Volume reduction of caudate nucleus is associated with movement coordination deficits in patients with hippocampal atrophy due to perinatal hypoxia-ischaemia

Sharon Geva,Sebastian Jentschke,Georgios P.D Argyropoulos,W.K Chong,David G Gadian,Faraneh Vargha-Khadem

doi:10.1016/j.nicl.2020.102429

Sharon Geva, Sebastian Jentschke + Show 4 more

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https://doi.org/10.1016/j.nicl.2020.102429

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Abstract

Acute sentinel hypoxia-ischaemia in neonates can target the hippocampus, mammillary bodies, thalamus, and the basal ganglia. Our previous work with paediatric patients with a history of hypoxia-ischaemia has revealed hippocampal and diencephalic damage that impacts cognitive memory. However, the structural and functional status of other brain regions vulnerable to hypoxia-ischaemia, such as the basal ganglia, has not been investigated in these patients. Furthermore, it is not known whether there are any behavioural sequelae of such damage, especially in patients with no diagnosis of neurological disorder. Based on the established role of the basal ganglia and the thalamus in movement coordination, we studied manual motor function in 20 participants exposed to neonatal hypoxia-ischaemia, and a group of 17 healthy controls of comparable age. The patients’ handwriting speed and accuracy was within the normal range (Detailed Assessment of Speed of Handwriting), and their movement adaptation learning (Rotary Pursuit task) was comparable to the control group’s performance. However, as a group, patients showed an impairment in the Grooved Pegboard task and a trend for impairment in speed of movement while performing the Rotary Pursuit task, suggesting that some patients have subtle deficits in fine, complex hand movements. Voxel-based morphometry and volumetry showed bilateral reduction in grey matter volume of the thalamus and caudate nucleus. Reduced volumes in the caudate nucleus correlated across patients with performance on the Grooved Pegboard task. In summary, the fine movement coordination deficit affecting the hand and the wrist in patients exposed to early hypoxic-ischaemic brain injury may be related to reduced volumes of the caudate nucleus, and consistent with anecdotal parental reports of clumsiness and coordination difficulties in this cohort.

Highlights

There is strong evidence indicating that a consequence of acute sentinel hypoxic-ischaemic (HI) events experienced early in life is da mage to specific subcortical brain structures, namely, the hippocampus which underpins cognitive memory and learning, the basal ganglia, which support habit memory and skill learning, as well as the thalamus (Caine and Watson, 2000; De Vries and Groenendaal, 2010; Dzieciol et al, 2017; Faro and Windle, 1969; Gadian et al, 2000; Guderian et al, 2015; Sie et al, 2000)
Given our a priori hypothesis on basal ganglia and thalamic structural abnormalities in the patient group, we report clusters confined within these regions in the DARTEL grey matter (GM) template in Montreal Neuro logical Institute (MNI) space using smallvolume correction, if whole brain-corrected level results are not found
In this study we investigated manual movement coordination in patients with a history of perinatal HI injury supported by clinical semiology and the documentation of bilaterally-reduced hippocampal volumes

Summary

Introduction

There is strong evidence indicating that a consequence of acute sentinel hypoxic-ischaemic (HI) events experienced early in life is da mage to specific subcortical brain structures, namely, the hippocampus which underpins cognitive memory and learning, the basal ganglia, which support habit memory and skill learning, as well as the thalamus (Caine and Watson, 2000; De Vries and Groenendaal, 2010; Dzieciol et al, 2017; Faro and Windle, 1969; Gadian et al, 2000; Guderian et al, 2015; Sie et al, 2000). Regions within the basal ganglia and the thalamus form part of the brain’s motor control circuits (Alexander et al, 1991; McFarland and Haber, 2000) and have well-established roles in motor coordination (Dudman and Krakauer, 2016; Galvan et al, 2016; Jin et al, 2014; Stephenson-Jones et al, 2011) This is consistent with anecdotal parental reports indicating that children who had suffered from early HI, later show clumsiness and incoordination even in the absence of diagnosed neuromotor deficits (Gadian et al, 2000)

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