Page 242 - MEGIN Book Of Abstracts - 2023

Wellcome Centre for Human Neuroimaging, UCL Institute of Variance in the pathophysiological impact of the
Neurology, London, UK; Department of Clinical and Move- hemizygosity of gamma-aminobutyric acid type
ment Neurosciences, UCL Institute of Neurology and The A receptor subunit genes between Prader-Willi
National Hospital for Neurology and Neurosurgery, Queen syndrome and Angelman syndrome (2021)
Square, London, UK; Center for Molecular and Behavioral
Neuroscience, Rutgers University, Newark, USA; Nuffield De- Egawa, Kiyoshi; Saitoh, Shinji; Asahina, Naoko; Shiraishi,
partment of Clinical Neurosciences, John Radcliffe Hospital, Hideaki
Oxford, UK; Department of Clinical Neuroscience, Umeå
University, Umeå, Sweden Department of Pediatrics, Hokkaido University Graduate
School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-
ABSTRACT Parkinson's disease dementia (PDD) and 8638, Japan; Department of Pediatrics and Neonatology,
dementia with Lewy bodies (DLB) are related condi- Nagoya City University Graduate School of Medical Sciences,
tions that are associated with cholinergic system dys- 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Ja-
function. Dysfunction of the nucleus basalis of Meynert pan; Department of Pediatrics, Hokkaido University Graduate
(NBM), a basal forebrain structure that provides the School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-
dominant source of cortical cholinergic innervation, 8638, Japan. Electronic address: [email protected]
has been implicated in the pathogenesis of both PDD
and DLB. Here we leverage the temporal resolution INTRODUCTION Angelman syndrome (AS) and Prader-
of magnetoencephalography with the spatial resolu- Willi syndrome (PWS) are neurodevelopmental disor-
tion of MRI tractography to explore the intersection of ders caused by loss of function of maternally expressed
functional and structural connectivity of the NBM in a UBE3A and paternally expressed contiguous genes
unique cohort of PDD and DLB patients undergoing on chromosome 15q11-13, respectively. A majority of
deep brain stimulation of this structure. We observe these syndromes suffer from a large deletion of the rel-
that NBM-cortical structural and functional connectiv- evant chromosome (AS Del or PWS Del), which includes
ity correlate within spatially and spectrally segregated biallelically expressed gamma-aminobutyric acid type
networks including: (i) a beta band network to supple- A receptor subunit (GABAaR) genes, while remaining
mentary motor area, where activity in this region was individuals present without the deletion (AS non-Del or
found to drive activity in the NBM; (ii) a delta/theta PWS non-Del). We previously reported that AS Del, but
band network to medial temporal lobe structures not AS non-Del individuals, show aberrantly desynchro-
encompassing the parahippocampal gyrus; and (iii) nized somatosensory-evoked magnetic fields (SEFs)
a delta/theta band network to visual areas including and speculated that it might reflect GABAergic dys-
lingual gyrus. These findings reveal functional net- function due to the hemizygosity of GABAaR genes. To
works of the NBM that are likely to subserve important verify its pathophysiological impact on PWS and AS, we
roles in motor control, memory and visual function, analyzed the SEFs of PWS individuals.
respectively. Furthermore, they motivate future studies
aimed at disentangling network contribution to disease METHOD SEFs were recorded from eight PWS Del and
phenotype. two PWS non-Del individuals. The latency and strength
of the first peak (N1m) were compared with those of
Keywords: DBS, DTI, MEG, coherence, oscillations AS Del/non-Del individuals and controls, most of which
were obtained earlier.
Brain: a journal of neurology (2021), Vol. 144, No. 3
(33521808) (14 citations) RESULTS In contrast to AS, both PWS Del and PWS non-
Del showed normal SEF waveforms. Desynchronized
response with delayed N1m peak latency was exclu-
sively indicated in AS Del. N1m strength was statisti-

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