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Background The choice of preprocessing pipeline introduces variability in neuroimaging analyses that affects the reproducibility of scientific findings. Features derived from structural and functional MRI data are sensitive to the algorithmic or parametric differences of preprocessing tasks, such as image normalization, registration, and segmentation to name a few. Therefore it is critical to understand and potentially mitigate the cumulative biases of pipelines in order to distinguish biological effects from methodological variance. Methods Here we use an open structural MRI dataset (ABIDE), supplemented with the Human Connectome Project, to highlight the impact of pipeline selection on cortical thickness measures. Specifically, we investigate the effect of (i) software tool (e.g. ANTS, CIVET, FreeSurfer), (ii) cortical parcellation (Desikan-Killiany-Tourville, Destrieux, Glasser), and (iii) quality control procedure (manual, automatic). We divide our statistical analyses by (i) method type, i.e. task-free (unsupervised) versus task-driven (supervised); and (ii) inference objective, i.e. neurobiological group differences versus individual prediction. Results Results show that software, parcellation, and quality control significantly affect task-driven neurobiological inference. Additionally, software selection strongly affects neurobiological (i.e. group) and individual task-free analyses, and quality control alters the performance for the individual-centric prediction tasks. Conclusions This comparative performance evaluation partially explains the source of inconsistencies in neuroimaging findings. Furthermore, it underscores the need for more rigorous scientific workflows and accessible informatics resources to replicate and compare preprocessing pipelines to address the compounding problem of reproducibility in the age of large-scale, data-driven computational neuroscience. [ABSTRACT FROM AUTHOR]

The use of neuroimaging tools, especially functional magnetic resonance imaging, in nutritional research has increased substantially over the past 2 decades. Neuroimaging is a research tool with great potential impact on the field of nutrition, but to achieve that potential, appropriate use of techniques and interpretation of neuroimaging results is necessary. In this article, we present guidelines for good methodological practice in functional magnetic resonance imaging studies and flag specific limitations in the hope of helping researchers to make the most of neuroimaging tools and avoid potential pitfalls. We highlight specific considerations for food-related studies, such as how to adjust statistically for common confounders, like, for example, hunger state, menstrual phase, and BMI, as well as how to optimally match different types of food stimuli. Finally, we summarize current research needs and future directions, such as the use of prospective designs and more realistic paradigms for studying eating behavior. [ABSTRACT FROM AUTHOR]

Parkinson's disease varies widely in clinical manifestations, course of progression and biomarker profiles from person to person. Identification of distinct Parkinson's disease subtypes is of great priority to illuminate underlying pathophysiology, predict progression and develop more efficient personalized care approaches. There is currently no clear way to define and divide subtypes in Parkinson's disease. Using data from the Parkinson's Progression Markers Initiative, we aimed to identify distinct subgroups via cluster analysis of a comprehensive dataset at baseline (i.e. cross-sectionally) consisting of clinical characteristics, neuroimaging, biospecimen and genetic information, then to develop criteria to assign patients to a Parkinson's disease subtype. Four hundred and twenty-one individuals with de novo early Parkinson's disease were included from this prospective longitudinal multicentre cohort. Hierarchical cluster analysis was performed using data on demographic and genetic information, motor symptoms and signs, neuropsychological testing and other non-motor manifestations. The key classifiers in cluster analysis were a motor summary score and three non-motor features (cognitive impairment, rapid eye movement sleep behaviour disorder and dysautonomia). We then defined three distinct subtypes of Parkinson's disease patients: 223 patients were classified as 'mild motor-predominant' (defined as composite motor and all three non-motor scores below the 75th percentile), 52 as 'diffuse malignant' (composite motor score plus either ≥1/3 non-motor score >75th percentile, or all three non-motor scores >75th percentile) and 146 as 'intermediate'. On biomarkers, people with diffuse malignant Parkinson's disease had the lowest level of cerebrospinal fluid amyloid-β (329.0 ± 96.7 pg/ml, P = 0.006) and amyloid-β/total-tau ratio (8.2 ± 3.0, P = 0.032). Data from deformation-based magnetic resonance imaging morphometry demonstrated a Parkinson's disease-specific brain network had more atrophy in the diffuse malignant subtype, with the mild motor-predominant subtype having the least atrophy. Although disease duration at initial visit and follow-up time were similar between subtypes, patients with diffuse malignant Parkinson's disease progressed faster in overall prognosis (global composite outcome), with greater decline in cognition and in dopamine functional neuroimaging after an average of 2.7 years. In conclusion, we introduce new clinical criteria for subtyping Parkinson's disease based on a comprehensive list of clinical manifestations and biomarkers. This clinical subtyping can now be applied to individual patients for use in clinical practice using baseline clinical information. Even though all participants had a recent diagnosis of Parkinson's disease, patients with the diffuse malignant subtype already demonstrated a more profound dopaminergic deficit, increased atrophy in Parkinson's disease brain networks, a more Alzheimer's disease-like cerebrospinal fluid profile and faster progression of motor and cognitive deficits. [ABSTRACT FROM AUTHOR]

Impulsivity refers to a tendency to act rapidly without full consideration of consequences. The trait is thought to result from the interaction between high arousal responses to potential rewards and poor self-control. Studies have suggested that impulsivity confers vulnerability to both addiction and obesity. However, results in this area are unclear, perhaps due to the high phenotypic complexity of addictions and obesity. Focusing on impulsivity, the aim of this review is to tackle the putative overlaps between addiction and obesity in four domains: (1) personality research, (2) neurocognitive tasks, (3) brain imaging, and (4) clinical evidence. We suggest that three impulsivity-related domains are particularly relevant for our understanding of similarities between addiction and obesity: lower self-control (high Disinhibition/low Conscientiousness), reward sensitivity (high Extraversion/Positive Emotionality), and negative affect (high Neuroticism/Negative Emotionality). Neurocognitive studies have shown that obesity and addiction are both associated with increased impulsive decision-making and attention bias in response to drug or food cues, respectively. Mirroring this, obesity and different forms of addiction seem to exhibit similar alterations in functional MRI brain activity in response to reward processing and during self-control tasks. Overall, our review provides an integrative approach to understand those facets of obesity that present similarities to addictive behaviors. In addition, we suggest that therapeutic interventions targeting inhibitory control may represent a promising approach for the prevention and/or treatment of obesity. [ABSTRACT FROM AUTHOR]

Background: Novelty-seeking (NS) and impulsive personality traits have been proposed to reflect an interplay between fronto-cortical and limbic systems, including the limbic striatum (LS). Although neuroimaging studies have provided some evidence for this, most are comprised of small samples and many report surprisingly large effects given the challenges of trying to relate a snapshot of brain function or structure to an entity as complex as personality. The current work tested a priori hypotheses about associations between striatal dopamine (DA) release, cortical thickness (CT), and NS in a large sample of healthy adults. Methods: Fifty-two healthy adults (45M/7F; age: 23.8±4.93) underwent two positron emission tomography scans with [11C]raclopride (specific for striatal DA D2/3 receptors) with or without amphetamine (0.3 mg/kg, p.o.). Structural magnetic resonance image scans were acquired, as were Tridimensional Personality Questionnaire data. Amphetamine-induced changes in [11C]raclopride binding potential values (ΔBPND) were examined in the limbic, sensorimotor (SMS) and associative (AST) striatum. CT measures, adjusted for whole brain volume, were extracted from the dorsolateral sensorimotor and ventromedial/limbic cortices. Results: BPND values were lower in the amphetamine vs. no-drug sessions, with the largest effect in the LS. When comparing low vs. high LS ΔBPND groups (median split), higher NS2 (impulsiveness) scores were found in the high ΔBPND group. Partial correlations (age and gender as covariates) yielded a negative relation between ASTS ΔBPND and sensorimotor CT; trends for inverse associations existed between ΔBPND values in other striatal regions and frontal CT. In other words, the greater the amphetamine-induced striatal DA response, the thinner the frontal cortex. Conclusions: These data expand upon previously reported associations between striatal DA release in the LS and both NS related impulsiveness and CT in the largest sample reported to date. The findings add to the plausibility of these associations while suggesting that the effects are likely weaker than has been previously proposed. [ABSTRACT FROM AUTHOR]

Background: MRI brain changes in Parkinson's disease (PD) are controversial. Objectives: We aimed to describe structural and functional changes in PD. Methods: Sixty-six patients with PD (57.94 ± 10.25 years) diagnosed according to the UK Brain Bank criteria were included. We performed a whole brain analysis using voxel-based morphometry (VBM-SPM 8 software), cortical thickness (CT) using CIVET, and resting-state fMRI using the Neuroimaging Analysis Kit software to compare patients and controls. For VBM and CT we classified subjects into three groups according to disease severity: mild PD [Hoehn and Yahr scale (HY) 1-1.5], moderate PD (HY 2-2.5), and severe PD (HY 3-5). results: We observed gray matter atrophy in the insula and inferior frontal gyrus in the moderate PD and in the insula, frontal gyrus, putamen, cingulated, and paracingulate gyri in the severe groups. In the CT analysis, in mild PD, cortical thinning was restricted to the superior temporal gyrus, gyrus rectus, and olfactory cortex; in the moderate group, the postcentral gyrus, supplementary motor area, and inferior frontal gyrus were also affected; in the severe PD, areas such as the precentral and postentral gyrus, temporal pole, fusiform, and occipital gyrus had reduced cortical thinning. We observed altered connectivity at the default mode, visual, sensorimotor, and cerebellar networks. conclusion: Subjects with mild symptoms already have cortical involvement; however, further cerebral involvement seems to follow Braak's proposed mechanism. Similar regions are affected both structurally and functionally. We believe the combination of different MRI techniques may be useful in evaluating progressive brain involvement and they may eventually be used as surrogate markers of disease progression. [ABSTRACT FROM AUTHOR]

Background: Onset of alcohol use by 14 relative to 21 years of age strongly predicts elevated risk for severe alcohol use problems, with 27% versus 4% of individuals exhibiting alcohol dependence within 10 years of onset. What remains unclear is whether this early alcohol use (i) is a marker for later problems, reflected as a pre-existing developmental predisposition, (ii) causes global neural atrophy or (iii) specifically disturbs neuro-maturational processes implicated in addiction, such as executive functions or reward processing. Since our group has demonstrated that a novel intervention program targeting personality traits associated with adolescent alcohol use can prevent the uptake of drinking and binge drinking by 40 to 60%, a crucial question is whether prevention of early onset alcohol misuse will protect adolescent neurodevelopment and which domains of neurodevelopment can be protected. Methods: A subsample of 120 youth at high risk for substance misuse and 30 low-risk youth will be recruited from the Co-Venture trial (Montreal, Canada) to take part in this 5-year follow-up neuroimaging study. The Co-Venture trial is a community-based cluster-randomised trial evaluating the effectiveness of school-based personality-targeted interventions on substance use and cognitive outcomes involving approximately 3800 Grade 7 youths. Half of the 120 high-risk participants will have received the preventative intervention program. Cognitive tasks and structural and functional neuroimaging scans will be conducted at baseline, and at 24- and 48-month follow-up. Two functional paradigms will be used: the Stop-Signal Task to measure motor inhibitory control and a modified version of the Monetary Incentive Delay Task to evaluate reward processing. Discussion: The expected results should help identify biological vulnerability factors, and quantify the consequences of early alcohol abuse as well as the benefits of early intervention using brain metrics. [ABSTRACT FROM AUTHOR]

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [11C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87±8.65) and 18 healthy male controls (age: 25.44±6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [11C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [11C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity. [ABSTRACT FROM AUTHOR]

Obesity is a neurobehavioral disorder that results from a combination of overeating and insufficient physical activity. Finely tuned mechanisms exist to match food intake to caloric expenditure. However, faced with abundant inexpensive and calorie-dense foods, many humans (and perhaps most) have a tendency to consume beyond their caloric needs. The brain controls food intake by sensing internal energy-balance signals and external cues of food availability, and by controlling feeding behavior; it is therefore at the centre of the obesity problem. This article reviews the recent use of functional brain imaging in humans to study the neural control of appetite, and how the neural systems involved may cause vulnerability to overeating in the obesogenic environment. [Copyright &y& Elsevier]

White matter tracts, which play a crucial role in the coordination of information flow between different regions of grey matter, are particularly vulnerable to multiple sclerosis. Many studies have shown that the white matter lesions in multiple sclerosis are associated with focal abnormalities of grey matter, but little is known about the alterations in the coordinated patterns of cortical morphology among regions in the disease. Here, we used cortical thickness measurements from structural magnetic resonance imaging to investigate the relationship between the white matter lesion load and the topological efficiency of structural cortical networks in multiple sclerosis. Network efficiency was defined using a ‘small-world’ network model that quantifies the effectiveness of information transfer within brain networks. In this study, we first classified patients (n = 330) into six subgroups according to their total white matter lesion loads, and identified structural brain networks for each multiple sclerosis group by thresholding the corresponding inter-regional cortical thickness correlation matrix, followed by a network efficiency analysis with graph theoretical approaches. The structural cortical networks in multiple sclerosis demonstrated efficient small-world architecture regardless of the lesion load, an organization that maximizes the information processing at a relatively low wiring cost. However, we found that the overall small-world network efficiency in multiple sclerosis was significantly disrupted in a manner proportional to the extent of total white matter lesions. Moreover, regional efficiency was also significantly decreased in specific brain regions, including the insula and precentral gyrus as well as regions of prefrontal and temporal association cortices. Finally, we showed that the lesions also altered many cortical thickness correlations in the frontal, temporal and parietal lobes. Our results suggest that the white matter lesions in multiple sclerosis might be associated with aberrant neuronal connectivity among widely distributed brain regions, and provide structural (morphological) evidence for the notion of multiple sclerosis as a disconnection syndrome. [ABSTRACT FROM PUBLISHER]

One of the most exciting recent hypotheses in neurology is that most neurodegenerative diseases are caused by the neuron to neuron propagation of prion-like misfolded proteins. In Parkinson disease, the theory initially emerged from postmortem studies demonstrating a caudal-rostral progression of pathology from lower brainstem to neocortex. Later, animal studies showed that the hallmark protein of PD, α-synuclein, exhibited all the characteristics of a prion. Here, we describe our work using human neuroimaging to test the theory that PD pathology advances via a propagating process along the connectome. We found that the pattern and progression of brain atrophy follow neuronal connectivity, correlate with clinical features, and identify an epicenter in the brainstem. [ABSTRACT FROM AUTHOR]

Introduction Studies investigating brain indices of sexual arousal have begun to elucidate the brain's role in processing subjective arousal; however, most research has focused on men, used discrete ratings of subjective arousal, and used stimuli too short to induce significant arousal in women. Aim To examine brain regions modulated by changes in subjective sexual arousal (SSA) rating intensity in men and women. Methods Two groups (20 men, 20 women) viewed movie clips (erotic or humorous) while continuously evaluating changes in their SSA using a Likert-like scale (0 = not aroused, 10 = most aroused) and answering discrete questions about liking the movies and wanting sexual stimulation. Brain activity was measured using functional magnetic resonance imaging. Main Outcome Measures Blood oxygen level-dependent responses and continuous and discrete measurements of sexual arousal. Results Erotic movies induced significant SSA in men and women. No sex difference in mean SSA was found in response to the erotic movies on continuous or discrete measurements. Several brain regions were correlated with changes in SSA. Parametric modulation with rating intensity showed a specific group of regions within the parietal lobe that showed significant differences in activity among low, medium, and high SSA. Conclusion Multiple regions were concordant with changes in SSA; however, a subset of regions in men and women was modulated by SSA intensity, a subset previously linked to attentional processes, monitoring of internal body representation, and processing of sensory information from the genitals. This study highlights that similar brain regions are activated during subjective assessment of sexual arousal in men and women. The data further highlight the fact that SSA is a complex phenomenon made up of multiple interoceptive and attentional processes. [ABSTRACT FROM AUTHOR]

The extent to which we learn from positive and negative outcomes of decisions is modulated by the neurotransmitter dopamine. Dopamine neurons burst fire in response to unexpected rewards and pause following negative outcomes. This dual signaling mechanism is hypothesized to drive both approach and avoidance behavior. Here we test a prediction deriving from a computational reinforcement learning model, in which approach is mediated via activation of the direct cortico-striatal pathway due to striatal D1 receptor stimulation, while avoidance occurs via disinhibition of indirect pathway striatal neurons secondary to a reduction of D2 receptor stimulation. Using positron emission tomography with two separate radioligands, we demonstrate that individual differences in human approach and avoidance learning are predicted by variability in striatal D1 and D2 receptor binding, respectively. Moreover, transient dopamine precursor depletion improved learning from negative outcomes. These findings support a bidirectional modulatory role for striatal dopamine in reward and avoidance learning via segregated D1 and D2 cortico-striatal pathways. [ABSTRACT FROM AUTHOR]

Summary: The metabolic effects of stress are known to have significant health effects in both humans and animals. Most of these effects are mediated by the major stress hormonal axis in the body, the hypothalamic–pituitary–adrenal (HPA) axis. Within the central nervous system (CNS), the hippocampus, the amygdala and the prefrontal cortex as part of the limbic system are believed to play important roles in the regulation of the HPA axis. With the advent of structural and functional neuroimaging techniques, the role of different CNS structures in the regulation of the HPA axis can be investigated more directly. In the current paper, we summarize the findings obtained in our laboratory in the context of stress and HPA axis regulation. Our laboratory has developed and contributed to the development of manual and automated segmentation protocols from structural magnetic resonance imaging (MRI) scans for assessment of hippocampus, amygdala, medial temporal lobe and frontal lobe structures. Employing these protocols, we could show significant age-related changes in HC volumes, which were different between men and women, with pre-menopausal women showing smaller age-related volume decline compared to men. We could recently extent these findings by showing how estrogen therapy after menopause leads to higher volumes in the HC. Investigating possible neurotoxicity effects of steroids, we showed effects of long-term steroid exposure on HC volumes, and investigated variability of HC volumes in relation to HPA axis regulation in young and elderly populations. Here, we were able to follow-up from non-imaging studies showing that subjects low in self-esteem have higher cortisol stress responses, and the HC emerged as the critical link between these variables. Recently, we have made two more important discoveries with regard to HC volume: we could show that HC volume is as variable in young as it is in older adults, in subjects ranging in age from 18 to 80 years. Also, we have linked birth weight and maternal care to HC volumes in young adults, demonstrating the effects of variations in maternal care on the integrity of the CNS. Besides structural assessments, there is increasing interest in functional techniques to investigate possible links between CNS activity and HPA axis regulation. These two approaches complement each other; some aspects of HPA axis regulation might be linked to the integrity of a specific CNS structure, while other aspects might be linked to the function of a specific structure with no involvement of CNS morphology. Thus, we have developed a mental arithmetic stress task that can be employed in functional neuroimaging studies, and have used it in a number of functional neuroimaging studies. Employing positron emission tomography (PET), we were able to demonstrate that stress causes dopamine release if subjects reported low maternal care early in life. Finally, employing the task in functional magnetic resonance imaging (fMRI), we could show how exposure to stress and activation of the HPA axis are associated with decreased activity in major portions of the limbic system, a result that allows to speculate on the effects of stress on cognitive and emotional regulation in the brain. Taken together, the use of neuroimaging techniques in Psychoneuroendocrinology opens exciting new possibilities for the investigation of stress effects in the central nervous system. [Copyright &y& Elsevier]

Background: Stress-induced metabolic changes can have detrimental health effects. Newly developed paradigms to investigate stress in neuroimaging environments allow the assessment of brain activation changes in association with the perception of and the metabolic response to stress. Methods: We exposed human subjects to a psychosocial stressor in one positron emission tomography (n = 10) and one functional magnetic resonance imaging (fMRI; n = 40) experiment. Results: We observed a profound deactivation of limbic system components including hippocampus, hypothalamus, medio-orbitofrontal cortex and anterior cingulate cortex in subjects who reacted to the stressor with a significant increase of the endocrine stress marker cortisol. Further, in the fMRI study, the degree of deactivation in the hippocampus was correlated with the release of cortisol in response to the stress task. Conclusions: The observed deactivation of limbic system structures suggests elevated activation at rest and during nonstressful situations. A model is proposed where the observed reduction in limbic system activity is essential for the initiation of the stress response. [Copyright &y& Elsevier]