Biology subjects

Gillberg, C.

Publications and source records attributed to Gillberg, C..

3 recordsLinked to original sources

bioRxiv2018

Both rare and common genetic variants contribute to autism in the Faroe Islands

The number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls. Data from SNP array and whole exome sequencing revealed that individuals with autism compared to controls had a higher burden of copy-number variants (p < 0.05), higher inbreeding status (p < 0.005) and higher load of homozygous deleterious variants (p < 0.01). Our analysis supports the role of several genes/loci associated with autism (e.g. NRXN1, ADNP, 22q11 deletion) and identified new truncating (e.g. GRIK2, ROBO1, NINL and IMMP2L) or recessive deleterious variants (e.g. KIRELL3 and CNTNAP2) affecting autism-risk genes. It also revealed three genes involved in synaptic plasticity, RIMS4, KALRN and PLA2G4A, carrying de novo deleterious variants in individuals with autism without intellectual disability. In summary, our analysis provides a better understanding of the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants and pointing at new autism-risk genes. It also indicates that more knowledge about how multiple genetic hits affect neuronal function will be necessary to fully understand the genetic architecture of autism.

genetics↗

bioRxiv2018

Neural gain control measured through cortical gamma oscillations is associated with individual variations in sensory sensitivity.

Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations, and their suppression by strong excitatory drive may stem from inhibitory-based gain control of network excitation. Individual variations in the gamma suppression may therefore reflect efficiency of gain control and subjective sensitivity to everyday sensory events. To test this prediction, we assessed the link between self-reported sensory sensitivity and changes in magneto-encephalographic gamma oscillations as a function of motion velocity of high-contrast visual gratings. The induced gamma oscillations increased in frequency and decreased in power with increasing stimulation intensity. As expected, weaker suppression of the gamma response correlated with sensory hypersensitivity. Robustness of this result was confirmed by its replication in the two samples: neurotypical subjects and people with autism, who had generally higher sensory sensitivity. We conclude that intensity-related suppression of gamma response is a promising biomarker of homeostatic control of the excitation-inhibition balance in the visual cortex.

neuroscience↗

bioRxiv2017

Modulation of visual gamma oscillation by excitatory drive and the excitation/inhibition balance in the visual cortex

Gamma-band oscillations arise from the interplay between neural excitation (E) and inhibition (I) and may provide a non-invasive window into the state of cortical circuitry. A bell-shaped modulation of gamma response power by increasing the intensity of sensory input was observed in animals and is thought to reflect neural gain control. Here we sought to find a similar input-output relationship in humans with MEG via modulating the intensity of a visual stimulation by changing the velocity/temporal-frequency of visual motion.\n\nIn the first experiment, adult participants observed static and moving gratings. The frequency of the MEG gamma response monotonically increased with motion velocity whereas power followed a bell-shape. In the second experiment, on a large group of children and adults, we found that despite drastic developmental changes in frequency and power of gamma oscillations, the relative suppression at high motion velocities was scaled to the same range of values across the life-span.\n\nIn light of animal and modeling studies, the modulation of gamma power and frequency at high stimulation intensities characterizes the capacity of inhibitory neurons to counterbalance increasing excitation in visual networks. Gamma suppression may thus provide a non-invasive measure of inhibitory-based gain control in the healthy and diseased brain.

neuroscience↗