Biology subjects

Cabrera-Alvarez, J.

Publications and source records attributed to Cabrera-Alvarez, J..

4 recordsLinked to original sources

bioRxiv2024

Individual alpha frequency tACS reduces functional connectivity across the default mode network

Structured AbstractO_ST_ABSObjectivesC_ST_ABSResearch on the influence of transcranial alternating current stimulation over alpha functional connectivity (FC) is scarce, and at the same time poses as a potential treatment for various diseases. This study aimed to investigate the effects of individualized alpha frequency tACS (IAF-tACS) on FC within the default mode network (DMN) in healthy individuals, particularly focusing on the precuneus (PCU) as a major hub within the network. Materials and Methods27 healthy participants were recruited, which underwent a 20-minute IAF-tACS session and three magnetoencephalography (MEG) recordings: two pre-stimulation and one post-stimulation. Participants were randomly assigned to either the stimulation or sham group. FC was evaluated through the corrected imaginary phase locking value (ci-PLV) and leakage corrected amplitude envelope correlation (AEC-c). Statistical analyses compared both Pre-Post FC ratio between groups through ratio t-tests and intragroup FC changes through repeated measures t-tests, with FDR correction applied to account for multiple comparisons. An additional analysis simulated the influence of the cortical folding on the effect of tACS over FC. ResultsIAF-tACS significantly decreased AEC-c within the PCU and DMN in the stimulation group compared to the sham group, especially influencing antero-posterior links between hubs of the DMN. No significant changes were observed in ci-PLV connectivity metrics. Negative correlations were found between AEC-c FC changes and power alterations in posterior DMN areas, suggesting a complex interaction between cortical folding and electric field direction. ConclusionsAgainst our initial hypothesis, IAF-tACS reduced FC in the DMN, possibly due to phase disparities introduced by cortical gyrification. These findings suggest that tACS might modulate FC in a more complex manner than previously thought, highlighting the need for further research into the personalized application of neuromodulation techniques, as well as its potential therapeutic implications for conditions like Alzheimers disease.

neuroscience↗

bioRxiv2024

Dynamics of Brain Connectivity across the Alzheimer's Disease Spectrum: a magnetoencephalography study

Alzheimers disease (AD) represents a major challenge in neurodegenerative disease research, as it is characterized by a complex pathophysiology that involves not only structural but also functional changes in the brain. While changes in static functional connectivity have already been linked to AD, there is still a lack of research studying dynamic functional connectivity (dFC) across the AD continuum, which could be crucial for identifying potential biomarkers for early diagnosis and tracking disease progression. This study leverages the high temporal resolution of MEG to dissect the dynamics of brain connectivity alterations across various stages of AD and their association with cognitive decline and structural brain changes. 321 participants were included in this study, categorized into healthy control, subjective cognitive decline (SCD), and mild cognitive impairment (MCI) groups. Amplitude envelope correlation with leakage correction was calculated over MEG signals using a sliding window, and the correlation across epochs was studied to assess dFC at whole-brain and node level. Finally, we explored dFC associations with cognitive scores, grey matter volume, and white matter fractal anisotropy. The study unveils a significant reduction in whole-brain dFC, especially within the alpha and beta frequency bands, as individuals advance along the AD continuum. Notably, the frontal and temporal lobes, as well as regions within the default mode network, exhibited pronounced dFC reductions. Finally, dFC significantly correlated with cognitive performance and changes in structural brain, suggesting the potential of the proposed dFC metric as sensitive indicator for monitoring disease progression. This investigation provides crucial insights into the temporal dynamics of brain connectivity alterations in the early stages of the AD spectrum, underlining the importance of dFC changes as reflective of cognitive and anatomical degeneration. The findings hint towards a strong relationship between connectivity profiles and white matter integrity, especially for high frequency activity in the association cortices. Key PointsO_LIDynamic functional connectivity declines over the AD spectrum. C_LIO_LIDynamic functional connectivity reductions are most prominent in orbitofrontal, temporal, and DMN-related areas. C_LIO_LICognitive performance, brain volumetrics, and white matter integrity parameters positively correlate with dynamic functional connectivity over the whole AD spectrum, and most significantly among mild cognitive impairment participants. C_LI

neuroscience↗

bioRxiv2023

A multiscale closed-loop neurotoxicity model of Alzheimer's disease progression explains functional connectivity alterations

While the accumulation of amyloid-beta (A{beta}) and hyperphosphorylated-tau (hp-tau) as two classical histopathological biomarkers are crucial in Alzheimers disease (AD), their detailed interaction with the electrophysiological changes at the meso- and macroscale are not yet fully understood. We developed a mechanistic mequltiscale model of AD progression, linking proteinopathy to its effects on neural activity and vice-versa. We integrated a heterodimer model of prion-like protein propagation, and a network of Jansen-Rit electrical oscillators whose model parameters varied due to neurotoxicity. Changes in inhibition guided the electrophysiological alterations found in AD, and both A{beta} and hp-tau-related inhibition changes were able to produce similar effects independently. Additionally, we found a causal disconnection between cellular hyperactivity and interregional hypersynchrony. Finally, we demonstrated that early A{beta} and hp-tau depositions location determine the spatiotemporal profile of the proteinopathy. The presented model combines the molecular effects of bothA{beta} and hp-tau together with a mechanistic protein propagation model and network effects within a unique closed-loop model. This holds the potential to enlighten the interplay between AD mechanisms on various scales, aiming to develop and test novel hypotheses on the contribution of different AD-related variables to the disease evolution. Significance StatementThis research presents a groundbreaking closed-loop model of AD mechanisms, bridging the gap between protein distribution and neural activity. Contrary to prior assumptions, the study reveals that interregional hyper-synchrony and cellular hyperactivity are not directly linked. Notably, the model identifies neural inhibition as a potential causal factor in neurophysiological AD alterations and posits early depositions of A{beta} as a determinant of the spatiotemporal profile of proteinopathy. The significance of this mechanistic disease framework lies in its potential to produce insights into AD evolution and to guide novel treatment strategies. It underscores the importance of further experiments and modelling efforts to refine our understanding of AD, offering hope for more effective treatments and personalized care in the fight against dementia.

neuroscience↗

bioRxiv2023

Modeling the role of the thalamus in resting-state functional connectivity: nature or structure

The thalamus is a central brain structure that serves as a relay station for sensory inputs from the periphery to the cortex and regulates cortical arousal. Traditionally, it has been regarded as a passive relay that transmits information between brain regions. However, recent studies have suggested that the thalamus may also play a role in shaping functional connectivity (FC) in a task-based context. Based on this idea, we hypothesized that due to its centrality in the network and its involvement in cortical activation, the thalamus may also contribute to resting-state FC, a key neurological biomarker widely used to characterize brain function in health and disease. To investigate this hypothesis, we constructed ten in-silico brain network models based on neuroimaging data (MEG, MRI, and dwMRI), and simulated them including and excluding the thalamus. and raising the noise into thalamus to represent the afferences related to the reticular activating system (RAS) and the relay of peripheral sensory inputs. We simulated brain activity and compared the resulting FC to their empirical MEG counterparts to evaluate models performance. Results showed that a parceled version of the thalamus with higher noise, able to drive damped cortical oscillators, enhanced the match to empirical FC. However, with an already active self-oscillatory cortex, no impact on the dynamics was observed when introducing the thalamus. We also demonstrated that the enhanced performance was not related to the structural connectivity of the thalamus, but to its higher noisy inputs. Additionally, we highlighted the relevance of a balanced signal-to-noise ratio in thalamus to allow it to propagate its own dynamics. In conclusion, our study sheds light on the role of the thalamus in shaping brain dynamics and FC in resting-state and allowed us to discuss the general role of criticality in the brain at the mesoscale level. Author summarySynchrony between brain regions is an essential aspect of coordinated brain function and serves as a biomarker of health and disease. The thalamus, due to its centrality and widespread connectivity with the cortex, is a crucial structure that may contribute to this synchrony by allowing distant brain regions to work together. In this study, we used computational models to investigate the thalamuss role in generating brain synchrony at rest. Our findings suggest that the structural connectivity of the thalamus is not its primary contribution to brain synchrony. Instead, we found that the thalamus plays a critical role in driving cortical activity, and when it is not driving this activity, its impact on brain synchrony is null. Our study provides valuable insights into the thalamocortical networks role in shaping brain dynamics and FC in resting state, laying the groundwork for further research in this area.

neuroscience↗