Miguel Castelo-Branco

YNICL Journal 2025 Journal Article

“Actor-critic” dichotomous hyperactivation and hypoconnectivity in obsessive–compulsive disorder

• Ana Araújo
• Isabel C. Duarte
• Teresa Sousa
• Sofia Meneses
• Ana T. Pereira
• Trevor Robbins
• António Macedo
• Miguel Castelo-Branco

Dysfunctional response inhibition, mediated by the striatum and its connections, is thought to underly the clinical manifestations of obsessive-compulsive disorder (OCD). However, the exact neural mechanisms remain controversial. In this study, we undertook a novel approach by positing that a) inhibition is a dynamic construct inherently susceptible to numerous failures, which require error-processing, and b) the actor-critic framework of reinforcement learning can integrate neural patterns of inhibition and error-processing in OCD with their behavioural correlates. We invited nineteen adults with OCD and 21 age-matched healthy controls to perform an fMRI-adjusted stop-signal task. Then, we extracted brain activation and connectivity values regarding distinct task phases in the "actor" and "critic" regions, here corresponding to the caudate's head and dorsal putamen, and midbrain's nuclei (ventral tegmental area and substantia nigra). During response preparation phases of the inhibitory process, individuals with OCD exhibited decreased functional connectivity between the "critic" structures and frontal regions involved in cognitive and executive control. Activity analysis revealed task-related hyperactivation in the midbrain alongside error-processing-specific hyperactivation in the striatum, which was correlated with excessive behavioural slowness, also found in the clinical group. Finally, we identified a remarkable opponency between activity in the ventral tegmental area and caudate leading to direct increases and indirect decreases in symptom severity. We propose a unique "actor-critic"-based domain- and timing-dependent neural profile in OCD, reflecting "harm-avoidant" styles for response suppression, and influencing symptom severity. The dichotomy of hypoconnectivity and hyperactivation in the "critic" along with the opponent relationship between the "actor" and the "critic" in determining symptom severity suggests the implication of neural adaptation mechanisms in OCD with potential relevance for neurobiologically-driven therapies.

YNIMG Journal 2024 Journal Article

A human cortical adaptive mutual inhibition circuit underlying competition for perceptual decision and repetition suppression reversal

• Teresa Sousa
• Alexandre Sayal
• João V. Duarte
• Gabriel N. Costa
• Miguel Castelo-Branco

A model based on inhibitory coupling has been proposed to explain perceptual oscillations. This 'adapting reciprocal inhibition' model postulates that it is the strength of inhibitory coupling that determines the fate of competition between percepts. Here, we used an fMRI-based adaptation technique to reveal the influence of neighboring neuronal populations, such as reciprocal inhibition, in motion-selective hMT+/V5. If reciprocal inhibition exists in this region, the following predictions should hold: 1. stimulus-driven response would not simply decrease, as predicted by simple repetition-suppression of neuronal populations, but instead, increase due to the activity from adjacent populations; 2. perceptual decision involving competing representations, should reflect decreased reciprocal inhibition by adaptation; 3. neural activity for the competing percept should also later on increase upon adaptation. Our results confirm these three predictions, showing that a model of perceptual decision based on adapting reciprocal inhibition holds true. Finally, they also show that the net effect of the well-known repetition suppression phenomenon can be reversed by this mechanism.

YNIMG Journal 2024 Journal Article

Rapid effects of tryptamine psychedelics on perceptual distortions and early visual cortical population receptive fields

• Marta Lapo Pais
• Marta Teixeira
• Carla Soares
• Gisela Lima
• Patrícia Rijo
• Célia Cabral
• Miguel Castelo-Branco

N, N-dimethyltryptamine (DMT) is a psychedelic tryptamine acting on 5-HT2A serotonin receptors, which is associated with intense visual hallucinatory phenomena and perceptual changes such as distortions in visual space. The neural underpinnings of these effects remain unknown. We hypothesised that changes in population receptive field (pRF) properties in the primary visual cortex (V1) might underlie visual perceptual experience. We tested this hypothesis using magnetic resonance imaging (MRI) in a within-subject design. We used a technique called pRF mapping, which measures neural population visual response properties and retinotopic maps in early visual areas. We show that in the presence of visual effects, as documented by the Hallucinogen Rating Scale (HRS), the mean pRF sizes in V1 significantly increase in the peripheral visual field for active condition (inhaled DMT) compared to the control. Eye and head movement differences were absent across conditions. This evidence for short-term effects of DMT in pRF may explain perceptual distortions induced by psychedelics such as field blurring, tunnel vision (peripheral vision becoming blurred while central vision remains sharp) and the enlargement of nearby visual space, particularly at the visual locations surrounding the fovea. Our findings are also consistent with a mechanistic framework whereby gain control of ongoing and evoked activity in the visual cortex is controlled by activation of 5-HT2A receptors.

YNIMG Journal 2022 Journal Article

A two-stage framework for neural processing of biological motion

• João Valente Duarte
• Rodolfo Abreu
• Miguel Castelo-Branco

It remains to be understood how biological motion is hierarchically computed, from discrimination of local biological motion animacy to global dynamic body perception. Here, we addressed this functional separation of the correlates of the perception of local biological motion from perception of global motion of a body. We hypothesized that local biological motion processing can be isolated, by using a single dot motion perceptual decision paradigm featuring the biomechanical details of local realistic motion of a single joint. To ensure that we were indeed tackling processing of biological motion properties we used discrimination instead of detection task. We discovered using representational similarity analysis that two key early dorsal and two ventral stream regions (visual motion selective hMT+ and V3A, extrastriate body area EBA and a region within fusiform gyrus FFG) showed robust and separable signals related to encoding of local biological motion and global motion-mediated shape. These signals reflected two independent processing stages, as revealed by representational similarity analysis and deconvolution of fMRI responses to each motion pattern. This study showed that higher level pSTS encodes both classes of biological motion in a similar way, revealing a higher-level integrative stage, reflecting scale independent biological motion perception. Our results reveal a two-stage framework for neural computation of biological motion, with an independent contribution of dorsal and ventral regions for the initial stage.

YNICL Journal 2021 Journal Article

A fundamental distinction in early neural processing of implicit social interpretation in schizophrenia and bipolar disorder

• Nuno Madeira
• Ricardo Martins
• João Valente Duarte
• Gabriel Costa
• António Macedo
• Miguel Castelo-Branco

BACKGROUND: Social cognition impairment is a key phenomenon in serious mental disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). Although genetic and neurobiological studies have suggested common neural correlates, here we hypothesized that a fundamental dissociation of social processing occurs at an early level in these conditions. METHODS: Based on the hypothesis that key structures in the social brain, namely the temporoparietal junction, should present distinctive features in SCZ and BPD during low-level social judgment, we conducted a case-control study in SCZ (n = 20) and BPD (n = 20) patients and controls (n = 20), using task-based fMRI during a Theory of Mind (ToM) visual paradigm leading to interpretation of social meaning based on simple geometric figures. RESULTS: We found opposite neural responses in two core ToM regions: SCZ patients showed social content-related deactivation (relative to controls and BPD) of the right supramarginal gyrus, while the opposite pattern was found in BPD; reverse patterns, relative to controls and SCZ, were found in the left posterior superior temporal gyrus, a region involved in inferring other's intentions. Receiver-operating-characteristic curve analysis showed 88% accuracy in discriminating the two clinical groups based on these neural responses. CONCLUSIONS: These contrasting activation patterns of the temporoparietal junction in SCZ and BPD represent mechanistic differences of social cognitive dysfunction that may be explored as biomarkers or therapeutic targets.

YNICL Journal 2021 Journal Article

Differential early subcortical involvement in genetic FTD within the GENFI cohort

• Martina Bocchetta
• Emily G. Todd
• Georgia Peakman
• David M. Cash
• Rhian S. Convery
• Lucy L. Russell
• David L. Thomas
• Juan Eugenio Iglesias

BACKGROUND: Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups. METHODS: 480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR® plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more). RESULTS: In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9-10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2-3%), hippocampus (particularly presubiculum and CA1, 2-3%), amygdala (all subregions, 2-6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3-4%) and amygdala (accessory basal and superficial nuclei, 2-4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%). CONCLUSIONS: C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms.

YNICL Journal 2021 Journal Article

Disease-related cortical thinning in presymptomatic granulin mutation carriers

• Sergi Borrego-Écija
• Roser Sala-Llonch
• John van Swieten
• Barbara Borroni
• Fermín Moreno
• Mario Masellis
• Carmela Tartaglia
• Caroline Graff

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an increased CTh loss associated with age and estimated proximity to symptoms onset in GRN carriers, even before the disease onset.

YNIMG Journal 2020 Journal Article

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

• Alexandre Sayal
• Teresa Sousa
• João V. Duarte
• Gabriel N. Costa
• Ricardo Martins
• Miguel Castelo-Branco

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.

YNICL Journal 2020 Journal Article

Morphometry and gyrification in bipolar disorder and schizophrenia: A comparative MRI study

• Nuno Madeira
• João Valente Duarte
• Ricardo Martins
• Gabriel Nascimento Costa
• António Macedo
• Miguel Castelo-Branco

Schizophrenia is believed to be a neurodevelopmental disease with high heritability. Differential diagnosis is often challenging, especially in early phases, namely with other psychotic disorders or even mood disorders. such as bipolar disorder with psychotic symptoms. Key pathophysiological changes separating these two classical psychoses remain poorly understood, and current evidence favors a more dimensional than categorical differentiation between schizophrenia and bipolar disorder. While established biomarkers like cortical thickness and grey matter volume are heavily influenced by post-onset changes and thus provide limited possibility of accessing early pathologies, gyrification is assumed to be more specifically determined by genetic and early developmental factors. The aim of our study was to compare both classical and novel morphometric features in these two archetypal psychiatric disorders. We included 20 schizophrenia patients, 20 bipolar disorder patients and 20 age- and gender-matched healthy controls. Data analyses were performed with CAT12/SPM12 applying general linear models for four morphometric measures: gyrification and cortical thickness (surface-based morphometry), and whole-brain grey matter/grey matter volume (voxel-based morphometry - VBM). Group effects were tested using age and gender as covariates (and total intracranial volume for VBM). Voxel-based morphometry analysis revealed a schizophrenia vs. control group effect on regional grey matter volume (p < 0.05, familywise error correction) in the right globus pallidus. There was no group effect on white matter volume when correcting for multiple comparisons neither on cortical thickness. Gyrification changes in clinical samples were found in the left supramarginal gyrus (BA40) - increased and reduced gyrification, respectively, in BPD and SCZ patients - and in the right inferior frontal gyrus (BA47), with a reduction in gyrification of the SCZ group when compared with controls. The joint analysis of different morphometric features, namely measures such as gyrification, provides a promising strategy for the elucidation of distinct phenotypes in psychiatric disorders. Different morphological change patterns, highlighting specific disease trajectories, could potentially generate neuroimaging-derived biomarkers, helping to discriminate schizophrenia from bipolar disorder in early phases, such as first-episode psychosis patients.

YNICL Journal 2019 Journal Article

Evidence for impaired olfactory function and structural brain integrity in a disorder of ciliary function, Usher syndrome

• João Nuno Ramos
• João Carlos Ribeiro
• Andreia Carvalho Pereira
• Sónia Ferreira
• Isabel Catarina Duarte
• Miguel Castelo-Branco

Diseases involving cilia dysfunction, such as Usher Syndrome (USH), often involve visual and auditory loss. Psychophysical evidence has suggested that this may also hold true for the peripheral olfactory domain. Here we aimed to go a step further by attempting to establish relations between the integrity of cortical structures and olfactory function in this condition. We investigated olfactory function for USH types 1 (USH1) and 2 (USH2). Bilateral olfactory bulb (OB) volume and olfactory sulcus (OS) depth were also analysed. Thirty-three controls with no previous olfactory deficits were age, sex and handedness-matched to 32 USH patients (11 USH1, 21 USH2). A butanol detection threshold test was performed to measure olfactory function. For OB volume and OS depth, morphometric measurements were performed using magnetic resonance imaging (MRI) based on detailed segmentation by three independent operators. Averaged values across these were used for the statistical analyses. Total intracranial volume was estimated using Freesurfer to account for head size variability. Olfactory threshold was significantly lower in controls when compared to USH, USH1, and USH2. OS depth was found to be shallower in both hemispheres in USH patients when compared with the control group. OB volume was not significantly different between control and USH groups, or respective subgroups. Nevertheless, butanol threshold was negatively correlated with the left OB volume for the USH type 1 subgroup. The main effect of OS depth reduction was found to be mainly due to the comparison between USH2 and controls. Our results provide evidence for morphometric changes and olfactory dysfunction in patients with USH. This correlated with a reduction in left OB volume in the USH1 subgroup, the most severe USH phenotype. The main effect of reduced OS depth was found to stem mainly from USH2 raising questions regarding a possible complex interaction between sensory olfactory loss and central cortical changes in this disease.

YNIMG Journal 2019 Journal Article

Neural correlates of anticipatory cardiac deceleration and its association with the speed of perceptual decision-making, in young and older adults

• Maria J. Ribeiro
• Miguel Castelo-Branco

Warning stimuli in sensorimotor tasks induce a state of preparedness characterized by increased alertness, focused attention and immobility. This state of attentive anticipation is associated with heart rate deceleration. Ageing affects the amplitude of the anticipatory cardiac deceleration responses; yet, the impact of this physiological change on cognitive performance is still to be elucidated. In fact, how cardiac deceleration relates to brain function and cognitive performance in the context of perceptual decision-making and different levels of decision complexity remains unknown. Here, we aimed to investigate the relationship between cardiac deceleration, brain function, and performance in perceptual decision tasks and how these associate with age-related changes. We measured simultaneously the electrocardiogram, the pupilogram, and the electroencephalogram in 36 young and 39 older adults, while they were engaged in two auditory cued reaction time tasks: a detection task and a go/no-go task requiring inhibitory control. We observed robust cardiac deceleration responses that increased with increasing task complexity. Notably, stronger modulation of the cardiac response across tasks was associated with the ability to maintain response speed as decision complexity increased suggesting a link between cardiac deceleration and facilitation of perceptual decisions. Additionally, cardiac deceleration appears to have a cortical origin as it correlated with frontocentral event-related potentials. In contrast, beta oscillations at baseline and task-related beta suppression were not predictive of cardiac deceleration suggesting a dissociation between sensorimotor oscillatory activity and this cardiac response. Importantly, we found age-related changes in anticipatory cardiac deceleration associated with deficits in perceptual decision-making.

YNIMG Journal 2019 Journal Article

The inner fluctuations of the brain in presymptomatic Frontotemporal Dementia: The chronnectome fingerprint

• Enrico Premi
• Vince D. Calhoun
• Matteo Diano
• Stefano Gazzina
• Maura Cosseddu
• Antonella Alberici
• Silvana Archetti
• Donata Paternicò

Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials.

YNICL Journal 2019 Journal Article

White matter hyperintensities in progranulin-associated frontotemporal dementia: A longitudinal GENFI study

• Carole H. Sudre
• Martina Bocchetta
• Carolin Heller
• Rhian Convery
• Mollie Neason
• Katrina M. Moore
• David M. Cash
• Ione O.C. Woollacott

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders with both sporadic and genetic forms. Mutations in the progranulin gene (GRN) are a common cause of genetic FTD, causing either a behavioural presentation or, less commonly, language impairment. Presence on T2-weighted images of white matter hyperintensities (WMH) has been previously shown to be more commonly associated with GRN mutations rather than other forms of FTD. The aim of the current study was to investigate the longitudinal change in WMH and the associations of WMH burden with grey matter (GM) loss, markers of neurodegeneration and cognitive function in GRN mutation carriers. 336 participants in the Genetic FTD Initiative (GENFI) study were included in the analysis: 101 presymptomatic and 32 symptomatic GRN mutation carriers, as well as 203 mutation-negative controls. 39 presymptomatic and 12 symptomatic carriers, and 73 controls also had longitudinal data available. Participants underwent MR imaging acquisition including isotropic 1 mm T1-weighted and T2-weighted sequences. WMH were automatically segmented and locally subdivided to enable a more detailed representation of the pathology distribution. Log-transformed WMH volumes were investigated in terms of their global and regional associations with imaging measures (grey matter volumes), biomarker concentrations (plasma neurofilament light chain, NfL, and glial fibrillary acidic protein, GFAP), genetic status (TMEM106B risk genotype) and cognition (tests of executive function). Analyses revealed that WMH load was higher in both symptomatic and presymptomatic groups compared with controls and this load increased over time. In particular, lesions were seen periventricularly in frontal and occipital lobes, progressing to medial layers over time. However, there was variability in the WMH load across GRN mutation carriers - in the symptomatic group 25.0% had none/mild load, 37.5% had medium and 37.5% had a severe load - a difference not fully explained by disease duration. GM atrophy was strongly associated with WMH load both globally and in separate lobes, and increased WMH burden in the frontal, periventricular and medial regions was associated with worse executive function. Furthermore, plasma NfL and to a lesser extent GFAP concentrations were seen to be associated with increased lesion burden. Lastly, the presence of the homozygous TMEM106B rs1990622 TT risk genotypic status was associated with an increased accrual of WMH per year. In summary, WMH occur in GRN mutation carriers and accumulate over time, but are variable in their severity. They are associated with increased GM atrophy and executive dysfunction. Furthermore, their presence is associated with markers of WM damage (NfL) and astrocytosis (GFAP), whilst their accrual is modified by TMEM106B genetic status. WMH load may represent a target marker for trials of disease modifying therapies in individual patients but the variability across the GRN population would prevent use of such markers as a global outcome measure across all participants in a trial.

YNICL Journal 2018 Journal Article

Data driven diagnostic classification in Alzheimer's disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of Aβ species

• Francisco Oliveira
• Antoine Leuzy
• João Castelhano
• Konstantinos Chiotis
• Steen Gregers Hasselbalch
• Juha Rinne
• Alexandre Mendonça
• Markus Otto

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 lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification. We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid β (Aβ) species concentrations. 243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of Aβ38, Aβ40 and Aβ42 were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF Aβ concentrations were calculated. Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than Aβ concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. Aβ38 and Aβ40 correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with Aβ42, the Aβ42/Aβ40 or Aβ42/Aβ38 ratios were found compared to normalization based on cerebellar gray matter.

YNIMG Journal 2018 Journal Article

Evidence for distinct levels of neural adaptation to both coherent and incoherently moving visual surfaces in visual area hMT+

• Teresa Sousa
• Alexandre Sayal
• João V. Duarte
• Gabriel N. Costa
• Ricardo Martins
• Miguel Castelo-Branco

Visual adaptation describes the processes by which the visual system alters its operating properties in response to changes in the environment. It is one of the mechanisms controlling visual perceptual bistability – when two perceptual solutions are available – by controlling the duration of each percept. Moving plaids are an example of such ambiguity. They can be perceived as two surfaces sliding incoherently over each other or as a single coherent surface. Here, we investigated, using fMRI, whether activity in the human motion complex (hMT+), a region tightly related to the perceptual integration of visual motion, is modulated by distinct forms of visual adaptation to coherent or incoherent perception of moving plaids. Our hypothesis is that exposure to global coherent or incoherent moving stimuli leads to different levels of measurable adaptation, reflected in hMT+ activity. We found that the strength of the measured visual adaptation effect depended on whether subjects integrated (coherent percept) or segregated (incoherent percept) surface motion signals. Visual motion adaptation was significant both for coherent motion and globally incoherent surface motion. Although not as strong as to the coherent percept, visual adaptation due to the incoherent percept also affects hMT+. This shows that adaptation can contribute to regulate percept duration during visual bistability, with distinct weights, depending on the type of percept. Our findings suggest a link between bistability and adaptation mechanisms, both due to coherent and incoherent motion percepts, but in an asymmetric manner. These asymmetric adaptation weights have strong implications in models of perceptual decision and may explain asymmetry of perceptual interpretation periods.

YNIMG Journal 2018 Journal Article

Radial asymmetries in population receptive field size and cortical magnification factor in early visual cortex

• Maria Fatima Silva
• Jan W. Brascamp
• Sónia Ferreira
• Miguel Castelo-Branco
• Serge O. Dumoulin
• Ben M. Harvey

Human visual cortex does not represent the whole visual field with the same detail. Changes in receptive field size, population receptive field (pRF) size and cortical magnification factor (CMF) with eccentricity are well established, and associated with changes in visual acuity with eccentricity. Visual acuity also changes across polar angle. However, it remains unclear how RF size, pRF size and CMF change across polar angle. Here, we examine differences in pRF size and CMF across polar angle in V1, V2 and V3 using pRF modeling of human fMRI data. In these visual field maps, we find smaller pRFs and larger CMFs in horizontal (left and right) than vertical (upper and lower) visual field quadrants. Differences increase with eccentricity, approximately in proportion to average pRF size and CMF. Similarly, we find larger CMFs in the lower than upper quadrant, and again differences increase with eccentricity. However, pRF size differences between lower and upper quadrants change direction with eccentricity. Finally, we find slightly smaller pRFs in the left than right quadrants of V2 and V3, though this difference is very small, and we find no differences in V1 and no differences in CMF. Moreover, differences in pRF size and CMF vary gradually with polar angle and are not limited to the meridians or visual field map discontinuities. PRF size and CMF differences do not consistently follow patterns of cortical curvature, despite the link between cortical curvature and polar angle in V1. Thus, the early human visual cortex has a radially asymmetric representation of the visual field. These asymmetries may underlie consistent reports of asymmetries in perceptual abilities.

YNICL Journal 2017 Journal Article

Primary visual cortical remapping in patients with inherited peripheral retinal degeneration

• Sónia Ferreira
• Andreia Carvalho Pereira
• Bruno Quendera
• Aldina Reis
• Eduardo Duarte Silva
• Miguel Castelo-Branco

Human studies addressing the long-term effects of peripheral retinal degeneration on visual cortical function and structure are scarce. Here we investigated this question in patients with Retinitis Pigmentosa (RP), a genetic condition leading to peripheral visual degeneration. We acquired functional and anatomical magnetic resonance data from thirteen patients with different levels of visual loss and twenty-two healthy participants to study primary (V1) visual cortical retinotopic remapping and cortical thickness. We identified systematic visual field remapping in the absence of structural changes in the primary visual cortex of RP patients. Remapping consisted in a retinotopic eccentricity shift of central retinal inputs to more peripheral locations in V1. Importantly, this was associated with changes in visual experience, as assessed by the extent of the visual loss, with more constricted visual fields resulting in larger remapping. This pattern of remapping is consistent with expansion or shifting of neuronal receptive fields into the cortical regions with reduced retinal input. These data provide evidence for functional changes in V1 that are dependent on the magnitude of peripheral visual loss in RP, which may be explained by rapid cortical adaptation mechanisms or long-term cortical reorganization. This study highlights the importance of analyzing the retinal determinants of brain functional and structural alterations for future visual restoration approaches.

JBHI Journal 2016 Journal Article

Optic Disc Localization in Retinal Images Based on Cumulative Sum Fields

• Ivo Soares
• Miguel Castelo-Branco
• Antonio M. G. Pinheiro

This paper describes an automatic method for the optic disc localization in retinal images, which is effective and reliable with multiple datasets. Particularly, the described method reveals very effective dealing with retinal images with large pathological signs. The algorithm begins with a new vessel enhancement method based on a modified corner detector. Subsequently, a weighted version of the vessel enhancement is combined with morphological operators, to detect the four main vessels orientations {0°, 45°, 90°, 135°}. These four image functions have all the necessary information to determine an initial optic disc localization, resulting in two images that are respectively divided along the vertical or horizontal orientations with different division sizes. Each division is averaged creating a 2-D step function, and a cumulative sum of the different sizes step functions is calculated in the vertical and horizontal orientations, resulting in an initial optic disc position. The final optic disc localization is determined by a vessel convergence algorithm using its two most relevant features; high vasculature convergence and high intensity values. The proposed method was evaluated in eight publicly available datasets, including the STARE and DRIVE datasets. The optic disc was localized correctly in 1752 out of the 1767 retinal images (99. 15%) with an average computation time of 18. 34 s.

YNIMG Journal 2013 Journal Article

Long term cortical plasticity in visual retinotopic areas in humans with silent retinal ganglion cell loss

• Otília C. d'Almeida
• Catarina Mateus
• Aldina Reis
• Manuela M. Grazina
• Miguel Castelo-Branco

Visual cortical plasticity induced by overt retinal lesions (scotomas) has remained a controversial phenomenon. Here we studied cortical plasticity in a silent model of retinal ganglion cell loss, documented by in vivo optical biopsy using coherence tomography. The cortical impact of non-scotomatous subtle retinal ganglion cell functional and structural loss was investigated in carriers of the mitochondrial DNA 11778G>A mutation causing Leber's hereditary optic neuropathy. We used magnetic resonance imaging (MRI) to measure cortical thickness and fMRI to define retinotopic cortical visual areas V1, V2 and V3 in silent carriers and matched control groups. Repeated Measures analysis of variance revealed a surprising increase in cortical thickness in the younger carrier group (below 21years of age). This effect dominated in extrastriate cortex, and notably V2. This form of structural plasticity suggests enhanced plastic developmental mechanisms in extrastriate retinotopic regions close to V1 and not receiving direct retinocortical input.

YNIMG Journal 2001 Journal Article

Activity patterns in human motion sensitive areas depend on the interpretation of global motion

• Miguel Castelo-Branco
• Elia Formisano
• Walter H. Backes
• Friedhelm E. Zanella
• Wolf Singer
• Rainer Goebel