Publications by authors named "Miguel Castelo-Branco"

257 Publications

Automatic classification of idiopathic Parkinson's disease and atypical Parkinsonian syndromes combining [C]raclopride PET uptake and MRI grey matter morphometry.

J Neural Eng 2021 Apr 29;18(4). Epub 2021 Apr 29.

Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal.

To explore the viability of developing a computer-aided diagnostic system for Parkinsonian syndromes using dynamic [C]raclopride positron emission tomography (PET) and T1-weighted magnetic resonance imaging (MRI) data.The biological heterogeneity of Parkinsonian syndromes renders their statistical classification a challenge. The unique combination of structural and molecular imaging data allowed different classifier designs to be tested. Datasets from dynamic [C]raclopride PET and T1-weighted MRI scans were acquired from six groups of participants. There were healthy controls (CTRL= 15), patients with Parkinson's disease (PD= 27), multiple system atrophy (MSA= 8), corticobasal degeneration (CBD= 6), and dementia with Lewy bodies (DLB= 5). MSA, CBD, and DLB patients were classified into one category designated as atypical Parkinsonism (AP). The distribution volume ratio (DVR) kinetic parameters obtained from the PET data were used to quantify the reversible tracer binding to D2/D3 receptors in the subcortical regions of interest (ROI). The grey matter (GM) volumes obtained from the MRI data were used to quantify GM atrophy across cortical, subcortical, and cerebellar ROI.The classifiers CTRL vs PD and CTRL vs AP achieved the highest balanced accuracy combining DVR and GM (DVR-GM) features (96.7%, 92.1%, respectively), followed by the classifiers designed with DVR features (93.3%, 88.8%, respectively), and GM features (69.6%, 86.1%, respectively). In contrast, the classifier PD vs AP showed the highest balanced accuracy (78.9%) using DVR features only. The integration of DVR-GM (77.9%) and GM features (72.7%) produced inferior performances. The classifier CTRL vs PD vs AP showed high weighted balanced accuracy when DVR (80.5%) or DVR-GM features (79.9%) were integrated. GM features revealed poorer performance (59.5%).This work was unique in its combination of structural and molecular imaging features in binary and triple category classifications. We were able to demonstrate improved binary classification of healthy/diseased status (concerning both PD and AP) and equate performance to DVR features in multiclass classifications.
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http://dx.doi.org/10.1088/1741-2552/abf772DOI Listing
April 2021

Social Attention Deficits in Children With Autism Spectrum Disorder: Task Dependence of Objects vs. Faces Observation Bias.

Front Psychiatry 2021 22;12:640599. Epub 2021 Mar 22.

CIBIT - Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal.

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: ASD ( = 23) and typical neurodevelopment (TD) ( = 23), matched for chronological age and intellectual performance. Eye-tracking measures of visual scanning, while exploring and describing scenes from three different tasks from the Autism Diagnostic Observation Schedule (ADOS), were analyzed: "Description of a Picture," "Cartoons," and "Telling a Story from a Book." Our analyses revealed a three-way interaction between Group, Task, and Social vs. Object Stimuli. We found a striking main effect of group and a task dependence of attentional allocation: while the TD attended first and longer to faces, ASD participants became similar to TD when they were asked to look at pictures while telling a story. Our results suggest that social attention allocation is task dependent, raising the question whether spontaneous attention deficits can be rescued by guiding goal-directed actions.
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http://dx.doi.org/10.3389/fpsyt.2021.640599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019800PMC
March 2021

Cardiac microcalcification burden: Global assessment in high cardiovascular risk subjects with Na[F]F PET-CT.

J Nucl Cardiol 2021 Apr 6. Epub 2021 Apr 6.

Cardiology Department, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.

Background: Fluorine-18 sodium fluoride (Na[F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients.

Methods And Results: Thirty-four high CV risk individuals without previous CV events were scanned with Na[F]F PET-CT. Cardiac Na[F]F uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01], which is positively correlated with predicted fatal CV risk by SCORE (r = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (r = 0.61), body mass index (r = 0.66), abdominal perimeter (r = 0.74), thoracic fat volume (r = 0.47), and epicardial adipose tissue (r = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na[F]F uptake.

Conclusions: In a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.
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http://dx.doi.org/10.1007/s12350-021-02600-2DOI Listing
April 2021

Phase-IIa randomized, double-blind, sham-controlled, parallel group trial on anodal transcranial direct current stimulation (tDCS) over the left and right tempo-parietal junction in autism spectrum disorder-StimAT: study protocol for a clinical trial.

Trials 2021 Apr 6;22(1):248. Epub 2021 Apr 6.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Deutschordenstr.50, 60528, Frankfurt, Germany.

Background: Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction, and stereotyped, repetitive behaviour and sensory interests. To date, there is no effective medication that can improve social communication and interaction in ASD, and effect sizes of behaviour-based psychotherapy remain in the low to medium range. Consequently, there is a clear need for new treatment options. ASD is associated with altered activation and connectivity patterns in brain areas which process social information. Transcranial direct current stimulation (tDCS) is a technique that applies a weak electrical current to the brain in order to modulate neural excitability and alter connectivity. Combined with specific cognitive tasks, it allows to facilitate and consolidate the respective training effects. Therefore, application of tDCS in brain areas relevant to social cognition in combination with a specific cognitive training is a promising treatment approach for ASD.

Methods: A phase-IIa pilot randomized, double-blind, sham-controlled, parallel-group clinical study is presented, which aims at investigating if 10 days of 20-min multi-channel tDCS stimulation of the bilateral tempo-parietal junction (TPJ) at 2.0 mA in combination with a computer-based cognitive training on perspective taking, intention and emotion understanding, can improve social cognitive abilities in children and adolescents with ASD. The main objectives are to describe the change in parent-rated social responsiveness from baseline (within 1 week before first stimulation) to post-intervention (within 7 days after last stimulation) and to monitor safety and tolerability of the intervention. Secondary objectives include the evaluation of change in parent-rated social responsiveness at follow-up (4 weeks after end of intervention), change in other ASD core symptoms and psychopathology, social cognitive abilities and neural functioning post-intervention and at follow-up in order to explore underlying neural and cognitive mechanisms.

Discussion: If shown, positive results regarding change in parent-rated social cognition and favourable safety and tolerability of the intervention will confirm tDCS as a promising treatment for ASD core-symptoms. This may be a first step in establishing a new and cost-efficient intervention for individuals with ASD.

Trial Registration: The trial is registered with the German Clinical Trials Register (DRKS), DRKS00014732 . Registered on 15 August 2018.

Protocol Version: This study protocol refers to protocol version 1.2 from 24 May 2019.
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http://dx.doi.org/10.1186/s13063-021-05172-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025356PMC
April 2021

Can EEG Be Adopted as a Neuroscience Reference for Assessing Software Programmers' Cognitive Load?

Sensors (Basel) 2021 Mar 27;21(7). Epub 2021 Mar 27.

Department of Informatics Engineering, CISUC-Centre for Informatics and Systems of the University of Coimbra, University of Coimbra, P-3030-790 Coimbra, Portugal.

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 investigate whether electroencephalography (EEG) can be applied to accurately identify programmers' cognitive load associated with the comprehension of code with different complexity levels. Therefore, a controlled experiment involving 26 programmers was carried. We found that features related to Theta, Alpha, and Beta brain waves have the highest discriminative power, allowing the identification of code lines and demanding higher mental effort. The EEG results reveal evidence of mental effort saturation as code complexity increases. Conversely, the classic software complexity metrics do not accurately represent the mental effort involved in code comprehension. Finally, EEG is proposed as a reference, in particular, the combination of EEG with eye tracking information allows for an accurate identification of code lines that correspond to peaks of cognitive load, providing a reference to help in the future evaluation of the space and time accuracy of programmers' cognitive state monitored using wearable devices compatible with software development activities.
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http://dx.doi.org/10.3390/s21072338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037053PMC
March 2021

Longitudinal normative OCT retinal thickness data for wild-type mice, and characterization of changes in the 3×Tg-AD mice model of Alzheimer's disease.

Aging (Albany NY) 2021 Apr 2;13(7):9433-9454. Epub 2021 Apr 2.

University of Coimbra, Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), Coimbra, Portugal.

Mice are widely used as models for many diseases, including eye and neurodegenerative diseases. However, there is a lack of normative data for retinal thickness over time, especially at young ages. In this work, we present a normative thickness database from one to four-months-old, for nine layers/layer-aggregates, including the total retinal thickness, obtained from the segmentation of spectral-domain optical coherence tomography (SD-OCT) data from the C57BL6/129S mouse strain. Based on fifty-seven mice, this normative database provides an opportunity to study the ageing of control mice and characterise disease models' ageing, such as the triple transgenic mouse model of Alzheimer's disease (3×Tg-AD) used in this work. We report thickness measurements, the differences in thickness per layer, demonstrate a nasal-temporal asymmetry, and the variation of thickness as a function to the distance to the optic disc centre. Significant differences were found between the transgenic group's thickness and the normative database for the entire period covered in this study. Even though it is well accepted that retinal nerve fibre layer (RNFL) thinning is a hallmark of neurodegeneration, our results show a thicker RNFL-GCL (RNFL-Ganglion cell layer) aggregate for the 3×Tg-AD mice until four-months-old.
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http://dx.doi.org/10.18632/aging.202916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064224PMC
April 2021

Training the social brain: Clinical and neural effects of an 8-week real-time functional magnetic resonance imaging neurofeedback Phase IIa Clinical Trial in Autism.

Autism 2021 Mar 25:13623613211002052. Epub 2021 Mar 25.

CNC.IBILI-Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

Lay Abstract: Neurofeedback is an emerging therapeutic approach in neuropsychiatric disorders. Its potential application in autism spectrum disorder remains to be tested. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback in targeting social brain regions in autism spectrum disorder. In this clinical trial, autism spectrum disorder patients were enrolled in a program with five training sessions of neurofeedback. Participants were able to control their own brain activity in this social brain region, with positive clinical and neural effects. Larger, controlled, and blinded clinical studies will be required to confirm the benefits.
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http://dx.doi.org/10.1177/13623613211002052DOI Listing
March 2021

Successful metabolic control in diabetes type 1 depends on individual neuroeconomic and health risk-taking decision endophenotypes: a new target in personalized care.

Psychol Med 2021 Mar 18:1-9. Epub 2021 Mar 18.

Coimbra Institute for Biomedical Imaging and Translational Research, CIBIT/ICNAS, University of Coimbra, Portugal.

Background: Neurobehavioral decision profiles have often been neglected in chronic diseases despite their direct impact on major public health issues such as treatment adherence. This remains a major concern in diabetes, despite intensive efforts and public awareness initiatives regarding its complications. We hypothesized that high rates of low adherence are related to risk-taking profiles associated with decision-making phenotypes. If this hypothesis is correct, it should be possible to define these endophenotypes independently based both on dynamic measures of metabolic control (HbA1C) and multidimensional behavioral profiles.

Methods: In this study, 91 participants with early-stage type 1 diabetes fulfilled a battery of self-reported real-world risk behaviors and they performed an experimental task, the Balloon Analogue Risk Task (BART).

Results: K-means and two-step cluster analysis suggest a two-cluster solution providing information of distinct decision profiles (concerning multiple domains of risk-taking behavior) which almost perfectly match the biological partition, based on the division between stable or improving metabolic control (MC, N = 49) v. unstably high or deteriorating states (NoMC, N = 42). This surprising dichotomy of behavioral phenotypes predicted by the dynamics of HbA1C was further corroborated by standard statistical testing. Finally, the BART game enabled to identify groups differences in feedback learning and consequent behavioral choices under ambiguity, showing distinct group choice behavioral patterns.

Conclusions: These findings suggest that distinct biobehavioral endophenotypes can be related to the success of metabolic control. These findings also have strong implications for programs to improve patient adherence, directly addressing risk-taking profiles.
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http://dx.doi.org/10.1017/S0033291721000386DOI Listing
March 2021

Directly Exploring the Neural Correlates of Feedback-Related Reward Saliency and Valence During Real-Time fMRI-Based Neurofeedback.

Front Hum Neurosci 2020 5;14:578119. Epub 2021 Feb 5.

Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal.

The potential therapeutic efficacy of real-time fMRI Neurofeedback has received increasing attention in a variety of psychological and neurological disorders and as a tool to probe cognition. Despite its growing popularity, the success rate varies significantly, and the underlying neural mechanisms are still a matter of debate. The question whether an individually tailored framework positively influences neurofeedback success remains largely unexplored. To address this question, participants were trained to modulate the activity of a target brain region, the visual motion area hMT+/V5, based on the performance of three imagery tasks with increasing complexity: imagery of a static dot, imagery of a moving dot with two and with four opposite directions. Participants received auditory feedback in the form of vocalizations with either negative, neutral or positive valence. The modulation thresholds were defined for each participant according to the maximum BOLD signal change of their target region during the localizer run. We found that 4 out of 10 participants were able to modulate brain activity in this region-of-interest during neurofeedback training. This rate of success (40%) is consistent with the neurofeedback literature. Whole-brain analysis revealed the recruitment of specific cortical regions involved in cognitive control, reward monitoring, and feedback processing during neurofeedback training. Individually tailored feedback thresholds did not correlate with the success level. We found region-dependent neuromodulation profiles associated with task complexity and feedback valence. Findings support the strategic role of task complexity and feedback valence on the modulation of the network nodes involved in monitoring and feedback control, key variables in neurofeedback frameworks optimization. Considering the elaborate design, the small sample size here tested ( = 10) impairs external validity in comparison to our previous studies. Future work will address this limitation. Ultimately, our results contribute to the discussion of individually tailored solutions, and justify further investigation concerning volitional control over brain activity.
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http://dx.doi.org/10.3389/fnhum.2020.578119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893090PMC
February 2021

The dual nature of the BOLD signal: Responses in visual area hMT+ reflect both input properties and perceptual decision.

Hum Brain Mapp 2021 Apr 12;42(6):1920-1929. Epub 2021 Feb 12.

Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal.

Neuroimaging studies have suggested that hMT+ encodes global motion interpretation, but this contradicts the notion that BOLD activity mainly reflects neuronal input. While measuring fMRI responses at 7 Tesla, we used an ambiguous moving stimulus, yielding the perception of two incoherently moving surfaces-component motion-or only one coherently moving surface-pattern motion, to induce perceptual fluctuations and identify perceptual organization size-matched domains in hMT+. Then, moving gratings, exactly matching either the direction of component or pattern motion percepts of the ambiguous stimulus, were shown to the participants to investigate whether response properties reflect the input or decision. If hMT+ responses reflect the input, component motion domains (selective to incoherent percept) should show grating direction stimulus-dependent changes, unlike pattern motion domains (selective to the coherent percept). This hypothesis is based on the known direction-selective nature of inputs in component motion perceptual domains versus non-selectivity in pattern motion perceptual domains. The response amplitude of pattern motion domains did not change with grating direction (consistently with their non-selective input), in contrast to what happened for the component motion domains (consistently with their selective input). However, when we analyzed relative ratio measures they mirrored perceptual interpretation. These findings are consistent with the notion that patterns of BOLD responses reflect both sensory input and perceptual read-out.
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http://dx.doi.org/10.1002/hbm.25339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978123PMC
April 2021

Investigating the Spatial Associations Between Amyloid-β Deposition, Grey Matter Volume, and Neuroinflammation in Alzheimer's Disease.

J Alzheimers Dis 2021 ;80(1):113-132

Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal.

Background: It has been proposed that amyloid-β (Aβ) plays a causal role in Alzheimer's disease (AD) by triggering a series of pathologic events-possibly including neuroinflammation-which culminate in progressive brain atrophy. However, the interplay between the two pathological molecular events and how both are associated with neurodegeneration is still unclear.

Objective: We aimed to estimate the spatial inter-relationship between neurodegeneration, neuroinflammation and Aβ deposition in a cohort of 20 mild AD patients and 17 healthy controls (HC).

Methods: We resorted to magnetic resonance imaging to measure cortical atrophy, using the radiotracer 11C-PK11195 PET to measure neuroinflammation levels and 11C-PiB PET to assess Aβ levels. Between-group comparisons were computed to explore AD-related changes in the three types of markers. To examine the effects of each one of the molecular pathologic mechanisms on neurodegeneration we computed: 1) ANCOVAs with the anatomic data, controlling for radiotracer uptake differences between groups and 2) voxel-based multiple regression analysis between-modalities. In addition, associations in anatomically defined regions of interests were also investigated.

Results: We found significant differences between AD and controls in the levels of atrophy, neuroinflammation, and Aβ deposition. Associations between Aβ aggregation and brain atrophy were detected in AD in a widely distributed pattern, whereas associations between microglia activation and structural measures of neurodegeneration were restricted to few anatomically regions.

Conclusion: In summary, Aβ deposition, as opposed to neuroinflammation, was more associated with cortical atrophy, suggesting a prominent role of Aβ in neurodegeneration at a mild stage of the AD.
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http://dx.doi.org/10.3233/JAD-200840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075404PMC
January 2021

A link between synaptic plasticity and reorganization of brain activity in Parkinson's disease.

Proc Natl Acad Sci U S A 2021 01;118(3)

Institute of Nuclear Sciences Applied to Health, University of Coimbra, 3000-548 Coimbra, Portugal;

The link between synaptic plasticity and reorganization of brain activity in health and disease remains a scientific challenge. We examined this question in Parkinson's disease (PD) where functional up-regulation of postsynaptic D receptors has been documented while its significance at the neural activity level has never been identified. We investigated cortico-subcortical plasticity in PD using the oculomotor system as a model to study reorganization of dopaminergic networks. This model is ideal because this system reorganizes due to frontal-to-parietal shifts in blood oxygen level-dependent (BOLD) activity. We tested the prediction that functional activation plasticity is associated with postsynaptic dopaminergic modifications by combining positron emission tomography/functional magnetic resonance imaging to investigate striatal postsynaptic reorganization of dopamine D receptors (using C-raclopride) and neural activation in PD. We used covariance (connectivity) statistics at molecular and functional levels to probe striato-cortical reorganization in PD in on/off medication states to show that functional and molecular forms of reorganization are related. D binding across regions defined by prosaccades showed increased molecular connectivity between both caudate/putamen and hyperactive parietal eye fields in PD in contrast with frontal eye fields in controls, in line with the shift model. Concerning antisaccades, parietal-striatal connectivity dominated in again in PD, unlike frontal regions. Concerning molecular-BOLD covariance, a striking sign reversal was observed: PD patients showed negative frontal-putamen functional-molecular associations, consistent with the reorganization shift, in contrast with the positive correlations observed in controls. Follow-up analysis in off-medication PD patients confirmed the negative BOLD-molecular correlation. These results provide a link among BOLD responses, striato-cortical synaptic reorganization, and neural plasticity in PD.
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http://dx.doi.org/10.1073/pnas.2013962118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826364PMC
January 2021

Protective effects of cognitive and brain reserve in multiple sclerosis: Differential roles on social cognition and 'classic cognition'.

Mult Scler Relat Disord 2021 Feb 26;48:102716. Epub 2020 Dec 26.

Department of Neurology, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra 3000-075, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

Background: According to cognitive reserve (CR) and brain reserve (BR) theories, lifetime intellectual enrichment and maximal brain volume protect against cognitive decline.

Objective: To examine the effects of CR and BR on social cognition in multiple sclerosis (MS), and compare it with 'classic cognition'.

Methods: We included 60 MS patients and 60 healthy controls matched on age, sex, and education. Education was used has a proxy of CR and intracranial volume (ICV) as a proxy of BR. Participants underwent Theory of Mind (ToM) testing (Eyes Test, Videos Test), comprehensive neuropsychological assessment and 3Tesla brain MRI. Cortical and subcortical grey matter (GM) volumes were calculated.

Results: We found positive effects of education and ICV on general cognitive status and ToM performance, respectively. Higher education moderated the impact of subcortical GM atrophy on 'classic' cognitive status (R2=0.219, p=<0.001). Conversely, greater ICV attenuated the impact of cortical GM atrophy on Eyes Test (R=0.158, p=0.002) and Videos Test (R=0.198, p=0.001). Stratification for disease duration showed that the protective effect of education/ICV occurred in early stages of disease (<10 years).

Conclusion: CR and BR have differential protective roles in MS, with BR having a positive effect on social cognition and CR on 'classic' cognitive domains.
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http://dx.doi.org/10.1016/j.msard.2020.102716DOI Listing
February 2021

Frontoparietal microstructural damage mediates age-dependent working memory decline in face and body information processing: Evidence for dichotomic hemispheric bias mechanisms.

Neuropsychologia 2021 01 13;151:107726. Epub 2020 Dec 13.

Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), Faculty of Medicine, University of Coimbra, Portugal. Electronic address:

Age-associated damage in the microstructure of frontally-based connections (e.g. genu of the corpus callosum and superior longitudinal fasciculus) is believed to lead to impairments in processing speed and executive function. Using mediation analysis, we tested the potential contribution of callosal and frontoparietal association tracts to age-dependent effects on cognition/executive function as measured with 1-back working memory tasks for visual stimulus categories (i.e. faces and non-emotional bodies) in a group of 55 healthy adults (age range 23-79 years). Constrained spherical deconvolution-based tractography was employed to reconstruct the genu/prefrontal section of the corpus callosum (GCC) and the central/second branch of the superior longitudinal fasciculus (CB-SLF). Age was associated with (i) reductions in fractional anisotropy (FA) in the GCC and in the right and left CB-SLF and (iii) decline in visual object category processing. Mediation analysis revealed that microstructural damage in right hemispheric CB-SLF is associated with age-dependent decline in face processing likely reflecting the stimulus-specific/holistic nature of face processing within dedicated/specialized frontoparietal routes. By contrast, microstructural damage in left hemispheric CB-SLF associated with age-dependent decline in non-emotional body processing, consistent with the more abstract nature of non-emotional body categories. In sum, our findings suggest that frontoparietal microstructural damage mediates age-dependent decline in face and body information processing in a manner that reflects the hemispheric bias of holistic vs. abstract nature of face and non-emotional body category processing.
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http://dx.doi.org/10.1016/j.neuropsychologia.2020.107726DOI Listing
January 2021

Telehealth Opportunities in the COVID-19 Pandemic Early Days: What Happened, Did Not Happen, Should Have Happened, and Must Happen in the Near Future?

Telemed J E Health 2020 Dec 1. Epub 2020 Dec 1.

Digital Care of UVIC-UCC, Barcelona, Spain.

The objective of this communication is to offer a better understanding of the value of telemedicine in health care, particularly its role in creating opportunities for continuity of care to patients in a complex and novel setting as were the circumstances of the early COVID-19 pandemic times. Crisis time is also a time for opportunities. With regard to telehealth, all players (providers, staff, and patients) should be informed about its benefits and should also become familiar with the use of the various telehealth options and this will only be achieved through large information campaigns necessary enriched by local teaching and training programs in both public and private institutions. The final aim is to launch the debate and foster ideas useful throughout the pandemic. This article covers the experiences of physicians as well as health professionals in the Iberian Peninsula (Spain and Portugal), to provide a clearer idea of what has happened and how we can improve it with the possibilities provided by telemedicine, while at the same time to put in evidence that public health systems need to be rethought to provide solutions to situations such as that we are experiencing.
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http://dx.doi.org/10.1089/tmj.2020.0386DOI Listing
December 2020

The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes.

PLoS One 2020 29;15(10):e0240907. Epub 2020 Oct 29.

Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

Glucose metabolism is pivotal for energy and neurotransmitter synthesis and homeostasis, particularly in Glutamate and GABA systems. In turn, the stringent control of inhibitory/excitatory tonus is known to be relevant in neuropsychiatric conditions. Glutamatergic neurotransmission dominates excitatory synaptic functions and is involved in plasticity and excitotoxicity. GABAergic neurochemistry underlies inhibition and predicts impaired psychophysical function in diabetes. It has also been associated with cognitive decline in people with diabetes. Still, the relation between metabolic homeostasis and neurotransmission remains elusive. Two 3T proton MR spectroscopy studies were independently conducted in the occipital cortex to provide insight into inhibitory/excitatory homeostasis (GABA/Glutamate) and to evaluate the impact of chronic metabolic control on the levels and regulation (as assessed by regression slopes) of the two main neurotransmitters of the CNS in type 2 diabetes (T2DM) and type 1 diabetes (T1DM). Compared to controls, participants with T2DM showed significantly lower Glutamate, and also GABA. Nevertheless, higher levels of GABA/Glx (Glutamate+Glutamine), and lower levels of Glutamate were associated with poor metabolic control in participants with T2DM. Importantly, the relationship between GABA/Glx and HbA1c found in T2DM supports a relationship between inhibitory/excitatory balance and metabolic control. Interestingly, this neurometabolic profile was undetected in T1DM. In this condition we found strong evidence for alterations in MRS surrogate measures of neuroinflammation (myo-Inositol), positively related to chronic metabolic control. Our results suggest a role for Glutamate as a global marker of T2DM and a sensitive marker of glycemic status. GABA/Glx may provide a signature of cortical metabolic state in poorly controlled patients as assessed by HbA1c levels, which indicate long-term blood Glucose control. These findings are consistent with an interplay between abnormal neurotransmission and metabolic control in particular in type 2 diabetes thereby revealing dissimilar contributions to the pathophysiology of neural dysfunction in both types of diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240907PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595380PMC
December 2020

The role of anterior and posterior insula in male genital response and in visual attention: an exploratory multimodal fMRI study.

Sci Rep 2020 10 28;10(1):18463. Epub 2020 Oct 28.

CPUP, Faculty of Psychology and Educational Sciences, University of Porto, Porto, Portugal.

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 attention to sexual stimuli. In 19 healthy men, fMRI, eye movement, and penile tumescence data were collected during a visual sexual stimulation task. After a whole-brain analysis comparing neutral and sexual clips and confirming a role for the bilateral insulae, we selected two bilateral seed regions in anterior and posterior insula for functional connectivity analysis. Single-ROI-GLMs were run for the FC target regions. Single-ROI-GLMs were performed based on areas to which participants fixate: "Faces", "Genitals," and "Background" with the contrast "Genitals > Faces". Single-ROI-GLMs with baseline, onset, and sustained PT response for the sexual clips were performed. We found stronger effects for the posterior than the anterior insula. In the target regions of the posterior insula, we found three different pathways: the first involved in visual attention, onset of erection, and sustained erection; the second involved only in the onset of erection, and the third limited to sustained erection.
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http://dx.doi.org/10.1038/s41598-020-74681-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595210PMC
October 2020

The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial.

JMIR Res Protoc 2020 10 26;9(10):e19189. Epub 2020 Oct 26.

See Authors' Contributions, .

Background: The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient. Therefore, there is a growing need for a reliable, feasible, and cost-effective, noninvasive diagnostic tool for these conditions. LiverMultiScan is one such promising tool that uses multi-parametric magnetic resonance imaging (mpMRI) to characterize liver tissue and to aid in the diagnosis and monitoring of liver diseases of various etiologies.

Objective: The primary objective of this trial (RADIcAL1) is to evaluate the cost-effectiveness of the introduction of LiverMultiScan as a standardized diagnostic test for liver disease in comparison to standard care for NAFLD, in different EU territories.

Methods: RADIcAL1 is a multi-center randomized control trial with 2 arms conducted in 4 European territories (13 sites, from across Germany, Netherlands, Portugal, and the United Kingdom). In total, 1072 adult patients with suspected fatty liver disease will be randomized to be treated according to the result of the mpMRI in the intervention arm, so that further diagnostic evaluation is recommended only when values for metrics of liver fat or fibro-inflammation are elevated. Patients in the control arm will be treated as per center guidelines for standard of care. The primary outcome for this trial is to compare the difference in the proportion of patients with suspected NAFLD incurring liver-related hospital consultations or liver biopsies between the study arms, from the date of randomization to the end of the study follow-up. Secondary outcomes include patient feedback from a patient satisfaction questionnaire, at baseline and all follow-up visits to the end of the study, and time, from randomization to diagnosis by the physician, as recorded at the final follow-up visit.

Results: This trial is currently open for recruitment. The anticipated completion date for the study is December 2020.

Conclusions: This randomized controlled trial will provide the evidence to accelerate decision making regarding the inclusion of mpMRI-based tools in existing NAFLD/NASH clinical care. RADIcAL1 is among the first and largest European health economic studies of imaging technologies for fatty liver disease. Strengths of the trial include a high-quality research design and an in-depth assessment of the implementation of the cost-effectiveness of the mpMRI diagnostic. If effective, the trial may highlight the health economic burden on tertiary-referral hepatology clinics imposed by unnecessary consultations and invasive diagnostic investigations, and demonstrate that including LiverMultiScan as a NAFLD diagnostic test may be cost-effective compared to liver-related hospital consultations or liver biopsies.

Trial Registration: ClinicalTrials.gov NCT03289897 https://clinicaltrials.gov/ct2/show/NCT03289897.

International Registered Report Identifier (irrid): DERR1-10.2196/19189.
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http://dx.doi.org/10.2196/19189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652684PMC
October 2020

BCIAUT-P300: A Multi-Session and Multi-Subject Benchmark Dataset on Autism for P300-Based Brain-Computer-Interfaces.

Front Neurosci 2020 18;14:568104. Epub 2020 Sep 18.

Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal.

There is a lack of multi-session P300 datasets for Brain-Computer Interfaces (BCI). Publicly available datasets are usually limited by small number of participants with few BCI sessions. In this sense, the lack of large, comprehensive datasets with various individuals and multiple sessions has limited advances in the development of more effective data processing and analysis methods for BCI systems. This is particularly evident to explore the feasibility of deep learning methods that require large datasets. Here we present the BCIAUT-P300 dataset, containing 15 autism spectrum disorder individuals undergoing 7 sessions of P300-based BCI joint-attention training, for a total of 105 sessions. The dataset was used for the 2019 IFMBE Scientific Challenge organized during MEDICON 2019 where, in two phases, teams from all over the world tried to achieve the best possible object-detection accuracy based on the P300 signals. This paper presents the characteristics of the dataset and the approaches followed by the 9 finalist teams during the competition. The winner obtained an average accuracy of 92.3% with a convolutional neural network based on EEGNet. The dataset is now publicly released and stands as a benchmark for future P300-based BCI algorithms based on multiple session data.
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http://dx.doi.org/10.3389/fnins.2020.568104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556208PMC
September 2020

The Retinal Inner Plexiform Synaptic Layer Mirrors Grey Matter Thickness of Primary Visual Cortex with Increased Amyloid Load in Early Alzheimer's Disease.

Neural Plast 2020 21;2020:8826087. Epub 2020 Sep 21.

Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal.

The retina may serve as putative window into neuropathology of synaptic loss in Alzheimer's disease (AD). Here, we investigated synapse-rich layers versus layers composed by nuclei/cell bodies in an early stage of AD. In addition, we examined the associations between retinal changes and molecular and structural markers of cortical damage. We recruited 20 AD patients and 17 healthy controls (HC). Combining optical coherence tomography (OCT), magnetic resonance (MR), and positron emission tomography (PET) imaging, we measured retinal and primary visual cortex (V1) thicknesses, along with V1 amyloid (A) retention ([11C]-PiB PET tracer) and neuroinflammation ([11C]-PK11195 PET tracer). We found that V1 showed increased amyloid-binding potential, in the absence of neuroinflammation. Although thickness changes were still absent, we identified a positive association between the synapse-rich inner plexiform layer (IPL) and V1 in AD. This retinocortical interplay might reflect changes in synaptic function resulting from A deposition, contributing to early visual loss.
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http://dx.doi.org/10.1155/2020/8826087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525303PMC
September 2020

Distinct mechanisms drive hemispheric lateralization of object recognition in the visual word form and fusiform face areas.

Brain Lang 2020 11 15;210:104860. Epub 2020 Sep 15.

CIBIT- Center for Biomedical Imaging and Translational Research, ICNAS, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Electronic address:

The Visual Word Form Area (VWFA) and the Fusiform Face Area (FFA) represent classical examples of functional lateralization. The known hypothesis that lateralization of the VWFA and FFA are related remains controversial. We hypothesized that lateralization is independent and might be associated with lateralized high-level top-down mechanisms. For the VWFA this could emerge from left-lateralized language regions. This driving force might modulate local reorganization/recycling of function. Using an fMRI recognition paradigm, we quantified lateralization and investigated effective connectivity to examine mechanisms associated with lateralization in these regions (n = 58). Laterality patterns were more pronounced for VWFA than for FFA. Granger Causality Analysis found top-down effects only for the VWFA (left-lateralized, stemming from Broca's area). FFA exerted top-down effects on low-level visual areas. These findings suggest that distinct mechanisms are associated with hemispheric lateralization in object recognition: left lateralized top-down for VWFA and only early visual top-down effects concerning the FFA.
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http://dx.doi.org/10.1016/j.bandl.2020.104860DOI Listing
November 2020

The blood-brain barrier is disrupted in Machado-Joseph disease/spinocerebellar ataxia type 3: evidence from transgenic mice and human post-mortem samples.

Acta Neuropathol Commun 2020 08 31;8(1):152. Epub 2020 Aug 31.

CNC - Center for Neuroscience and Cell Biology of Coimbra, Molecular Therapy of Brain Disorders Group, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal.

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 transgenic mouse model of MJD and in human post-mortem brain tissues.Firstly, we investigated the BBB permeability in MJD mice by: i) assessing the extravasation of the Evans blue (EB) dye and blood-borne proteins (e.g fibrinogen) in the cerebellum by immunofluorescence, and ii) in vivo Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI). The presence of ataxin-3 aggregates in brain blood vessels and the levels of tight junction (TJ)-associated proteins were also explored by immunofluorescence and western blotting. Human brain samples were used to confirm BBB permeability by evaluating fibrinogen extravasation, co-localization of ataxin-3 aggregates with brain blood vessels and neuroinflammation.In the cerebellum of the mouse model of MJD, there was a 5-fold increase in EB accumulation when compared to age-matched controls. Moreover, vascular permeability displayed a 13-fold increase demonstrated by DCE-MRI. These results were validated by the 2-fold increase in fibrinogen extravasation in transgenic animals comparing to controls. Interestingly, mutant ataxin-3 aggregates were detected in cerebellar blood vessels of transgenic mice, accompanied by alterations of TJ-associated proteins in cerebellar endothelial cells, namely a 29% decrease in claudin-5 oligomers and a 10-fold increase in an occludin cleavage fragment. These results were validated in post-mortem brain samples from MJD patients as we detected fibrinogen extravasation across BBB, the presence of ataxin-3 aggregates in blood vessels and associated microgliosis.Altogether, our results prove BBB impairment in MJD/SCA3. These findings contribute for a better understanding of the disease mechanisms and opens the opportunity to treat MJD with medicinal products that in normal conditions would not cross the BBB.
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http://dx.doi.org/10.1186/s40478-020-00955-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457506PMC
August 2020

Ventral Caudate and Anterior Insula Recruitment During Value Estimation of Passionate Rewarding Cues.

Front Neurosci 2020 29;14:678. Epub 2020 Jul 29.

Coimbra Institute for Biomedical Imaging and Translational Research, Institute for Nuclear Sciences Applied to Health, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

"Wanting", a component of reward processing, is a motivational property that guides decision making in goal-oriented behavior. This includes behavior aiming at supporting relational bonds, even at the group level. Accordingly, group belongingness works as this motivational property, which is fundamentally different from romantic or maternal love. While primary rewards (or learned associations, such as money) have been largely used to study the conceptual framework associated with "wanting," other cues triggering behavior, such as passionate motives, are less well-studied. We investigated the neural correlates of value estimation of a passion-driven incentive in neuropsychologically defined football fans. We asked the participants ( = 57) to compute the value of football tickets (the cues that trigger passionate behavior in this "tribal love" context). The trials were all different, comprising tickets for different matches. The participants had no restrictions on the amount to be introduced. This enabled a parametric functional magnetic resonance imaging design based on the explicit estimated value given by the participants in a trial-by-trial approach. Using a whole-brain approach (to prevent biased focus on value-related regions), only the activity in the ventral caudate and left anterior insula showed a critical relationship with the reported value. Higher normalized values led to more activity in the striatum and left insula. The parametric map shows that these regions encode the magnitude of incentive by indexing self-relevant value. Other regions were involved in value computation, such as the ventromedial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex, but did not exhibit parametric patterns. The involvement of the nucleus accumbens in value estimation was only found in region of interest -based analysis, which emphasizes the role of the ventral caudate for the presently studied social "reinforcer" cue.
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http://dx.doi.org/10.3389/fnins.2020.00678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403482PMC
July 2020

Peptide-lipid nanoconstructs act site-specifically towards glioblastoma growth impairment.

Eur J Pharm Biopharm 2020 Oct 20;155:177-189. Epub 2020 Aug 20.

Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; Coimbra Chemistry Centre, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal; Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, Faculty of Medicine, Rua Larga, Pólo I, 1st floor, 3004-504 Coimbra, Portugal. Electronic address:

Ultra-small nanostructured lipid carriers (usNLCs) have been hypothesized to promote site-specific glioblastoma (GB) drug delivery. Envisioning a multitarget purpose towards tumor cells and microenvironment, a surface-bioconjugated usNLC prototype is herein presented. The comeback of co-delivery by repurposing atorvastatin and curcumin, as complementary therapy, was unveiled and characterized, considering colloidal properties, stability, and drug release behavior. Specifically, the impact of the surface modification of usNLCs with hyaluronic acid (HA) conjugates bearing the cRGDfK and Hk(R) peptides, and folic acid (FA) on GB cells was sequentially evaluated, in terms of cytotoxicity, internalization, uptake mechanism and hemolytic character. As proof-of-principle, the biodistribution, tolerability, and efficacy of the nanocarriers were assessed, the latter in GB-bearing mice through magnetic resonance imaging and spectroscopy. The hierarchical modification of the usNLCs promotes a preferential targeting behavior to the brain, while simultaneously sparing the elimination by clearance organs. Moreover, usNLCs were found to be well tolerated by mice and able to impair tumor growth in an orthotopic xenograft model, whereas for mice administered with the non-encapsulated therapeutic compounds, tumor growth exceeded 181% in the same period. Relevant biomarkers extracted from metabolic spectroscopy were ultimately identified as a potential tumor signature.
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http://dx.doi.org/10.1016/j.ejpb.2020.08.015DOI Listing
October 2020

Preparation of an Academic Clinical Trial.

Methods Mol Biol 2021 ;2197:317-330

CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.

Clinical trials are research studies performed in humans to evaluate the efficacy and safety of an intervention. They are the primary method by which researchers discover if a new treatment (drug, diet, medical device) is safe and effective in humans. DNA vaccines are considered, by definition, advanced therapy medicinal products (ATMPs). ATMPs are medicines for human use that are based on genes, tissues, or cells. They offer groundbreaking new opportunities for the treatment of disease and injury. Clinical trials using ATMPs are subject to specific regulatory requirements. This chapter will describe the most important steps when planning a clinical trial with DNA vaccines, such as regulatory and submission requirements, designing of a successful clinical trial protocol, stakeholders' responsibilities, and feasibility assessment.
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http://dx.doi.org/10.1007/978-1-0716-0872-2_18DOI Listing
March 2021

Ethics of DNA Vaccine Transfer for Clinical Research.

Methods Mol Biol 2021 ;2197:307-316

CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.

Several experimental human DNA vaccines are currently undergoing Phase I, II, and III clinical trials in order to investigate their efficacy and safety. Human clinical trials must follow guidelines and procedures that have been approved by the regulatory authorities and ethics committees. Ethical clinical research is much more than applying an informed consent to participants. In this chapter we will review the ethical standards and provide a framework to evaluate and design ethical clinical research. Despite being universal standards supported by universal guidelines, they must be adapted to the conditions in each country where the clinical research is being conducted.
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http://dx.doi.org/10.1007/978-1-0716-0872-2_17DOI Listing
March 2021

How positive emotional content overrules perceptual history effects: Hysteresis in emotion recognition.

J Vis 2020 08;20(8):19

Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal.

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 context, potentially leading to a phenomenon known as perceptual hysteresis. Here, we aimed to explore temporal context-related mechanisms underlying perceptual hysteresis during emotion recognition. We hypothesized that dependence on recent perceptual experience might reveal important clues about the role of short-term memory on the perception of emotional stimuli. Behavioral data were acquired using reality-based, changing emotion expressions morphed from a source to a target emotion with different valences, always passing through a neutral expression. Participants identified the onset and offset of what they perceived as the neutral expression interval. Our results showed that current perception of emotional expression is affected by recent temporal context, thus revealing perceptual hysteresis. We also found a relation between recent perceptual history effects and stimulus emotional Content: The positive valence of the stimulus emotional content appeared to abolish perceptual history effects, whereas negatively loaded stimuli induced clear short-term memory effects and positive hysteresis. Our findings show direct competition between recent perceptual experience and stimulus emotional content during decision making, which affects the formation of current percepts in emotion recognition.
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http://dx.doi.org/10.1167/jov.20.8.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438663PMC
August 2020

Volitional Modulation of the Left DLPFC Neural Activity Based on a Pain Empathy Paradigm-A Potential Novel Therapeutic Target for Pain.

Front Neurol 2020 21;11:714. Epub 2020 Jul 21.

Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal.

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 pain empathy. We conducted a neurofeedback experiment using real-time functional magnetic resonance imaging (rt-fMRI-NF) to investigate the association between activity in the left DLPFC (our neurofeedback target area) and the perspective assumed by the participant ("first-person"/"Self" or "third-person"/"Other" perspective of a pain-inducing stimulus), based on a customized pain empathy task. Our main goals were to assess the participants' ability to volitionally modulate activity in their own DLPFC through an imagery task of pain empathy and to investigate into which extent this ability depends on feedback. Our results demonstrate participants' ability to significantly modulate brain activity of the neurofeedback target area for the "first-person"/"Self" and "third-person"/"Other" perspectives. Results of both perspectives show that the participants were able to modulate (with statistical significance) the activity already in the first run of the session, in spite of being naïve to the task and even in the absence of feedback information. Moreover, they improved modulation throughout the session, particularly in the "Self" perspective. These results provide new insights on the role of DLPFC in pain and pain empathy mechanisms and validate the proposed protocol, paving the way for future interventional studies in clinical populations with empathic deficits.
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http://dx.doi.org/10.3389/fneur.2020.00714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394699PMC
July 2020

The conscious experience of color constancy and neural responses to subliminal deviations - A behavioral and EEG/ERP oddball study.

Conscious Cogn 2020 09 7;84:102987. Epub 2020 Aug 7.

CNC.IBILI-Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Portugal; CIBIT, Coimbra Institute for Biomedical Imaging and Translational Research, ICNAS, University of Coimbra, Portugal. Electronic address:

Introduction: Color constancy, a property of conscious color experience, maintains object color appearance across illuminant changes. We investigated the neural correlates of subliminal vs. conscious stimulus deviations of color constancy manipulations.

Methods: Behavioral and Oddball EEG/ERP experiments were conducted (n = 20). Psychophysical illuminant variation discrimination thresholds were first estimated, to establish individual perceptual awareness ranges, allowing for simulation of natural daylight spectral and spatial variations on colored surfaces, at different ambiguity levels.

Results: Behavioral results validated illuminant choice. ERPs showed a significant modulation of posterior P1 component specifically for the subliminal global uniform deviation condition, respecting color constancy. Neural correlates of conscious percepts were identified at posterior N2-P3 latencies, parietal (P3b) and frontal regions.

Conclusions: We identified an early subliminal correlate of low-level illuminant change, which reflects automatic unconscious detection of global color constancy deviations. Its suppression under conscious perception is probably due to top-down suppression according to prediction error models.
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http://dx.doi.org/10.1016/j.concog.2020.102987DOI Listing
September 2020

Identification of competing neural mechanisms underlying positive and negative perceptual hysteresis in the human visual system.

Neuroimage 2020 11 11;221:117153. Epub 2020 Jul 11.

Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Portugal; Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal; ICNAS Produção, University of Coimbra, Portugal. Electronic address:

Hysteresis is a well-known phenomenon in physics that relates changes in a system with its prior history. It is also part of human visual experience (perceptual hysteresis), and two different neural mechanisms might explain it: persistence (a cause of positive hysteresis), which forces to keep a current percept for longer, and adaptation (a cause of negative hysteresis), which in turn favors the switch to a competing percept early on. In this study, we explore the neural correlates underlying these mechanisms and the hypothesis of their competitive balance, by combining behavioral assessment with fMRI. We used machine learning on the behavioral data to distinguish between positive and negative hysteresis, and discovered a neural correlate of persistence at a core region of the ventral attention network, the anterior insula. Our results add to the understanding of perceptual multistability and reveal a possible mechanistic explanation for the regulation of different forms of perceptual hysteresis.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117153DOI Listing
November 2020