Biology subjects

Horsthuis, D. J.

Publications and source records attributed to Horsthuis, D. J..

4 recordsLinked to original sources

bioRxiv2023

Response inhibition and error-monitoring in cystinosis (CTNS gene mutations): Behavioral and electrophysiological evidence of a diverse set of difficulties

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. Behaviorally, some deficits in executive function have been noted in this population, but the underlying neural processes are not understood. Using standardized cognitive assessments and a Go/No-Go response inhibition task in conjunction with high-density electrophysiological recordings (EEG), we sought to investigate the behavioral and neural dynamics of inhibition of a prepotent response and of error monitoring (critical components of executive function) in individuals with cystinosis, when compared to age-matched controls. Thirty-seven individuals diagnosed with cystinosis (7-36 years old, 24 women) and 45 age-matched controls (27 women) participated in this study. Analyses focused on N2 and P3 No-Go responses and error-related positivity (Pe). Atypical inhibitory processing was shown behaviorally. Electrophysiological differences were additionally found between the groups, with individuals with cystinosis showing larger No-Go P3s. Error-monitoring was likewise different between the groups, with those with cystinosis showing reduced Pe amplitudes.

neuroscience↗

bioRxiv2023

Event-related potential (ERP) evidence of early visual processing differences in cystinosis

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. Behavioral difficulties have been reported in cystinosis in the visual and visual-processing domain. Very little is known, however, about how the brains of people living with cystinosis process visual information, although cysteamine accumulation in the retina is a prominent feature of cystinosis. Here, electrophysiology was recorded during a Go/No-Go task to investigate early visual processing in cystinosis, compared to an age-matched control group. Analyses focused on early stages of cortical visual processing. The groups differed in their initial cortical response, with individuals with cystinosis exhibiting a significantly larger visual evoked potential (VEP) in the 130 to 150 ms time window. The timing and topography of this response suggested an enhanced P1 in cystinosis that could be the result of cortical hyperexcitability and/or differences in attentional engagement and explain, at least partially, the visual and visual-spatial difficulties described in this population. The groups also differed in the associations between neural responses and verbal abilities: While controls with higher IQ scores presented larger neural responses, that relationship was not observed in cystinosis.

neuroscience↗

bioRxiv2020

Atypical response inhibition and error processing in 22q11.2 Deletion Syndrome and Schizophrenia: Towards neuromarkers of disease progression and risk

22q11.2 deletion syndrome (also known as DiGeorge syndrome or velo-cardio-facial syndrome) is characterized by increased vulnerability to neuropsychiatric symptoms, with approximately 30% of individuals with the deletion going on to develop schizophrenia. Clinically, deficits in executive function have been noted in this population, but the underlying neural processes are not well understood. Using a Go/No-Go response inhibition task in conjunction with high-density electrophysiological recordings (EEG), we sought to investigate the behavioral and neural dynamics of inhibition of a prepotent response (a critical component of executive function) in individuals with 22q11.2DS with and without psychotic symptoms, when compared to individuals with idiopathic schizophrenia and age-matched neurotypical controls. Twenty-eight participants diagnosed with 22q11.2DS (14-35 years old; 14 with at least one psychotic symptom), 15 individuals diagnosed with schizophrenia (18-63 years old) and two neurotypical control groups (one age-matched to the 22q11.2DS sample, the other age-matched to the schizophrenia sample) participated in this study. Analyses focused on the N2 and P3 no-go responses and error-related negativity (Ne) and positivity (Pe). Atypical inhibitory processing was shown behaviorally and by significantly reduced P3, Ne, and Pe responses in 22q11.2DS and schizophrenia. Interestingly, whereas P3 was only reduced in the presence of psychotic symptoms, Ne and Pe were equally reduced in schizophrenia and 22q11.2DS, regardless of the presence of symptoms. We argue that while P3 may be a marker of disease severity, Ne and Pe might be candidate markers of risk.

neuroscience↗

bioRxiv2019

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.\n\nHere, 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.

neuroscience↗