João Miguel Castelhano

• PhD. MSc. Biomedical Engineering
• Engineer at University of Coimbra

The relation of gamma-band synchrony to holistic perception in which concerns the effects of sensory processing, high level perceptual gestalt formation, motor planning and response is still controversial. To provide a more direct link to emergent perceptual states we have used holistic EEG/ERP paradigms where the moment of perceptual "discovery" o...

It remains an outstanding question whether gamma-band oscillations reflect unitary cognitive processes within the same task. EEG/MEG studies do lack the resolution or coverage to address the highly debated question whether single gamma activity patterns are linked with multiple cognitive modules or alternatively each pattern associates with a speci...

It has been hypothesized that neural synchrony underlies perceptual coherence. The hypothesis of loss of central perceptual coherence has been proposed to be at the origin of abnormal cognition in autism spectrum disorders and Williams syndrome, a neurodevelopmental disorder linked with autism, and a clearcut model for impaired central coherence. W...

Hemispheric functional asymmetries are a key aspect of human brain organization. Revealing how causal manipulations of hemispheric (im)balances dynamically change pre and postsynaptic GABA regulation, in terms of mean and variance changes, is essential to understand plasticity of brain asymmetries in health and disease. This has direct implications...

Recently, there has been a resurgence in experimental and conceptual efforts to understand how brain rhythms can serve to organize visual information. Oscillations can provide temporal structure for neuronal processing and form a basis for integrating information across brain areas. Here, we use a bistable paradigm and a data‐driven approach to tes...

Comprehending digital content written in natural language online is vital for many aspects of life, including learning, professional tasks, and decision-making. However, facing comprehension difficulties can have negative consequences for learning outcomes, critical thinking skills, decision-making, error rate, and productivity. This paper introduc...

Cognitive human error and recent cognitive taxonomy on human error causes of software defects support the intuitive idea that, for instance, mental overload, attention slips, and working memory overload are important human causes for software bugs. In this paper, we approach the EEG as a reliable surrogate to MRI-based reference of the programmer’s...

In this study, we present iMind, a novel prototype tool designed to predict individuals’ comprehension difficulties with online content at local levels, such as paragraphs or multiple lines. iMind seamlessly captures the physiological responses of the Autonomic Nervous System (ANS) using commercially available wearable sensors (wristbands) in conju...

Background: Functional neuroimaging can provide pathophysiological information in perinatal asphyxia (PA). However, fundamental unresolved questions remain related to the influence of neurovascular coupling (NVC) maturation on functional responses in early development. We aimed to probe the feasibility and compare the responses to multiple sensory...

Peripheral signs of age‐related hearing loss (ARHL) have been well documented, although ARHL is not well understood if it contributes to adaptive plasticity of cortical regions and how it interacts with functional responses of high‐order centers associated with cognitive function. Therefore, the present study investigates electrophysiological audit...

Color perception entails competing temporal context mechanisms such as adaptation versus memory persistence ¹ . Perceptual dynamics in color cone pathways can be studied using the phenomenon of hysteresis, well-known in the framework of physical dynamical systems. It postulates analogous mechanisms: a) visual persistence defining positive hysteresi...

The Default Mode Network (DMN) and the Theory of Mind (ToM) networks play a crucial role in our understanding of the neurocognition of the self. The DMN is commonly associated with introspection, while the ToM is involved in perspective-taking. There is no research investigating the overlap between the DMN and ToM in relation to causal effects such...

Research into the neurobiological and psychosocial mechanisms involved in fibromyalgia has progressed remarkably in recent years. Despite this, current accounts of fibromyalgia fail to capture the complex, dynamic, and mutual crosstalk between neurophysiological and psychosocial domains. We conducted a comprehensive review of the existing literatur...

Functional MRI (fMRI) with ¹H‐MRS was combined on the hippocampus and visual cortex of animal models of obesity (high‐fat diet, HFD) and type 2 diabetes (T2D) to identify the involved mechanisms and temporal evolution of neurometabolic changes in these disorders that could serve as potentially reliable clinical biomarkers. HFD rats presented elevat...

Transcranial magnetic stimulation (TMS) can be useful for therapeutic purposes for a variety of clinical conditions. Numerous studies have indicated the potential of this non- invasive brain stimulation technique to recover brain function and to study physiological mechanisms. Following this line, the articles contemplated in this Research Topic sh...

Complexity is the key element of software quality. This article investigates the problem of measuring code complexity and discusses the results of a controlled experiment to compare different views and methods to measure code complexity. Participants (27 programmers) were asked to read and (try to) understand a set of programs, while the complexity...

Transcranial magnetic stimulation (TMS) can be useful for therapeutic purposes for a variety of clinical conditions. Numerous studies have indicated the potential of this non-invasive brain stimulation technique to recover brain function and to study physiological mechanisms. Following this line, the articles contemplated in this special issue show...

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We prese...

Although stroke is the main cause of brain damage worldwide, stroke therapies are based on blood reperfusion and do not target cerebral parenchyma. Ischemic stroke (representing 87% of all strokes) causes cerebral damage due to oxygen and tissue energy depletion, which lead to acidosis, inflammation, excitotoxicity and oxidative stress. Carbon mono...

Background: Several functional magnetic resonance imaging (fMRI) studies investigated the brain correlates of psychogenic erectile dysfunction (PED) and premature ejaculation (PE), representing the most common sexual dysfunctions in men. These studies allowed a wide set of brain regions in PED and PE patients when compared to healthy men. In the pr...

Objectives We aimed to investigate the antiepileptic effects of cathodal transcranial direct current stimulation (c-tDCS) and mechanisms of action based on its effects on the neurotransmitters responsible for the abnormal synchrony patterns seen in pharmacoresistant epilepsy. This is the first study to test the impact of neurostimulation on epilept...

Deficits in mitochondrial function and redox deregulation have been attributed to Huntington's disease (HD), a genetic neurodegenerative disorder largely affecting the striatum. However, whether these changes occur in early stages of the disease and can be detected in vivo is still unclear. In the present study, we analyzed changes in mitochondrial...

Facial emotion perception can be studied from the point of view of dynamic systems whose output may depend not only on current input but also on prior history — a phenomenon known as hysteresis. In cognitive neuroscience, hysteresis has been described as positive (perceptual persistence) or negative (fatigue of current percept) depending on whether...

Machine Learning has been extensively used in studies that utilized neurophysiological data (e.g., fMRI, EEG, ECG) in capturing brain and the Autonomic Nervous System (ANS) activity in various software engineering (SE) tasks such as code comprehension and development. However, there is a lack of research efforts to review machine learning technique...

The present paper describes the use of nonintrusive biofeedback sensors (e.g., ECG) and eye-tracker to study the cognitive load (CL) associated with two mental tasks: a) content reading and comprehension b) code review. The paper addresses the theoretical underpinnings of the comprehension assessment included in content reading (for understanding)...

Error-related electroencephalographic (EEG) signals have been widely studied concerning the human cognitive capability of differentiating between erroneous and correct actions. Midfrontal error-related negativity (ERN) and theta band oscillations are believed to underlie post-action error monitoring. However, it remains elusive how early monitoring...

Machado-Joseph disease (MJD) or Spinocerebellar ataxia type 3 (SCA3) is the most common form of dominant SCA worldwide. Magnetic Resonance Imaging (MRI) and Proton Magnetic Resonance Spectroscopy (¹H-MRS) provide promising non-invasive diagnostic and follow-up tools, also serving to evaluate therapies efficacy. However, pre-clinical studies showing...

Code review is an essential practice in software engineering to spot code defects in the early stages of software development. Modern code reviews (e.g., acceptance or rejection of pull requests with Git) have become less formal than classic Fagan's inspections, lightweight, and more reliant on individuals (i.e., reviewers). However, reviewers may...

Invasive brain recordings using many electrodes across a wide range of tasks provide a unique opportunity to study the role of oscillatory patterning and functional connectivity. We used large-scale recordings (stereo EEG) within and beyond the human hippocampus to investigate the role of distinct frequency oscillations during real-time execution o...

The neural correlates of software programming skills have been the target of an increasing number of studies in the past few years. Those studies focused on error-monitoring during software code inspection. Others have studied task-related cognitive load as measured by distinct neurophysiological measures. Most studies addressed only syntax errors...

Error monitoring is the metacognitive process by which we are able to detect and signal our errors once a response has been made. Monitoring when the outcome of our actions deviates from the intended goal is crucial for behavior, learning, and the development of higher-order social skills. Here, we explored the neuronal substrates of error monitori...

Introduction: To design more effective interventions, such as neurostimulation, for stroke rehabilitation, there is a need to understand early physiological changes that take place that may be relevant for clinical monitoring. We aimed to study changes in neurophysiology following recent ischemic stroke, both at rest and with motor planning and ex...

Defects in mitochondrial function and mitochondrial-related redox deregulation have been attributed to Huntington disease (HD), a genetic neurodegenerative disorder largely affecting the striatum. However, whether these changes occur in early stages of the disease and can be detected in vivo is still unclear. Thus, in the present study, we analyzed...

O período entre 2018 e 2022 mostrou-nos que o problema dos incêndios à escala global não está a diminuir, antes pelo contrário. Parece que as consequências das alterações climáticas já estão a afectar a ocorrência de incêndios florestais em várias partes do Mundo, de uma forma que só esperaríamos que acontecesse vários anos mais tarde. Em muitos pa...

Objectives: Transcranial magnetic stimulation, in particular continuous theta burst (cTBS), has been proposed for stroke rehabilitation, based on the concept that inhibition of the healthy hemisphere helps promote the recovery of the lesioned one. We aimed to study its effects on cortical excitability, oscillatory patterns, and motor function, the...

Several studies have demonstrated that error-related neuronal signatures can be successfully detected and used to improve the performance of brain-computer interfaces. However, this has been tested mainly in well-controlled environments and based on temporal features, such as the amplitude of event-related potentials. In this study, we propose a cl...

Code reviews and software inspections are essential for building reliable software. However, current code reviews practice in the software industry (e.g., acceptance or rejection of pull requests with Git) deviates considerably from classic (and expensive) Fagan's inspections. Modern code reviews are lightweight and asynchronous and do not rely on...

There is an increasing interest in the neural effects of psychoactive drugs, in particular tryptamine psychedelics, which has been incremented by the proposal that they have potential therapeutic benefits, based on their molecular mimicry of serotonin. It is widely believed that they act mainly through 5HT2A receptors but their effects on neural ac...

Software programming is a modern activity that poses strong challenges to the human brain. The neural mechanisms that support this novel cognitive faculty are still unknown. On the other hand, reading and calculation abilities represent slightly less recent human activities, in which neural correlates are relatively well understood. We hypothesize...

While dynamic ocular motor abnormalities (e.g., gaze-evoked nystagmus (GEN), low optokinetic nystagmus (OKN), pursuit and vestibulo-ocular reflex (VOR) gains, and dysmetric saccades) have been shown to be potential biomarkers in spinocerebellar ataxia type 3 (SCA3), the value of static abnormalities (e.g., convergent [esodeviation] and divergent st...

An emergent research area in software engineering and software reliability is the use of wearable biosensors to monitor the cognitive state of software developers during software development tasks. The goal is to gather physiologic manifestations that can be linked to error-prone scenarios related to programmers’ cognitive states. In this paper we...

Social attention deficits represent a central impairment of patients suffering from autism spectrum disorder (ASD), but the nature of such deficits remains controversial. We compared visual attention regarding social (faces) vs. non-social stimuli (objects), in an ecological diagnostic context, in 46 children and adolescents divided in two groups:...

Face perception plays an important role in our daily social interactions, as it is essential to recognize emotions. The N170 Event Related Potential (ERP) component has been widely identified as a major face‐sensitive neuronal marker. However, despite extensive investigations conducted to examine this electroencephalographic pattern, there is yet n...

Assessing comprehension difficulties requires the ability to assess cognitive load. Changes in cognitive load induced by comprehension difficulties could be detected with an adequate time resolution using different biofeedback measures (e.g., changes in the pupil diameter). However, identifying the Spatio-temporal sources of content comprehension d...

Abstract Several studies highlighted the role of insula on several functions and in sexual behavior. This exploratory study examines the relationships among genital responses, brain responses, and eye movements, to disentangle the role played by the anterior and posterior insula during different stages of male sexual response and during visual atte...

Blood-brain barrier (BBB) disruption is a common feature in neurodegenerative diseases. However, BBB integrity has not been assessed in spinocerebellar ataxias (SCAs) such as Machado-Joseph disease/SCA type 3 (MJD/SCA3), a genetic disorder, triggered by polyglutamine-expanded ataxin-3. To investigate that, BBB integrity was evaluated in a transgeni...

The human visual system is constantly processing multiple and often conflicting sensory cues to make perceptual decisions. Given the nonlinear nature of emotion recognition, this often leads to different percepts of the same physical facial expression. Moreover, the state of the emotion recognition system might depend on the trajectory of temporal...

The ability to perceive and feel another person' pain as if it were one's own pain, e.g., pain empathy, is related to brain activity in the “pain-matrix” network. A non-core region of this network in Dorsolateral Prefrontal Cortex (DLPFC) has been suggested as a modulator of the attentional-cognitive dimensions of pain processing in the context of...

Objective. fMRI-based neurofeedback (NF) interventions represent the method of choice for the neuromodulation of localized brain areas. Although we have already validated an fMRI-NF protocol targeting the facial expressions processing network (FEPN), its dissemination is hampered by the economical and logistical constraints of fMRI-NF interventions...

Previous studies about the modulation of the vasculature by CO were performed exclusively in male or sexually‐immature animals. Understanding the sex differences regarding systemic drug processing and pharmacodynamics is an important feature for safety assessment of drug dosing and efficacy. In this work, we used CORM‐A1 as source of CO to examine...

Background The success of translational research depends on how well animal models mimic the pathophysiology of the human phenotype, and on the identification of disease mechanisms such as enhanced glycation. Methods Here, we studied cardiac MRI and metabolic phenotypes in human type 2 diabetes (N = 106; 55 patients+51 controls) and animal models...

The study of the physiological effects underlying brain response to transcranial magnetic stimulation is important to understand its impact on neurorehabilitation. We aim to analyze the impact of a transcranial magnetic stimulation protocol, the continuous theta burst (cTBS), on human neurophysiology, particularly on contralateral motor rhythms. cT...

Background: It has been claimed that the retina can be used as a window to study brain disorders. However, concerning Alzheimer's disease (AD), it still remains controversial whether changes occurring in the brain and retina are associated. We aim to understand when changes start appearing in the retina and brain, how changes progress, and if they...

This study aims to investigate the relationship between structural changes in the retina and white matter in the brain, in early Alzheimer’s disease (AD). Twenty-three healthy controls (mean age = 63.4±7.5 years) and seventeen AD patients (mean age = 66.5±6.6 years) were recruited for this study. By combining two imaging techniques—optical coherenc...

This paper provides a study using Electroencephalography (EEG) to investigate the brain activity during code comprehension tasks. Three different code complexity levels according to five complexity metrics were considered. The use of EEG for this purpose is relevant, since the existing studies were mostly focused on neuroimaging techniques. Using L...

Nonalcoholic fatty liver disease (NAFLD) is caused by excessive liver lipid accumulation, but insulin resistance is specifically associated with impaired lipid saturation, oxidation, and storage (esterification), besides increased de novo lipogenesis. We hypothesized that dietary glycotoxins could impair hepatic lipid metabolism in obesity contribu...

Software programming is a complex and relatively recent human activity, involving the integration of mathematical, recursive thinking and language processing. The neural correlates of this recent human activity are still poorly understood. Error monitoring during this type of task, requiring the integration of language, logical symbol manipulation...

The understanding of the natural history of Alzheimer's disease (AD) and temporal trajectories of in vivo molecular mechanisms requires longitudinal approaches. A behavioral and multimodal imaging study was performed at 4/8/12 and 16 months of age in a triple transgenic mouse model of AD (3xTg-AD). Behavioral assessment included the open field and...

Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but la...

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3, the most common dominant spinocerebellar ataxia (SCA) worldwide, is caused by over-repetition of a CAG repeat in the ATXN3/MJD1 gene, which translates into a polyglutamine tract within the ataxin-3 protein. There is no treatment for this fatal disorder. Despite evidence of the safety an...

Huntington's disease (HD) is a neurodegenerative disorder causing cognitive and motor impairments, evolving to death within 15-20 years after symptom onset. We previously established a mouse model with the entire human HD gene containing 128 CAG repeats (YAC128) which accurately recapitulates the natural history of the human disease. Defined time p...

The present study aimed to explore the differential role of the frontoparietal network in processing different visual object categories, matched for difficulty level, during a 1-back paradigm. To achieve this goal we first mapped the effort-related frontoparietal saliency network, by contrasting activation elicited by face, object, place, body and...

Methamphetamine (METH) abuse/misuse is a worldwide problem, and despite extensive characterization of its neurotoxicity over the last years, many questions remain unanswered. Recently, it was shown that METH compromises the blood-brain barrier (BBB) and causes a disturbance in the water homeostasis leading to brain edema. Importantly, water transpo...

Objective Electroencephalographic biomarkers have been widely investigated in autism, in the search for diagnostic, prognostic and therapeutic outcome measures. Here we took advantage of the information available in temporal oscillatory patterns evoked by simple perceptual decisions to investigate whether stimulus dependent oscillatory signatures c...

Background: Type-2 diabetes mellitus (T2DM) is a metabolic disorder with a broad range of complications in the brain that depend on the conditions that precede its onset, such as obesity and metabolic syndromes. It has been suggested that neurotransmitter and metabolic perturbations may emerge even before the early stages of T2DM and that high-cal...

Introduction: Machado-Joseph disease (MJD) is the most common dominantly-inherited ataxia. It is associated with the expansion of a (CAG)n tract in the MJD1/ATXN3 gene. This over-repetition is translated into an expanded polyglutamine (polyQ) tract within ataxin-3, conferring toxic properties to this protein and resulting in severe clinical feature...

High-frequency activity (HFA) is believed to subserve a functional role in cognition, but these patterns are often not accessible to scalp EEG recordings. Intracranial studies provide a unique opportunity to link the all-encompassing range of high-frequency patterns with holistic perception. We tested whether the functional topography of HFAs (up t...

Figure A in S1 File. Group Average Time-frequency activity per condition. Event-related spectral power (dB) were computed in EEGLAB per subject and condition. This figure summarizes the TF results per condition and cluster of electrodes (three horizontal panels with distinct colors). The black lines mark the time-frequency blobs that are significan...

The relationship between EEG and fMRI data is poorly covered in the literature. Extensive work has been conducted in resting-state and epileptic activity, highlighting a negative correlation between the alpha power band of the EEG and the BOLD activity in the default-mode-network. The identification of an appropriate task-specific relationship betw...

Presentation about interictal and ictal high frequency oscillations.