Disambiguating the role of blood flow and global signal with partial information decomposition

Global signal (GS) is an ubiquitous construct in resting state functional magnetic resonance imaging (rs-fMRI), associated to nuisance, but containing by definition most of the neuronal signal. Global signal regression (GSR) effectively removes the impact of physiological noise and other artifacts, but at the same time it alters correlational patterns in unpredicted ways. Performing GSR taking into account the underlying physiology (mainly the blood arrival time) has been proven to be beneficial. From these observations we aimed to: 1) characterize the effect of GSR on network-level functional connectivity in a large dataset; 2) assess the complementary role of global signal and vessels; and 3) use the framework of partial information decomposition to further look into the joint dynamics of the global signal and vessels, and their respective influence on the dynamics of cortical areas. We observe that GSR affects intrinsic connectivity networks in the connectome in a non-uniform way. Furthermore, by estimating the predictive information of blood flow and the global signal using partial information decomposition, we observe that both signals are present in different amounts across intrinsic connectivity networks. Simulations showed that differences in blood arrival time can largely explain this phenomenon, while using hemodynamic and calcium mouse recordings we were able to confirm the presence of vascular effects, as calcium recordings lack hemodynamic information. With these results we confirm network-specific effects of GSR and the importance of taking blood flow into account for improving de-noising methods. Additionally, and beyond the mere issue of data denoising, we quantify the diverse and complementary effect of global and vessel BOLD signals on the dynamics of cortical areas

Deletion of autism risk gene Shank3 disrupts prefrontal connectivity

Mutations in the synaptic scaffolding protein Shank3 are a major cause of autism, and are associated with prominent intellectual and language deficits. However, the neural mechanisms whereby SHANK3 deficiency affects higher order socio-communicative functions remain unclear. Using high-resolution functional and structural MRI in adult male mice, here we show that loss of Shank3 (Shank3B-/-) results in disrupted local and long-range prefrontal and fronto-striatal functional connectivity. We document that prefrontal hypo-connectivity is associated with reduced short-range cortical projections density, and reduced gray matter volume. Finally, we show that prefrontal disconnectivity is predictive of social communication deficits, as assessed with ultrasound vocalization recordings. Collectively, our results reveal a critical role of SHANK3 in the development of prefrontal anatomy and function, and suggest that SHANK3 deficiency may predispose to intellectual disability and socio-communicative impairments via dysregulation of higher-order cortical connectivity

Complete hemispherotomy leads to lateralized functional organization and lower level of consciousness in the isolated hemisphere

Objective To quantify whole‐brain functional organization after complete hemispherotomy, characterizing unexplored plasticity pathways and the conscious level of the dissected hemispheres. Methods Evaluation with multimodal magnetic resonance imaging in two pediatric patients undergoing right hemispherotomy including complete callosotomy with a perithalamic section. Regional cerebral blood flow and fMRI network connectivity assessed the functional integrity of both hemispheres after surgery. The level of consciousness was tested by means of a support vector machine classifier which compared the intrinsic organization of the dissected hemispheres with those of patients suffering from disorders of consciousness. Results After hemispherotomy, both patients showed typical daily functionality. We found no interhemispheric transfer of functional connectivity in either patient as predicted by the operation. The healthy left hemispheres displayed focal blood hyperperfusion in motor and limbic areas, with preserved network‐level organization. Unexpectedly, the disconnected right hemispheres showed sustained network organization despite low regional cerebral blood flow. Subcortically, functional connectivity was increased in the left thalamo‐cortical loop and between the cerebelli. One patient further showed unusual ipsilateral right cerebello‐cortical connectivity, which was explained by the mediation of the vascular system. The healthy left hemisphere had higher probability to be classified as in a minimally conscious state compared to the isolated right hemisphere. Significance Complete hemispherotomy leads to a lateralized whole‐brain organization, with the remaining hemisphere claiming most of the brain's energetic reserves supported by subcortical structures. Our results further underline the contribution of nonneuronal vascular signals on contralateral connectivity, shedding light on the nature of network organization in the isolated tissue. The disconnected hemisphere is characterized by a level of consciousness which is necessary but insufficient for conscious processing, paving the way for more specific inquiries about its role in awareness in the absence of behavioral output

Disambiguating the role of blood flow and global signal with partial information decomposition

Figures from the paper ' Disambiguating the role of blood flow and global signal with partial information decomposition'.https://www.biorxiv.org/content/10.1101/596247v2<br

Poster_OHBM_GS_Colenbier.pdf

Poster presented at OHBM and Resting State conferences in 2018, describing the partial information decomposition approach to disambiguate the role of global signal and BOLD in vessels in influencing the grey matter regions

voxelwise resting state HRF shape (WM and GM)

We used our rsHRF tool https://www.nitrc.org/projects/rshrf to retrieve a proxy of the hemodynamic response function from BOLD signal recorded at each voxel, both in grey and in white matter.These figures report the average relevant parameters (Height, Full Width at Half Maximum, Time to Peak) from Human Connectome Project data.We report results using two sets of basis functions: Canonical Shape with two derivatives (Canon2dd), and Finite Impulse Response (FIR).The 3D nifti images can be found here https://neurovault.org/collections/3584/</div