLF). The SLF branches have been only recently described in humans, and there is no detailed analysis of their distinct functional roles and involvement in disorders such as ADHD. Therefore, I first investigated the functional anatomy of the SLF branches by combining a meta-analytic approach with tractography, and revealed novel findings about the anatomical and functional segregation and integration of brain functions within fronto-parietal networks. Then, I showed, for the first time, that the three SLF branches are all significantly right-lateralised in ADHD patients but not in controls, and provided preliminary evidence that the pattern of lateralisation of the SLF I may be related to poor attentive performance in ADHD patients.Finally, I conducted functional and structural connectivity analysis to test whether a relationship exists between brain abnormalities and treatment response in adult ADHD. I employed a longitudinal crossover follow-up design. 60 non-medicated adult ADHD patients were recruited and underwent behavioural assessment (Qb test) and magnetic resonance imaging (MRI) scanning twice, once under placebo and once under a clinically effective dose of MPH. Clinical and behavioural response was measured after two months of treatment with MPH. I demonstrated for the first time that there is a relationship between ‘connectivity’ abnormalities within fronto-parietal networks and treatment response in adult ADHD, both at the anatomical and functional level.Ultimately, my investigation contributed towards the identification of potential biomarkers of treatment response, which in the future may help clinicians deliver more individualised treatments.<br/

Soziale und agonistische Konfrontationen zwischen männlichen Dark Agouti Ratten: neuronale Aktivierung in limbischen Hirngebieten und Auswirkungen auf die 5-HT1A-Rezeptordichte

This thesis comprises three studies on the territorial behavior of male Dark Agouti rats during resident-intruder (RI) tests and its underlying neuronal basis. The first study determined the behavioral profile of non-selected rats and investigated telencephalic limbic brain regions activated during social and agonistic encounters using c-Fos as a neuronal marker. Study 2 aimed to identify changes in 5-HT1A receptor density in the limbic telencephalon and the dorsal raphe nucleus following inter-male encounters. In study 3, the influence of a provocation phase, prior to the RI test, on the aggressive behavior and the c-Fos expression was examined. The studies found individual differences in the offensive behavior of Dark Agouti rats depending on the actual context and behavior of the intruder. In frontal cortices and amygdala, neuronal activation and 5-HT1A-receptor density was increased, which suggest overlapping of the neuronal networks of stress coping and aggressive behavior

The neural correlates of reinforcement sensitivity theory: a systematic review of the (f)MRI literature

Objectives: Reinforcement Sensitivity Theory (RST) is a theory of motivation, emotion and learning, that has been translated into an account of personality. RST proposes neural structures that form the basis of systems responsible for reward (BAS), punishment (FFFS) and conflict processing (BIS). This systematic review collated studies examining psychometric measures of RST alongside structural and function MRI data to (i) examine how psychometric RST is associated with the proposed neural topologies of RST, (ii) identify any common associations between psychometric RST and other brain regions, and (iii) provide recommendations for advancing the current literature base. Methods: Initial search terms identified 10952 papers. After processing, 39 papers that investigated the association between RST scales and neural functioning in healthy adult samples were included in this review. Results: There was general support for associations between the BAS and the structure/activity of the pre-frontal cortex and ventral striatum with some additional findings for the ventral pallidum and ventral tegmental area. There was also some support for associations between BIS/FFFS and structure/activity of frontal regions, cingulate cortices and the amygdala. Conclusions: Overall, psychometric correlates of RST were associated with activity in proposed neural circuitry, with the most consistent support being found for the BAS; however, psychometric and experimental limitations still hamper the differentiation of the BIS and FFFS systems in their activation of deeper brain networks. Future studies need to include revised RST scales that separate the BIS and FFFS and implement more rigorous tasks that allow for the examination of each system both independently and codependently

The role of the medial prefrontal cortex in delay discounting

Indiana University-Purdue University Indianapolis (IUPUI)Increased delay discounting (DD) has been associated with and is theorized to contribute to alcoholism and substance abuse. It is also been associated with numerous other mental disorders and is believed to be a trans-disease process (i.e., a process that occurs in and contributes to multiple different pathologies). Consequently insights gained from studying DD are likely to apply to many different diseases. Studies on the neurobiological underpinnings of DD have two main interpretations. The first interpretation is that two different neurobehavioral systems exist, one favoring delayed rewards (executive system) and one favoring immediate rewards (impulsive system), and the system with the greater relative activation determines choice made by an individual. Alternatively, a single valuation system may exist. This system integrates different information about outcomes and generates a value signal that then guides decision making. Preclinical investigations have steered clear of these two different interpretations and rather focused on the role of individual structures in DD. One such structure, the rat mPFC, may generate an outcome representation of delayed rewards that is critically involved in attributing value to delayed rewards. Moreover, there is evidence indicating the rat mPFC may correspond to the primate dlPFC, an executive system structure. The current body of work set about testing the hypotheses that the mPFC is necessary for attributing value to delayed rewards and that decreasing the activity in an executive system area, and thus the executive system, shifts inter-temporal preference towards immediate rewards. To this end the rat mPFC was inactivated using an hM4Di inhibitory designer receptor exclusively activated by designer drugs (DREADD; experiment 1) or microinjections of tetrodotoxin (TTX; experiment 2) while animals completed an adjusting amount DD task. Activation of the hM4Di inhibitory DREADD receptor caused a decrease in DD, opposite of what was predicted. Electrophysiological recordings revealed a subpopulation of neurons actually increased their firing in response to hM4Di receptor activation, potentially explaining the unpredicted results. Microinjections of TTX to completely silence neural activity in the mPFC failed to produce a change in DD. Together both results indicate that mPFC activity is capable of manipulating but is not necessary for DD and the attribution of value to the delayed reward. Consequently, a secondary role for the rat mPFC in DD is proposed in line with single valuation system accounts of DD. Further investigations determining the primary structures responsible for sustaining delayed reward valuation and how manipulating the mPFC may be a means to decrease DD are warranted, and continued investigation that delineates the neurobiological processes of delayed reward valuation may provide valuable insight to both addiction and psychopathology

Cognitive Control and Affective Processing Dysregulation in Veterans with Comorbid PTSD and mTBI: an fMRI Study

Mariko Frances Weber: Cognitive Control and Affective Processing Dysregulation in Veterans with Comorbid PTSD and mTBI: an fMRI Study (Under the direction of Aysenil Belger) Background: Deficits in cognitive control and affective processing are important aspects of comorbid PTSD and mTBI for which there are no effective treatments. Understanding the neural basis of symptoms and domain specific deficits is an important step in developing therapies for treating individuals with PTSD-mTBI. No studies have addressed this question, as most have examined PTSD or mTBI separately. We therefore utilize a large functional magnetic resonance imaging (fMRI) dataset to test the relationship between individual symptom severity, neurocognitive deficits and task-based functional activation. Methods: The relationship between the severity of clinical symptoms and neurocognitive deficits in patients with PTSD-mTBI and functional activation during an affective 1-back task, affective face matching task, and number Stroop task (n = 100) was assessed using correlation analysis. Results: Activity in cortico-limbic regions, and regions associated with striatal, default mode, and salience networks were found to be significantly associated with increased symptom severity and greater impairments in neurocognition. Discussion: Our findings suggest that researchers and clinicians should examine individuals neural and symptom profiles before making a treatment decision and that unique variable associations should be the focus rather than the average of the group as a whole. Furthermore, our results indicate a relationship between functional activity and clinical symptoms and neurocognitive deficits that suggest network level regional contribution to diagnoses, as well as greater resting baseline activity that is associated with increased symptom severity.Doctor of Philosoph