Mapping alterations in the local synchrony of the cerebral cortex in schizophrenia.

BACKGROUND: Observations from different fields of research coincide in indicating that a defective gamma-aminobutyric acid (GABA) interneuron system may be among the primary factors accounting for the varied clinical expression of schizophrenia. GABA interneuron deficiency is locally expressed in the form of neural activity desynchronization. We mapped the functional anatomy of local synchrony in the cerebral cortex in schizophrenia using functional connectivity MRI. METHODS: Data from 86 patients with schizophrenia and 137 control subjects were obtained from publicly available repositories. Resting-state functional connectivity maps based on Iso-Distant Average Correlation measures across three distances were estimated detailing the local functional structure of the cerebral cortex. RESULTS: Patients with schizophrenia showed weaker local functional connectivity (i.e., lower MRI signal synchrony) in (i) prefrontal lobe areas, (ii) somatosensory, auditory, visual, and motor cortices, (iii) paralimbic system at the anterior insula and anterior cingulate cortex, and (iv) hippocampus. The distribution of the defect in cortical area synchrony largely coincided with the synchronization effect of the GABA agonist alprazolam previously observed using identical functional connectivity measures. There was also a notable resemblance between the anatomy of our findings and cortical areas showing higher density of parvalbumin (prefrontal lobe and sensory cortices) and somatostatin (anterior insula and anterior cingulate cortex) GABA interneurons in humans. CONCLUSIONS: Our results thus provide detail of the functional anatomy of synchrony changes in the cerebral cortex in schizophrenia and suggest which elements of the interneuron system are affected. Such information could ultimately be relevant in the search for specific treatments.

Central Sensitization and Chronic Pain Personality Profile: Is There New Evidence? A Case-Control Study.

BACKGROUND: Personality traits are relevant for pain perception in persistent pain disorders, although they have not been studied in depth in sensitized and nonsensitized patients with knee osteoarthritis (OA). OBJECTIVE: To explain and compare the personality profile of patients with OA, with and without central sensitization (CS), and fibromyalgia (FM). SETTING: Participants were selected at the Rheumatology Department in two major hospitals in Spain. PARTICIPANTS: Case-control study where the sample consists of 15 patients with OA and CS (OA-CS), 31 OA without CS (OA-noCS), 47 FM, and 22 controls. We used a rigorous and systematic process that ensured the sample strictly fulfilled all the inclusion/exclusion criteria, so the sample is very well delimited. PRIMARY OUTCOME MEASURES: Personality was assessed by the Temperament and Character Inventory of Cloninger. RESULTS: The percentile in harm-avoidance dimension for the FM group is higher compared to OA groups and controls. The most frequent temperamental profiles in patients are cautious, methodical, and explosive. Patients with FM are more likely to report larger scores in harm-avoidance, with an increase in logistic regression adjusted odds ratio (ORadj) between 4.2% and 70.2%. CONCLUSIONS: Harm-avoidance seems to be the most important dimension in personality patients with chronic pain, as previously found. We found no differences between OA groups and between sensitized groups, but there are differences between FM and OA-noCS, so harm-avoidance might be the key to describe personality in patients with CS rather than the presence of prolonged pain, as found in the literature before.

The effects of exposure to road traffic noise at school on central auditory pathway functional connectivity.

As the world becomes more urbanized, more people become exposed to traffic and the risks associated with a higher exposure to road traffic noise increase. Excessive exposure to environmental noise could potentially interfere with functional maturation of the auditory brain in developing individuals. The aim of the present study was to assess the association between exposure to annual average road traffic noise (LAeq) in schools and functional connectivity of key elements of the central auditory pathway in schoolchildren. A total of 229 children from 34 representative schools in the city of Barcelona with ages between 8 and 12 years (49.2% girls) were evaluated. LAeq was obtained as the mean of 2-consecutive day measurements inside classrooms before lessons started following standard procedures to obtain an indicator of long-term road traffic noise levels. A region-of-interest functional connectivity Magnetic Resonance Imaging (MRI) approach was adopted. Functional connectivity maps were generated for the inferior colliculus, medial geniculate body of the thalamus and primary auditory cortex as key levels of the central auditory pathway. Road traffic noise in schools was significantly associated with stronger connectivity between the inferior colliculus and a bilateral thalamic region adjacent to the medial geniculate body, and with stronger connectivity between the medial geniculate body and a bilateral brainstem region adjacent to the inferior colliculus. Such a functional connectivity strengthening effect did not extend to the cerebral cortex. The anatomy of the association implicating subcortical relays suggests that prolonged road traffic noise exposure in developing individuals may accelerate maturation in the basic elements of the auditory pathway. Future research is warranted to establish whether such a faster maturation in early pathway levels may ultimately reduce the developing potential in the whole auditory system.

Effects of remifentanil on brain responses to noxious stimuli during deep propofol sedation.

BACKGROUND: The safety of anaesthesia has improved as a result of better control of anaesthetic depth. However, conventional monitoring does not inform on the nature of nociceptive processes during unconsciousness. A means of inferring the quality of potentially painful experiences could derive from analysis of brain activity using neuroimaging. We have evaluated the dose effects of remifentanil on brain response to noxious stimuli during deep sedation and spontaneous breathing. METHODS: Optimal data were obtained in 26 healthy subjects. Pressure stimulation that proved to be moderately painful before the experiment was applied to the thumbnail. Functional MRI was acquired in 4-min periods at low (0.5 ng ml-1), medium (1 ng ml-1), and high (1.5 ng ml-1) target plasma concentrations of remifentanil at a stable background infusion of propofol adjusted to induce a state of light unconsciousness. RESULTS: At low remifentanil doses, we observed partial activation in brain areas processing sensory-discriminative and emotional-affective aspects of pain. At medium doses, relevant changes were identified in structures highly sensitive to general brain arousal, including the brainstem, cerebellum, thalamus, auditory and visual cortices, and the frontal lobe. At high doses, no significant activation was observed. CONCLUSIONS: The response to moderately intense focal pressure in pain-related brain networks is effectively eliminated with safe remifentanil doses. However, the safety margin in deep sedation-analgesia would be narrowed in minimising not only nociceptive responses, but also arousal-related biological stress.

Neurogenetics of Dynamic Connectivity Patterns Associated With Obsessive-Compulsive Symptoms in Healthy Children.

Background: Obsessive-compulsive symptoms (OCSs) during childhood predispose to obsessive-compulsive disorder and have been associated with changes in brain circuits altered in obsessive-compulsive disorder samples. OCSs may arise from disturbed glutamatergic neurotransmission, impairing cognitive oscillations and promoting overstable functional states. Methods: A total of 227 healthy children completed the Obsessive Compulsive Inventory-Child Version and underwent a resting-state functional magnetic resonance imaging examination. Genome-wide data were obtained from 149 of them. We used a graph theory-based approach and characterized associations between OCSs and dynamic functional connectivity (dFC). dFC evaluates fluctuations over time in FC between brain regions, which allows characterizing regions with stable connectivity patterns (attractors). We then compared the spatial similarity between OCS-dFC correlation maps and mappings of genetic expression across brain regions to identify genes potentially associated with connectivity changes. In post hoc analyses, we investigated which specific single nucleotide polymorphisms of these genes moderated the association between OCSs and patterns of dFC. Results: OCSs correlated with decreased attractor properties in the left ventral putamen and increased attractor properties in (pre)motor areas and the left hippocampus. At the specific symptom level, increased attractor properties in the right superior parietal cortex correlated with ordering symptoms. In the hippocampus, we identified two single nucleotide polymorphisms in glutamatergic neurotransmission genes (GRM7, GNAQ) that moderated the association between OCSs and attractor features. Conclusions: We provide evidence that in healthy children, the association between dFC changes and OCSs may be mapped onto brain circuits predicted by prevailing neurobiological models of obsessive-compulsive disorder. Moreover, our findings support the involvement of glutamatergic neurotransmission in such brain network changes.

Distinctive alterations in the functional anatomy of the cerebral cortex in pain-sensitized osteoarthritis and fibromyalgia patients.

BACKGROUND: Pain-sensitized osteoarthritis and fibromyalgia patients characteristically show nociceptive system augmented responsiveness as a common feature. However, sensitization can be originally related to the peripheral injury in osteoarthritis patients, whereas pain and bodily discomfort spontaneously occur in fibromyalgia with no apparent origin. We investigated the distinct functional repercussion of pain sensitization in the cerebral cortex in both conditions. METHODS: Thirty-one pain-sensitized knee osteoarthritis patients and 38 fibromyalgia patients were compared with matched control groups. And new samples of 34 sensitized knee osteoarthritis and 63 fibromyalgia patients were used to directly compare each condition. A combined measure of local functional connectivity was estimated to map functional alterations in the cerebral cortex at rest. RESULTS: In osteoarthritis, weaker local connectivity was identified in the insula, which is a cortical area processing important aspects of the brain response to painful stimulation. In contrast, fibromyalgia patients showed weaker connectivity in the sensorimotor cortex extensively affecting the cortical representation of the body. CONCLUSIONS: In osteoarthritis, weaker insular cortex connectivity is compatible with reduced neural activity during metabolic recovery after repeated activation. In the fibromyalgia neurophysiological context, weaker connectivity may better express both reduced neural activity and increased excitability, particularly affecting the sensorimotor cortex in patients with spontaneous body pain. Such a combination is compatible with a central gain enhancement mechanism, where low sensory tolerance results from the over-amplification of central sensory reception to compensate a presumably weak sensory input. We propose that deficient proprioception could be a factor contributing to weak sensory input.

One Year of Recombinant Human Growth Hormone Treatment in Adults with Prader-Willi Syndrome Improves Body Composition, Motor Skills and Brain Functional Activity in the Cerebellum.

We compared body composition, biochemical parameters, motor function, and brain neural activation in 27 adults with Prader-Willi syndrome and growth-hormone deficiency versus age-and sex-matched controls and baseline versus posttreatment values of these parameters after one year of recombinant human growth hormone (rhGH) treatment. To study body composition, we analyzed percentage of fat mass, percentage of lean mass, and muscle-mass surrogate variables from dual X-ray absorptiometry. Biochemical parameters analyzed included IGF-I, glucose metabolism, and myokines (myostatin, irisin, and IL6). To explore muscle function, we used dynamometer-measured handgrip strength, the Timed Up and Go (TUG) test, and the Berg Balance Scale (BBS). To study brain activation, we acquired functional magnetic resonance images during three motor tasks of varying complexity. After one year of treatment, we observed an increase in lean mass and its surrogates, a decrease in fat mass, improvements in TUG test and BBS scores, and increased neural activation in certain cerebellar areas. The treatment did not significantly worsen glucose metabolism, and no side-effects were reported. Our findings support the benefits of rhGH treatment in adults with Prader-Willi syndrome and growth-hormone deficiency on body composition and suggest that it may also improve balance and brain neural activation.

Tapentadol effects on brain response to pain in sensitized patients with knee osteoarthritis.

OBJECTIVE: Pain sensitization, in the form of knee tenderness and anatomically spread hyperalgesia, is notably common in patients with knee OA and is often refractory to conventional interventions. Tapentadol, as an opioid receptor agonist and noradrenaline reuptake inhibitor, has been proposed as a potentially effective symptomatic treatment for pain-sensitized OA patients. We empirically tested whether tapentadol could attenuate brain response to painful stimulation on the tender knee using functional MRI. METHODS: Painful pressure stimulation was applied to the articular interline and the tibial surface, a commonly sensitized site surrounding the joint. Thirty patients completed the crossover trial designed to compare prolonged release tapentadol and placebo effects administered over 14 days. RESULTS: We found no effects in the direction of the prediction. Instead, patients administered with tapentadol showed stronger activation in response to pressure on the tender site in the right prefrontal cortex and somatosensory cortices. The somatosensory effect was compatible with the spread of neural activation around the knee cortical representation. Consistent with the functional MRI findings, the patients showed higher clinical ratings of pain sensitization under tapentadol and a significant positive association was identified between the number of tapentadol tablets and the evoked subjective pain. CONCLUSION: The tapentadol effect paradoxically involved both the spread of the somatosensory cortex response and a stronger activation in prefrontal areas with a recognized role in the appraisal of pain sensations. Further studies are warranted to explore how OA patients may benefit from powerful analgesic drugs without the associated risks of prolonged use. TRIAL REGISTRATION: EudraCT, https://eudract.ema.europa.eu, 2016-005082-31.

Mapping the neural systems driving breathing at the transition to unconsciousness.

After falling asleep, the brain needs to detach from waking activity and reorganize into a functionally distinct state. A functional MRI (fMRI) study has recently revealed that the transition to unconsciousness induced by propofol involves a global decline of brain activity followed by a transient reduction in cortico-subcortical coupling. We have analyzed the relationships between transitional brain activity and breathing changes as one example of a vital function that needs the brain to readapt. Thirty healthy participants were originally examined. The analysis involved the correlation between breathing and fMRI signal upon loss of consciousness. We proposed that a decrease in ventilation would be coupled to the initial decline in fMRI signal in brain areas relevant for modulating breathing in the awake state, and that the subsequent recovery would be coupled to fMRI signal in structures relevant for controlling breathing during the unconscious state. Results showed that a slight reduction in breathing from wakefulness to unconsciousness was distinctively associated with decreased activity in brain systems underlying different aspects of consciousness including the prefrontal cortex, the default mode network and somatosensory areas. Breathing recovery was distinctively coupled to activity in deep brain structures controlling basic behaviors such as the hypothalamus and amygdala. Activity in the brainstem, cerebellum and hippocampus was associated with breathing variations in both states. Therefore, our brain maps illustrate potential drives to breathe, unique to wakefulness, in the form of brain systems underlying cognitive awareness, self-awareness and sensory awareness, and to unconsciousness involving structures controlling instinctive and homeostatic behaviors.

Cerebellar Dysfunction in Adults with Prader Willi Syndrome.

Severe hypotonia during infancy is a hallmark feature of Prader Willi syndrome (PWS). Despite its transient expression, moto development is delayed and deficiencies in motor coordination are present at older ages, with no clear pathophysiological mechanism yet identified. The diverse motor coordination symptoms present in adult PWS patients could be, in part, the result of a common alteration(s) in basic motor control systems. We aimed to examine the motor system in PWS using functional MRI (fMRI) during motor challenge. Twenty-three adults with PWS and 22 matched healthy subjects participated in the study. fMRI testing involved three hand motor tasks of different complexity. Additional behavioral measurements of motor function were obtained by evaluating hand grip strength, functional mobility, and balance. Whole brain activation maps were compared between groups and correlated with behavioral measurements. Performance of the motor tasks in PWS engaged the neural elements typically involved in motor processing. While our data showed no group differences in the simplest task, increasing task demands evoked significantly weaker activation in patients in the cerebellum. Significant interaction between group and correlation pattern with measures of motor function were also observed. Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced cerebellar activation during movement coordination.

Differences between the child and adult brain in the local functional structure of the cerebral cortex.

Imaging studies on neuronal network formation provide relevant information as to how the brain matures during adolescence. We used a novel imaging approach combining well-established MRI measures of local functional connectivity that jointly provide qualitatively different information relating to the functional structure of the cerebral cortex. To investigate the adolescent transition into adulthood, we comparatively assessed 169 preadolescents aged 8-12 years and 121 healthy adults. Whole-brain functional connectivity maps were generated using multi-distance measures of intracortical neural activity coupling defined within iso-distant local areas. Such Iso-Distant Average Correlation (IDAC) measures therefore represent the average temporal correlation of a given brain unit, or voxel, with other units situated at increasingly separated iso-distant intervals. The results indicated that between-group differences in the functional structure of the cerebral cortex are extensive and implicate part of the lateral prefrontal cortex, a medial frontal/anterior cingulate region, the superior parietal lobe extending to the somatosensory strip and posterior cingulate cortex, and local connections within the visual cortex, hippocampus, amygdala and insula. We thus provided detail of the cerebral cortex functional structure maturation during the transition to adulthood, which may serve to establish more accurate links between adolescent performance gains and cerebral cortex maturation. Remarkably, our study provides new information as to the cortical maturation processes in prefrontal areas relevant to executive functioning and rational learning, medial frontal areas playing an active role in the cognitive appraisal of emotion and anxiety, and superior parietal cortices strongly associated with bodily self-consciousness in the context of body image formation.

Mapping the Synchronization Effect of Gamma-Aminobutyric Acid Inhibition on the Cerebral Cortex Using Magnetic Resonance Imaging.

Background: Functional magnetic resonance imaging (fMRI) of spontaneous brain activity permits the identification of functional networks on the basis of region synchrony. The functional coupling between the elements of a neural system increases during brain activation. However, neural synchronization may also be the effect of inhibitory gamma-aminobutyric acid (GABA) neurons in states of brain inhibition such as sleep or pharmacological sedation. We investigated the effects of an oral dose of alprazolam, a classical benzodiazepine known to enhance inhibitory neurotransmission, using recently developed measures of local functional connectivity. Methods: In a randomized, double-blind, placebo-controlled, crossover design, 32 non-treatment-seeking individuals with social anxiety underwent two identical resting-state fMRI sessions on separate days after receiving 0.75 mg of alprazolam and placebo. Functional connectivity maps of the cerebral cortex were generated by using multidistance functional connectivity measures defined within iso-distant local areas. Results: Relative to placebo, increased intracortical functional connectivity was observed in the alprazolam condition in visual, auditory, and sensorimotor cortices, and in areas of sensory integration such as the posterior insula and orbitofrontal cortex (OFC). Alprazolam significantly reduced subjective arousal compared with placebo, and the change was associated with variations in multidistance functional connectivity measures in the OFC. Discussion: In conclusion, we report evidence that alprazolam significantly modifies neural activity coupling at rest in the form of functional connectivity enhancement within the cerebral cortex. The effect of alprazolam was particularly evident in the cortical sensory system, which would further suggest a differentiated effect of GABA inhibition on sensory processing.

Dysfunctional Brain Reward System in Child Obesity.

Eating habits leading to obesity may reflect nonhomeostatic behavior based on excessive immediate-reward seeking. However, it is currently unknown to what extent excess weight is associated with functional alterations in the brain's reward system in children. We tested the integrity of reward circuits using resting-state functional connectivity magnetic resonance imaging in a population of 230 children aged 8-12 years. The major components of the reward system were identified within the ventral striatum network defined on the basis of the nucleus accumbens connectivity pattern. The functional structure of the cerebral cortex was characterized using a combination of local functional connectivity measures. Higher body mass index was associated with weaker connectivity between the cortical and subcortical elements of the reward system, and enhanced the integration of the sensorimotor cortex to superior parietal areas relevant to body image formation. Obese children, unlike WHO-defined overweight condition, showed functional structure alterations in the orbitofrontal cortex and amygdala region similar to those previously observed in primary obsessive-compulsive disorder and Prader-Willi syndrome associated with obsessive eating behavior. Results further support the view that childhood obesity is not simply a deviant habit with restricted physical health consequences but is associated with reward system dysfunction characterizing behavioral control disorders.

Brain Functional Connectivity Correlates of Subclinical Obsessive-Compulsive Symptoms in Healthy Children.

OBJECTIVE: Commonly observed subclinical obsessive-compulsive symptoms in healthy children may predispose to obsessive-compulsive disorder (OCD). Therefore, investigating the underlying neurobiology may be relevant to identify alterations in specific brain circuits potentially accounting for clinical heterogeneity in OCD without the confounding effects of clinical samples. We analyzed the brain correlates of different obsessive-compulsive symptoms in a large group of healthy children using functional connectivity measures. METHOD: We evaluated 227 healthy children (52% girls; mean [SD] age 9.71 [0.86] years; range, 8-12.1 years). Participants underwent clinical assessment with the Obsessive-Compulsive Inventory-Child Version and a resting-state functional magnetic resonance imaging examination. Total and symptom-specific severity were correlated with voxelwise global functional connectivity degree values. Significant clusters were then used as seeds of interest in seed-to-voxel analyses. Modulating effects of age and sex were also assessed. RESULTS: Global functional connectivity of the left ventral putamen and medial dorsal thalamus correlated negatively with total obsessive-compulsive symptom severity. Seed-to-voxel analyses revealed specific negative correlations from these clusters with limbic, sensorimotor, and insular regions in association with obsessing, ordering, and doubt-checking symptoms, respectively. Hoarding symptoms were associated with negative correlations between the left medial dorsal thalamus and a widespread pattern of regions, with such associations modulated by sex and age. CONCLUSION: Our findings concur with prevailing neurobiological models of OCD on the importance of cortico-striato-thalamo-cortical dysfunction to account for symptom severity. Notably, we showed that changes in cortico-striato-thalamo-cortical connectivity are present at subclinical stages, which may result in an increased vulnerability for OCD. Moreover, we mapped different symptom dimensions onto specific cortico-striato-thalamo-cortical circuit attributes.

Largest scale dissociation of brain activity at propofol-induced loss of consciousness.

The brain is a functional unit made up of multilevel connected elements showing a pattern of synchronized activity that varies in different states. The wake-sleep cycle is a major variation of brain functional condition that is ultimately regulated by subcortical arousal- and sleep-promoting cell groups. We analyzed the evolution of functional MRI (fMRI) signal in the whole cortex and in a deep region including most sleep- and wake-regulating subcortical nuclei at loss of consciousness induced by the hypnotic agent propofol. Optimal data were obtained in 21 of the 30 healthy participants examined. A dynamic analysis of fMRI time courses on a time-scale of seconds was conducted to characterize consciousness transition, and functional connectivity maps were generated to detail the anatomy of structures showing different dynamics. Inside the magnet, loss of consciousness was marked by the participants ceasing to move their hands. We observed activity synchronization after loss of consciousness within both the cerebral cortex and subcortical structures. However, the evolution of fMRI signal was dissociated, showing a transient reduction of global cortico-subcortical coupling that was restored during the unconscious state. An exception to cortico-subcortical decoupling was a brain network related to self-awareness (i.e. the default mode network) that remained connected to subcortical brain structures. Propofol-induced unconsciousness is thus characterized by an initial, transitory dissociated synchronization at the largest scale of brain activity. Such cortico-subcortical decoupling and subsequent recoupling may allow the brain to detach from waking activity and reorganize into a functionally distinct state.

Brain activity during traditional textbook and audiovisual-3D learning.

INTRODUCTION: Audiovisual educational tools have increasingly been used during the past years to complement and compete with traditional textbooks. However, little is known as to how the brain processes didactic information presented in different formats. We directly assessed brain activity during learning using both traditional textbook and audiovisual-3D material. METHODS: A homogeneous sample of 30 young adults with active study habits was assessed. Educational material on the subject of Cardiology was adapted to be presented during the acquisition of functional MRI. RESULTS: When tested after image acquisition, participants obtained similar examination scores for both formats. Evoked brain activity was robust during both traditional textbook and audiovisual-3D lessons, but a greater number of brain systems were implicated in the processing of audiovisual-3D information, consistent with its multisource sensory nature. However, learning was not associated with group mean brain activations, but was instead predicted by distinct functional MRI signal changes in the frontal lobes and showed distinct cognitive correlates. In the audiovisual-3D version, examination scores were positively correlated with late-evoked prefrontal cortex activity and working memory, and negatively correlated with language-related frontal areas and verbal memory. As for the traditional textbook version, the fewer results obtained suggested the opposite pattern, with examination scores negatively correlating with prefrontal cortex activity evoked during the lesson. CONCLUSIONS: Overall, the results indicate that a similar level of knowledge may be achieved via different cognitive strategies. In our experiment, audiovisual learning appeared to benefit from prefrontal executive resources (as opposed to memorizing verbal information) more than traditional textbook learning.

Effects of prenatal exposure to particulate matter air pollution on corpus callosum and behavioral problems in children.

OBJECTIVE: Air pollution (AP) may affect neurodevelopment, but studies about the effects of AP on the growing human brain are still scarce. We aimed to investigate the effects of prenatal exposure to AP on lateral ventricles (LV) and corpus callosum (CC) volumes in children and to determine whether the induced brain changes are associated with behavioral problems. METHODS: Among the children recruited through a set of representative schools of the city of Barcelona, (Spain) in the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) study, 186 typically developing participants aged 8-12 years underwent brain MRI on the same 1.5 T MR unit over a 1.5-year period (October 2012-April 2014). Brain volumes were derived from structural MRI scans using automated tissue segmentation. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) and the criteria of the Attention Deficit Hyperactivity Disorder DSM-IV list. Prenatal fine particle (PM2.5) levels were retrospectively estimated at the mothers' residential addresses during pregnancy with land use regression (LUR) models. To determine whether brain structures might be affected by prenatal PM2.5 exposure, linear regression models were run and adjusted for age, sex, intracranial volume (ICV), maternal education, home socioeconomic vulnerability index, birthweight and mothers' smoking status during pregnancy. To test for associations between brain changes and behavioral outcomes, negative binomial regressions were performed and adjusted for age, sex, ICV. RESULTS: Prenatal PM2.5 levels ranged from 11.8 to 39.5 µg/m3 during the third trimester of pregnancy. An interquartile range increase in PM2.5 level (7 µg/m3) was significantly linked to a decrease in the body CC volume (mm3) (ß = -53.7, 95%CI [-92.0, -15.5] corresponding to a 5% decrease of the mean body CC volume) independently of ICV, age, sex, maternal education, socioeconomic vulnerability index at home, birthweight and mothers' smoking status during the third trimester of pregnancy. A 50 mm3 decrease in the body CC was associated with a significant higher hyperactivity subscore (Rate Ratio (RR) = 1.09, 95%CI [1.01, 1.17) independently of age, sex and ICV. The statistical significance of these results did not survive to False Discovery Rate correction for multiple comparisons. CONCLUSIONS: Prenatal exposure to PM2.5 may be associated with CC volume decrease in children. The consequences might be an increase in behavioral problems.

Testing the effects of gentle vibrotactile stimulation on symptom relief in fibromyalgia.

BACKGROUND: Sensory disturbances in fibromyalgia extend beyond nociception. It has been proposed that imbalance in the mutual competition between painful input and non-painful sensory activity may, to a significant extent, account for the augmented subjective perception of pain. In this context, non-nociceptive somatosensory stimulation could arguably attenuate fibromyalgia symptoms by restoring the sensory balance. We specifically tested the effect of vibrotactile stimulation on symptom relief in fibromyalgia patients with a randomized, double-blind, sham-controlled, crossover clinical trial. METHODS: Seventy-seven female patients were randomized and data from 63 valid cases were analyzed. Active intervention involved extensive body stimulation with gentle mechanical vibrations administered during 3 h at night for 3 weeks, and the placebo effect was controlled using identical instruments to simulate an alternative treatment option. The primary outcome measure combined pain, fatigue, and complaints of poor cognition. RESULTS: Vibrotactile stimulation was significantly superior to sham in alleviating fibromyalgia symptoms globally. However, univariate analyses showed that the effect was not universal. Benefits were perceived on unpleasant somatic sensations such as generalized pain and fatigue, but not on poor cognition, anxiety, and depression. Vibrotactile stimulation was notably well tolerated and sleep quality significantly improved despite the fact that vibrations were administered at night. CONCLUSIONS: Results thus provide new evidence that non-nociceptive somatosensory stimulation may favorably act upon altered somatosensory balance in fibromyalgia. From a clinical perspective, both the degree of improvement and the easy application of our proposal would seem to support a potential role for vibrotactile stimulation in the symptomatic treatment of fibromyalgia. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT03227952 . Registered 24 July, 2017.

Brain Structure and Function in School-Aged Children With Sluggish Cognitive Tempo Symptoms.

OBJECTIVE: Sluggish cognitive tempo (SCT) is a cluster of symptoms associated with poor function in various domains of major life activities that may comprise a novel attention disorder distinct from attention-deficit/hyperactivity disorder (ADHD). Nevertheless, very little is known about the neural substrate of SCT in children. The present study aimed to examine associations between SCT symptoms and brain structure and function in school-aged children. METHOD: We performed a cross-sectional MRI study in 178 children 8 to 12 years old from primary schools in Barcelona, Spain. Data were collected between January 2012 and March 2013. Parents completed the Sluggish Cognitive Tempo-Child Behavior Checklist (SCT-CBCL). Participants underwent magnetic resonance imaging to assess regional brain volume, white matter integrity using diffusion tensor imaging, and functional connectivity in major neural networks. RESULTS: SCT symptoms were associated with altered anatomy of the frontal lobe in the form of increased regional volume. The anomalously large cortical regions were less mature in terms of functional connectivity. Importantly, all the anatomical and functional anomalies identified remained significant after adjusting the analyses for ADHD symptom scores. CONCLUSION: Our results suggest that SCT symptoms are associated with distinct features of brain structure and function that differ from the classical neural substrates described in ADHD.

Mapping Alterations of the Functional Structure of the Cerebral Cortex in Obsessive-Compulsive Disorder.

We mapped alterations of the functional structure of the cerebral cortex using a novel imaging approach in a sample of 160 obsessive-compulsive disorder (OCD) patients. Whole-brain functional connectivity maps were generated using multidistance measures of intracortical neural activity coupling defined within isodistant local areas. OCD patients demonstrated neural activity desynchronization within the orbitofrontal cortex and in primary somatosensory, auditory, visual, gustatory, and olfactory areas. Symptom severity was significantly associated with the degree of functional structure alteration in OCD-relevant brain regions. By means of a novel imaging perspective, we once again identified brain alterations in the orbitofrontal cortex, involving areas purportedly implicated in the pathophysiology of OCD. However, our results also indicated that weaker intracortical activity coupling is also present in each primary sensory area. On the basis of previous neurophysiological studies, such cortical activity desynchronization may best be interpreted as reflecting deficient inhibitory neuron activity and altered sensory filtering.