Auditory sensory memory span for duration is severely curtailed in females with Rett syndrome

Abstract

Rett syndrome (RTT), a rare neurodevelopmental disorder caused by mutations in the MECP2 gene, is typified by profound cognitive impairment and severe language impairment, rendering it very difficult to accurately measure auditory processing capabilities behaviorally in this population. Here we leverage the mismatch negativity (MMN) component of the event-related potential to measure the ability of RTT patients to decode and store occasional duration deviations in a stream of auditory stimuli. Sensory memory for duration, crucial for speech comprehension, has not been studied in RTT. High-density electroencephalography was successfully recorded in 18 females with RTT and 27 age-matched typically developing (TD) controls (aged 6–22 years). Data from seven RTT and three TD participants were excluded for excessive noise. Stimuli were 1 kHz tones with a standard duration of 100 ms and deviant duration of 180 ms. To assess the sustainability of sensory memory, stimulus presentation rate was varied with stimulus onset asynchronies (SOAs) of 450, 900, and 1800 ms. MMNs with maximum negativity over fronto-central scalp and a latency of 220–230 ms were clearly evident for each presentation rate in the TD group, but only for the shortest SOA in the RTT group. Repeated-measures ANOVA revealed a significant group by SOA interaction. MMN amplitude correlated with age in the TD group only. MMN amplitude was not correlated with the Rett Syndrome Severity Scale. This study indicates that while RTT patients can decode deviations in auditory duration, the span of this sensory memory system is severely foreshortened, with likely implications for speech decoding abilities.

Assessing the integrity of auditory processing and sensory memory in adults with cystinosis (CTNS gene mutations)

“…In the MMN time window, despite showing robust MMN responses across SOAs, individuals with cystinosis showed a slightly decreased response to the 1800 ms SOA when compared to their age-matched peers. In children and adolescents, such reductions were likewise observed, not only for the 1800 ms, but also for the 900 ms SOA, which we interpreted as a sign of reduced short-term auditory sensory memory [ 55 , 56 ]. Hence, such difficulties might still be present in adulthood, though less markedly so.…”

“…As can been seen from the MMN data herein, even at the slowest rate, a robust MMN was generated for both groups. In contrast, in data collected from individuals with Rett Syndrome using the same paradigm, an MMN was only detected at the fastest rate and was completely absent at the two slower rates [ 56 ]. Clearly then, this manipulation was not sufficient to assay potentially more modest differences in this clinically less affected group.…”

“…The Digit Span subtest (Forward, Backward, and Sequencing measures) of the Wechsler Adult Intelligence Scale, WAIS-IV [ 69 ] was utilized to assess working memory. A traditional duration MMN oddball paradigm [ 17 , 56 , 70 ] was employed. Participants watched a muted movie of their choice on a laptop (Dell Latitude E6430 ATG or E5420M) while sitting in a sound- and electrically-shielded booth (Industrial Acoustics Company Inc, Bronx, NY).…”

Assessing auditory processing endophenotypes associated with Schizophrenia in individuals with 22q11.2 deletion syndrome

“…76 ). Previous work from our lab using this same MMN paradigm showed that increasing SOA effectively indexed weakness in maintenance of the memory trace in Rett Syndrome 75 . Given that memory deficits have been described in 22q11.2DS, we expected attenuated MMN amplitudes with longer SOAs.…”

“…Here, we sought to measure the relationship between auditory brain function and cognitive function, focusing on cognitive abilities known to be vulnerable in this population. Given the working memory difficulties previously described in 22q11.2DS, presentation rate (stimulus onset asynchronies: SOAs) was parametrically varied, which allowed us to examine not only the impact of increasing demands on the sensory memory system 75,76 , but also the integrity of sensory adaptation effects 75,77 .…”