A detailed psychological and EEG study of a new form of autism (SLC12A2-syndrome)

We have recently identified a new childhood onset neurological disorder caused by variants in the SLC12A2 gene. The SLC12A2 gene encodes the NKCC1 ion channel which regulates chloride flow across neuronal membranes during neurodevelopment. We identified genetic mutations in the SLC12A2 - which reduce NKCC1 ion channel function - in children with autism, developmental delay and hearing impairment. Children with variants in exon 21 of SLC12A2 appear to only have hearing impairment with no other neurological impairment.

The student would use a combination of detailed clinical studies and state of the art electroencephalogram (EEG) techniques to define the cognitive and behavioural impact of SLC12A2 variants on childhood development. A general cognitive profile would be identified using the British Abilities Scale. A detailed study for features of autism would be undertaken using the social responsiveness scale. Language ability (childhood communication checklist) and features of attention deficit hyperactivity disorder (Connors scale) would also be studied. This would provide the first detailed cognitive and behavioural description of this newly discovered neurological disorder. A series of information leaflets designed to be useful to families affected by SCL12A2-syndrome would be designed based on this.

The underlying alterations to brain neurophysiology in SLC12A2-syndrome are unknown. We will use EEG to assess alterations in neuronal activity in brain circuits relevant to autism and cognition. We will record resting state data from each participant, where the child sits still with their eyes closed for up to 5 minutes. We will also assess steady state visual evoked responses (SSVEP), where the child passively views a series of visual stimuli, to explore potential abnormalities of brain circuitry in our cohort. This will enable us to investigate whether certain neural markers correlate with specific aspects of the cognitive and behavioural phenotype. Resting state data will enable us to assess multiple neural processes previously suggested to be atypical in autism. We will assess functional connectivity and signal complexity. For the SSVEP paradigm, the visual stimulus will be a 2Hz changing contrast image (checkerboard) of spatial frequency 2.4 cycles per degree. This will enable key properties of the resultant visual evoked potentials (P1 and N1) to be assessed, particularly in relation to indicating neural variability. Previously, the P1 and N1 ERP components have been investigated in relation to aberrant neurogenesis of a rodent model, with the peak latency of the N1 being shown to be affected14 but to date no such investigations have been considered in humans. Data will be collected using our research-grade Ant-Neuro 32 channel portable EEG system, which we have previously found to be suitable for use with children with mild-moderate intellectual disability. Analyses will be performed in EEGLAB.