Functional Evaluation in Patients With Urea Cycle Disorders (UCD) During a Driving Task

Primary Objective

* To use fNIRS to study brain functional behavior in subjects with UCD by measuring the changes in HbO, HbR and HbT concentrations versus healthy control volunteers during the baseline driving task on the left and right prefrontal cortex (LPFC, RPFC).

Secondary Objective

* To include other cortical regions such as temporal and occipital regions, to investigate the neurocognitive changes in these regions which may or may not change with driving. Thus, we will measure changes in HbO, HbR and HbT concentrations during the baseline driving task in four more brain regions (left and right parietal and occipital regions, LPA, RPA, LOL, ROL).

This is a non-therapeutic, non-interventional study in which brain fNIRS (functional near-infrared spectroscopy) measures will be compared under simulated driving conditions between patients with UCD vs. age and sex-matched control participants.

Participants who agree to participate will have Information about their medical history collected, have a basic neurological exam and answer questions about their health, diet, and driving habits. They will complete some simple thinking and memory tests. These tests will help investigators understand skills like memory, attention, and problem-solving. Participants will also wear a soft cap with small sensors called an fNIRS (functional near-infrared spectroscopy) device while they complete a driving simulator activity. This cap is noninvasive and measures how the brain uses oxygen while they drive in the simulator.

All study activities will be completed on the day of enrollment.

Primary outcomes

• Changes in Oxyhemoglobin (HbO), Deoxyhemoglobin (HbR) and Total Hemoglobin (HbT) concentrations in the right and left prefrontal cortex in participants with urea cycle disorders (UCD) compared to healthy control volunteers [Day 1, during driving simulator task]: Investigators will compare prefrontal cortex hemoglobin concentrations during low cognitive load between patients with UCD and healthy age and sex matched control participants using functional near-infrared spectroscopy (fNIRS). Mean values of hemoglobin concentration differences on the right and left prefrontal cortex between individuals, with and without UCD, during the low cognitive load task will be calculated and compared using two sample t-tests (for normally distributed data) or Wilcoxon rank sum tests (for nonnormally distributed data). P values will be adjusted for multiple comparisons using the Bonferroni method.

Secondary outcomes

• Changes in HbO, HbR and HbT concentrations in the left and right parietal and occipital brain regions in participants with urea cycle disorders (UCD) compared to healthy control volunteers [Day 1, during driving simulator task]: Investigators will compare left and right parietal and occipital regions hemoglobin concentrations during low cognitive load between patients with UCD and healthy age and sex matched control participants using functional near-infrared spectroscopy (fNIRS). Mean values of hemoglobin concentration differences on the left and right parietal and occipital regions between individuals, with and without UCD, during the low cognitive load task will be calculated and compared using two sample t-tests (for normally distributed data) or Wilcoxon rank sum tests (for nonnormally distributed data). P values will be adjusted for multiple comparisons using the Bonferroni method.

Sex: All, ages: 16 Years to 40 Years, accepts healthy volunteers

Inclusion Criteria:

* Individuals 16 to 40 years with molecular or biochemical confirmation of a urea cycle disorder.
* Healthy individuals will serve as an age and sex matched comparison group. Active driver's license for at least 6 months
* Read and understand English. as the tasks have not been validated in other languages
* IQ >=70.

Exclusion Criteria:

* Skin disease that affects the scalp
* Past or present vascular disease
* Head trauma with loss of consciousness in the last year or evidence of cognitive impairment due to and persisting after head trauma
* Motor movement disorder which may cause excessive movement or impede use of the steering wheel and/or pedal
* Premature birth or birth before 32 weeks of gestation
* The participant is taking a stimulant or antidepressant
* Allergy to any component of the device, although expected to be rare
* History of psychosis
* Self-reported motion or cyber sickness
* Self-reported illicit substance use
* Vision disorder

• Andrea Gropman, M.D., Principal investigator, St. Jude Children's Research Hospital