Abstract
Individuals with Down syndrome (DS) show high inter-subject variability in cognitive ability and have an ultra-high risk of developing dementia (90% lifetime prevalence). Elucidating factors underlying variability in cognitive function can inform us about intellectual disability (ID) and may improve our understanding of factors associated with later cognitive decline. Increased neuronal inhibition has been posited to contribute to ID in DS. Combining electroencephalography (EEG) with dynamic causal modeling (DCM) provides a non-invasive method for investigating excitatory/inhibitory mechanisms. Resting-state EEG recordings were obtained from 36 adults with DS with no evidence of cognitive decline. Theta–alpha activity (4–13 Hz) was characterized in relation to general cognitive ability (raw Kaufmann’s Brief Intelligence Test second Edition (KBIT-2) score). Higher KBIT-2 was associated with higher frontal alpha peak amplitude and higher theta–alpha band power across distributed regions. Modeling this association with DCM revealed intrinsic self-inhibition was the key network parameter underlying observed differences in 4–13 Hz power in relation to KBIT-2 and age. In particular, intrinsic self-inhibition in right V1 was negatively correlated with KBIT-2. Results suggest intrinsic self-inhibition within the alpha network is associated with individual differences in cognitive ability in adults with DS, and may provide a potential therapeutic target for cognitive enhancement.
Highlights
Down syndrome (DS) is caused by an extra copy of chromosome 21 and is the most common genetic cause of intellectual disability (ID) worldwide, affecting 1 in 800 births.While almost all individuals with DS have an ID (IQ < 70), there is a high degree of variation in cognitive ability between individuals (Startin et al 2016)
We show that general cognitive ability in adults with Down syndrome (DS) is associated with particular, distributed signatures in scalp activity across theta–alpha frequency ranges
dynamic causal modeling (DCM) indicates that across our model space, between-subject differences in intrinsic self-inhibition producing the differing EEG spectra are associated with individual differences in general cognitive ability
Summary
Down syndrome (DS) is caused by an extra copy of chromosome 21 and is the most common genetic cause of intellectual disability (ID) worldwide, affecting 1 in 800 births (de Graaf et al 2015). Electroencephalography (EEG) measurements reveal oscillatory brain activity across distinct frequency bands These bands are believed to represent different dynamic network states and have been associated with a variety of different functions. Alpha activity may have utility as a marker of intact distributed network activity, and may potentially be associated with cognitive ability Consistent with this notion, previous research has suggested adults with DS show atypical alpha-band features compared to adults of the typically-developing (TD) population, including a slower alpha peak frequency (APF), with the APF within the theta range for some individuals (Gunnarson 1945; Ono et al 1992; Soininen et al 1993; Murata et al 1994; Locatelli et al 1996; Velikova et al 2011). We applied DCM for cross-spectral densities (Kiebel et al, 2009; Moran et al, 2009) to infer the cortical circuitry changes underlying these oscillatory correlates; thereby offering insights—at the level of canonical microcircuits (CMCs) —into the neuronal architectures of adults who present with both ID and a genetic susceptibility for dementia
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