Pre‐attentive processing in children with early and continuously‐treated PKU. Effects of concurrent Phe level and lifetime dietary control

Abstract

Sixty-four children, aged 7 to 14 years, with early-treated PKU, were compared with control children on visual evoked potential (VEP) amplitudes and latencies and auditory mismatch negativity (MMN) amplitudes. It was further investigated whether indices of dietary control would be associated with these evoked potentials parameters. There were no significant differences between controls and children with PKU in VEP- and MMN-indices. However, higher lifetime Phe levels were, in varying degree and stronger than concurrent Phe level, related to increased N75 amplitudes, suggesting abnormalities in attention, and longer P110 latencies, indicating a reduction in speed of neural processing, possibly due to deficits in myelination or reduced dopamine levels in brain and retina. Similarly, higher lifetime Phe levels and Index of Dietary Control (IDC) were associated with decreased MMN amplitudes, suggesting a reduced ability to respond to stimulus change and poorer triggering of the frontally mediated attention switch. In summary, the present study in children with PKU investigated bottom-up information processing, i.e., triggered by external events, a fundamental prerequisite for the individual’s responsiveness to the outside world. Results provide evidence that quality of dietary control may affect the optimal development of these pre-attentive processes, and suggest the existence of windows of vulnerability to Phe exposure.

Content Validity of the ADHD Rating Scale (ADHD RS-IV) and Adult ADHD Self-Report Scale (ASRS) in Phenylketonuria

“…[5][6][7] Even modest elevations in Phe levels may impair high-level executive functioning. [8][9][10] Among the common concerns encompassed within executive functioning are reduced attention span [11][12][13][14][15] and hyperactivity/ impulsivity. [16][17][18] In a 2003 study designed to document the symptom dimensions of attention-deficit/hyperactivity disorder (ADHD) in children with PKU, Antshel and Waisbren demonstrated that ADHD inattentive symptoms occur significantly more often in children aged 7 to 16 years old with PKU when compared to their unaffected siblings 19 using the ADHD Rating Scale IV (ADHD RS-IV).…”

Evaluation of Neuropsychiatric Function in Phenylketonuria: Psychometric Properties of the ADHD Rating Scale-IV and Adult ADHD Self-Report Scale Inattention Subscale in Phenylketonuria

“…Neurocognitive symptoms, however, are observed in some of these patients, even among those who adhere closely to dietary treatment [6][7][8], and only modest elevations in phenylalanine levels may impair high-level executive functioning [9][10][11]. Common neurocognitive symptoms include reduced attention span/inattention symptoms [12][13][14][15][16][17] and hyperactivity/impulsivity [18][19][20].…”

Event‐related potential measures of executive functioning from preschool to adolescence

“…A parallel has been drawn between the gradual integration of executive functions and the prolonged development of the prefrontal cortex, but it is also clear that executive functions depend upon a wider neural system . In addition to magnetic resonance imaging (MRI) studies, event‐related potential (ERP) measures have contributed to our increasing comprehension of the developing neural substrates underlying this cognitive domain . This method has several advantages over MRI, including being relatively easy, practical, and cost‐effective to use with younger children, and providing more precise information about the timing of brain events underlying behavioural performance .…”

“…19 In addition to magnetic resonance imaging (MRI) studies, event-related potential (ERP) measures have contributed to our increasing comprehension of the developing neural substrates underlying this cognitive domain. [20][21][22][23][24][25] This method has several advantages over MRI, including being relatively easy, practical, and costeffective to use with younger children, and providing more precise information about the timing of brain events underlying behavioural performance. 26,27 Its high temporal resolution affords a closer look into various processing stages that lead to a single behavioural response, and provides another source of information in the investigation of the developmental differentiation of executive functions.Here, we provide an overview of ERP studies relevant to executive function development from preschool to adolescence.…”