approfondimento - Computational neuroscience - # Topographical Organization of the Human Pulvinar Complex

Multiscale Gradient Organization of the Human Pulvinar Complex: Integrating Functional Connectivity, Structural Connectivity, and Receptor Expression

Q: How might the multimodal gradient architecture of the pulvinar complex be altered in specific neurological or psychiatric disorders, and how could this inform targeted therapeutic interventions?

The multimodal gradient architecture of the pulvinar complex is crucial for its role in integrating information across various cortical networks. In specific neurological or psychiatric disorders, such as autism spectrum disorders (ASD), Parkinson’s disease, and schizophrenia, alterations in this gradient organization may manifest as disrupted connectivity patterns and receptor expression profiles. For instance, reduced availability of D2/3 receptors in the pulvinar has been correlated with functional connectivity to regions implicated in social communication, suggesting that the pulvinar's role in processing social cues may be compromised in ASD. Similarly, in Parkinson’s disease, the anterior pulvinar, characterized by high expression of serotonin transporters and low expression of D2 receptors, has shown reduced volume, indicating a potential link between pulvinar structure and mood regulation. Understanding these alterations can inform targeted therapeutic interventions. For example, pharmacological treatments that modulate serotonergic or dopaminergic systems could be tailored to restore the balance of receptor expression and connectivity in the pulvinar. Additionally, deep brain stimulation targeting specific pulvinar regions may enhance communication between the pulvinar and associated cortical networks, potentially alleviating symptoms in conditions like epilepsy or mood disorders. By leveraging the insights gained from the multimodal gradient architecture, clinicians can develop more precise and effective treatment strategies that address the underlying neurobiological disruptions in these disorders.

Q: What are the potential limitations of using group-level receptor expression data from PET imaging to infer the relationship between neurotransmitter systems and pulvinar organization, and how could this be addressed in future studies?

Using group-level receptor expression data from positron emission tomography (PET) imaging presents several limitations when inferring the relationship between neurotransmitter systems and pulvinar organization. One significant limitation is the inherent variability in receptor expression across individuals, which can obscure the true relationship between neurotransmitter systems and pulvinar connectivity. Group-level averages may mask important individual differences, leading to generalized conclusions that do not accurately reflect the neurobiological reality for specific individuals. Additionally, PET imaging is subject to partial volume effects, particularly in small structures like the pulvinar, where the spatial resolution may not be sufficient to capture nuanced receptor distributions. This can result in inaccurate estimates of receptor density and coexpression patterns, further complicating the interpretation of the data. To address these limitations, future studies could employ advanced imaging techniques, such as ultra-high field MRI, which offers improved spatial resolution and may provide more detailed insights into pulvinar organization. Furthermore, integrating multimodal approaches that combine PET with other imaging modalities, such as functional MRI (fMRI) and diffusion-weighted imaging (DWI), could enhance the understanding of how receptor expression correlates with functional and structural connectivity. Longitudinal studies tracking changes in receptor expression and connectivity over time in the same individuals could also provide valuable insights into the dynamic nature of pulvinar organization and its relationship with neurotransmitter systems.

Concetti Chiave

The human pulvinar complex exhibits a continuous, gradient-like organization of functional connectivity, structural connectivity, and receptor expression patterns that aligns with the hierarchical organization of cortico-cortical connectivity.

Sintesi

The study investigates the organizational principles underlying the pulvinar-cortical connectivity in the human brain using a multimodal approach. Key findings:

The pulvinar complex exhibits a continuous, gradient-like organization that goes beyond discrete anatomical subdivisions. Diffusion embedding analysis reveals multiple topographical gradients of structural connections, functional coactivation, and molecular binding patterns.
The main gradient of pulvinar-cortical functional connectivity mirrors the principal gradient of cortico-cortical functional connectivity, reflecting a hierarchical progression from unimodal sensory/motor to multimodal associative cortical regions.
This unimodal-to-transmodal functional gradient aligns with gradients of structural connectivity and receptor expression, particularly for markers of serotonergic, noradrenergic, and dopaminergic neurotransmission.
A secondary gradient of pulvinar-cortical connectivity progresses from visual to sensorimotor processing regions, corresponding to the medio-lateral structural connectivity gradient and a gradient of mu-opioid and serotonin transporter expression.
The multimodal gradient architecture of the pulvinar provides a framework for understanding its role in higher-order perceptual and cognitive functions, as well as its involvement in various neurological and psychiatric disorders.

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Statistiche

"The pulvinar complex serves as a pivotal hub in a myriad of cortico-subcortical networks that interconnect various cortical regions of the brain."
"Functional MRI-based parcellation studies have provided insights into functional specialization within sub-regions of the human pulvinar."
"Nearly 90% of the global variance in structural connectivity values was explained by the first two connectivity gradients (GSC1-GSC2)."
"The first three gradient embeddings (GRC1-GRC3) explained globally ∼80% of the variance in receptor coexpression data both for the left and right pulvinar."

Citazioni

"Connectivity gradients serve as low-dimensional representations of the topographical organization patterns of connectivity, whether functional or structural connectivity."
"We contend that our findings mark a significant stride towards a more comprehensive understanding of pulvinar anatomy and function, providing a nuanced characterization of its role in health and disease."
"Our proposed model confirms the hypothesis of a 'replication principle', illustrating that the pulvinar complex harbors multiple representations of cortico-cortical functional connectivity organized hierarchically by their information processing significance across its ventro-dorsal and medio-lateral axes."

Approfondimenti chiave tratti da

The replication principle revisited: a shared functional organization between pulvinar-cortical and cortico-cortical connectivity and its structural and molecular imaging correlates

by Basile,G. A.... alle www.biorxiv.org 07-12-2024

https://www.biorxiv.org/content/10.1101/2024.07.11.603063v1

Domande più approfondite

How might the multimodal gradient architecture of the pulvinar complex be altered in specific neurological or psychiatric disorders, and how could this inform targeted therapeutic interventions?

The multimodal gradient architecture of the pulvinar complex is crucial for its role in integrating information across various cortical networks. In specific neurological or psychiatric disorders, such as autism spectrum disorders (ASD), Parkinson’s disease, and schizophrenia, alterations in this gradient organization may manifest as disrupted connectivity patterns and receptor expression profiles. For instance, reduced availability of D2/3 receptors in the pulvinar has been correlated with functional connectivity to regions implicated in social communication, suggesting that the pulvinar's role in processing social cues may be compromised in ASD. Similarly, in Parkinson’s disease, the anterior pulvinar, characterized by high expression of serotonin transporters and low expression of D2 receptors, has shown reduced volume, indicating a potential link between pulvinar structure and mood regulation.
Understanding these alterations can inform targeted therapeutic interventions. For example, pharmacological treatments that modulate serotonergic or dopaminergic systems could be tailored to restore the balance of receptor expression and connectivity in the pulvinar. Additionally, deep brain stimulation targeting specific pulvinar regions may enhance communication between the pulvinar and associated cortical networks, potentially alleviating symptoms in conditions like epilepsy or mood disorders. By leveraging the insights gained from the multimodal gradient architecture, clinicians can develop more precise and effective treatment strategies that address the underlying neurobiological disruptions in these disorders.

What are the potential limitations of using group-level receptor expression data from PET imaging to infer the relationship between neurotransmitter systems and pulvinar organization, and how could this be addressed in future studies?

Using group-level receptor expression data from positron emission tomography (PET) imaging presents several limitations when inferring the relationship between neurotransmitter systems and pulvinar organization. One significant limitation is the inherent variability in receptor expression across individuals, which can obscure the true relationship between neurotransmitter systems and pulvinar connectivity. Group-level averages may mask important individual differences, leading to generalized conclusions that do not accurately reflect the neurobiological reality for specific individuals.
Additionally, PET imaging is subject to partial volume effects, particularly in small structures like the pulvinar, where the spatial resolution may not be sufficient to capture nuanced receptor distributions. This can result in inaccurate estimates of receptor density and coexpression patterns, further complicating the interpretation of the data.
To address these limitations, future studies could employ advanced imaging techniques, such as ultra-high field MRI, which offers improved spatial resolution and may provide more detailed insights into pulvinar organization. Furthermore, integrating multimodal approaches that combine PET with other imaging modalities, such as functional MRI (fMRI) and diffusion-weighted imaging (DWI), could enhance the understanding of how receptor expression correlates with functional and structural connectivity. Longitudinal studies tracking changes in receptor expression and connectivity over time in the same individuals could also provide valuable insights into the dynamic nature of pulvinar organization and its relationship with neurotransmitter systems.

Given the pulvinar's central role in integrating information across cortical networks, how might its gradient-based organization contribute to the emergence of conscious perception and subjective experience?

The pulvinar's gradient-based organization plays a pivotal role in the integration of information across cortical networks, which is essential for the emergence of conscious perception and subjective experience. The gradients identified in the pulvinar reflect a hierarchical organization that spans from low-level sensory processing areas to higher-order associative regions. This organization allows the pulvinar to facilitate the flow of information between different cortical areas, enabling the brain to synthesize sensory inputs into coherent perceptual experiences.
For instance, the principal gradient of functional connectivity, which transitions from unimodal sensory areas to multimodal associative regions, suggests that the pulvinar acts as a relay station that enhances communication between regions involved in processing different types of information. This integration is crucial for conscious perception, as it allows the brain to construct a unified representation of the environment, incorporating inputs from various sensory modalities.
Moreover, the pulvinar's involvement in attentional processes, as indicated by its connectivity patterns with frontoparietal and limbic networks, further underscores its role in shaping subjective experience. By modulating the flow of information based on attentional demands, the pulvinar can influence which sensory inputs are prioritized for conscious awareness, thereby affecting the content of subjective experience.
In summary, the pulvinar's gradient-based organization not only facilitates the integration of diverse sensory information but also plays a critical role in the attentional modulation necessary for conscious perception. This highlights the importance of the pulvinar in the broader context of cognitive functions and subjective experience, suggesting that disruptions in its organization could have profound implications for perception and awareness in both healthy individuals and those with neurological or psychiatric disorders.