Heated environment increases blood pressure drop and postural sway during initial orthostasis in healthy subjects.

PURPOSE: We tested the hypothesis that heat stress influences the closed-loop cardio-postural control by an increased blood pressure (BP) drop and postural sway. METHODS: Fourteen healthy individuals (eight women) performed two orthostatic tests under thermal reference (TC; ~ 24 ºC) and HOT (~ 38 ºC) conditions. The center-of-pressure (COP) displacements and the electromyography (EMG) activity of the calf muscles (medial gastrocnemius and tibialis anterior) were recorded during the initial orthostasis (ORT onset) after the supine-to-stand challenge. At the same period, BP (beat-to-beat) was continuously monitored, and supine-to-stand variations (∆%) were calculated. Sublingual temperature (Tsl) was measured as a surrogate of internal temperature. RESULTS: Tsl increased in HOT compared to TC (TC 36.5 ± 0.3 vs. HOT 36.7 ± 0.3 ºC; p < 0.01). COP distance was greater in HOT compared to TC condition (TC 596.6 ± 242.4 vs. HOT 680.2 ± 249.1 mm; p < 0.01). EMG activity of the gastrocnemius decreased in HOT compared to TC condition (TC 95.5 ± 19.8 vs. HOT 78.4 ± 22.8%mV; p = 0.02). EMG of tibialis did not change between TC and HOT (TC 83.5 ± 42.9 vs. HOT 66.1 ± 31.9% mV; p = 0.29). BP showed a greater fall in HOT compared to TC condition (∆%TC - 24.5 ± 13.2 vs. ∆%HOT - 33.2 ± 20.2%; p = 0.01). CONCLUSION: Heat stress causes a greater fall in blood pressure and a reduction in musculoskeletal pump activity during orthostatic onset. These effects could be potential mechanisms that underlie augmented postural instability under a heated environment.

Extracellular glutamate and GABA transients at the transition from interictal spiking to seizures.

Focal epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood. We used fluorescent glutamate and GABA sensors in an awake rodent model of neocortical seizures to resolve the spatiotemporal evolution of both neurotransmitters in the extracellular space. Interictal spikes were accompanied by brief glutamate transients which were maximal at the initiation site and rapidly propagated centrifugally. GABA transients lasted longer than glutamate transients and were maximal ∼1.5 mm from the focus where they propagated centripetally. Prior to seizure initiation GABA transients were attenuated, whilst glutamate transients increased, consistent with a progressive failure of local inhibitory restraint. As seizures increased in frequency, there was a gradual increase in the spatial extent of spike-associated glutamate transients associated with interictal spikes. Neurotransmitter imaging thus reveals a progressive collapse of an annulus of feed-forward GABA release, allowing seizures to escape from local inhibitory restraint.

Anti-seizure gene therapy for focal cortical dysplasia.

Focal cortical dysplasias are a common subtype of malformation of cortical development, which frequently presents with a spectrum of cognitive and behavioural abnormalities as well as pharmacoresistant epilepsy. Focal cortical dysplasia type II is typically caused by somatic mutations resulting in mammalian target of rapamycin (mTOR) hyperactivity, and is the commonest pathology found in children undergoing epilepsy surgery. However, surgical resection does not always result in seizure freedom, and is often precluded by proximity to eloquent brain regions. Gene therapy is a promising potential alternative treatment and may be appropriate in cases that represent an unacceptable surgical risk. Here, we evaluated a gene therapy based on overexpression of the Kv1.1 potassium channel in a mouse model of frontal lobe focal cortical dysplasia. An engineered potassium channel (EKC) transgene was placed under control of a human promoter that biases expression towards principal neurons (CAMK2A) and packaged in an adeno-associated viral vector (AAV9). We used an established focal cortical dysplasia model generated by in utero electroporation of frontal lobe neural progenitors with a constitutively active human Ras homolog enriched in brain (RHEB) plasmid, an activator of mTOR complex 1. We characterized the model by quantifying electrocorticographic and behavioural abnormalities, both in mice developing spontaneous generalized seizures and in mice only exhibiting interictal discharges. Injection of AAV9-CAMK2A-EKC in the dysplastic region resulted in a robust decrease (∼64%) in the frequency of seizures. Despite the robust anti-epileptic effect of the treatment, there was neither an improvement nor a worsening of performance in behavioural tests sensitive to frontal lobe function. AAV9-CAMK2A-EKC had no effect on interictal discharges or behaviour in mice without generalized seizures. AAV9-CAMK2A-EKC gene therapy is a promising therapy with translational potential to treat the epileptic phenotype of mTOR-related malformations of cortical development. Cognitive and behavioural co-morbidities may, however, resist an intervention aimed at reducing circuit excitability.

Comparison of 25-hydroxyvitamin D and bilirubin levels between patients with essential tremor and Parkinson's disease / Comparação dos níveis de 25-hidroxivitamina D e bilirrubina entre pacientes com tremor essencial e doença de Parkinson

Introduction: Differential diagnoses between essential tremor and Parkinson's disease is challenging in some individuals, with both disorders sharing similarities. Considering these links, we hypothesized that both conditions have a similar profile for some antioxidant molecules, including 25-hydroxyvitamin D and bilirubin. Methods: We performed a cross-sectional study comparing serum levels of 25-hydroxyvitamin D and bilirubin in 31 ET patients, 38 PD, and 65 controls matched for age. We used the Fahn-Tolosa-Marin scale for the severity of tremors in the ET group. We used Hohen-Yahr and MDS-UPDRS part III scales in the PD group. In addition, we evaluated sociodemographic characteristics, including age, sex, ethnicity, years of study, duration of disease, and use of primidone. Results: We found no differences in serum levels for 25-hydroxyvitamin D or bilirubin subtype levels between the ET and PD groups. We found low levels of indirect bilirubin in the PD group compared to the controls. We did not find differences between ET and controls in all biomarkers of the study. Conclusion: ET and PD patients have similar profiles for 25-hydroxyvitamin D and bilirubin serum levels. The discovery of differences in oxidative stress biomarkers in both conditions, mainly low-cost substances available clinically, can assist in the differential diagnosis and, in the future, prognostication and better therapy management (AU).

Introdução: O diagnóstico diferencial entre tremor essencial (TE) e a doença de Parkinson (DP) é desafiador em alguns indivíduos com ambas as afecções apresentando algumas similaridades. Assim sendo, hipotetizamos que ambas têm perfil similar de algumas moléculas antioxidantes, incluindo 25-hidroxivitamina D e bilirrubina. Méto-dos: Realizamos um estudo transversal comparando os níveis séricos de 25-hidroxivitamina D e bilirrubinas em 31 indivíduos com TE, 38 com DP e 65 controles pareados por idade. A escala de Fahn-Tolosa-Marin foi usada para avaliação da gravidade do tremor no grupo com TE e Hohen-Yahr e UPDRS parte III na avaliação do grupo com DP. Também foram avaliadas as características sociodemográficas. Resultados: Não encontramos diferenças nos níveis séricos de 25-hidroxivitamina D ou bilirrubina entre os grupos TE e DP. Encontramos baixos níveis de bilirrubina indireta no grupo DP comparado aos controles. Não encontramos diferenças entre os grupos com TE e controles em nenhum dos biomarcadores do estudo. Conclusão: Pacientes com TE e DP apresentam níveis séricos semelhantes de 25-Hidroxivitamina D e bilirrubinas. Diferenças nos biomarcadores de estresse oxidativo em ambas as condi-ções, principalmente substâncias de baixo custo disponíveis na clínica, pode auxiliar no diagnóstico diferencial e, futuramente, no prognóstico e otimização terapêutica (AU).

Peer review of the pesticide risk assessment of the active substance metconazole.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Belgium, and co-rapporteur Member State, the United Kingdom, for the pesticide active substance are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of metconazole as a fungicide on cereals and oilseed rape and as a plant growth regulator on oilseed rape. The reliable end points appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Efeitos do treinamento resistido sobre indicadores de saúde de sobreviventes de câncer de mama / Effects of resistance training on health indicators in breast cancer survivors

O objetivo deste estudo foi investigar os efeitos do treinamento resistido sobre indicadores de saúde em sobreviventes de câncer de mama. Vinte e duas mulheres com histórico de mastectomia e linfadenectomia completaram 12 semanas de treinamento. Avaliações de força, índice de massa corporal, composição corporal, aspectos hematológicos, bioquímicos e de estabilidade de membrana eritrocitária foram realizadas antes e depois do período de treinamento. Em todos os exercícios, ocorreram ganhos significantes de força máxima e resistência de força. Além disso, houve diminuição do percentual de gordura corporal, aumento do percentual de massa magra, redução de eritrócitos, plaquetas e hemoglobina, bem como mudanças desejáveis para todas as variáveis de perfil lipídico. Em conjunto, esses achados destacam o impacto multidimensional do treinamento resistido sobre a saúde de sobreviventes de câncer de mama e revelam a necessidade de monitoramento constante desse público.

The present study aimed to investigate the effects of resistance training on health indicators in breast cancer survivors. Twenty-two women with a history of mastectomy and lymphadenectomy completed 12 weeks of training. Strength, body mass index, body composition, hematological, and biochemical aspects, and erythrocyte membrane stability were performed before and after the training. In all exercises, there were significant gains in maximal force and force endurance. Moreover, there was a decrease in body fat percentage, an increase in lean mass percentage, a reduction in erythrocytes, platelets, and hemoglobin, as well as desirable changes for all lipid profile variables. Altogether, these findings highlight the multidimensional impact of resistance training on the health of breast cancer survivors and reveal the need for constant monitoring of this public.

Sexual Dysfunction in Parkinson's Disease: A Systematic Review of the Arizona Sexual Experience Scale Sexual Dysfunction in Parkinson Disease: A Systematic Review of the Arizona Sexual Experience Scale.

OBJECTIVE: Parkinson's disease (PD) affects older individuals and can cause sexual dysfunction (SD). SD is a determinant of general well-being; but is infrequently assessed in professionally. The Arizona Sexual Experience Scale (ASEX) measures SD; unlike other scales, it is minimally invasive and requires little time to complete. This review aimed to assess the prevalence of SD in patients with PD using ASEX. METHODS: Were searched the keywords, "sexual dysfunction," "Parkinson's disease" and "ASEX" in 9 databases. RESULTS: The prevalence of SD ranged from 65%-90%. SD was associated with older age at disease onset, higher Unified Parkinson Disease Rating Scale scores, age and depression (p ranged from .001 to <.05). The most observed SD was erectile dysfunction in men. CONCLUSION: SD is common among patients with PD. ASEX, although not specific to PD, is an easy and quickly applied tool that can help evaluate SD and guide treatments in PD.

On-demand cell-autonomous gene therapy for brain circuit disorders.

Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity. Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and "healthy" surrounding or intermingled neurons. We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy. We used an immediate early gene promoter to drive the expression of Kv1.1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity. Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors. Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders.

Parkinson's Disease Medication Adherence Scale: Conceptualization, Scale Development, and Clinimetric Testing Plan.

Background: Medication adherence is a crucial component in the management of patients with chronic diseases needing a long-term pharmacotherapy. Parkinson's disease (PD) is a chronic, degenerative disease with complex drug treatment that poses challenging barriers to patient adherence. The adoption of best practices of scale development can contribute to generate solid concepts and, in the long run, a more stable knowledge base on the underlying constructs of medication adherence in PD measured by the items of the first scale to be created for this purpose. Purpose: To present the development process and clinimetric testing plan of the Parkinson's Disease Medication Adherence Scale (PD-MAS). Method: We adopted a hybrid approach plan based on the United States Food and Drug Administration and Benson and Clark Guide that will create a patient-reported outcome instrument. We presented an overview of consecutive and interrelated steps, containing a concise description of each one. International research centers from Brazil and United States were initially involved in the planning and implementation of the methodological steps of this study. Results: We developed a four-phase multimethod approach for the conceptualization and the clinimetric testing plan of the PD-MAS. First, we describe the development process of the conceptual framework of the PD-MAS underpinning the scale construct; second, we formalized the development process of the first version of the PD-MAS from the generation of item pools to the content validation and pre-testing; third, we established the steps for the first pilot testing and revision; fourth, we describe the steps plan for the first pilot testing and revision, to finally describe its clinimetric testing plan and validation. Conclusion: The overview presentation of the development phases and the clinimetric testing plan of the PD-MAS demonstrate the feasibility of creating an instrument to measure the multidimensional and multifactorial components of the medication adherence process in people with PD.

Study of the effects of kinesthetic motor imagery in patients with heart failure.

OBJECTIVE: The aim was to investigate the acute effect of kinesthetic motor imagery of the 2-minute walk test on hemodynamic and cardiopulmonary variables in patients with heart failure. METHODS: Twenty participants were recruited for the analysis of these variables before and after the execution and imagination of the 2-minute walk test, with the number of laps executed and imagined being recorded. RESULTS: The main results observed showed that (1) there was no difference in the number of laps executed and imagined (p=0.41), indicating that the participants actually imagined the test and (2) the motor imagery of the 2-minute walk test immediately increased (p<0.001) the heart and respiratory rates. CONCLUSION: The motor imagery seems to have acute effects on the cardiopulmonary anticipatory responses of a patient with heart failure.

Exercise training and detraining effects on body composition, muscle strength and lipid, inflammatory and oxidative markers in breast cancer survivors under tamoxifen treatment.

AIMS: The present study aimed to verify the effects of resistance training (RT) and successive detraining on body composition, muscle strength and lipid profile as primary outcome, and the oxidative stress and inflammatory markers as second outcome of postmenopausal Breast Cancer (BC) survivors undergoing tamoxifen (TA). MAIN METHODS: Fourteen postmenopausal BC survivors underwent 12 weeks of resistance exercise training and subsequently 12 weeks of detraining. Anthropometric parameters, lipid profile, muscle strength, inflammatory cytokines and the oxidative stress markers, were assessed before, after the training period and after detraining period. KEY FINDINGS: One-way ANOVA showed that fat mass decrease (39.4 ± 6.9 to 37.7 ± 6.8%) and free-fat mass increase (39.3 ± 4.9 to 40.3 ± 5.6%) after RT. Muscle strength increased in response to training but decreased after the detraining period. Triglycerides (156 ± 45 to 123 ± 43 mg/dL) and total cholesterol (202 ± 13 to 186 ± 16 mg/dL) decreased after the RT and HDL-cholesterol (47 ± 9 to 56 ± 9 mg/dL) increased after RT and remained higher (53 ± 10 mg/dL) than after detraining. IL-6 increases (24.65 ± 10.85 to 41.42 ± 22.88 pg/mL) and IL-17 (2.42 ± 0.32 to 1.69 ± 0.19 pg/mL), TBARS (1.91 ± 0.19 to 1.03 ± 0.1 µmol/L), SOD (24.65 ± 10.85 to 41.42 ± 22.88 U/gHb) and Catalase activity (445.9 ± 113.0 to 345.8 ± 81.7 k/gHb·s) reduced after RT and remained lower after detraining. SIGNIFICANCE: Resistance exercise training improves health markers of BC survivors undergoing TA and detraining are not sufficient to reverse the positive effects in oxidative stress markers.

A cura em psicanálise: efeitos orgânicos e subjetivos de uma análise / The cure in psychoanalysis: organics and subjective effects of an analysis

INTRODUÇÃO: O presente artigo é fruto de uma revisão bibliográfica com o intuito de evidenciar os efeitos do tratamento psicanalítico, não apenas enquanto algo da ordem do reportado pelos pacientes, mas também enquanto algo que pode ser mensurado a partir de alterações bioquímicas verificadas durante e após o tratamento psicanalítico. OBJETIVOS: Verificar se a psicanálise pode ter seus efeitos cientificamente mensuráveis para além dos relatos dos pacientes e dos analistas e, em último caso, apontar para uma possível eficácia do tratamento com relação às psicopatologias contemporâneas. MÉTODO: Pesquisa bibliográfica sistemática de artigos científicos, publicados de 2008 até a presente data, que demonstravam os efeitos verificáveis de uma análise nos pacientes, sejam alterações funcionais ou bioquímicas. RESULTADOS: Foram encontradas inúmeras evidências dos efeitos de um trabalho psicanalítico no decorrer do tratamento, e também, após o término do mesmo. CONCLUSÃO: Com este estudo foi possível verificar que a psicanálise é efetiva para uma série de transtornos mentais e que pode ser o tratamento padrão ouro, quando respeitados os devidos cuidados com relação à formação dos analistas. Novas pesquisas devem ser realizadas, fazendo um comparativo mais amplo entre a psicanálise e outras modalidades no campo da saúde mental.

INTRODUCTION: This article results from a bibliographic review to highlight the effects of the psychoanalysis treatment, not only based on the issues reported by the patients but also in other outcomes measurable by biochemistry changes that are verified during and after the treatment. OBJECTIVES: To verify if psychoanalysis with its effects can be scientifically measured beyond the report of the patients and the analysts and, in the last case, to point out the efficacy of the treatment for contemporary psychopathology. METHODS: It was carried out a systematic literature review of referenced articles, considering the period from the year 2008 to current days, which aimed to demonstrate verifiable effects in the patients that were submitted to psychoanalysis, considering either functional or biochemistry changes. RESULTS: It was found that several evidences of the effects during the psychoanalytical process and also after the end of the treatment. CONCLUSION: With this work, it was possible to verify that psychoanalysis is an effective treatment for several mental disorders and can be a standard gold treatment once is respected the appropriate attention to the formation of the analysts. New researches must be done to compare psychoanalysis and other types of treatment in the mental health field.

Application of physical exercise therapies in breast cancer survivors and their effects on the inflammatory profile: A narrative review.

BACKGROUND: One of the adverse effects of cancer treatments is the exacerbation of inflammation, which generates numerous limitations and contributes to the development of several comorbidities and the recurrence of cancer itself. Physical exercise (PE) has been proposed as an efficient complementary strategy to combat the inflammatory effects of oncological treatments and to prevent the development of comorbidities, but its adequate application in breast cancer survivors (BCS) requires the establishment of consensuses and practical recommendations. OBJECTIVE: This study aimed to review the randomized controlled trials that evaluated the influence of PE in the inflammatory profile of BCS. METHODS: The search for articles published between 1999 and 2020 was done in PsycINFO, PubMed, Cochrane, Science Direct, and Scopus databases. RESULTS: Current knowledge reveals the effectiveness of PE in the functional independence and health of BCS. Evidence of the capacity of PE to improve the inflammatory profile and the immune response in BCS has also been described. However, the heterogeneity of the studies regarding structural training variables, types of exercise, stages of intervention, and severity of the disease, still do not allow the establishment of precise guidelines for the prescription and progression of exercise to improve the inflammatory process in BCS. DISCUSSION: . This review suggests a possible strategy to be used in the assessment, training prescription, and rehabilitation of BCS, to support the development of new studies and the work of exercise professionals in the prescription and application of physical training to improve health and inflammatory status in BCS.

LGI1 downregulation increases neuronal circuit excitability.

OBJECTIVE: Leucine-rich glioma-inactivated 1 (LGI1) is a secreted transsynaptic protein that interacts presynaptically with Kv1.1 potassium channels and a disintegrin and metalloprotease (ADAM) protein 23, and postsynaptically influences α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors through a direct link with the ADAM22 cell adhesion protein. Haploinsufficiency of LGI1 or autoantibodies directed against LGI1 are associated with human epilepsy, generating the hypothesis that a subacute reduction of LGI1 is sufficient to increase network excitability. METHODS: We tested this hypothesis in ex vivo hippocampal slices and in neuronal cultures, by subacutely reducing LGI1 expression with shRNA. RESULTS: Injection of shRNA-LGI1 in the hippocampus increased dentate granule cell excitability and low-frequency facilitation of mossy fibers to CA3 pyramidal cell neurotransmission. Application of the Kv1 family blocker, α-dendrotoxin, occluded this effect, implicating the involvement of Kv1.1. This subacute reduction of LGI1 was also sufficient to increase neuronal network activity in neuronal primary culture. SIGNIFICANCE: These results indicate that a subacute reduction in LGI1 potentiates neuronal excitability and short-term synaptic plasticity, and increases neuronal network excitability, opening new avenues for the treatment of limbic encephalitis and temporal lobe epilepsies.

Measuring Medication Adherence in Parkinson's Disease: A Systematic Review of Contributing Components in Rating Scales.

BACKGROUND: Poor medication adherence in chronic illnesses such as Parkinson's disease (PD) is a significant but potentially addressable issue if core components are systematically measured. OBJECTIVE: To assess whether rating scales used in PD adequately cover essential components of medication adherence. METHODS: We accessed 5 databases targeting articles published before October 2019 and using rating scales to measure medication adherence in PD. The ABC Taxonomy from the European Ascertaining Barriers to Compliance Consortium and World Health Organization recommendations were used as the evaluation standard of 5 essential adherence dimensions (patient-based, health system-based, social-based, therapy-based, and health condition-based), 3 phases (initiation, implementation, and discontinuation), and 2 factors (intentional and nonintentional). RESULTS: We screened 192 and selected 16 studies, collectively using 5 medication adherence rating scales. No scale covered all essential components of medication adherence (dimensions, phases, factors). The Morisky Medication Adherence Scales were the most frequently used (11 studies), but they measure only 2 dimensions and phases. The Stendal Adherence to Medication Score (used in 1 study) measured all phases but only 2 dimensions, and the Brief Medication Questionnaire (used in 3 studies) measured 3 dimensions and 2 phases. Distinctions between intentional and nonintentional factors were not completely considered in any scale. CONCLUSIONS: Although multiple studies target medication adherence in PD, the used scales did not measure all recommended components, highlighting the need to develop a sensitive, specific, and comprehensive tool for measuring medication adherence among patients with PD.

Using the medicine ball throw test to predict upper limb muscle power: validity evidence / Teste do arremesso de bola medicinal para predizer potência muscular de membros superiores: evidências de validade

Abstract Muscle power is the product of muscle force and velocity, which translates into the ability to produce force in a short time interval. Periodic evaluations of strength and power, coupled with training strategies for these capacities, are of great value to athletes and multi-sports coaches, since they are key determinants for team success. Specifically, in rugby, where passing is a predominant and determinant element of sporting success, few field tests are available for assessing upper limb muscle power. The purpose of this point of view is to correct the upper limb power prediction equation previously published by our group and to highlight its concepts and applicability in sports, especially in rugby.

Resumo Potência muscular é o produto entre força e velocidade, que se traduz na capacidade de produzir força em um curto intervalo de tempo. Avaliações periódicas de força e potência, combinadas a estratégias de treinamento para essas capacidades, são de grande valor para atletas e treinadores multi-esportivos, pois são determinantes para o sucesso da equipe. Especificamente no rugby, onde o passe é elemento predominante e determinante do sucesso esportivo, poucos testes de campo estão disponíveis para avaliar força muscular de membro superior. O objetivo deste ponto de vista é corrigir a equação de predição de potência do membro superior previamente publicada pelo nosso grupo e destacar seus conceitos e aplicabilidade nos esportes, especialmente no rugby.

Spontaneous resolution of chronic subdural hematoma: Does only the size matter?

BACKGROUND: Chronic subdural hematomas (CSDHs) usually occur late in adults and older after mild head trauma. Surgical intervention is the first treatment option in CSDH with conservative management being adopted in few cases. CASE DESCRIPTION: We report a case of a 71-year-old man who presented a spontaneous resolution of a large CSDH. He presented with a difficulty of speech and an ataxic gait. Head (computed tomography scan) showed a low-density lesion located in the right frontal-temporal-parietal region. CONCLUSION: In this report, we discuss the spontaneous resolution of a large CSDH in elderly patients, without surgical intervention. Gradually, several successful nonsurgical therapies for the treatment of these hematomas are reported, although further studies are essential to establish the role of these nonsurgical treatments of CSDHs.

Dendritic NMDA receptors in parvalbumin neurons enable strong and stable neuronal assemblies.

Parvalbumin-expressing (PV+) GABAergic interneurons mediate feedforward and feedback inhibition and have a key role in gamma oscillations and information processing. The importance of fast synaptic recruitment and action potential initiation and repolarization, and rapid synchronous GABA release by PV+ cells, is well established. In contrast, the functional significance of PV+ cell NMDA receptors (NMDARs), which generate relatively slow postsynaptic currents, is unclear. Underlining their potential importance, several studies implicate PV+ cell NMDAR disruption in impaired network function and circuit pathologies. Here, we show that dendritic NMDARs underlie supralinear integration of feedback excitation from local pyramidal neurons onto mouse CA1 PV+ cells. Furthermore, by incorporating NMDARs at feedback connections onto PV+ cells in spiking networks, we show that these receptors enable cooperative recruitment of PV+ interneurons, strengthening and stabilising principal cell assemblies. Failure of this phenomenon provides a parsimonious explanation for cognitive and sensory gating deficits in pathologies with impaired PV+ NMDAR signalling.