Biology subjects

Fernandes, H. M.

Publications and source records attributed to Fernandes, H. M..

6 recordsLinked to original sources

bioRxiv2022

Brain dynamics predictive of response to psilocybin for treatment-resistant depression

Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.

neuroscience↗

bioRxiv2022

Altered dynamical integration/segregation balance during anesthesia-induced loss of consciousness

In recent years, brain imaging studies have begun to shed light on the neural correlates of physiologically-reversible altered states of consciousness such as deep sleep, anesthesia, psychedelic experiences. The emerging consensus is that normal waking consciousness requires the exploration of a dynamical repertoire enabling both global integration i.e. long-distance interactions between brain regions, and segregation, i.e. local processing in functionally specialized clusters. Altered states of consciousness have notably been characterized by a tipping of the integration/segregation balance away from this equilibrium. Historically, functional MRI (fMRI) has been the modality of choice for such investigations. However, fMRI does not enable characterization of the integration/segregation balance at sub-second temporal resolution. Here, we investigated global brain spatiotemporal patterns in electrocorticography (ECoG) data of a monkey (Macaca fuscata) under either ketamine or propofol general anaesthesia. We first studied the effects of these anesthetics from the perspective of band-specific synchronization across the entire ECoG array, treating individual channels as oscillators. We further aimed to determine whether synchrony within spatially localized clusters of oscillators was differently affected by the drugs in comparison to synchronization over spatially distributed subsets of ECoG channels, thereby quantifying changes in integration/segregation balance on physiologically-relevant time scales. The findings reflect global brain dynamics characterized by a loss of long-range integration in multiple frequency bands under both ketamine and propofol anaesthesia, most pronounced in the beta (13-30Hz) and low-gamma bands (30-80Hz), and with strongly preserved local synchrony in all bands.

neuroscience↗

bioRxiv2020

Sweet anticipation: Predictability of familiar music in autism

Autism has been characterised by different behavioural and cognitive profiles compared to typically developing (TD) individuals, and increasingly these differences have been associated with differences in structural and functional brain connectivity. It is currently unknown as to whether autistic and TD listeners process music in the same way: emotionally, mnemonically, and perceptually. The present study explores the brains dynamical landscape linked to music familiarity in an fMRI dataset from autistic and TD individuals. Group analysis using leading eigenvector dynamics analysis (LEiDA) revealed significantly higher probability of occurrence of a brain network in TD compared to autistic individuals during listening to familiar music. This network includes limbic and paralimbic areas (amygdala, hippocampus, parahippocampal gyrus, and temporal pole). No significant differences were found between autistic and TD individuals while listening to a scrambled, i.e. unfamiliar and more unpredictable, version of the same music track. These findings provide novel neuroimaging insights into how autistic prediction monitoring may shape brain networks during listening to familiar musical excerpts.

neuroscience↗

bioRxiv2020

The dynamics of the improvising brain: a study of musical creativity using jazz improvisation

The neuroscience of jazz improvisation has shown promising results for understanding domain-specific and domain-general processes of creativity. Here, we used fMRI to measure for the first time the dynamic neural substrates of musical creativity in 16 skilled jazz pianists while they played by memory, improvised freely (iFreely) and by melody (iMelody), and during resting-state. We used the Leading Eigenvector Dynamics Analysis (LEiDA) to examine how different modes of improvisation (musical creativity) evolve over time, and which cognitive mechanisms are responsible for different stages of musical creation. Our results reveal that a substate comprising auditory, sensorimotor and posterior salience networks had a significantly higher probability of occurrence (POc) in both modes of improvisation than in resting-state and play by memory. Another substate comprising the default mode (DMN), executive control (ECN) and language networks had significantly lower POc in iFreely than in resting-state, with iMelody having a higher POc than iFreely. Such indicates that iMelody, a more constrained form of creativity involves a higher recurrence of subsystems responsible for goal-directed cognition and cognitive control processes. On the other hand, iFreely recruits brain networks responsible for generation of spontaneous musical creativity. Overall, this study brings new insights into the large-scale brain mechanisms supporting and promoting the complex process of creativity, specifically in the context of jazz improvisation, as well as the relevance of different improvisation modes in creativity research.

neuroscience↗

bioRxiv2017

Disrupted structural connectivity in Pediatric Bipolar Disorder

Bipolar disorder (BD) has been linked to disrupted structural and functional connectivity between prefrontal networks and limbic brain regions. Studies of patients with pediatric bipolar disorder (PBD) can help elucidate the developmental origins of altered structural connectivity underlying BD and provide novel insights into the aetiology of BD. Here we compare the network properties of whole-brain structural connectomes of PBD patients with psychosis and euthymic matched healthy controls. Our results show widespread changes in the structural connectivity of PBD patients in both cortical and subcortical networks, notably affecting the orbitofrontal cortex, frontal gyrus, amygdala, hippocampus and basal ganglia. Graph theoretical analysis revealed that PBD connectomes have fewer hubs, weaker rich club organization, different modular fingerprint and inter-modular communication, compared to healthy participants. The relationship between network features and neurocognitive and psychotic scores was also assessed. Patients IQ and psychotic symptoms significantly correlated with the local efficiency of the orbitofrontal cortex. Our findings reveal that PBD is associated with significant widespread changes in structural network topology, thus strengthening the hypothesis of a reduced capacity for integrative processing of information across brain regions. Localised network changes involve core regions for emotional processing and regulation, as well as memory and executive function, some of which correlate with neurocognitive faculties and symptoms. Together, our findings provide the first comprehensive characterisation of the alterations in local and global structural brain connectivity and network topology, which may contribute to the deficits in cognition and emotion processing and regulation found in PBD.

neuroscience↗

bioRxiv2016

Uncovering the underlying mechanisms and whole-brain dynamics of therapeutic deep brain stimulation for Parkinson’s disease

Deep brain stimulation (DBS) for Parkinsons disease is a highly effective treatment in controlling otherwise debilitating symptoms yet the underlying brain mechanisms are currently not well understood. We used whole-brain computational modeling to disclose the effects of DBS ON and OFF during collection of resting state fMRI in ten Parkinsons Disease patients. Specifically, we explored the local and global impact of DBS in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts the global brain dynamics of patients nearer to that of healthy people by significantly changing the bifurcation parameters in brain regions implicated in Parkinsons Disease. We also found higher communicability and coherence brain measures during DBS ON compared to DBS OFF. Finally, by modeling stimulation we identified possible novel DBS targets. These results offer important insights into the underlying effects of DBS, which may in time offer a route to more efficacious treatments.

neuroscience↗