Nine decades of electrocorticography: A comparison between epidural and subdural recordings.

In recent years, electrocorticography (ECoG) has arisen as a neural signal recording tool in the development of clinically viable neural interfaces. ECoG electrodes are generally placed below the dura mater (subdural) but can also be placed on top of the dura (epidural). In deciding which of these modalities best suits long-term implants, complications and signal quality are important considerations. Conceptually, epidural placement may present a lower risk of complications as the dura is left intact but also a lower signal quality due to the dura acting as a signal attenuator. The extent to which complications and signal quality are affected by the dura, however, has been a matter of debate. To improve our understanding of the effects of the dura on complications and signal quality, we conducted a literature review. We inventorized the effect of the dura on signal quality, decodability and longevity of acute and chronic ECoG recordings in humans and non-human primates. Also, we compared the incidence and nature of serious complications in studies that employed epidural and subdural ECoG. Overall, we found that, even though epidural recordings exhibit attenuated signal amplitude over subdural recordings, particularly for high-density grids, the decodability of epidural recorded signals does not seem to be markedly affected. Additionally, we found that the nature of serious complications was comparable between epidural and subdural recordings. These results indicate that both epidural and subdural ECoG may be suited for long-term neural signal recordings, at least for current generations of clinical and high-density ECoG grids.

Developmental Toxicity Studies: The Path towards Humanized 3D Stem Cell-Based Models.

Today, it is recognized that medicines will eventually be needed during pregnancy to help prevent to, ameliorate or treat an illness, either due to gestation-related medical conditions or pre-existing diseases. Adding to that, the rate of drug prescription to pregnant women has increased over the past few years, in accordance with the increasing trend to postpone childbirth to a later age. However, in spite of these trends, information regarding teratogenic risk in humans is often missing for most of the purchased drugs. So far, animal models have been the gold standard to obtain teratogenic data, but inter-species differences have limited the suitability of those models to predict human-specific outcomes, contributing to misidentified human teratogenicity. Therefore, the development of physiologically relevant in vitro humanized models can be the key to surpassing this limitation. In this context, this review describes the pathway towards the introduction of human pluripotent stem cell-derived models in developmental toxicity studies. Moreover, as an illustration of their relevance, a particular emphasis will be placed on those models that recapitulate two very important early developmental stages, namely gastrulation and cardiac specification.

Distinct representation of ipsilateral hand movements in sensorimotor areas.

There is ample evidence that the contralateral sensorimotor areas play an important role in movement generation, with the primary motor cortex and the primary somatosensory cortex showing a detailed spatial organization of the representation of contralateral body parts. Interestingly, there are also indications for a role of the motor cortex in controlling the ipsilateral side of the body. However, the precise function of ipsilateral sensorimotor cortex in unilateral movement control is still unclear. Here, we show hand movement representation in the ipsilateral sensorimotor hand area, in which hand gestures can be distinguished from each other and from contralateral hand gestures. High-field functional magnetic resonance imaging (fMRI) data acquired during the execution of six left- and six right-hand gestures by healthy volunteers showed ipsilateral activation mainly in the anterior section of precentral gyrus and the posterior section of the postcentral gyrus. Despite the lower activation in ipsilateral areas closer to the central sulcus, activity patterns for the 12 hand gestures could be mutually distinguished in these areas. The existence of a unique representation of ipsilateral hand movements in the human sensorimotor cortex favours the notion of transcallosal integrative processes that support optimal coordination of hand movements.

The epidemiology of multiple sclerosis in the entre Douro e Vouga region of northern Portugal: a multisource population-based study.

BACKGROUND: The prevalence of Multiple Sclerosis (MS) has been increasing worldwide and the north-south gradient of prevalence may be disappearing in the Northern hemisphere. The few previous prevalence studies performed in Portugal have reported a lower prevalence than the average for Western Europe. The aim of this study is to estimate the prevalence of MS in the Entre Douro e Vouga region, in Northern Portugal. METHODS: Multiple overlapping sources were used to ascertain all cases from the reference population: records from hospitals in the region and neighbouring regions; diagnostic databases of primary care physicians; and applications for disability benefits. The prevalence date was set at 1 January 2014. The reference population was 274,859 inhabitants. Patients' neurologists were contacted to retrieve clinical information and confirm the diagnosis based. RESULTS: A total of 177 patients were identified after eliminating duplicates from different sources. The female to male ratio was 1.9 and the mean age at disease onset was 33.5 (standard deviation: 10.3). Clinically isolated syndrome accounted for 9.0% of patients, relapsing remitting for 58.8%, secondary progressive for 20.3% and primary progressive for 11.8%. The prevalence was estimated in 64.4 patients per 100,000 (95% confidence interval: 54.9;73.9). CONCLUSIONS: In this study we report a higher point prevalence of MS than had been previously described in Portugal, but still far from the higher values recently reported in other Southern European countries.

Electrocorticography Evidence of Tactile Responses in Visual Cortices.

There is ongoing debate regarding the extent to which human cortices are specialized for processing a given sensory input versus a given type of information, independently of the sensory source. Many neuroimaging and electrophysiological studies have reported that primary and extrastriate visual cortices respond to tactile and auditory stimulation, in addition to visual inputs, suggesting these cortices are intrinsically multisensory. In particular for tactile responses, few studies have proven neuronal processes in visual cortex in humans. Here, we assessed tactile responses in both low-level and extrastriate visual cortices using electrocorticography recordings in a human participant. Specifically, we observed significant spectral power increases in the high frequency band (30-100 Hz) in response to tactile stimuli, reportedly associated with spiking neuronal activity, in both low-level visual cortex (i.e. V2) and in the anterior part of the lateral occipital-temporal cortex. These sites were both involved in processing tactile information and responsive to visual stimulation. More generally, the present results add to a mounting literature in support of task-sensitive and sensory-independent mechanisms underlying functions like spatial, motion, and self-processing in the brain and extending from higher-level as well as to low-level cortices.

Tracking cognitive impairment in multiple sclerosis using the Brain on Track test: a validation study.

BACKGROUND: The accurate and regular monitoring cognitive performance in multiple sclerosis (MS) patients is critical to develop new prevention and management strategies for cognitive impairment (CI). The Brain on Track (BoT) test is a self-administered web-based tool developed for cognitive screening and monitoring. The objective of this study was to validate the use of the BoT in MS, by assessing its ability to distinguish between MS patients and matched controls, as well as detect CI among MS patients, by analysing its correlation with standard cognitive tests and its reliability and learning effects in repeatable use. METHODS: The BoT was applied in 30 patients with MS consecutively selected and 30 age- and education-matched controls, first in a hospital clinic, under supervision, and then 1 week later from home. After these first two trials, MS patients repeated the test from home every 4 weeks for 3 months. A standard neuropsychological battery was also applied to MS patients at baseline. RESULTS: The Cronbach's alpha was 0.89. Test scores were significantly different between MS patients and controls (Cohen's d = 0.87; p < 0.01). Among MS patients, scores were significantly lower in those with CI documented in the standard neuropsychological battery than in their cognitively preserved counterparts (Cohen's d = 2.0; p < 0.001). The BoT scores presented a good correlation with standard neuropsychological tests, particularly for information processing speed. Regarding test-retest reliability, 10/11 subtests presented two-way mixed single intraclass consistency correlation coefficients > 0.70. CONCLUSION: The BoT showed good neuropsychological parameters in MS patients, endorsing the use of self-administered computerized tests in this setting.

Correction to: Tracking cognitive impairment in multiple sclerosis using the Brain on Track test: a validation study.

The above article was published online with an error in author name's affiliations. Affiliation 8 has to be added to Maria Pia Amato and has to be deleted from Vitor Tedim.

Correction to: Aging with multiple sclerosis: prevalence and profile of cognitive impairment.

The above article was published online with an error in author name's affiliation. The Author Claudia Niccolai has changed her affiliation to IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.

Encoding of kinetic and kinematic movement parameters in the sensorimotor cortex: A Brain-Computer Interface perspective.

For severely paralyzed people, Brain-Computer Interfaces (BCIs) can potentially replace lost motor output and provide a brain-based control signal for augmentative and alternative communication devices or neuroprosthetics. Many BCIs focus on neuronal signals acquired from the hand area of the sensorimotor cortex, employing changes in the patterns of neuronal firing or spectral power associated with one or more types of hand movement. Hand and finger movement can be described by two groups of movement features, namely kinematics (spatial and motion aspects) and kinetics (muscles and forces). Despite extensive primate and human research, it is not fully understood how these features are represented in the SMC and how they lead to the appropriate movement. Yet, the available information may provide insight into which features are most suitable for BCI control. To that purpose, the current paper provides an in-depth review on the movement features encoded in the SMC. Even though there is no consensus on how exactly the SMC generates movement, we conclude that some parameters are well represented in the SMC and can be accurately used for BCI control with discrete as well as continuous feedback. However, the vast evidence also suggests that movement should be interpreted as a combination of multiple parameters rather than isolated ones, pleading for further exploration of sensorimotor control models for accurate BCI control.

Fully Implanted Brain-Computer Interface in a Locked-In Patient with ALS.

Options for people with severe paralysis who have lost the ability to communicate orally are limited. We describe a method for communication in a patient with late-stage amyotrophic lateral sclerosis (ALS), involving a fully implanted brain-computer interface that consists of subdural electrodes placed over the motor cortex and a transmitter placed subcutaneously in the left side of the thorax. By attempting to move the hand on the side opposite the implanted electrodes, the patient accurately and independently controlled a computer typing program 28 weeks after electrode placement, at the equivalent of two letters per minute. The brain-computer interface offered autonomous communication that supplemented and at times supplanted the patient's eye-tracking device. (Funded by the Government of the Netherlands and the European Union; ClinicalTrials.gov number, NCT02224469 .).

Aging with multiple sclerosis: prevalence and profile of cognitive impairment.

BACKGROUND: The increase in life expectancy of patients with multiple sclerosis (MS) requires a better knowledge of disease features in the older patients group. OBJECTIVE: To describe the prevalence and profile of cognitive impairment (CI) in older patients with MS and perform a comparison with younger patients. METHODS: Patients were consecutively recruited for 6 months. Cognitive performance was assessed through the Brief Repeatable Battery and the Stroop Test. CI was defined as impairment in ≥ 2 cognitive domains. RESULTS: We identified 111 patients older than 55 years (mean age 59.7 years). The prevalence of CI was 77.4%, which was significantly higher than in younger patients (42.8%; p < 0.01). Information processing speed was the most impaired domain (68.8%), followed by verbal learning (49.5%), executive function (47.7%), and visuospatial learning (26.6%). We found no significant differences in the prevalence of impairment in the distinct cognitive domains between older and younger patients with CI. Depression and fatigue were not associated with increased CI among patients in the older age group (p > 0.70). CONCLUSION: There is a remarkably high frequency of CI in older patients with MS. The similar profile of CI between older and younger patients suggests that CI is mostly directly related to MS itself and not to comorbid age-related disorders.

GridLoc: An automatic and unsupervised localization method for high-density ECoG grids.

Precise localization of electrodes is essential in the field of high-density (HD) electrocorticography (ECoG) brain signal analysis in order to accurately interpret the recorded activity in relation to functional anatomy. Current localization methods for subchronically implanted HD electrode grids involve post-operative imaging. However, for situations where post-operative imaging is not available, such as during acute measurements in awake surgery, electrode localization is complicated. Intra-operative photographs may be informative, but not for electrode grids positioned partially or fully under the skull. Here we present an automatic and unsupervised method to localize HD electrode grids that does not require post-operative imaging. The localization method, named GridLoc, is based on the hypothesis that the anatomical and vascular brain structures under the ECoG electrodes have an effect on the amplitude of the recorded ECoG signal. More specifically, we hypothesize that the spatial match between resting-state high-frequency band power (45-120 Hz) patterns over the grid and the anatomical features of the brain under the electrodes, such as the presence of sulci and larger blood vessels, can be used for adequate HD grid localization. We validate this hypothesis and compare the GridLoc results with electrode locations determined with post-operative imaging and/or photographs in 8 patients implanted with HD-ECoG grids. Locations agreed with an average difference of 1.94 ±â€¯0.11 mm, which is comparable to differences reported earlier between post-operative imaging and photograph methods. The results suggest that resting-state high-frequency band activity can be used for accurate localization of HD grid electrodes on a pre-operative MRI scan and that GridLoc provides a convenient alternative to methods that rely on post-operative imaging or intra-operative photographs.

Patients with paediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: An Italian collaborative study.

BACKGROUND: Patients with paediatric-onset multiple sclerosis (POMS) could be at an increased risk for cognitive impairment (CI), given the potential harmful effects of disease activity in neurodevelopment. However, there is scarce information on their long-term cognitive outcomes. OBJECTIVE: To compare the prevalence and profile of CI between adults with a history of POMS and those with classic, adult-onset multiple sclerosis (AOMS). METHODS: Cognitive performance was assessed through the Brief Repeatable Battery (BRB) and the Stroop Test in consecutive patients referred to six Italian MS centres. CI was defined as impairment in ⩾2 cognitive domains. RESULTS: In all, 119 patients with POMS and 712 with AOMS were included in this analysis. The prevalence of CI was 48.0% in AOMS, 44.5% in POMS; with similar neuropsychological profile between the two groups. However, when adjusting for current age, we found a significantly increased risk for CI (odds ratio (OR) = 1.71; p = 0.02) and for impairment in information processing speed (OR = 1.86; p < 0.01) in patients with POMS. A higher Expanded Disability Status Scale (EDSS) was also identified in POMS ( p = 0.03) compared with AOMS patients. CONCLUSION: Patients with a history of POMS appear to be at higher risk of physical and cognitive disability than AOMS patients, after correcting for age effects, with particular involvement of information processing speed.

The etiology of spontaneous intracerebralhemorrhage: Insights from a neuropathological series.

The etiology of intracerebral hemorrhage (ICH) is frequently undetermined. We aimed to assess the impact of the neuropathological study on the etiologic diagnosis of ICH. Patients with ICH admitted to a tertiary hospital in the last 14 years were identified, and histological samples of surgically-drained ICH were retrieved. Blinded from neuropathological results, a clinical etiology was hypothesized. Pathological samples were reviewed, and immunohistochemistry study for ß-amyloid was performed in all the cases where structural abnormalities were not identified. From 2002 - 2016, 113 patients with ICH underwent surgical drainage and had specimens taken for histology. The mean age was 51.6 years (SD = 19.2). Clinical and imaging data defined a presumable etiology in 47 patients (44.2%), including 30 patients with suspected structural pathology, 11 patients under anticoagulation, and 8 patients with probable hypertensive hemorrhage, while most had an undetermined etiology. Using neuropathological analysis, a definitive diagnosis was possible in 88.5% of the patients. Arteriovenous malformations (38.1%) and cavernous hemangiomas (16.8%) represented the most common findings. In 9.7%, the blood vessels showed cerebral amyloid angiopathy (CAA). The neuropathological study established a definite etiology in an additional 44.3% of patients other than only using the clinical and imaging data.
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Decoding hand gestures from primary somatosensory cortex using high-density ECoG.

Electrocorticography (ECoG) based Brain-Computer Interfaces (BCIs) have been proposed as a way to restore and replace motor function or communication in severely paralyzed people. To date, most motor-based BCIs have either focused on the sensorimotor cortex as a whole or on the primary motor cortex (M1) as a source of signals for this purpose. Still, target areas for BCI are not confined to M1, and more brain regions may provide suitable BCI control signals. A logical candidate is the primary somatosensory cortex (S1), which not only shares similar somatotopic organization to M1, but also has been suggested to have a role beyond sensory feedback during movement execution. Here, we investigated whether four complex hand gestures, taken from the American sign language alphabet, can be decoded exclusively from S1 using both spatial and temporal information. For decoding, we used the signal recorded from a small patch of cortex with subdural high-density (HD) grids in five patients with intractable epilepsy. Notably, we introduce a new method of trial alignment based on the increase of the electrophysiological response, which virtually eliminates the confounding effects of systematic and non-systematic temporal differences within and between gestures execution. Results show that S1 classification scores are high (76%), similar to those obtained from M1 (74%) and sensorimotor cortex as a whole (85%), and significantly above chance level (25%). We conclude that S1 offers characteristic spatiotemporal neuronal activation patterns that are discriminative between gestures, and that it is possible to decode gestures with high accuracy from a very small patch of cortex using subdurally implanted HD grids. The feasibility of decoding hand gestures using HD-ECoG grids encourages further investigation of implantable BCI systems for direct interaction between the brain and external devices with multiple degrees of freedom.

Unsupervised analysis of whole transcriptome data from human pluripotent stem cells cardiac differentiation.

The main objective of the present work was to highlight differences and similarities in gene expression patterns between different pluripotent stem cell cardiac differentiation protocols, using a workflow based on unsupervised machine learning algorithms to analyse the transcriptome of cells cultured as a 2D monolayer or as 3D aggregates. This unsupervised approach effectively allowed to portray the transcriptomic changes that occurred throughout the differentiation processes, with a visual representation of the entire transcriptome. The results allowed to corroborate previously reported data and also to unveil new gene expression patterns. In particular, it was possible to identify a correlation between low cardiomyocyte differentiation efficiencies and the early expression of a set of non-mesodermal genes, which can be further explored as predictive markers of differentiation efficiency. The workflow here developed can also be applied to analyse other stem cell differentiation transcriptomic datasets, envisaging future clinical implementation of cellular therapies.

Insights Into Pediatric Asthma: A Population Study From Alto Minho Health Center.

Background Asthma represents one of the most common diseases in childhood, with a prevalence ranging between 9% and 13% in Portugal. Therefore, it holds significant importance in pediatric health. While existing studies have shed light on asthma in the Portuguese population, they have predominantly concentrated on urban centers, with the population of Alto Minho remaining underrepresented in the literature. This study aims to understand the main factors of exposure, exacerbation, and the most prevalent allergens in a pediatric sample from the Alto Minho Local Health Unit, Portugal. Methodology A retrospective cohort study was conducted among 239 pediatric asthma patients aged between five and 18 years at the Alto Minho Health Center. Data on demographics, clinical information, family history, environmental exposures, exacerbating factors, and prick test results were analyzed. Results Of the 239 patients, 64.44% were male and 35.56% were female. The majority of the sample exhibited a normal body mass index (82.17%) and a family history of atopy (66.67%). Noteworthy patterns emerged in comorbidities, notably an increased association with allergic rhinitis, the most frequent concomitant atopic pathology (79.50%), followed by atopic dermatitis (27.61%) and food allergy (10.88%). Sensitization to dust mites, particularly Dermatophagoides pteronyssinus, was widespread among the participants. Environmental exposures were marked by significant factors such as proximity to plants and trees, soft toys, and living in rural areas. Exacerbating factors included common triggers such as exercise, seasonal variations, and even laughter. Statistically significant associations were found between atopic comorbidities, exacerbation factors, exposure factors, and prick test results. Conclusions Our findings align with global trends, emphasizing the prevalence of atopic pathologies in pediatric asthma. Sensitization patterns and environmental exposures are indicative of regional influences. Study limitations include sample size and data standardization issues. Despite these limitations, the study significantly contributes to understanding pediatric asthma in Alto Minho, offering valuable insights for prompt diagnosis and targeted treatments.

DNA ploidy is an independent predictor of survival in breast invasive ductal carcinoma: a long-term multivariate analysis of 393 patients.

PURPOSE: To evaluate "classic" prognostic parameters, as well as DNA ploidy and S-phase fraction (SPF), in relation to disease-free (DFS) and disease-specific (DSS) survival in breast invasive ductal carcinoma (IDC) with long-term follow-up study. METHODS: The study involved 393 patients with IDC and median follow-up of 134 months (50-240). Histological grading, tumor size, axillary nodal involvement, pathological staging and hormone receptor status were considered as established prognostic markers. Ploidy and SPF were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables. RESULTS: There were 105 (26.7 %) deaths and 140 (35.6 %) disease recurrences during follow-up. Two hundred thirty-one (58.8 %) tumors were aneuploid. High SPF and aneuploidy were associated with tumors with higher grade of differentiation, greater size and negative hormone receptors. Higher SPF and advanced disease stage are correlated. In univariate analysis, all the clinicopathological and cytometric features, including patients <40 years and a subgroup presenting hypertetraploid/multiploid tumors, are significantly correlated with clinical outcome, apart from SPF and estrogen receptors for DFS. In multivariate analysis, nodal involvement, DNA aneuploidy and lack of progesterone receptors (for DSS) retained statistically significant association with shorter survival. In node-negative patients, ploidy (for DFS) and estrogen receptors (for DSS) significantly predicted survival. In both subgroups of node-positive patients and those (n = 195) with intermediate differentiation tumors (G2), aneuploidy was an indicator of worse prognosis. CONCLUSIONS: Along with nodal status and hormone receptor expression, DNA ploidy is an independent predictor of long-term survival in IDC.