The cortical thickness of tricenarian cocaine users assembles features of an octogenarian brain.

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross-sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n1 = 30) and their age-paired controls (YC, n1 = 30), and compare it with octogenarian elder controls (EC, n1 = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC. We also found that regarding CT of the right inferior temporal gyrus, right inferior parietal cortex, and left superior parietal cortex, the CUD group exhibited parameters that fell in between EC and YC groups. Finally, CT of the right pars triangularis bordering with orbitofrontal gyrus, right superior temporal gyrus, and right precentral gyrus were reduced in CUD when contrasted with YC, but those areas were unrelated to CT of EC. Despite the 50-year age gap between our age groups, CT of tricenarian cocaine users assembles features of an octogenarian brain, reinforcing the accelerated aging hypothesis in CUD.

Cingulate cortical thickness in cocaine use disorder: mediation effect between early life stress and cocaine consumption.

OBJECTIVE: The cingulate gyrus is implicated in the neurobiology of addiction, such as chronic cocaine consumption. Early life stress (ELS) is an important moderator of cocaine use disorder (CUD). Therefore, we investigated the effect of CUD on cingulate cortical thickness and tested whether a history of ELS could influence the effects of CUD. METHODS: Participants aged 18-50 years (78 with CUD due to crack cocaine consumption and 53 healthy controls) underwent magnetic resonance imaging and the cingulate thickness (rostral anterior, caudal anterior, posterior, and isthmus regions) was analysed. The clinical assessment comprised the Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index. Group comparisons adjusting by sex, age, and education were performed. Mediation models were generated where lifetime cocaine use, CTQ score, and cortical thickness corresponded to the independent variable, intermediary variable, and outcome, respectively. RESULTS: Group comparisons revealed significant differences in six out of eight cingulate cortices, showing lower thickness in the CUD group. Furthermore, years of regular cocaine use was the variable most associated with cingulate thickness. Negative correlations were found between CTQ scores and the isthmus cingulate (right hemisphere), as well as with the rostral anterior cingulate (left hemisphere). In the mediation analysis, we observed a significant negative direct effect of lifetime cocaine use on the isthmus cingulate and an indirect effect of cocaine use mediated by CTQ score. CONCLUSION: Our findings suggest that a history of ELS could aggravate the negative effects of chronic cocaine use on the cingulate gyrus, particularly in the right isthmus cingulate cortex.

Thrifty-Eating Behavior Phenotype at the Food Court - Programming Goes Beyond Food Preferences.

Introduction: Prenatal growth impairment leads to higher preference for palatable foods in comparison to normal prenatal growth subjects, which can contribute to increased body fat mass and a higher risk for developing chronic diseases in small-for-gestational-age (SGA) individuals throughout life. This study aimed to investigate the effect of SGA on feeding behavior in children and adolescents, as well as resting-state connectivity between areas related to reward, self-control, and value determination, such as orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), amygdala and dorsal striatum (DS). Methods: Caregivers and their offspring were recruited from two independent cohorts in Brazil (PROTAIA) and Canada (MAVAN). Both cohorts included anthropometric measurements, food choice tasks, and resting-state functional magnetic resonance imaging (fMRI) data. Results: In the Brazilian sample (17 ± 0.28 years, n=70), 21.4% of adolescents were classified as SGA. They exhibited lower monetary-related expenditure to buy a snack compared to controls in the food choice test. Decreased functional connectivity (n=40) between left OFC and left DL-PFC; and between right OFC and: left amygdala, right DS, and left DS were observed in the Brazilian SGA participants. Canadian SGA participants (14.9%) had non-significant differences in comparison with controls in a food choice task at 4 years old ( ± 0.01, n=315). At a follow-up brain scan visit (10.21 ± 0.140 years, n=49), SGA participants (28.6%) exhibited higher connectivity between the left OFC and left DL-PFC, also higher connectivity between the left OFC and right DL-PFC. We did not observe significant anthropometric neither nutrients' intake differences between groups in both samples. Conclusions: Resting-state fMRI results showed that SGA individuals had altered connectivity between areas involved in encoding the subjective value for available goods and decision-making in both samples, which can pose them in disadvantage when facing food options daily. Over the years, the cumulative exposure to particular food cues together with the altered behavior towards food, such as food purchasing, as seen in the adolescent cohort, can play a role in the long-term risk for developing chronic non-communicable diseases.

Sex differences in brain regional homogeneity during acute abstinence in cocaine use disorder.

There are significant sex differences in the clinical characteristics of cocaine use disorder (CUD). As this is a brain disorder that involves changes in functional connectivity, we investigated the existence of sex differences among people with CUD and controls. We used a data-driven method comparing males (n = 20, CK-M) and females with CUD (n = 20, CK-F) and healthy controls (20 males, HC-M and 20 females, HC-F). The participants undertook a resting-state functional magnetic resonance imaging exam. Regional homogeneity (ReHo) was performed to identify group and sex differences. Persons with CUD of both sexes presented lower ReHo parameters than controls, especially within the parietal lobule. Males with CUD showed higher ReHo than females in three right-side brain areas: postcentral gyrus, putamen and fusiform gyrus. It was found that abstinence symptoms severity was associated with lower ReHo values in the right postcentral gyrus and the right fusiform gyrus. Participants with CUD exhibited altered ReHo parameters compared to controls, similar to what is found in ageing-related disorders. Our data also indicate that cocaine has sex-specific effects on brain functioning when analysing ReHo.

Zika virus congenital microcephaly severity classification and the association of severity with neuropsychomotor development.

BACKGROUND: Zika virus infection during pregnancy is linked to birth defects, most notably microcephaly, which is associated with neurodevelopmental delays. OBJECTIVE: The goals of the study were to propose a method for severity classification of congenital microcephaly based on neuroradiologic findings of MRI scans, and to investigate the association of severity with neuropsychomotor developmental scores. We also propose a semi-automated method for MRI-based severity classification of microcephaly. MATERIALS AND METHODS: We conducted a cross-sectional investigation of 42 infants born with congenital Zika infection. Bayley Scales of Infant and Toddler Development III (Bayley-III) developmental evaluations and MRI scans were carried out at ages 13-39 months (mean: 24.8 months; standard deviation [SD]: 5.8 months). The severity score was generated based on neuroradiologist evaluations of brain malformations. Next, we established a distribution of Zika virus-microcephaly severity score including mild, moderate and severe and investigated the association of severity with neuropsychomotor developmental scores. Finally, we propose a simplified semi-automated procedure for estimating the severity score based only on volumetric measures. RESULTS: The results showed a correlation of r=0.89 (P<0.001) between the Zika virus-microcephaly severity score and the semi-automated method. The trimester of infection did not correlate with the semi-automated method. Neuropsychomotor development correlated with the severity classification based on the radiologic readings and semi-automated method; the more severe the imaging scores, the lower the neuropsychomotor developmental scores. CONCLUSION: These severity classification methods can be used to evaluate severity of microcephaly and possible association with developmental consequences. The semi-automated methods thus provide an alternative for predicting severity of microcephaly based on only one MRI sequence.

Increased Glucose Activity in Subgenual Anterior Cingulate and Hippocampus of High Performing Older Adults, Despite Amyloid Burden.

BACKGROUND: Individuals at 80 years of age or above with exceptional memory are considered SuperAgers (SA), an operationalized definition of successful cognitive aging. SA showed increased thickness and altered functional connectivity in the anterior cingulate cortex as a neurobiological signature. However, their metabolic alterations are yet to be uncovered. OBJECTIVE: Herein, a metabolic (FDG-PET), amyloid (PIB-PET), and functional (fMRI) analysis of SA were conducted. METHODS: Ten SA, ten age-matched older adults (C80), and ten cognitively normal middle-aged (C50) adults underwent cognitive testing and multimodal neuroimaging examinations. Anterior and posterior regions of the cingulate cortex and hippocampal areas were primarily examined, then subregions of anterior cingulate were segregated. RESULTS: The SA group showed increased metabolic activity in the left and right subgenual anterior cingulate cortex (sACC, p < 0.005 corrected, bilateral) and bilateral hippocampi (right: p < 0.0005 and left: p < 0.005, both corrected) as compared to that in the C80 group. Amyloid deposition was above threshold in 30% of SA and C80 (p > 0.05). The SA group also presented decreased connectivity between right sACC and posterior cingulate (p < 0.005, corrected) as compared to that of the C80 group. CONCLUSION: These results support the key role of sACC and hippocampus in SA, even in the presence of amyloid deposition. It also suggests that sACC may be used as a potential biomarker in older adults for exceptional memory ability. Further longitudinal studies measuring metabolic biomarkers may help elucidate the interaction between these areas in the cognitive aging process.

White matter deficits in cocaine use disorder: convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomic analysis.

White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users (n = 75) and healthy controls (HC) (n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD (n = 8) and HC (n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) (p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU (p = 0.0421) and female sex (p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA (p = 0.006) and higher RD (p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed (p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.

Cortical thickness and subcortical volume abnormalities in male crack-cocaine users.

Crack-cocaine offers a higher risk of abuse than intranasal and intravenous use of cocaine. Yet, current treatments remain disappointing and our understanding of the mechanism of crack-cocaine neurotoxicity is still incomplete. Magnetic resonance images studies on brain changes of crack-cocaine addicts show divergent data. The present study investigated gray matter (GM) abnormalities in crack-cocaine dependents (n = 18) compared to healthy controls (n = 17). MRI data was analysed using FreeSurfer and voxel-based morphometry (VBM). FreeSurfer analysis showed that CD had decreased cortical thickness (CT) in the left inferior temporal cortex (lTC), left orbitofrontal cortex (lOFC) and left rostro frontal cortex (lRFC), enlargement in left inferior lateral ventricle, and smaller GM volume in right hippocampus and right ventral diencephalon. VBM analysis showed that CD had significantly decreased GM volume in left Putamen and left nucleus accumbens. Furthermore, we found a negative correlation between duration of crack-cocaine use and lTC CT. These results provide compelling evidence for GM abnormalities in CD and also suggest that duration of crack-cocaine use may be associated with CT alterations.

Evaluating fMRI-Based Estimation of Eye Gaze During Naturalistic Viewing.

The collection of eye gaze information during functional magnetic resonance imaging (fMRI) is important for monitoring variations in attention and task compliance, particularly for naturalistic viewing paradigms (e.g., movies). However, the complexity and setup requirements of current in-scanner eye tracking solutions can preclude many researchers from accessing such information. Predictive eye estimation regression (PEER) is a previously developed support vector regression-based method for retrospectively estimating eye gaze from the fMRI signal in the eye's orbit using a 1.5-min calibration scan. Here, we provide confirmatory validation of the PEER method's ability to infer eye gaze on a TR-by-TR basis during movie viewing, using simultaneously acquired eye tracking data in five individuals (median angular deviation < 2°). Then, we examine variations in the predictive validity of PEER models across individuals in a subset of data (n = 448) from the Child Mind Institute Healthy Brain Network Biobank, identifying head motion as a primary determinant. Finally, we accurately classify which of the two movies is being watched based on the predicted eye gaze patterns (area under the curve = 0.90 ± 0.02) and map the neural correlates of eye movements derived from PEER. PEER is a freely available and easy-to-use tool for determining eye fixations during naturalistic viewing.

An fMRI study of inhibitory control and the effects of exposure to violence in Latin-American early adolescents: alterations in frontoparietal activation and performance.

We used functional magnetic resonance to investigate the effects of exposure to violence on early adolescent brain function in an inhibitory control task. We investigated the association among scores on self-reported exposure to violence, performance and brain activation. Thirty-seven early adolescents (ages 10-14) from a Latin-American urban region participated in the study. Results showed that recent and chronic exposure to violence was associated with less activation of a network of frontal regions, including the anterior cingulate gyrus and the superior frontal cortex; recent exposure to violence was also associated with less activation of the superior parietal lobe. Results also showed that less activation correlated with more prominent deterioration in the performance in the inhibitory control task (increased latency with time). The findings suggest that early adolescence exposure to violence is associated with differences in activation of a neural network commonly associated with executive function and control. The results underscore the urgency of addressing exposure to violence in adolescence, a period of high susceptibility to the environment, and are discussed in the light of the evidence of the effects of violence on adolescent brain function. Executive function training may be a candidate for targeted cognitive interventions aimed at mitigating these effects.

Violence and Latin-American preadolescents: A study of social brain function and cortisol levels.

The present study investigated exposure to violence and its association with brain function and hair cortisol concentrations in Latin-American preadolescents. Self-reported victimization scores (JVQ-R2), brain imaging (fMRI) indices for a social cognition task (the 'eyes test'), and hair cortisol concentrations were investigated, for the first time, in this population. The eyes test is based on two conditions: attributing mental state or sex to pictures of pairs of eyes (Baron-Cohen, Wheelwright, Hill, Raste, & Plumb, 2001). The results showed an association among higher victimization scores and (a) less activation of posterior temporoparietal right-hemisphere areas, in the mental state condition only (including right temporal sulcus and fusiform gyrus); (b) higher functional connectivity indices for the Amygdala and Right Fusiform Gyrus (RFFG) pair of brain regions, also in the mental state condition only; (c) higher hair cortisol concentrations. The results suggest more exposure to violence is associated with significant differences in brain function and connectivity. A putative mechanism of less activation in posterior right-hemisphere regions and of synchronized Amygdala: RFFG time series was identified in the mental state condition only. The results also suggest measurable effects of exposure to violence in hair cortisol concentrations, which contribute to the reliability of self-reported scores by young adolescents. The findings are discussed in light of the effects of exposure to violence on brain function and on social-cognitive development in the adolescent brain. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=qHcXq7Y9PBk.

Decoupling of the Occipitotemporal Cortex and the Brain's Default-Mode Network in Dyslexia and a Role for the Cingulate Cortex in Good Readers: A Brain Imaging Study of Brazilian Children.

The goal of the present study was to investigate intrinsic and reading-related brain function associated with dyslexia and typical readers in monolingual Brazilian children. Two fMRI studies were carried out: a resting-state and a word-reading study. The results show (a) underconnectivity between the occipitotemporal region (visual word form area) and the brain's default-mode network in dyslexic readers and (b) more activation of the anterior cingulate cortex for typical readers relative to dyslexic readers. The findings provide evidence for brain connectivity and function differences in an underrepresented population in fMRI studies of dyslexia; the results suggest atypical intrinsic function, and differences in directed attention processes in dyslexia.

Atlas selection for hippocampus segmentation: Relevance evaluation of three meta-information parameters.

Current state-of-the-art methods for whole and subfield hippocampus segmentation use pre-segmented templates, also known as atlases, in the pre-processing stages. Typically, the input image is registered to the template, which provides prior information for the segmentation process. Using a single standard atlas increases the difficulty in dealing with individuals who have a brain anatomy that is morphologically different from the atlas, especially in older brains. To increase the segmentation precision in these cases, without any manual intervention, multiple atlases can be used. However, registration to many templates leads to a high computational cost. Researchers have proposed to use an atlas pre-selection technique based on meta-information followed by the selection of an atlas based on image similarity. Unfortunately, this method also presents a high computational cost due to the image-similarity process. Thus, it is desirable to pre-select a smaller number of atlases as long as this does not impact on the segmentation quality. To pick out an atlas that provides the best registration, we evaluate the use of three meta-information parameters (medical condition, age range, and gender) to choose the atlas. In this work, 24 atlases were defined and each is based on the combination of the three meta-information parameters. These atlases were used to segment 352 vol from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Hippocampus segmentation with each of these atlases was evaluated and compared to reference segmentations of the hippocampus, which are available from ADNI. The use of atlas selection by meta-information led to a significant gain in the Dice similarity coefficient, which reached 0.68 ±â€¯0.11, compared to 0.62 ±â€¯0.12 when using only the standard MNI152 atlas. Statistical analysis showed that the three meta-information parameters provided a significant improvement in the segmentation accuracy.

Identification of autism spectrum disorder using deep learning and the ABIDE dataset.

The goal of the present study was to apply deep learning algorithms to identify autism spectrum disorder (ASD) patients from large brain imaging dataset, based solely on the patients brain activation patterns. We investigated ASD patients brain imaging data from a world-wide multi-site database known as ABIDE (Autism Brain Imaging Data Exchange). ASD is a brain-based disorder characterized by social deficits and repetitive behaviors. According to recent Centers for Disease Control data, ASD affects one in 68 children in the United States. We investigated patterns of functional connectivity that objectively identify ASD participants from functional brain imaging data, and attempted to unveil the neural patterns that emerged from the classification. The results improved the state-of-the-art by achieving 70% accuracy in identification of ASD versus control patients in the dataset. The patterns that emerged from the classification show an anticorrelation of brain function between anterior and posterior areas of the brain; the anticorrelation corroborates current empirical evidence of anterior-posterior disruption in brain connectivity in ASD. We present the results and identify the areas of the brain that contributed most to differentiating ASD from typically developing controls as per our deep learning model.

Decreased comfort food intake and allostatic load in adolescents carrying the A3669G variant of the glucocorticoid receptor gene.

BACKGROUND: The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is associated with altered tissue sensitivity to glucocorticoids (GCs). GCs modulate the food reward circuitry and are implicated in increased intake of palatable foods, which can lead to the metabolic syndrome and obesity. We hypothesized that presence of the G variant of the A3669G SNP would affect preferences for palatable foods and alter metabolic, behavioural, and neural outcomes. METHODS: One hundred thirty-one adolescents were genotyped for the A3669G polymorphism, underwent anthropometric assessment and nutritional evaluations, and completed behavioural measures. A subsample of 74 subjects was followed for 5 years and performed a brain functional magnetic resonance imaging (fMRI) paradigm to verify brain activity in response to food cues. RESULTS: Sugar and total energy consumption were lower in A3669G G allele variant carriers. On follow-up, this group also had reduced serum insulin concentrations, increased insulin sensitivity, and lower anxiety scores. Because of our unbalanced sample sizes (31/37 participants non-G allele carriers/total), our imaging data analysis failed to find whole brain-corrected significant results in between-group t-tests. CONCLUSION: These results highlight that a genetic variation in the GR gene is associated, at the cellular level, with significant reduction in GC sensitivity, which, at cognitive and behavioural levels, translates to altered food intake and emotional stress response. This genetic variant might play a major role in decreasing risk for metabolic and psychiatric diseases.

Amygdala-based intrinsic functional connectivity and anxiety disorders in adolescents and young adults.

Anxiety disorders (AD) are the most prevalent group of psychiatric disorders in adolescents and young adults. Nevertheless, the pathophysiology of anxiety disorders is still poorly understood. This study investigated differences in the functional connectivity of intrinsic amygdala-based networks of participants with and without AD. Resting state fMRI data were obtained from 18 participants with an AD and 19 healthy comparison individuals. Psychiatric diagnosis was assessed using standardized structured interviews. The comparison between groups was carried out using functional connectivity maps from six seed regions defined using probabilistic maps bilaterally within the amygdala (basolateral, superficial and centromedial amygdala). We found significant between-group differences in five clusters, which showed aberrant functional connectivity with the left basolateral amygdala: right precentral gyrus, right cingulate gyrus, bilateral precuneus, and right superior frontal gyrus in subjects with AD as compared with the comparison subjects. For the comparison subjects, the correlations between the amygdala and the five clusters were either non-significant, or negative. The present study suggests there is an intrinsic disruption in the communication between left basolateral amygdala and a network of brain regions involved with emotion regulation, and with the default mode network in adolescents and young adults with anxiety disorders.

Interaction between perceived maternal care, anxiety symptoms, and the neurobehavioral response to palatable foods in adolescents.

Studies in rodents have shown that early life trauma leads to anxiety, increased stress responses to threatening situations, and modifies food intake in a new environment. However, these associations are still to be tested in humans. This study aimed to verify complex interactions among anxiety diagnosis, maternal care, and baseline cortisol on food intake in a new environment in humans. A community sample of 32 adolescents and young adults was evaluated for: psychiatric diagnosis using standardized interviews, maternal care using the Parental Bonding Inventory (PBI), caloric consumption in a new environment (meal choice at a snack bar), and salivary cortisol. They also performed a brain fMRI task including the visualization of palatable foods vs. neutral items. The study found a three-way interaction between anxiety diagnosis, maternal care, and baseline cortisol levels on the total calories consumed (snacks) in a new environment. This interaction means that for those with high maternal care, there were no significant associations between cortisol levels and food intake in a new environment. However, for those with low maternal care and who have an anxiety disorder (affected), cortisol was associated with higher food intake; whereas for those with low maternal care and who did not have an anxiety disorder (resilient), cortisol was negatively associated with lower food intake. In addition, higher anxiety symptoms were associated with decreased activation in the superior and middle frontal gyrus when visualizing palatable vs. neutral items in those reporting high maternal care. These results in humans mimic experimental research findings and demonstrate that a combination of anxiety diagnosis and maternal care moderate the relationship between the HPA axis functioning, anxiety, and feeding behavior in adolescents and young adults.

Intrinsic Brain Connectivity Following Long-Term Treatment with Methylphenidate in Children with Attention-Deficit/Hyperactivity Disorder.

INTRODUCTION: Although widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD) across the life span, the effects of methylphenidate (MPH) on the brain are not completely understood. Functional neuroimaging techniques may help increase knowledge about the mechanisms of MPH action. OBJECTIVE: To evaluate changes in functional connectivity patterns of the default mode network (DMN) in children with ADHD following long-term treatment with MPH. METHODS: Twenty-three right-handed treatment-naïve boys with ADHD underwent a protocol of intrinsic functional connectivity before and after 6 months of treatment with MPH. Functional connectivity was analyzed using a region of interest (ROI) approach and independent component analysis (ICA). RESULTS: ROI analyses showed no significant changes in connectivity between regions of the DMN following treatment, with a relatively small increase in the anterior-posterior connectivity of the network. ICA revealed a significant increase in connectivity between the left putamen and the DMN (p < 0.001, corrected). There was a correlation between the reduction of symptoms and the increased connectivity between the putamen and the DMN after treatment (rho = -0.65, p = 0.017). CONCLUSION: Dysfunctions in cortical-subcortical circuits have often been associated with the pathophysiology of ADHD. Our findings suggest that effective treatment with MPH in children with ADHD may affect brain functioning by increasing connectivity between the DMN and subcortical nuclei.

Decreasing ADHD phenotypic heterogeneity: searching for neurobiological underpinnings of the restrictive inattentive phenotype.

During the process of developing the DSM-5, a new phenotype of ADHD was proposed-the ADHD restrictive inattentive presentation (ADHD-RI), describing subjects with high endorsement of inattentive symptoms and a low level of hyperactivity. However, this phenotype was not included in the DSM-5 because of the lack of robust neurobiological data. We aimed to assess the specific neurobiological underpinnings of individuals presenting ADHD-RI. We compared a sample of 301 subjects (101 ADHD-Combined; 50 ADHD-RI; 50 ADHD predominantly inattentive type and 100 typically developing subjects) aged 8-15 years, using a complete neuropsychological battery, molecular genetic data (DRD4 and DAT1 most studied polymorphisms) and functional MRI during a Go-No/Go task. Subjects with ADHD-RI had a significantly different neuropsychological profile compared with the other groups, including lower psychomotor speeds, longer reaction times and the worst overall performance in the global neurocognitive index. The proportion of subjects with the presence of DRD4-7 repeat allele was significantly higher in ADHD-RI. The fMRI data suggested that more attention-related posterior brain regions (especially temporo-occipital areas) are activated in ADHD-RI during both Go and No-Go cues compared to TD controls and ADHD predominantly inattentive type. ADHD-RI may represent a different phenotype than other types of ADHD. In addition, our results suggest that reducing the phenotypic heterogeneity may aid in the search for the neurobiological underpinnings of ADHD.

Automated methods for hippocampus segmentation: the evolution and a review of the state of the art.

The segmentation of the hippocampus in Magnetic Resonance Imaging (MRI) has been an important procedure to diagnose and monitor several clinical situations. The precise delineation of the borders of this brain structure makes it possible to obtain a measure of the volume and estimate its shape, which can be used to diagnose some diseases, such as Alzheimer's disease, schizophrenia and epilepsy. As the manual segmentation procedure in three-dimensional images is highly time consuming and the reproducibility is low, automated methods introduce substantial gains. On the other hand, the implementation of those methods is a challenge because of the low contrast of this structure in relation to the neighboring areas of the brain. Within this context, this research presents a review of the evolution of automatized methods for the segmentation of the hippocampus in MRI. Many proposed methods for segmentation of the hippocampus have been published in leading journals in the medical image processing area. This paper describes these methods presenting the techniques used and quantitatively comparing the methods based on Dice Similarity Coefficient. Finally, we present an evaluation of those methods considering the degree of user intervention, computational cost, segmentation accuracy and feasibility of application in a clinical routine.