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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.

BackgroundA growing body of literature has demonstrated the importance of discourse assessment in patients who suffered from brain injury, both in the left and right hemispheres, as discourse represents a key component of functional communication. However, little is known about the relationship between gray matter density and macrolinguistic processing.PurposeThis study aimed to investigate this relationship in a group of participants with middle–low to low socioeconomic status.MethodTwenty adults with unilateral left hemisphere (n= 10) or right hemisphere (n= 10) chronic ischemic stroke and 10 matched (age, education, and socioeconomic status) healthy controls produced three oral narratives based on sequential scenes. Voxel-based morphometry analysis was conducted using structural magnetic resonance imaging.ResultsCompared to healthy controls, the left hemisphere group showed cohesion impairments, whereas the right hemisphere group showed impairments in coherence and in producing macropropositions. Cohesion positively correlated with gray matter density in the right primary sensory area (PSA)/precentral gyrus and the pars opercularis. Coherence, narrativity, and index of lexical informativeness were positively associated with the left PSA/insula and the superior temporal gyrus. Macropropositions were mostly related to the left PSA/insula and superior temporal gyrus, left cingulate, and right primary motor area/insula.DiscussionOverall, the present results suggest that both hemispheres are implicated in macrolinguistic processes in narrative discourse. Further studies including larger samples and with various socioeconomic status should be conducted.Supplemental Materialhttps://doi.org/10.23641/asha.14347550

Objective Resting-state functional magnetic resonance imaging (R-fMRI) studies of the neural correlates of medication treatment in attention-deficit/hyperactivity disorder (ADHD) have not been systematically reviewed. Our objective was to systematically identify, assess and summarize within-subject R-fMRI studies of pharmacological-induced changes in patients with ADHD. We critically appraised strengths and limitations, and provide recommendations for future research. Method Systematic review of published original reports in English meeting criteria in pediatric and adult patients with ADHD up to July 1, 2020. A thorough search preceded selection of studies matching prespecified criteria. Strengths and limitations of selected studies, regarding design and reporting, were identified based on current best practices. Results We identified and reviewed 9 studies (5 pediatric and 4 adult studies). Sample sizes were small-medium (16–38 patients), and included few female participants. Medications were methylphenidate, amphetamines, and atomoxetine. Wide heterogeneity was observed in designs, analyses and results, which could not be combined quantitatively. Qualitatively, the multiplicity of brain regions and networks identified, some of which correlated with clinical improvements, do not support a coherent mechanistic hypothesis of medication effects. Overall, reports did not meet current standards to ensure reproducibility. Conclusion In this emerging field, the few studies using R-fMRI to analyze the neural correlates of medications in patients with ADHD suggest a potential modulatory effect of stimulants and atomoxetine on several intrinsic brain activity metrics. However, methodological heterogeneity and reporting issues need to be addressed in future research to validate findings which may contribute to clinical care. Such a goal is not yet at hand.

Objective Individuals with Parkinson's disease (PD) and freezing of gait (FOG) present peripheral and central sensitivity disturbances that impair motor performance. This study aimed to investigate long-term effects of plantar sensory stimulation on brain activity, brain connectivity, and gait velocity of individuals with PD and FOG. Methods Twenty-five participants were enrolled in this clinical trial (NCT02594540). Plantar sensory stimulation was delivered using the Automated Mechanical Peripheral Stimulation therapy (AMPS). Volunteers were randomly assigned to real or placebo AMPS groups and received eight sessions of treatment. The primary outcome was brain activity (task-based fMRI-active ankle dorsi-plantar flexion). Secondary outcomes were brain connectivity (resting state-RS fMRI) and gait velocity. fMRI was investigated on the left, right, and mid-sensory motor regions, left and right basal ganglia. Results No changes in brain activity were observed when task-based fMRI was analyzed. After real AMPS, RS functional connectivity between basal ganglia and sensory-related brain areas increased (insular and somatosensory cortices). Gait velocity also increased after real AMPS. A positive correlation was found between gait velocity and the increased connectivity between sensory, motor and supplementary motor cortices. Conclusion Plantar sensory stimulation through AMPS was not able to modify brain activity. AMPS increased the RS brain connectivity mainly in areas related to sensory processing and sensorimotor integration. Plantar stimulation could be a way to improve plantar sensitivity and consequently ameliorate gait performance. However, the mechanisms behind the way AMPS influences brain pathways are still not completely known.

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.

IntroductionPrenatal 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).MethodsCaregivers 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.ResultsIn 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.ConclusionsResting-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.

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.

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 p p = 0.0421) and female sex (p p = 0.006) and higher RD (p 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.

New large neuroimaging studies, such as the Adolescent Brain Cognitive Development study (ABCD) and Human Connectome Project (HCP) Development studies are adopting a new T1-weighted imaging sequence with prospective motion correction (PMC) in favor of the more traditional 3-Dimensional Magnetization-Prepared Rapid Gradient-Echo Imaging (MPRAGE) sequence. In this study, we used a developmental dataset (ages 5-21, N=348) from the Healthy Brain Network Initiative and directly compared the MPRAGE and MPRAGE with PMC (MPRAGE+PMC) sequences to determine if the morphometric measurements obtained from both protocols are equivalent or if there is an advantage to use one. The sequences were also compared through quality control measurements. Inter- and intra-sequence reliability were assessed with another set of participants (N=71) that performed two MPRAGE and two MPRAGE+PMC sequences within the same imaging session, with one MPRAGE (MPRAGE1) and MPRAGE+PMC (MPRAGE+PMC1) pair at the beginning of the session and another pair (MPRAGE2 and MPRAGE+PMC2) at the end of the session. With morphometric measurements such as volume and cortical thickness, Intraclass correlation coefficients (ICC) scores showed that intra-sequence reliability is the highest with the MPRAGE+PMC sequences and lowest with the MPRAGE sequences. Regarding inter-sequence reliability, ICC scores were higher for the MPRAGE1-MPRAGE+PMC1 pair at the beginning of the session than the MPRAGE1-MPRAGE2 pair, possibly due to the higher motion artifacts in the MPRAGE2 run. Results also indicate that the MPRAGE+PMC sequence is robust, but not foolproof, to high head motion. For quality control metrics, the traditional MPRAGE presented better results than MPRAGE+PMC in 5 of the 7 measurements. In conclusion, morphometric measurements evaluated here showed high inter-sequence reliability between the MPRAGE and MPRAGE+PMC sequences, especially in images with low head motion. Researchers conducting studies with highly kinetic populations are highly recommended to use the MPRAGE+PMC sequence, due to its robustness to head motion and higher reliability scores. However, due to potential higher quality control measures, neuroimaging researchers with low head motion participants can still consider using the MPRAGE sequence, however, can also choose to use the MPRAGE+PMC sequence to increase the reliability of the data. Highlights The MPRAGE sequences with and without Prospective Motion Correction (PMC) are compared in a large sample size (N=419) in a “real world” scenario, where we did not explicitly ask subjects to move or maintain still during the acquisition of the structural images MPRAGE sequence with PMC (MPRAGE+PCM) presents higher intra-sequence reliability results in morphometric measurements compared to the traditional MPRAGE sequence without PMC. High inter-sequence (MPRAGE with and without PMC) reliability scores were also observed. Researchers are recommended use the MPRAGE+PMC as their structural T1 weighted pulse imaging sequence for future and current studies, especially in studies with hyperkinetic populations Due to potential higher quality control measures of the traditional MPRAGE sequence, neuroimaging researchers with low head motion participants can still consider using the MPRAGE sequence without PMC

A common coordinate space enabling comparison across individuals is vital to understanding human brain organization and individual differences. By leveraging dimensionality reduction algorithms, high-dimensional fMRI data can be represented in a low-dimensional space to characterize individual features. Such a representative space encodes the functional architecture of individuals and enables the observation of functional changes across time. However, determining comparable functional features across individuals in resting-state fMRI in a way that simultaneously preserves individual-specific connectivity structure can be challenging. In this work we propose scalable joint embedding to simultaneously embed multiple individual brain connectomes within a common space that allows individual representations across datasets to be aligned. Using Human Connectome Project data, we evaluated the joint embedding approach by comparing it to the previously established orthonormal alignment model. Alignment using joint embedding substantially increased the similarity of functional representations across individuals while simultaneously capturing their distinct profiles, allowing individuals to be more discriminable from each other. Additionally, we demonstrated that the common space established using resting-state fMRI provides a better overlap of task-activation across participants. Finally, in a more challenging scenario - alignment across a lifespan cohort aged from 6 to 85 - joint embedding provided a better prediction of age (r2 = 0.65) than the prior alignment model. It facilitated the characterization of functional trajectories across lifespan. Overall, these analyses establish that joint embedding can simultaneously capture individual neural representations in a common connectivity space aligning functional data across participants and populations and preserve individual specificity.

BackgroundZika virus infection during pregnancy is linked to birth defects, most notably, microcephaly, which in its turn, is associated with neurodevelopmental delays.ObjectiveThe goal of the study is to propose a method for severity classification of congenital microcephaly based on neuroradiological 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.MethodsCross-sectional investigation of 42 infants born with congenital Zika infection. Bayley-III developmental evaluations and MRI scans were carried out at ages 13-39 months (mean: 24.8, SD: 5.8). The severity score was generated based on neuroradiologist evaluations of brain malformations. Next, we established a distribution of Zika virus-microcephaly severity score into 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.ResultsResults 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 radiological readings and with the semi-automated method; the more severe the imaging scores, the lower neuropsychomotor developmental scores.ConclusionThe severity classification methods may be used to evaluate severity of microcephaly and possible association with developmental consequences. The semi-automated methods thus may be an alternative for prediction of severity of microcephaly using only one MRI sequence.

Background Traumatic spinal cord injury (TSCI) is one of the most devastating injuries that has a physical impact on patients. The CHORDATA® method involves suspension and pendulous exercises and has been clinically used to treat patients with TSCI. Although empirically used to treat neurological patients, there is no scientific evidence of the efficacy of this method. Purpose To evaluate the chronic effects of CHORDATA® method on torque, muscle activation, muscle thickness, and functionality in patients with traumatic spinal cord injury. Methods Twenty-six male patients with medullar thoracic injury were randomly categorised into two groups: intervention group (n = 14) and control group (n = 12). Rehabilitation program comprised of 16 sessions of body suspension and pendulum exercises (twice/week). The maximal voluntary isometric trunk flexion and extension torques, muscle activation and thickness (external and internal oblique, rectus and transversus abdominis, longissimus, and multifidus muscles), and functionality (adapted reach test) were evaluated before and after of rehabilitation program. Findings A significant increase was observed in maximal voluntary isometric torque (flexion, 58%; extension, 76%), muscle activation of the rectus abdominis muscle, and muscle thickness of all intervention group muscles, without changes in the control group. Compared to the pre-intervention period, the intervention group also showed improvement in functionality at post-intervention, but no such differences were noted in the control group. Interpretation The corporal suspension and pendulum exercises training improved rectus abdominis muscle activation, trunk muscles structure and strength, and reaching capacity in medullar thoracic injury patients.

To describe epilepsy after congenital Zika virus infection (ZIKV) and its relationship with structural neuroimaging findings.This was a cross-sectional study in children (aged 13-42 months) who were born with microcephaly due to ZIKV infection between 2015-2017. Patients underwent a brain imaging scan (magnetic resonance) and a video-EEG study.Among the patients (n = 43), 55.8 % were male, 88.4 % were born at term, mean head circumference at the birth was 29.7 ± 1.8 cm, and 44.8 % were infected in the first trimester of pregnancy. Neuroimaging was moderately abnormal in 30.2 % and severely abnormal in 46.5 % of patients. Early seizures (6 months of age) were observed in 41.9 %. EEG background was abnormal when asleep or awake in 72.1 % and during sleep in 62.8 %. The interictal epileptogenic activity was recorded on 41/43 of the EEGs and was predominantly multifocal (62.8 %). An ictal EEG was obtained in 22 patients and 31.8 % had more than one seizure type. Sleep EEG (background) patterns, interictal epileptogenic activity (p = 0.046), interictal discharge localization (p = 0.015), type of ictal epileptogenic activity (p = 0.002), and localization of ictal discharge (p = 0.024) were significantly different between neuroimaging groups. The mild neuroimaging group had a higher chance of having more frequently normal sleep EEG patterns, no interictal epileptogenic activity and a further increase in the probability of walking without limitations, and less neurodevelopment delay.In patients with congenital Zika virus syndrome, epilepsy tended to be early and refractory. EEG features correlated with degree of neuroimaging abnormalities.

While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents. Additionally, HOMA-IR and insulinemia were higher in participants with impaired food memory. SGA individuals had higher snack caloric density and greater chance for impaired food memory. There was also an interaction between the HOMA-IR and birth weight ratio influencing external eating behavior. We suggest that diminished insulin sensitivity correlates with activation in visual attention areas and inactivation in inhibitory control areas in healthy adolescents. Insulin resistance also associated with less consistency in implicit memory for a consumed meal, which may suggest lower ability to establish a dietary pattern, and can contribute to obesity. Differences in feeding behavior in SGA individuals were associated with insulin sensitivity and hippocampal alterations, suggesting that cognition and hormonal regulation are important components involved in their food intake modifications throughout life.

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., Highlights • We successfully applied Deep Learning to classify ASD and controls using ABIDE data • We extracted patterns of brain function in rs-fMRI and showed anterior-posterior underconnectivity in the autistic brain • Underconnected areas in ASD rs-fMRI data: Paracingulate Gyrus, Supramarginal Gyrus and Middle Temporal Gyrus • We surpass the state-of-the-art in deep learning classification of brain activation by achieving 70% accuracy

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.

In a recent PNAS paper by Pedersen et al. (1), the authors report impressive performance when attempting to predict phenotypic variables (e.g., duration of previous night’s sleep) using individual differences in brain network switching. Although the results are intriguing, we have major concerns regarding the prediction model used to generate the results reported in figure 3 of ref. 1. The results obtained with the elastic net regression are reasonable. Based on their analysis, the authors used behavior to predict network switching and … [↵][1]1To whom correspondence may be addressed. Email: Michael.Milham{at}childmind.org. [1]: #xref-corresp-1-1

The neurofunctional effects of Cognitive training (CT) are poorly understood. Our main objective was to assess fMRI brain activation patterns in children with ADHD who received CT as an add-on treatment to stimulant medication. We included twenty children with ADHD from a clinical trial of stimulant medication and CT (10 in medication + CT and 10 in medication + non-active training). Between-group differences were assessed in performance and in brain activation during 3 fMRI paradigms of working memory (N-back: 0-back, 1-back, 2-back, 3-back), sustained attention (Sustained Attention Task - SAT: 2 s, 5 s and 8 s delays) and inhibitory control (Go/No-Go). We found significant group x time x condition interactions in working memory (WM) and sustained attention on brain activation. In N-back, decreases were observed in the BOLD signal change from baseline to endpoint with increasing WM load in the right insula, right putamen, left thalamus and left pallidum in the CT compared to the non-active group; in SAT - increases in the BOLD signal change from baseline to endpoint with increasing delays were observed in bilateral precuneus, right insula, bilateral associative visual cortex and angular gyrus, right middle temporal, precentral, postcentral, superior frontal and middle frontal gyri in the CT compared to the non-active group. CT in ADHD was associated with changes in activation in task-relevant parietal and striato-limbic regions of sustained attention and working memory. Changes in brain activity may precede behavioral performance modifications in working memory and sustained attention, but not in inhibitory control.

PurposeTo estimate the effect size of a serious game for cardiopulmonary resuscitation (CPR) training in comparison with a video-based on-line course in terms of learning outcomes among medical students before simulation-based CPR using a manikin.MethodsParticipants were 45 first-year medical students randomly assigned to CPR self-training using either a video-based Apple Keynote presentation (n = 22) or a serious game developed in a 3D learning environment (n = 23) for up to 20 min. Each participant was evaluated on a written, multiple-choice test (theoretical test) and then on a scenario of cardiac arrest (practical test) before and after exposure to the self-learning methods. The primary endpoint was change in theoretical and practical baseline scores during simulated CPR. This study was conducted in 2017.ResultsBoth groups improved scores after exposure. The video group had superior performance in both the theoretical test (7.56±0.21 vs 6.51±0.21 for the game group; p = 0.001) and the practical test (9.67±0.21 vs 8.40±0.21 for the game group; p < 0.001). However, students showed a preference for using games, as suggested by the longer time they remained interested in the method (18.57±0.66 min for the game group vs 7.41±0.43 for the video group; p < 0.001).ConclusionsThe self-training modality using a serious game, after a short period of exposure, resulted in inferior students' performance in both theoretical and practical CPR tests compared to the video-based self-training modality. However, students showed a clear preference for using games rather than videos as a form of self-training.

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.

Multilayer network models have been proposed as an effective means of capturing the dynamic configuration of distributed neural circuits and quantitatively describing how communities vary over time. Beyond general insights into brain function, a growing number of studies have begun to employ these methods for the study of individual differences. However, test–retest reliabilities for multilayer network measures have yet to be fully quantified or optimized, potentially limiting their utility for individual difference studies. Here, we systematically evaluated the impact of multilayer community detection algorithms, selection of network parameters, scan duration, and task condition on test–retest reliabilities of multilayer network measures (i.e., flexibility, integration, and recruitment). A key finding was that the default method used for community detection by the popular generalized Louvain algorithm can generate erroneous results. Although available, an updated algorithm addressing this issue is yet to be broadly adopted in the neuroimaging literature. Beyond the algorithm, the present work identified parameter selection as a key determinant of test–retest reliability; however, optimization of these parameters and expected reliabilities appeared to be dataset-specific. Once parameters were optimized, consistent with findings from the static functional connectivity literature, scan duration was a much stronger determinant of reliability than scan condition. When the parameters were optimized and scan duration was sufficient, both passive (i.e., resting state, Inscapes, and movie) and active (i.e., flanker) tasks were reliable, although reliability in the movie watching condition was significantly higher than in the other three tasks. The minimal data requirement for achieving reliable measures for the movie watching condition was 20 min, and 30 min for the other three tasks. Our results caution the field against the use of default parameters without optimization based on the specific datasets to be employed – a process likely to be limited for most due to the lack of test–retest samples to enable parameter optimization.

The collection of eye movement information during functional magnetic resonance imaging (fMRI) is a valuable, though commonly overlooked component of monitoring variations in attention and task compliance, particularly for naturalistic viewing paradigms (e.g., movies). Predictive eye estimation regression (PEER) is a previously developed support vector regression-based method for retrospectively estimating eye gaze from fMRI data that simply adds a 1.5-minute calibration scan to any protocol. Here, we provide a large-scale assessment of PEER for inferring eye fixations on a TR-by-TR basis during movie viewing using a subset of data (n=448) from the Child Mind Institute Healthy Brain Network Biobank. Consistent with prior work, we demonstrate the ability of PEER to provide accurate estimates of fixation location throughout the course of fMRI scans and we establish head motion as the primary determinant of model accuracy. Minimum data requirement analyses suggest model estimation can be carried out with less than half the data obtained in the 1.5-minute calibration scan. We demonstrate the ability to predict the movie an individual is watching (i.e., Despicable Me, The Present) based on the PEER time series. Out-of-scanner eye tracker-based measurements obtained during a repeat viewing of the movie The Present was used to further validate the time series obtained using PEER. Consistent with prior findings in the eye tracking literature, the fixation sequences showed a high consistency across participants, reducing the ability to identify an individual based on their fixation sequence. Finally, examination of neural activations associated with the PEER time series replicated prior findings regarding the neural correlates of eye movements. In summary, we demonstrate that PEER is an inexpensive, easy-to-use tool for researchers to determine eye fixations from naturalistic viewing data that overcomes the cost and burdens of in-scanner eye tracking.

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.

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.

Background The corpus callosum index (CCI) can be easily and reliably obtained from conventional magnetic resonance imaging (MRI) and has been proposed as a possible marker of brain atrophy in MS. However, further validation of its correlation with volumetric measurements is still warranted. Objective To assess the correlation of the CCI with the corpus callosum volume (CCV), brain and lesion volumes, and level of disability in MS. Methods Cross-sectional, exploratory study including patients with relapsing-remitting MS. Clinical assessment comprised of physical and cognitive disability scales. MRI parameters included conventional volumetric measurements, the CCI (manual), and the CCV (automated). Results Twenty-four patients were included. There was a strong correlation between the CCI and CCV. The CCI correlated strongly with the white matter and lesion volumes, and moderately with the whole brain volume and scores on the Paced Auditory Serial Addition Test and MS Functional Composite. There were no correlations between the CCI and either gray matter volume or scores on the Expanded Disability Status Scale, the 9-Hole Peg Test, or the Timed 25-Foot Walk test. Conclusion The findings support the validity of the CCI as an easy-to-obtain marker of brain atrophy, lesion load, and cognitive dysfunction in patients with MS.

Alzheimers disease (AD) is characterized by mental and cognitive problems, particularly with memory, lan- guage, visuospatial skills (VS), and executive functions (EF). Advances in the neuroimaging of AD have highlighted dys- functions in functional connectivity networks (FCNs), especially in the memory related default mode network (DMN). However, little is known about the integrity and clinical significance of FNCs that process other cognitive functions than memory. We evaluated 22 patients with mild AD and 26 healthy controls through a resting state functional MRI scan. We aimed to identify different FCNs: the DMN, language, EF, and VS. Seed-based functional connectivity was calculated by placing a seed in the DMN (posterior cingulate cortex), language (Brocas and Wernickes areas), EF (right and left dorso- lateral prefrontal cortex), and VS networks (right and left associative visual cortex). We also performed regression analy- ses between individual connectivity maps for the different FCNs and the scores on cognitive tests. We found areas with significant decreases in functional connectivity in patients with mild AD in the DMN and Wernickes area compared with controls. Increased connectivity in patients was observed in the EF network. Regarding multiple linear regression analy- ses, a significant correlation was only observed between the connectivity of the DMN and episodic memory (delayed re- call) scores. In conclusion, functional connectivity alterations in mild AD are not restricted to the DMN. Other FCNs re- lated to language and EF may be altered. However, we only found significant correlations between cognition and func- tional connectivity in the DMN and episodic memory performance.

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.

Despite intensive study, the role of the dorsal medial frontal cortex (dMFC) in error monitoring and conflict processing remains actively debated. The current experiment manipulated conflict type (stimulus conflict only or stimulus and response selection conflict) and utilized a novel modeling approach to isolate error and conflict variance during a multimodal numeric Stroop task. Specifically, hemodynamic response functions resulting from two statistical models that either included or isolated variance arising from relatively few error trials were directly contrasted. Twenty-four participants completed the task while undergoing event-related functional magnetic resonance imaging on a 1.5-Tesla scanner. Response times monotonically increased based on the presence of pure stimulus or stimulus and response selection conflict. Functional results indicated that dMFC activity was present during trials requiring response selection and inhibition of competing motor responses, but absent during trials involving pure stimulus conflict. A comparison of the different statistical models suggested that relatively few error trials contributed to a disproportionate amount of variance (i.e., activity) throughout the dMFC, but particularly within the rostral anterior cingulate gyrus (rACC). Finally, functional connectivity analyses indicated that an empirically derived seed in the dorsal ACC/pre-SMA exhibited strong connectivity (i.e., positive correlation) with prefrontal and inferior parietal cortex but was anti-correlated with the default-mode network. An empirically derived seed from the rACC exhibited the opposite pattern, suggesting that sub-regions of the dMFC exhibit different connectivity patterns with other large scale networks implicated in internal mentations such as daydreaming (default-mode) versus the execution of top-down attentional control (fronto-parietal).

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.

There has been a growing interest in the neuroimaging community regarding resting state data (i.e., passive mental activity) and the subsequent activation of the so-called default mode network (DMN). Although this network was originally characterized by a pattern of deactivation during active cognitive states, more recent applications of data-driven techniques such as independent component analysis (ICA) have permitted the analysis of brain activation during extended periods of truly passive mental activity. However, ICA requires the resultant components to be evaluated for “goodness of fit” via either human raters or more automated techniques. To our knowledge, an investigation on the reliability of either technique in determining the component that best corresponds to default-mode activity has not been performed. Moreover, it is not clear how automated techniques, which are necessarily dependent upon a template mask, are affected by the structures used to compose the mask. The current study investigated both interrater (human-human) reliability and intermethod (human-machine) reliability for determining DMN activation in 42 healthy controls. Results indicated that near perfect interrater reliability was achieved, whereas intermethod reliability was only within the moderate range. The latter was significantly improved via a weighted combination of the anterior and posterior cingulate nodes of the DMN. Implications for fully automating the component selection process are discussed.

One of the most consistent electrophysiological deficits reported in the schizophrenia literature is the failure to inhibit, or properly gate, the neuronal response to the second stimulus of an identical pair (i.e., sensory gating). Although animal and invasive human studies have consistently implicated the auditory cortex, prefrontal cortex and hippocampus in mediating the sensory gating response, localized activation in these structures has not always been reported during non-invasive imaging modalities. In the current experiment, event-related FMRI and a variant of the traditional gating paradigm were utilized to examine how the gating network differentially responded to the processing of pairs of identical and non-identical tones. Two single-tone conditions were also presented so that they could be used to estimate the HRF for paired stimuli, reconstructed based on actual hemodynamic responses, to serve as a control non-gating condition. Results supported an emerging theory that the gating response for both paired-tone conditions was primarily mediated by auditory and prefrontal cortex, with potential contributions from the thalamus. Results also indicated that the left auditory cortex may play a preferential role in determining the stimuli that should be inhibited (gated) or receive further processing due to novelty of information. In contrast, there was no evidence of hippocampal involvement, suggesting that future work is needed to determine what role it may play in the gating response.

Contains fulltext : 167121.pdf (Publisher’s version ) (Open Access) Brainhack events offer a novel workshop format with participant-generated content that caters to the rapidly growing open neuroscience community. Including components from hackathons and unconferences, as well as parallel educational sessions, Brainhack fosters novel collaborations around the interests of its attendees. Here we provide an overview of its structure, past events, and example projects. Additionally, we outline current innovations such as regional events and post-conference publications. Through introducing Brainhack to the wider neuroscience community, we hope to provide a unique conference format that promotes the features of collaborative, open science.

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.To evaluate changes in functional connectivity patterns of the default mode network (DMN) in children with ADHD following long-term treatment with MPH.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).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).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.

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults.

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.

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.

Diffusion tensor imaging (DTI) has been used to evaluate white matter (WM) integrity in major depressive disorder (MDD), with several studies reporting differences between depressed patients and controls. However, these findings are variable and taken from relatively small studies often using suboptimal analytic approaches. The presented DTI study examined WM integrity in large samples of medication-free MDD patients (n=134) and healthy controls (n=54) using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) approaches, and rigorous statistical thresholds. Compared with health control subjects, MDD patients show no significant differences in fractional anisotropy, radial diffusivity, mean diffusivity, and axonal diffusivity with either the VBM or the TBSS approach. Our findings suggest that disrupted WM integrity does not have a major role in the neurobiology of MDD in this relatively large study using optimal imaging acquisition and analysis; however, this does not eliminate the possibility that certain patient subgroups show WM disruption associated with depression.

The search for an Alzheimer's disease (AD) biomarker is one of the most relevant contemporary research topics due to the high prevalence and social costs of the disease. Functional connectivity (FC) of the default mode network (DMN) is a plausible candidate for such a biomarker. We evaluated 22 patients with mild AD and 26 age- and gender-matched healthy controls. All subjects underwent resting functional magnetic resonance imaging (fMRI) in a 3.0 T scanner. To identify the DMN, seed-based FC of the posterior cingulate was calculated. We also measured the sensitivity/specificity of the method, and verified a correlation with cognitive performance. We found a significant difference between patients with mild AD and controls in average z-scores: DMN, whole cortical positive (WCP) and absolute values. DMN individual values showed a sensitivity of 77.3% and specificity of 70%. DMN and WCP values were correlated to global cognition and episodic memory performance. We showed that individual measures of DMN connectivity could be considered a promising method to differentiate AD, even at an early phase, from normal aging. Further studies with larger numbers of participants, as well as validation of normal values, are needed for more definitive conclusions.

Background A reliable and meaningful quantitative index of success is paramount in the trial of any new treatment. However, existing methods for defining response and remission for treatments tested for psychiatric disorders are limited in that they often minimize the variance in change over time among individual patients and generally use arbitrarily chosen levels of functioning at specified times during treatment. Purpose To suggest and determine the properties of an alternative measure of treatment success, the Illness Density Index (IDI), that may be more sensitive to fluctuations in symptoms over the course of treatment compared to existing measures. Methods We examined data from 64 depressed patients with multiple assessments of the Hamilton Depression Rating Scale (HDRS) over 12 weeks of randomized treatment in order to compare and contrast varying numerical definitions of response and remission, including percent change and linear slope over time. Results Examination of the indices comparing the within-sample rank of individual patients revealed that these indices agree in cases where patients have little or no response as well as clear and sustained response, while they differ in patients who have a slow (or late) response as well as relapse during the treatment course. Limitations The measure may not be useful for all types of studies, especially short-term treatment trials. Conclusions The IDI is highly correlated with both categorical (e.g., remission) and continuous (e.g., percent change) definitions of treatment success. Furthermore, it differentiates certain trajectories of change that current definitions do not. Thus, the proposed index may be a valuable addition to current measures of efficacy, especially when trying to identify biological substrates of illness or predictors of long-term outcome.

Changes in the default mode network (DMN) have been linked to multiple neurological disorders including schizophrenia. The anticorrelated relationship the DMN shares with task-related networks permits the quantification of this network both during task (task-induced deactivations: TID) and during periods of passive mental activity (extended rest). However, the effects of different methodologies (TID vs. extended rest) for quantifying the DMN in the same clinical population are currently not well understood. Moreover, several different analytic techniques, including independent component analyses (ICA) and seed-based correlation analyses exist for examining functional connectivity during extended resting states. The current study compared both methodologies and analytic techniques in a group of patients with schizophrenia (SP) and matched healthy controls (HC). Results indicated that TID analyses, ICA, and seed-based correlation all consistently identified the midline (anterior and posterior cingulate gyrus) and lateral parietal cortex as core regions of the DMN, as well as more variable involvement of temporal lobe structures. In addition, SP exhibited increased deactivation during task, as well as decreased functional connectivity with frontal regions and increased connectivity with posterior and subcortical areas during periods of extended rest. The increased posterior and reduced anterior connectivity may partially explain some of the cognitive dysfunction and clinical symptoms that are frequently associated with schizophrenia.

Selective attention produces enhanced activity (attention-related modulations [ARMs]) in cortical regions corresponding to the attended modality and suppressed activity in cortical regions corresponding to the ignored modality. However, effects of behavioral context (e.g., temporal vs. spatial tasks) and basic stimulus properties (i.e., stimulus frequency) on ARMs are not fully understood. The current study used functional magnetic resonance imaging to investigate selectively attending and responding to either a visual or auditory metronome in the presence of asynchronous cross-modal distractors of 3 different frequencies (0.5, 1, and 2 Hz). Attending to auditory information while ignoring visual distractors was generally more efficient (i.e., required coordination of a smaller network) and less effortful (i.e., decreased interference and presence of ARMs) than attending to visual information while ignoring auditory distractors. However, these effects were modulated by stimulus frequency, as attempting to ignore auditory information resulted in the obligatory recruitment of auditory cortical areas during infrequent (0.5 Hz) stimulation. Robust ARMs were observed in both visual and auditory cortical areas at higher frequencies (2 Hz), indicating that participants effectively allocated attention to more rapidly presented targets. In summary, results provide neuroanatomical correlates for the dominance of the auditory modality in behavioral contexts that are highly dependent on temporal processing.

Sounds provide important information about the spatial environment, including the location of approaching objects. Attention to sounds can be directed through automatic or more controlled processes, which have been well studied in the visual modality. However, little is known about the neural underpinnings of attentional control mechanisms for auditory signals. We studied healthy adults who underwent event‐related FMRI while performing a task that manipulated automatic and more controlled auditory orienting by varying the probability that cues correctly predicted target location. Specifically, we examined the effects of uninformative (50% validity ratio) and informative (75% validity ratio) auditory cues on reaction time (RT) and neuronal functioning. The stimulus‐onset asynchrony (SOA) between the cue and the target was either 100 or 800 ms. At the 100 ms SOA, RT was faster for valid than invalid trials for both cue types, and frontoparietal activation was greater for invalid than valid trials. At the 800 ms SOA, RT and functional activation depended on whether cues were informative or uninformative, and whether cues correctly or incorrectly predicted the target location. Contrary to our prediction, activation in a frontoparietal network was greater for uninformative than informative cues across several different comparisons and at both SOAs. This finding contrasts with similar research of visual orienting, and suggests that the auditory modality may be more biased toward automatic shifts of attention following uninformative cues. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.

Differing degrees of head motion have long been recognized as a potential confound in functional neuroimaging studies comparing neuropsychiatric populations to healthy normal volunteers, and studies often cite excessive head motion as a possible reason for the different patterns of functional activation frequently observed between groups. We empirically tested the degree of head motion in 16 patients with chronic schizophrenia and 16, age- and education-matched controls during the acquisition of functional magnetic resonance imaging data. We examined the degree of motion across three different indices (total motion, relative motion, task-correlated motion) during a complex attentional task and the effect of entering the motion parameters as additional regressors in a general linear model analysis. Results indicate that individuals with schizophrenia did not exhibit more task-correlated or total motion compared with controls. Moreover, the residual error term from the general linear model analysis was similar for both groups of subjects. In conclusion, current results suggest that stable patients with schizophrenia are capable of controlling head motion compared with matched normal controls. However, a direct comparison of the motion parameters is an essential step for any quality assurance protocol to determine whether additional corrective techniques need to be implemented. (JINS, 2007, 13, 839–845.)

Importance Currently, fewer than 40% of patients treated for major depressive disorder achieve remission with initial treatment. Identification of a biological marker that might improve these odds could have significant health and economic impact. Objective To identify a candidate neuroimaging “treatment-specific biomarker” that predicts differential outcome to either medication or psychotherapy. Design Brain glucose metabolism was measured with positron emission tomography prior to treatment randomization to either escitalopram oxalate or cognitive behavior therapy for 12 weeks. Patients who did not remit on completion of their phase 1 treatment were offered enrollment in phase 2 comprising an additional 12 weeks of treatment with combination escitalopram and cognitive behavior therapy. Setting Mood and anxiety disorders research program at an academic medical center. Participants Men and women aged 18 to 60 years with currently untreated major depressive disorder. Intervention Randomized assignment to 12 weeks of treatment with either escitalopram oxalate (10-20 mg/d) or 16 sessions of manual-based cognitive behavior therapy. Main Outcome and Measure Remission, defined as a 17-item Hamilton Depression Rating Scale score of 7 or less at both weeks 10 and 12, as assessed by raters blinded to treatment. Results Positive and negative predictors of remission were identified with a 2-way analysis of variance treatment (escitalopram or cognitive behavior therapy) × outcome (remission or nonresponse) interaction. Of 65 protocol completers, 38 patients with clear outcomes and usable positron emission tomography scans were included in the primary analysis: 12 remitters to cognitive behavior therapy, 11 remitters to escitalopram, 9 nonresponders to cognitive behavior therapy, and 6 nonresponders to escitalopram. Six limbic and cortical regions were identified, with the right anterior insula showing the most robust discriminant properties across groups (effect size = 1.43). Insula hypometabolism (relative to whole-brain mean) was associated with remission to cognitive behavior therapy and poor response to escitalopram, while insula hypermetabolism was associated with remission to escitalopram and poor response to cognitive behavior therapy. Conclusions and Relevance If verified with prospective testing, the insula metabolism-based treatment-specific biomarker defined in this study provides the first objective marker, to our knowledge, to guide initial treatment selection for depression. Trial Registration Registered at clinicaltrials.gov (NCT00367341)