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- A custom-built single-channel in-ear electroencephalography sensor for sleep phase detection: an interdependent solution for at-home sleep studiesPublication . Borges, Daniel Filipe; Soares, Joana Isabel; Silva, Heloísa; Felgueiras, João; Batista, Carla; Ferreira, Simão; Rocha, Nuno; Leal, AlbertoSleep is vital for health. It has regenerative and protective functions. Its disruption reduces the quality of life and increases susceptibility to disease. During sleep, there is a cyclicity of distinct phases that are studied for clinical purposes using polysomnography (PSG), a costly and technically demanding method that compromises the quality of natural sleep. The search for simpler devices for recording biological signals at home addresses some of these issues. We have reworked a single-channel in-ear electroencephalography (EEG) sensor grounded to a commercially available memory foam earplug with conductive tape. A total of 14 healthy volunteers underwent a full night of simultaneous PSG, in-ear EEG and actigraphy recordings. We analysed the performance of the methods in terms of sleep metrics and staging. In another group of 14 patients evaluated for sleep-related pathologies, PSG and in-ear EEG were recorded simultaneously, the latter in two different configurations (with and without a contralateral reference on the scalp). In both groups, the in-ear EEG sensor showed a strong correlation, agreement and reliability with the ‘gold standard’ of PSG and thus supported accurate sleep classification, which is not feasible with actigraphy. Single-channel in-ear EEG offers compelling prospects for simplifying sleep parameterisation in both healthy individuals and clinical patients and paves the way for reliable assessments in a broader range of clinical situations, namely by integrating Level 3 polysomnography devices. In addition, addressing the recognised overestimation of the apnea-hypopnea index, due to the lack of an EEG signal, and the sparse information on sleep metrics could prove fundamental for optimised clinical decision making.
- Hippotherapy improves gross motor function in children with cerebral palsy: evidence from a systematic reviewPublication . Bernardino, Inês; Borges, Daniel Filipe; Casalta Lopes, João; Soares, Joana Isabel; Borges, Daniel Filipe"Hippotherapy uses horse movement to promote physical and psychosocial rehabilitation and may benefit children with cerebral palsy (CP). Standardised instruments such as the Activity Scale for Kids-Performance (ASK©), the Gross Motor Function Classification System (GMFCS) and the Gross Motor Function Measure (GMFM) are needed to quantify effects on motor function. To systematically review the effects of hippotherapy on gross motor skills in children with CP. Although autism spectrum disorder (ASD) was included in the search strategy, no eligible ASD studies were identified. Following PRISMA guidelines, six databases (PubMed, EMBASE, Web of Science, SCOPUS, Cochrane and SciELO) were searched for English, Portuguese or Spanish studies employing ASK©, GMFCS or GMFM. Two reviewers independently screened records, extracted data and assessed risk of bias. Twenty-five studies (602 participants, mean age 7.1 years, 3–14) met inclusion criteria; all involved CP, none ASD. Interventions lasted 8–24 weeks (1–3 sessions/week). Two ASK© studies showed significant motor gains (Hedges g=0.48–0.62). GMFM was used in 22 studies; 20 reported clinically relevant improvements, particularly in dimensions D (standing) and E (walking, running, jumping). The sole GMFCS study reported no change in classification. Methodological quality was moderate, limited by small samples and lack of blinding. Hippotherapy improves gross motor function in CP, best demonstrated with GMFM. Evidence for ASD is absent, highlighting a research gap. Broader application of ASK© and GMFCS is still needed to better define benefits across neurodevelopmental disorders."
- Puzzling out presynaptic differentiationPublication . Pinto, Maria J.; Almeida, Ramiro D.Proper brain function in the nervous system relies on the accurate establishment of synaptic contacts during development. Countless synapses populate the adult brain in an orderly fashion. In each synapse, a presynaptic terminal loaded with neurotransmitters-containing synaptic vesicles is perfectly aligned to an array of receptors in the postsynaptic membrane. Presynaptic differentiation, which encompasses the events underlying assembly of new presynaptic units, has seen notable advances in recent years. It is now consensual that as a growing axon encounters the receptive dendrites of its partner, presynaptic assembly will be triggered and specified by multiple postsynaptically-derived factors including soluble molecules and cell adhesion complexes. Presynaptic material that reaches these distant sites by axonal transport in the form of pre-assembled packets will be retained and clustered, ultimately giving rise to a presynaptic bouton. This review focuses on the cellular and molecular aspects of presynaptic differentiation in the central nervous system, with a particular emphasis on the identity of the instructive factors and the intracellular processes used by neuronal cells to assemble functional presynaptic terminals. We provide a detailed description of the mechanisms leading to the formation of new presynaptic terminals. In brief, soma-derived packets of pre-assembled material are trafficked to distant axonal sites. Synaptogenic factors from dendritic or glial provenance activate downstream intra-axonal mediators to trigger clustering of passing material and their correct organization into a new presynaptic bouton. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases".
- Refining the link between psychopathy, antisocial behavior, and empathy: a meta-analytical approach across different conceptual frameworksPublication . Campos, Carlos; Pasion, Rita; Azeredo, Andreia; Eduarda, Ramião; Mazer, Prune; Machado, Inês; Barbosa, FernandoThe current meta-analysis included 431 records (N= 123,414) to comprehensively explore the complex interaction between psychopathy, antisocial behavior, and empathy. First, empathy domains (cognitive and affective) were used to provide critical insights for distinguishing antisocial behavior from psychopathy. Cognitive empathy was more impaired in antisocial groups (gcognitive= -.40; gaffective= -.11), while high psychopathy samples displayed larger deficits in affective empathy (gaffective= -.44; gcognitive= -.23), although this dissociation was not clear in correlational analyses. Secondly, the specific associations between empathy domains and psychopathy dimensions were evaluated. Psychopathy traits closely related to antisocial behavior were mildly associated with both empathy domains (r= -.07 to -.14). Callous-affective traits were largely associated with affective empathy (r= -.32 to -.35) and moderately correlated to cognitive empathy (r= -.26). Diverging results were found for the interpersonal dimension, as boldness-adaptive manifestations were unrelated to cognitive empathy (r= .05), while non-adaptive interpersonal traits were negatively associated with both empathy domains (rcognitive= -.14; raffective= -.25). Overall, these findings suggest that: (1) psychopathy and antisocial behavior display distinct empathic profiles; (2) psychopathy dimensions are differentially associated with cognitive and affective empathy; (3) the interaction between interpersonal traits and empathic processes is different across the conceptual models of psychopathy.
- Spike detection in the wild: Screening of suspected temporal lobe epilepsy cases using a tailored 2-channel wearable EEGPublication . Borges, Daniel Filipe; Soares, Joana Isabel; Dias, Daniela; Cordeiro, Helena; Leal, Alberto; Borges, Daniel FilipeTo clinically validate the contribution of a custom-built-wearable device (waEEG) compared to a full 10–20 electrode array ambulatory EEG (aEEG) for screening epilepsy cases in patients with suspected temporal lobe epilepsy (TLE) but negative routine EEGs. Patients (aged 16–91 years) with clinically suspected TLE who were referred for a 24 h aEEG were fitted with an additional 2-channel bipolar waEEG device and prospectively enrolled in the study until 20 TLE diagnoses were confirmed by aEEG. 41 patients were included and their waEEG was blindly reviewed by two experienced clinical neurophysiologists and a semi-automated spike detection software to categorize patients into TLE (spikes present) and non-TLE (no spikes) groups. The experts achieved good sensitivity (95%–100%) and accuracy (98%–93%) with excellent interrater agreement (kappa>0.80) in patient labelling. The semi-automated software performed poorly (40% sensitivity, 68% accuracy) and failed to classify TLE in more than half the cases. Classification was not affected by restricting spike detection to the evening and night time, which reduced the average length of the analyzed EEG from 23.4 to 10.4 h. Three false-positive spike detections were thoroughly analyzed and reclassified as artifacts due to eye and body movements and electrocardiographic contamination. To better control cardiac artifacts, the addition of an ECG channel to the waEEG is recommended. Detection of spikes with waEEG allows accurate detection of epilepsy in suspected TLE cases, with less technical and professional effort and improved acceptance. This screening tool could improve the yield of follow-up with a conventional aEEG and provide an accessible method for monitoring interictal epileptiform activity in TLE. Epilepsy is a chronic short circuit in the brain. In adults, it most often affects the temporal lobes, resulting in temporal lobe epilepsy (TLE). Seizures are infrequent but difficult to treat. Electroencephalography (EEG) is the best method to detect the electrical disturbances and is crucial to distinguish epilepsy from other non-epileptic disorders. Developing simple, inexpensive and easily accessible portable EEG methods that complement in-hospital assessment could significantly impact patient care. Our study aims to clinically validate a wearable epilepsy screening device to aid in TLE management, reduce delays in diagnosis and enable straightforward assessment of epileptic activity.
- The Dianalund experience: A review of the 6th ILAE School on Advanced EEG and EpilepsyPublication . Borges, Daniel Filipe; Primicerio, Giulia; Perjoc, Radu‐Ștefan; Bloch, Lars Ølgaard; Cacic Hribljan, MelitaThe 6th International League Against Epilepsy (ILAE)School on Advanced EEG and Epilepsy (DSSEE6) tookplace between July 20 and 28, 2024. It is a biennial courseheld in Dianalund @ Danish Epilepsy Center—Filadelfia,Denmark, since 2012. This year's event was hosted in ahybrid format and was organized under the auspices ofthe ILAE Academy and the Danish Epilepsy Society.
- The left-right side-specific neuroendocrine signaling from injured brain: An organizational principlePublication . Watanabe, Hiroyuki; Henrique Maia, Gisela Maria; Kobikov, Yaromir; Nosova, Olga; Sarkisyan, Daniil; Galatenko, Vladimir; Carvalho, Liliana; Maia, Gisela H.; Lukoyanov, Nikolay; Lavrov, Igor; Ossipov, Michael H.; Hallberg, Mathias; Schouenborg, Jens; Zhang, Mengliang; Bakalkin, GeorgyA neurological dogma is that the contralateral effects of brain injury are set through crossed descending neural tracts. We have recently identified a novel topographic neuroendocrine system (T-NES) that operates via a humoral pathway and mediates the left-right side-specific effects of unilateral brain lesions. In rats with completely transected thoracic spinal cords, unilateral injury to the sensorimotor cortex produced contralateral hindlimb flexion, a proxy for neurological deficit. Here, we investigated in acute experiments whether T-NES consists of left and right counterparts and whether they differ in neural and molecular mechanisms. We demonstrated that left- and right-sided hormonal signaling is differentially blocked by the δ-, κ- and µ-opioid antagonists. Left and right neurohormonal signaling differed in targeting the afferent spinal mechanisms. Bilateral deafferentation of the lumbar spinal cord abolished the hormone-mediated effects of the left-brain injury but not the right-sided lesion. The sympathetic nervous system was ruled out as a brain-to-spinal cord-signaling pathway since hindlimb responses were induced in rats with cervical spinal cord transections that were rostral to the preganglionic sympathetic neurons. Analysis of gene–gene co-expression patterns identified the left- and right-side-specific gene co-expression networks that were coordinated via the humoral pathway across the hypothalamus and lumbar spinal cord. The coordination was ipsilateral and disrupted by brain injury. These findings suggest that T-NES is bipartite and that its left and right counterparts contribute to contralateral neurological deficits through distinct neural mechanisms, and may enable ipsilateral regulation of molecular and neural processes across distant neural areas along the neuraxis.
- The perspectives of current health professionals regarding their interaction with specific technologyPublication . Amorim, Manuela; Mota, Sandra; Tavares, DianaTechnological evolution in healthcare has been continuous. To access the advantages and disadvantages of professional-machine interaction from the user's perspective in health professionals we developed an online questionnaire. A total of 107 responses were obtained from 12 health technologies areas, showing some differences between them. The majority are 5 to 10 years of experience (28.0%). Speed, safety and efficiency stands out as benefits and dehumanization of the care provided and the reduction of jobs as risks. The user's perspective contributes in an elementary way to the current and future industry in the health area, and therefore should not be neglected.
- The prevalence of post-therapy epilepsy in patients treated for high-grade glial tumors: a systematic review and meta-analysisPublication . Ferreira, Marta Pereira; Carvalho, Ruben Lopes; Soares, Joana Isabel; Casalta‑Lopes, João; Borges, Daniel Filipe; Borges, Daniel Filipe; Soares, Joana I.Gliomas are the most prevalent type of primary brain tumor of the adult central nervous system. High-grade gliomas (HGG) are the most common type of glioma. Epilepsy is often the first clinical manifestation of HGG. Since epilepsy leads to increased morbidity and mortality rates, seizure control is one of the main therapeutic goals for patients with glioma-related epilepsy. Post-therapy epilepsy is observed in a significant percentage of patients, hence, this work aimed to quantify the prevalence of post-therapy epilepsy after HGG treatment. Our search was conducted across PubMed®, EMBASE®, Web of Science™, Cochrane Library, Sicelo and Scopus, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This review included articles published in Portuguese or English that evaluate adult patients with newly diagnosed HGG, who were treated with at least surgery or radiation. Thirty-six studies reporting on 4036 HGG patients were included in our meta-analysis. The mean age ranged from 44 to 73 years. Glioblastoma was the most commonly observed HGG, representing 77,8% of all glioma patients. The pre-treatment seizure frequency was observed in 21,2%. All patients underwent surgery as the main therapy, and 1842 patients received standard adjuvant therapy. We also observed a pooled prevalence of post-therapy seizures of 25.5% (95% confidence interval of [19.9%; 31.1%]). Substantial heterogeneity in all assessed variables was observed. Conducting larger prospective studies with suitable epilepsy diagnostic methods would help provide a more precise estimate of the number of HGG patients who develop post-therapy epilepsy.
- The proteasome controls presynaptic differentiation through modulation of an on-site pool of polyubiquitinated conjugatesPublication . Pinto, Maria J.; Alves, Pedro L.; Martins, Luís; Pedro, Joana R.; Ryu, Hyun R.; Jeon, Noo Li; Taylor, Anne M.; Almeida, Ramiro D.Differentiation of the presynaptic terminal is a complex and rapid event that normally occurs in spatially specific axonal regions distant from the soma; thus, it is believed to be dependent on intra-axonal mechanisms. However, the full nature of the local events governing presynaptic assembly remains unknown. Herein, we investigated the involvement of the ubiquitin-proteasome system (UPS), the major degradative pathway, in the local modulation of presynaptic differentiation. We found that proteasome inhibition has a synaptogenic effect on isolated axons. In addition, formation of a stable cluster of synaptic vesicles onto a postsynaptic partner occurs in parallel to an on-site decrease in proteasome degradation. Accumulation of ubiquitinated proteins at nascent sites is a local trigger for presynaptic clustering. Finally, proteasome-related ubiquitin chains (K11 and K48) function as signals for the assembly of presynaptic terminals. Collectively, we propose a new axon-intrinsic mechanism for presynaptic assembly through local UPS inhibition. Subsequent on-site accumulation of proteins in their polyubiquitinated state triggers formation of presynapses.