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

Background Cystinosis, a rare lysosomal storage disease, is characterized by cystine crystallization and accumulation within tissues and organs, including the kidneys and brain. Its impact on neural function appears mild relative to its effects on other organs, but therapeutic advances have led to substantially increased life expectancy, necessitating deeper understanding of its impact on neurocognitive function in adulthood. We previously demonstrated intact auditory sensory processing, accompanied by mild sensory memory difficulties, in children and adolescents with cystinosis. Methods We investigated whether further progressive decrements in these processes would be observed in adults with cystinosis, comparing high-density auditory-evoked potential (AEP) recordings from adults with cystinosis (N = 15; ages: 19–38 years) to those of age-matched controls (N = 17). We employed a duration oddball paradigm with different stimulation rates, in which participants passively listened to regularly occurring standard tones interspersed with infrequently occurring deviant tones. Analyses focused on AEP components reflecting auditory sensory-perceptual processing (N1 and P2), sensory memory (mismatch negativity, MMN), and attentional orienting (P3a). Results Overall, adults with cystinosis produced highly similar sensory-perceptual AEP responses to those observed in controls suggesting intact early auditory cortical processing. However, significantly increased P2 and P3a amplitudes and reduced MMN at slower stimulation rates were observed, suggesting mild-to-moderate changes in auditory sensory memory and attentional processing. While cognitive testing revealed lower scores on verbal IQ and perceptual reasoning in cystinosis, these did not correlate with the AEP measures. Conclusions These neurophysiological data point to the emergence of subtle auditory processing deficits in early adulthood in cystinosis, warranting further investigation of memory and attentional processes in this population, and of their consequences for perceptual and cognitive function.

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

Background Cystinosis, a rare lysosomal storage disease, is characterized by cystine crystallization and accumulation within tissues and organs, including the kidneys and brain. Its impact on neural function appears mild relative to its effects on other organs, but therapeutic advances have led to substantially increased life expectancy, necessitating deeper understanding of its impact on neurocognitive function in adulthood. We previously demonstrated intact auditory sensory processing, accompanied by mild sensory memory difficulties, in children and adolescents with cystinosis. Methods We investigated whether further progressive decrements in these processes would be observed in adults with cystinosis, comparing high-density auditory-evoked potential (AEP) recordings from adults with cystinosis (N = 15; ages: 19–38 years) to those of age-matched controls (N = 17). We employed a duration oddball paradigm with different stimulation rates, in which participants passively listened to regularly occurring standard tones interspersed with infrequently occurring deviant tones. Analyses focused on AEP components reflecting auditory sensory-perceptual processing (N1 and P2), sensory memory (mismatch negativity, MMN), and attentional orienting (P3a). Results Overall, adults with cystinosis produced highly similar sensory-perceptual AEP responses to those observed in controls suggesting intact early auditory cortical processing. However, significantly increased P2 and P3a amplitudes and reduced MMN at slower stimulation rates were observed, suggesting mild-to-moderate changes in auditory sensory memory and attentional processing. While cognitive testing revealed lower scores on verbal IQ and perceptual reasoning in cystinosis, these did not correlate with the AEP measures. Conclusions These neurophysiological data point to the emergence of subtle auditory processing deficits in early adulthood in cystinosis, warranting further investigation of memory and attentional processes in this population, and of their consequences for perceptual and cognitive function.

High-frequency sound components of high-resolution audio are not detected in auditory sensory memory

High-resolution digital audio is believed to produce a better listening experience than the standard quality audio, such as compact disks (CDs) and digital versatile disks (DVDs). One common belief is that high-resolution digital audio is superior due to the higher frequency (> 22 kHz) of its sound components, a characteristic unique to this audio. This study examined whether sounds with high-frequency components were processed differently from similar sounds without these components in the auditory cortex. Mismatch negativity (MMN), an electrocortical index of auditory deviance detection in sensory memory, was recorded in young adults with normal hearing (N = 38) using two types of white noise bursts: original sound and digitally filtered sound from which high-frequency components were removed. The two sounds did not produce any MMN response and could not be discriminated behaviourally. In conclusion, even if high-resolution audio is superior to the standard format, the difference is apparently not detectable at the cortical level.

Effects of Visual Attentional Load on the Tactile Sensory Memory Indexed by Somatosensory Mismatch Negativity

Auditory sensory memory indexed by mismatch negativity has been broadly studied over the past century, but far less attention has been directed to tactile sensory memory. To investigate whether tactile sensory memory is affected by attention, we recorded somatosensory mismatch negativity (sMMN) from 24 healthy adults in two experiments to distinguish sustained attention from non-sustained attention. Using the roving somatosensory oddball paradigm, we analyzed the average dynamic changes in the amplitude and latency of sMMN amplitude and found a clear sMMN component at the central region at a 100–300 ms interval. The sMMN amplitude, which indexes the early detection of tactile stimuli with the sensory memory trace, was larger in the tactile attentional task. Additionally, the sMMN latency increased with the increasing visual attentional load, which indicates a decay of tactile sensory memory. Our results indicate that the more attention resources are allocated for a tactile sensation, the more favorable it is to the generation of tactile sensory memory.

Electrophysiological evidence for impaired auditory sensory memory in Cystinosis despite typical sensory processing: An MMN investigation

Cystinosis, a genetic rare disease characterized by cystine accumulation and crystallization, results in significant damage in a multitude of tissues and organs, such as the kidney, thyroid, eye, and brain. While Cystinosis’ impact on brain function is relatively mild compared to its effects on other organs, the increased lifespan of this population and thus potential for productive societal contributions have led to increased interest on the effects on brain function. Nevertheless, and despite some evidence of structural brain differences, the neural impact of the mutation is still not well characterized.Here, using a passive duration oddball paradigm (with different stimulus onset asynchronies (SOAs), representing different levels of demand on memory) and high-density electrophysiology, we tested basic auditory processing in a group of 22 children and adolescents diagnosed with Cystinosis (age range: 6-17 years old) and in neurotypical age-matched controls (N=24). We examined whether the N1 and mismatch negativity (MMN) significantly differed between the groups and if those neural measures correlated with verbal and non-verbal IQ. Individuals diagnosed with Cystinosis presented similar N1 responses to their age-matched peers, indicating typical basic auditory processing in this population. However, whereas both groups showed similar MMN responses for the shortest (450ms) SOA, suggesting intact change detection and sensory memory, individuals diagnosed with Cystinosis presented clearly reduced responses for the longer (900ms and 1800ms) SOAs. This could indicate reduced duration auditory sensory memory traces, and thus sensory memory impairment, in children and adolescents diagnosed with Cystinosis. Future work addressing other aspects of sensory and working memory is needed to understand the underlying bases of the differences described here, and their implication for higher order processing.