Functional neuroanatomy of mania

Funding Information: GC is supported by Fundação para a Ciência e Tecnologia (FCT) through a PhD Scholarship (SFRH/BD/130210/2017). AJO-M is supported by grant FCT-PTDC/MEC-PSQ/ 30302/2017-IC&DT-LISBOA-01-0145-FEDER, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020—Programa Operacional Regional de Lisboa, and the BOUNCE (grant agreement number 777167) and FAITH (grant agreement number 875358) projects, funded by the European Union’s Horizon 2020 research and innovation programme. GC and AJO-M are supported by grant FCT-PTDC/MED-NEU/31331/2017, funded by FCT/MCTES. Funding Information: AJO-M was national coordinator for Portugal of a non-interventional study (EDMS-ERI-143085581, 4.0) to characterize a Treatment-Resistant Depression Cohort in Europe, sponsored by Janssen-Cilag, Ltd (2019-2020), is recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and is national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36 and 2020-001348-25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33). None of the aforementioned agencies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. Publisher Copyright: © 2022, The Author(s).Mania, the diagnostic hallmark of bipolar disorder, is an episodic disturbance of mood, sleep, behavior, and perception. Improved understanding of the neurobiology of mania is expected to allow for novel avenues to address current challenges in its diagnosis and treatment. Previous research focusing on the impairment of functional neuronal circuits and brain networks has resulted in heterogenous findings, possibly due to a focus on bipolar disorder and its several phases, rather than on the unique context of mania. Here we present a comprehensive overview of the evidence regarding the functional neuroanatomy of mania. Our interpretation of the best available evidence is consistent with a convergent model of lateralized circuit dysfunction in mania, with hypoactivity of the ventral prefrontal cortex in the right hemisphere, and hyperactivity of the amygdala, basal ganglia, and anterior cingulate cortex in the left hemisphere of the brain. Clarification of dysfunctional neuroanatomic substrates of mania may contribute not only to improve understanding of the neurobiology of bipolar disorder overall, but also highlights potential avenues for new circuit-based therapeutic approaches in the treatment of mania.publishersversionpublishe

Sweet taste and obesity

Oliveira-Maia was supported by grants from the BIAL Foundation (176/10), and from Fundaçao ˜ para a Ciencia e Tecnologia (FCT) through a Junior Research and Career Development Award from the Harvard Medical School Portugal Program (HMSP/ICJ/0020/2011) and grant PTDC/MED-NEU/31331/2017; and is funded by a Starting Grant from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 950357). Ribeiro was funded by doctoral fellowships from Universidade de Lisboa (BD/2015Call) and FCT (SFRH/BD/128783/2017).For more than 50 years, there has been evidence for greater consumption of sweet- foods in overweight humans and animals, relative to those that have a normal weight. Furthermore, it has long been suggested that energy deficit resulting from dieting, while moving the individual from a higher weight set point, would result in heightened susceptibility to palatable tastants, namely to sweet tastants. This was the motivation behind the first studies comparing sweet taste perception between individuals with obesity and those of a normal weight. These studies, using direct measures of taste, have been characterized by significant methodological heterogeneity, contributing towards variability in results and conclusions. Nevertheless, some of these findings have been used to support the theory that patients with obesity have decreased taste perception, particularly for sweet tastants. A similar hypothesis has been proposed regarding evidence for reduced brain dopamine receptors in obesity and, in both cases, it is proposed that increased food consumption, and associated weight gain, result from the need to increase sensory and brain stimulation. However, the available literature is not conclusive on the association between obesity and reduced sweet taste perception, with both negative and contradictory findings in comparisons between individuals with obesity and normal weight control subjects, as well as within-subject comparisons before and after bariatric surgery. Nevertheless, following either Roux-en-Y gastric bypass or sleeve gastrectomy, there is evidence of changes in taste perception, particularly for reward-related measures of sweet tastants, that should be further tested and confirmed in large samples, using consensual methodology.publishersversionpublishe

The Insular Cortex Controls Food Preferences Independently of Taste Receptor Signaling

The insular cortex (IC) contains the primary sensory cortex for oral chemosensation including gustation, and its integrity is required for appropriate control of feeding behavior. However, it remains unknown whether the role of this brain area in food selection relies on the presence of peripheral taste input. Using multielectrode recordings, we found that the responses of populations of neurons in the IC of freely licking, sweet-blind Trpm5−/− mice are modulated by the rewarding postingestive effects of sucrose. FOS immunoreactivity analyses revealed that these responses are restricted to the dorsal insula. Furthermore, bilateral lesions in this area abolished taste-independent preferences for sucrose that can be conditioned in these Trpm5−/− animals while preserving their ability to detect sucrose. Overall, these findings demonstrate that, even in the absence of peripheral taste input, IC regulates food choices based on postingestive signals

a systematic review and meta-analysis

OKThere is significant evidence linking a 'reward deficiency syndrome' (RDS), comprising decreased availability of striatal dopamine D2-like receptors (DD2lR) and addiction-like behaviors underlying substance use disorders and obesity. Regarding obesity, a systematic review of the literature with a meta-analysis of such data is lacking. Following a systematic review of the literature, we performed random-effects meta-analyses to determine group differences in case-control studies comparing DD2lR between individuals with obesity and non-obese controls and prospective studies of pre- to post-bariatric surgery DD2lR changes. Cohen's d was used to measure effect size. Additionally, we explored factors potentially associated with group differences in DD2lR availability, such as obesity severity, using univariate meta-regression. In a meta-analysis including positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies, striatal DD2lR availability did not significantly differ between obesity and controls. However, in studies comprising patients with class III obesity or higher, group differences were significant, favoring lower DD2lR availability in the obesity group. This effect of obesity severity was corroborated by meta-regressions showing inverse associations between the body mass index (BMI) of the obesity group and DD2lR availability. Post-bariatric changes in DD2lR availability were not found, although a limited number of studies were included in this meta-analysis. These results support lower DD2lR in higher classes of obesity which is a more targeted population to explore unanswered questions regarding the RDS.publishersversionpublishe

Motor cortical inhibitory deficits in patients with obsessive-compulsive disorder–A systematic review and meta-analysis of transcranial magnetic stimulation literature

Funding Information: DR was supported by H2020-SC1-DTH-2019-875358-FAITH. AM and GC are supported by Fundação para a Ciência e Tecnologia (FCT) through Ph.D. Scholarships (respectively, SFRH/BD/144508/2019 and SFRH/BD/130210/2017). GC and AO-M are supported by grant FCT-PTDC/MED-NEU/31331/2017, funded by FCT/MCTES. AO-M was funded by a Starting Grant from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 950357). JB-C and AO-M were supported by grant FCT-PTDC/MEC-PSQ/30302/2017-IC&DT-LISBOA-01-0145-FEDER, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020–Programa Operacional Regional de Lisboa. JO was supported by BBRF-27595-2018 NARSAD. None of the agencies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. Publisher Copyright: Copyright © 2022 Rodrigues da Silva, Maia, Cotovio, Oliveira, Oliveira-Maia and Barahona-Corrêa.Introduction: Obsessive-compulsive disorder (OCD) is a highly prevalent chronic disorder, often refractory to treatment. While remaining elusive, a full understanding of the pathophysiology of OCD is crucial to optimize treatment. Transcranial magnetic stimulation (TMS) is a non-invasive technique that, paired with other neurophysiological techniques, such as electromyography, allows for in vivo assessment of human corticospinal neurophysiology. It has been used in clinical populations, including comparisons of patients with OCD and control volunteers. Results are often contradictory, and it is unclear if such measures change after treatment. Here we summarize research comparing corticospinal excitability between patients with OCD and control volunteers, and explore the effects of treatment with repetitive TMS (rTMS) on these excitability measures. Methods: We conducted a systematic review and meta-analysis of case-control studies comparing various motor cortical excitability measures in patients with OCD and control volunteers. Whenever possible, we meta-analyzed motor cortical excitability changes after rTMS treatment. Results: From 1,282 articles, 17 reporting motor cortex excitability measures were included in quantitative analyses. Meta-analysis regarding cortical silent period shows inhibitory deficits in patients with OCD, when compared to control volunteers. We found no statistically significant differences in the remaining meta-analyses, and no evidence, in patients with OCD, of pre- to post-rTMS changes in resting motor threshold, the only excitability measure for which longitudinal data were reported. Discussion: Our work suggests an inhibitory deficit of motor cortex excitability in patients with OCD when compared to control volunteers. Cortical silent period is believed to reflect activity of GABAB receptors, which is in line with neuroimaging research, showing GABAergic deficits in patients with OCD. Regardless of its effect on OCD symptoms, rTMS apparently does not modify Resting Motor Threshold, possibly because this measure reflects glutamatergic synaptic transmission, while rTMS is believed to mainly influence GABAergic function. Our meta-analyses are limited by the small number of studies included, and their methodological heterogeneity. Nonetheless, cortical silent period is a reliable and easily implementable measurement to assess neurophysiology in humans, in vivo. The present review illustrates the importance of pursuing the study of OCD pathophysiology using cortical silent period and other easily accessible, non-invasive measures of cortical excitability. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201764], identifier [CRD42020201764].publishersversionpublishe

Future Perspectives From a Case Report of Transcranial Magnetic Stimulation, Cognitive Behavioral Therapy, and Psychopharmacological Treatment for Post-traumatic Stress Disorder

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Repetitive Transcranial Magnetic Stimulation for Treatment of Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD.Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed.Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time.Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD

Relato de um caso clínico

Neuroleptic malignant syndrome is a neurological emergency caused by dysregulation of dopaminergic neurotransmission. While it is typically characterized by muscle rigidity, fever and altered mental status, it may have a heterogeneous and non-specific presentation, leading to delays in diagnosis and treatment. Treatment involves cessation of dopamine-receptor antagonists and supportive measures, but in more severe cases, bromocriptine, dantrolene, benzodiazepines and/or electroconvulsive therapy should be considered. We present the case of a 66-year-old man with severe neuroleptic malignant syndrome, diagnosed due to need for continuous invasive ventilation in an Intensive Care Unit, after successful treatment for respiratory sepsis. The patient recovered after electroconvulsive therapy and administration of bromocriptine. This unusually severe case illustrates the need for a high level of suspicion for neuroleptic malignant syndrome in critically ill patients with malignant catatonic syndromes, allowing for an early diagnosis and potentially lifesaving treatment.publishersversionpublishe