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Background: Fibromyalgia (FM) is a complex rheumatic disorder characterized by chronic nociplastic pain and central sensitization. Psychopathological conditions can influence FM symptoms, which worsen their condition. However, not all patients with FM have psychopathological disorders, indicating a heterogeneous population., Objective: To investigate the psychopathological profile and personality disorders in patients with FM and its relationship impact on this disease., Methods: An observational and cross-sectional comparative study was conducted with a sample of 90 women, mean age 48.7 years (SD = 8.12), from Hospital del Mar, Barcelona. The Personality Assessment Inventory (PAI) and the Fibromyalgia Impact Questionnaire (FIQ) were used for assessment., Results: FM patients predominantly exhibited psychopathological profiles resembling affective disorders (37.7%) and Cluster C personality disorders (58.8%). The severity of FM's impact was related to affective disorder symptoms, hypervigilance, derealization, somatization, and Cluster B personality disorder (emotional instability). Different rheumatic symptoms correlated with specific psychopathological patterns. Increased somatic symptoms on the FIQ were related to an unstable and dependent personality, while heightened emotional symptoms on the FIQ were associated with avoidance, borderline traits, and passive-aggressive reactions., Conclusion: Recognizing psychopathological aspects is crucial for managing FM. The PAI is a valuable tool for establishing its psychopathological multidimensional profile, which predominantly shows an affective spectrum conditions and comorbid Cluster C personality disorder, exacerbating the disease's impact., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Doreste, Pujol, Penelo, Pérez, Blanco-Hinojo, Martínez-Vilavella, Pardina-Torner, Ojeda, Monfort and Deus.)

Impulsivity is a multidimensional construct linked to a broad spectrum of psychopathological and neuropsychological disorders. The UPPS-P model has emerged as a valuable tool for assessing impulsivity from a multi-dimensional perspective. Despite its relevance, few studies have examined the psychometric properties of the UPPS-P scale scores in a large, representative sample of adolescents. This study aims to evaluate the psychometric properties of the Spanish UPPS-P in adolescents and to establish normative data for this population in Spain. To this end, 9024 students aged 11-19 from 66 different Spanish high schools were included. The fit for the expected 5-factor model, assessed through confirmatory factor analysis, was inadequate (CFI and TLI ≤ .85, RMSEA = .063), but becomes satisfactory when employing the more flexible ESEM approach (CFI and TLI ≥ .94, RMSEA = .038), which was invariant across gender and age. Internal consistency reliability was satisfactory (ω = .83 to .94). Convergent validity with the Barratt Impulsiveness Scale-11-A total score was good ( r = .53 to .60). We provide population norms of the UPPS-P, which may help practitioners to interpret the UPPS-P scores of adolescents from the general population in Spain. Subsequent research should explore implications for both clinical and non-clinical settings.

Neuroimaging research on functional connectivity can provide valuable information on the developmental differentiation of the infant cerebral cortex into its functional areas. We examined healthy neonates to comprehensively map brain functional connectivity using a combination of local measures that uniquely capture the rich spatial structure of cerebral cortex functional connections. Optimal functional MRI scans were obtained in 61 neonates. Local functional connectivity maps were based on Iso-Distance Average Correlation (IDAC) measures. Single distance maps and maps combining three distinct IDAC measures were used to assess different levels of cortical area functional differentiation. A set of brain areas showed higher connectivity than the rest of the brain parenchyma in each local distance map. These areas were consistent with those supporting basic aspects of the neonatal repertoire of adaptive behaviors and included the sensorimotor, auditory and visual cortices, the frontal operculum/anterior insula (relevant for sucking, swallowing and the sense of taste), paracentral lobule (processing anal and urethral sphincter activity), default mode network (relevant for self-awareness), and limbic-emotional structures such as the anterior cingulate cortex, amygdala and hippocampus. However, the results also indicate that brain areas presumed to be actively developing may not necessarily be mature. In fact, combined distance, second-level maps confirmed that the functional differentiation of the cerebral cortex into functional areas in neonates is far from complete. Our results provide a more comprehensive understanding of the developing brain systems, while also highlighting the substantial developmental journey that the neonatal brain must undergo to reach adulthood., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults)., Methods: Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis., Results: Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents., Conclusions: Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.

Introduction: Thyroid hormones play an essential role in hippocampal development, a key structure in psychosis. However, the role of these hormones in first-episode psychosis (FEP) has received limited attention. It has been hypothesized that thyroid hormones could cause morphological modifications in the hippocampal structure through the upregulation of brain-derived neurotrophic factor (BDNF). In this study, we primarily aimed to determine the relationship between thyroid-stimulating hormone (TSH) levels, peripheral BDNF levels, and hippocampal volume in antipsychotic-naïve FEP patients. We also aimed to determine whether TSH levels were associated with clinical symptomatology., Materials and Methods: A total of 50 antipsychotic-naïve FEP patients were included in the study. At baseline, we collected fasting blood samples and registered sociodemographic and clinical variables (substance use, DUP, PANSS, GAF, and CDSS). Structural T1 MRI was performed at baseline to quantify brain volumes. No control group was used for this study., Results: Of the 50 patients, more than one-third (36%) presented alterations in TSH levels, mainly elevated levels (32% of patients). The TSH levels were inversely correlated with both peripheral BDNF and hippocampal volume. On the multivariate analysis, the model that best predicted the relative hippocampal volume was a single variable model (TSH levels). No significant association was observed between TSH levels and clinical symptomatology., Discussion: These results suggest that thyroid hormones could have a neuroprotective effect on the hippocampus in FEP patients, possibly through their effect by increasing BDNF concentrations, which could attenuate brain injury and neuroinflammation. Nevertheless, thyroid hormones could also affect hippocampal volume through other pathways., Competing Interests: The authors declare that this study received funding from Otsuka and Janssen Cilag. The funders had the following involvement in the study: AM and DB have received financial support to attend meetings, travel support, and served as a speaker from Otsuka and Janssen Cilag. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Toll, Blanco-Hinojo, Berge, Manzano, El Abidi, Perez-Solà and Mané.)

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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Circulating white blood cells (leucocytes), which form the peripheral immune system, are crucial in inflammatory processes but their role in brain structural change in schizophrenia has been scarcely studied. With this study we want to determine how and which type of white blood cells are associated with hippocampal volume (as a key structure in schi- zophrenia etiopathology) in first episode psychosis (FEP) patients. Moreover, to determine the association between white blood cells and clinical symptomatology, including positive and negative symptoms, cognition and depression. For this purpose fifty drug-naïve FEP were included in this study. All patients underwent an assessment at baseline and at 1 year follow-up, including sociodemographic and clinical variables (substance use, DUP, PANSS, GAF and CDSS). Fasting blood samples were obtained before administering any medication at baseline. Structural T1 MRI was performed at baseline and brain volumes were quantified. In the present study, higher lymphocyte count was associated with larger right hippocampal volume at baseline in FEP drug-naive patients. Higher lymphocyte count was associated with lower depressive symptomatology measured with CDSS and Marder depressive factor from PANSS at baseline and 1-year follow -up. These results suggest that lymphocytes may have a protective effect in hippocampal volume at baseli- ne in antipsychotic naïve FEP and also, are associated with a better depressive course over follow up. These results open the door to identify new biomarkers and therapeutic targets for patients with schizophrenia., Competing Interests: Declaration of Competing Interest A. Mané and D. Bergé have received financial support to attend meetings, travel support, and served as a speaker from Otsuka and Janssen Cilag. The other authors of this manuscript do not have any conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, p FWE  = 0.037; right: d = -0.104, p FWE  = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, p FWE  = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, p FWE  < 0.001; right: d = -0.158, p FWE  < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, p FWE  = 0.006; right: d = 0.099, p FWE  = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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 (OR adj ) 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.

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022. The Author(s).)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

Introduction: Many drug trials for chronic pain fail because of high placebo response rates in primary endpoints. Neurophysiological measures can help identify pain-linked pathophysiology and treatment mechanisms. They can also help guide early stop/go decisions, particularly if they respond to verum treatment but not placebo. The neurologic pain signature (NPS), an fMRI-based measure that tracks evoked pain in 40 published samples and is insensitive to placebo in healthy adults, provides a potentially useful neurophysiological measure linked to nociceptive pain., Objectives: This study aims to validate the NPS in knee osteoarthritis (OA) patients and test the effects of naproxen on this signature., Methods: In 2 studies (50 patients, 64.6 years, 75% females), we (1) test the NPS and other control signatures related to negative emotion in knee OA pain patients; (2) test the effect of placebo treatments; and (3) test the effect of naproxen, a routinely prescribed nonsteroidal anti-inflammatory drug in OA., Results: The NPS was activated during knee pain in OA ( d = 1.51, P < 0.001) and did not respond to placebo ( d = 0.12, P = 0.23). A single dose of naproxen reduced NPS responses (vs placebo, NPS d = 0.34, P = 0.03 and pronociceptive NPS component d = 0.38, P = 0.02). Naproxen effects were specific for the NPS and did not appear in other control signatures., Conclusion: This study provides preliminary evidence that fMRI-based measures, validated for nociceptive pain, respond to acute OA pain, do not appear sensitive to placebo, and are mild-to-moderately sensitive to naproxen., Competing Interests: The authors have no conflicts of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

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., Competing Interests: Declaration of Competing Interest The authors report no financial interests or potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Despite a large body of schizophrenia research, we still have no reliable predictors to guide treatment from illness onset. The present study aimed to identify baseline clinical or neurobiological factors - including peripheral brain-derived neurotrophic factor (BDNF) levels and amygdala or hippocampal relative volumes - that could predict negative symptomatology and persistent negative symptoms in first-episode psychosis after 1 year of follow-up., Methods: We recruited 50 drug-naive patients with first-episode psychosis and 50 age- and sex-matched healthy controls to study brain volumes. We performed univariate and multiple and logistic regression analyses to determine the association between baseline clinical and neurobiological variables, score on the PANSS negative subscale and persistent negative symptoms after 1 year of follow-up., Results: Low baseline serum BDNF levels ( p = 0.011), decreased left amygdala relative volume ( p = 0.001) and more severe negative symptomatology ( p = 0.021) predicted the severity of negative symptoms at 1 year, as measured by the PANSS negative subscale. Low baseline serum BDNF levels ( p = 0.012) and decreased left amygdala relative volume ( p = 0.010) predicted persistent negative symptoms at 1 year., Limitations: We were unable to assess negative symptoms and their dimensions with next-generation scales, which were not available when the study was initiated., Conclusion: This study shows that a set of variables at baseline, including low BDNF levels, smaller left amygdala relative volume and score on the PANSS negative subscale are significant predictors of outcomes in first-episode psychosis. These findings might offer an initial step for tailoring treatments in first-episode psychosis., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Hyperphagia is one of the main problems of patients with Prader-Willi syndrome (PWS) to cope with everyday life. The underlying mechanisms are not yet well understood. Gut-brain hormones are an interrelated network that may be at least partially involved. We aimed to study the hormonal profile of PWS patients in comparison with obese and healthy controls. Thirty adult PWS patients (15 men; age 27.5 ± 8.02 years; BMI 32.4 ± 8.14 kg/m 2 ), 30 obese and 30 healthy controls were studied before and after eating a hypercaloric liquid diet. Plasma brain-derived neurotrophic factor (BDNF), leptin, total and active ghrelin, peptide YY (PYY), pancreatic polypeptide (PP), Glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and amylin were determined at times 0', 30', 60' and 120'. Cluster analysis was used. When considering all peptides together, two clusters were established according to fasting hormonal standardized concentrations. Cluster 1 encompassed most of obese (25/30) and healthy controls (28/30). By contrast, the majority of patients with PWS were located in Cluster 2 (23/27) and presented a similar fasting profile with hyperghrelinemia, high levels of leptin, PYY, GIP and GLP-1, compared to Cluster 1; that may reflect a dysfunction of these hunger/satiety hormones. When peptide behavior over the time was considered, PP concentrations were not sustained postprandially from 60 min onwards in Cluster 2. BDNF and amylin did not help to differentiate the two clusters. Thus, cluster analysis could be a good tool to distinguish and characterize the differences in hormone responses between PWS and obese or healthy controls.

Objective: To explore motor praxis in adults with Prader-Willi syndrome (PWS) in comparison with a control group of people with intellectual disability (ID) and to examine the relationship with brain structural measurements., Method: Thirty adult participants with PWS and 132 with ID of nongenetic etiology (matched by age, sex, and ID level) were assessed using a comprehensive evaluation of the praxis function, which included pantomime of tool use, imitation of meaningful and meaningless gestures, motor sequencing, and constructional praxis., Results: Results support specific praxis difficulties in PWS, with worse performance in the imitation of motor actions and better performance in constructional praxis than ID peers. Compared with both control groups, PWS showed increased gray matter volume in sensorimotor and subcortical regions. However, we found no obvious association between these alterations and praxis performance. Instead, praxis scores correlated with regional volume measures in distributed apparently normal brain areas., Conclusions: Our findings are consistent in showing significant impairment in gesture imitation abilities in PWS and, otherwise, further indicate that the visuospatial praxis domain is relatively preserved. Praxis disability in PWS was not associated with a specific, focal alteration of brain anatomy. Altered imitation gestures could, therefore, be a consequence of widespread brain dysfunction. However, the specific contribution of key brain structures (e.g., areas containing mirror neurons) should be more finely tested in future research.

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., Competing Interests: Declaration of Competing Interest The authors report no financial interests or potential conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

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., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

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.

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.

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., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)