Rewiring neurotransmission after parietal damage in the human bain – Neurotransmission

The project uses a hybrid PET/fMRI machine to jointly record bold signal changes and neurotransmitter binding potential remapping. Functional adaptations are investigated with resting state functional connectivity BOLD magnetic resonance imaging (rs-fMRI), a tool that has been proved efficient to study network reorganizations in brain damaged patients. Neurotransmitter changes are studied using Positron Emission Tomography neurochemical imaging (PETNI). To date, to the best of our knowledge, no PETNI studies have been conducted to identify reorganizations of neurotransmitter maps in patients with focal brain lesions (let alone have combined PETNI with rs-fMRI recordings in this context). Of course, examining all brain regions, types of lesions and neurotransmitter systems is impossible in a single project. The project focuses on the reorganizations of GABAergic([11C]Flumazenil) and Serotonergic ([18F]MPPF) neurotransmission induced by acute and slow growing focal lesions of the posterior parietal cortex (a major functional region of the human brain).

In progress

At a fundamental level this proposal should improve our understanding of neurotransmitter plasticity and provide a more robust theoretical framework through which understanding how the brain adapts to focal injuries affecting major eloquent areas. At a clinical level it should help designing more efficient rehabilitation procedures by improving our understanding of post-lesional adaptive mechanisms.

In progress

During the last century, clinical studies have shown that post-lesional recovery was often poor in stroke patients. By contrast, recent observations have reported that 95 % of individuals with slow growing tumors were able to underwent surgical cerebral resections (sometimes massive) without detectable functional consequence; a result consistent with animal studies showing, for strictly comparable injuries, that functional recovery is consistently better in serial than acute resections.
The origin of this difference remains debated. Electrophysiological and neuroimaging studies have identified both local and remote reorganizations in all patients (tumor and ischemic). However, distant adaptations (mostly ipsilateral within the major nodes of the lesioned network and contralateral within the anatomical homologous) appear to be less efficient in acute than progressive injuries. In particular, it has been shown that the restoration of functional connectivity toward pre-injury patterns (a positive predictor long-term recovery) is more difficult to reach in acute injuries, where maladaptive responses have often been described, notably because of an imbalance of interhemispheric inhibition. In agreement with these claims, it has been reported that the fraction of stroke patients who exhibit a good level of recovery (up to 30 % in young subjects) also exhibit a clear normalization of their functional connectivity patterns.
The reasons why remote network-reorganizations are only efficient in tumor patients and a minority of stroke subjects remain unclear. The present project aims to tackle this issue. We will use a hybrid PET/fMRI machine to jointly record bold signal changes and neurotransmitter binding potential remapping. Functional adaptations will be investigated with resting state functional connectivity BOLD magnetic resonance imaging (rs-fMRI), a tool that has been proved efficient to study network reorganizations in brain damaged patients. Neurotransmitter changes will be studied using Positron Emission Tomography neurochemical imaging (PETNI). To date, to the best of our knowledge, no PETNI studies have been conducted to identify reorganizations of neurotransmitter maps in patients with focal brain lesions (let alone have combined PETNI with rs-fMRI recordings in this context). Of course, examining all brain regions, types of lesions and neurotransmitter systems is impossible in a single project. Here, we will focus on the reorganizations of GABAergic and Serotonergic neurotransmission induced by acute and slow growing focal lesions of the posterior parietal cortex (a major functional region of the human brain). More specifically, using [11C]Flumazenil and [18F]MPPF we will measure changes in GABAA and 5-HT1A receptors binding potential in parietal patients with low grade glioma (LGG) and Ischemic Stroke (IS).
Our main objectives will be to understand how changes in GABAergic and Serotonergic neurotransmission (i) subserve efficient long-term recovery in LGG patients; (ii) differ between patients showing good (LGG, minority of IS) and poor (majority of IS) recovery; (iii) correlate with reorganizations of resting state functional connectivity. Based on the existing literature, we predict that finely-tuned normalizations of neurotransmitter and resting state connectivity maps will be observed relative to the pre-injured state, in patients with good recovery. By contrast, we anticipate coarse maladaptive regulations, within and outside functional networks, in patients with poor recovery.
At a fundamental level this proposal should improve our understanding of neurotransmitter plasticity and provide a more robust theoretical framework through which understanding how the brain adapts to focal injuries affecting major eloquent areas. At a clinical level it should help designing more efficient rehabilitation procedures by improving our understanding of post-lesional adaptive mechanisms.