Session Item

It is now well established that irradiation dose to the hippocampus has a negative impact on episodic memory and that a sparing approach led to a preservation of this neurocognitive function. Neuroimaging used to understand this impairment had focalized on structural parameters of the hippocampus. However, episodic memory is the result of complex connectivities between hippocampus and cortical brain areas. Moreover, other learning and memory processes are impaired in children after an irradiated posterior fossa tumor (PFT), especially working memory and procedural learning. The aim of this study was to explore the impact of a pediatric irradiation on long-term brain connectivity in circuits involved in learning and memories hypothesizing that irradiation of hippocampus has an impact on cortico-hippocampal circuit involved in episodic memory. In the same way, we hypothe that irradiation of cerebellum has an impact on cortico-cerebellar circuit involved in working memory and adaptative part of procedural learning; and irradiation of striatum has an impact on cortico-striatal connectivity involved in sequence learning part of procedural memory.

Twenty irradiated PFT survivors, fifteen non-irradiated and twenty-one healthy controls from the IMPALA study (NCT04324450) performed both a battery of memory tests assessing episodic, procedural and working memories, and a resting state functional MRI. Using a seed-based approach we built connectivity maps from 3DT1 manually contoured brain structures involved in memory (hippocampus, anterior and posterior cerebellum, caudate nucleus and putamen). Group comparisons were made and differences in connectivity were correlated with mnesic scores and mean irradiation dose received by the same brain structures reported from the initial dosimetry plans.

Irradiated PFT had atypical connectivity in left cortico-hippocampal circuit, in right anterior cortico-cerebellar circuit, in left cortico-putamen circuit and in both cortico-caudate nucleus circuits compared to other groups. At behavioral level, all mnesic systems were impaired in irradiated PFT and relationships were found between cortico-hippocampal connectivity and episodic memory scores (especially learning a list of words r=0.58, p<0.01); and between cortico-striatal connectivity and sequence learning scores (r=0.62, p<0.01). Dosimetry data were available for seventeen irradiated PFT. Mean dose of irradiation to the caudate nucleus (r=-0.80, p<0.01), left putamen (r=-0.62, p=0.01) and left hippocampus (r=0.51, p=0.04) were linked with atypical connectivity in corresponding cortico-subcortical circuits.

This work highlights the long-term impact of irradiation on brain connectivity at rest in different brain circuits involved in learning and memory in pediatric PFT showing a specific dose-effect of irradiation for sus-tentorial structures. This is a step toward defining dose constraints to these structures in the future.