Automatic cortical representation of auditory pitch changes in Rett syndrome.
BACKGROUND
Over the typical course of Rett syndrome, initial language and communication abilities deteriorate dramatically between the ages of 1 and 4 years, and a majority of these children go on to lose all oral communication abilities. It becomes extremely difficult for clinicians and caretakers to accurately assess the level of preserved auditory functioning in these children, an issue of obvious clinical import. Non-invasive electrophysiological techniques allow for the interrogation of auditory cortical processing without the need for overt behavioral responses. In particular, the mismatch negativity (MMN) component of the auditory evoked potential (AEP) provides an excellent and robust dependent measure of change detection and auditory sensory memory. Here, we asked whether females with Rett syndrome would produce the MMN to occasional changes in pitch in a regularly occurring stream of auditory tones.


METHODS
Fourteen girls with genetically confirmed Rett syndrome and 22 age-matched neurotypical controls participated (ages 3.9-21.1 years). High-density electrophysiological recordings from 64 scalp electrodes were made while participants passively listened to a regularly occurring stream of 503-Hz auditory tone pips that was occasionally (15 % of presentations) interrupted by a higher-pitched deviant tone of 996 Hz. The MMN was derived by subtracting the AEP to these deviants from the AEP produced to the standard.


RESULTS
Despite clearly anomalous morphology and latency of the AEP to simple pure-tone inputs in Rett syndrome, the MMN response was evident in both neurotypicals and Rett patients. However, we found that the pitch-evoked MMN was both delayed and protracted in duration in Rett, pointing to slowing of auditory responsiveness.


CONCLUSIONS
The presence of the MMN in Rett patients suggests preserved abilities to process pitch changes in auditory sensory memory. This work represents a beginning step in an effort to comprehensively map the extent of auditory cortical functioning in Rett syndrome. These easily obtained objective brain measures of auditory processing have promise as biomarkers against which future therapeutic efforts can be assayed.
Department of Neuroscience, The Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 USA ; Department of Pediatrics, The Sheryl and Daniel R. Tishman Cognitive Neurophysiology Laboratory, Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, NY 10461 USA ; The Dominic P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461 USA.
John J
JJ
Foxe
Department of Pediatrics, The Sheryl and Daniel R. Tishman Cognitive Neurophysiology Laboratory, Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, NY 10461 USA ; The Dominic P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461 USA.
Kelly M
KM
Burke
Department of Pediatrics, The Sheryl and Daniel R. Tishman Cognitive Neurophysiology Laboratory, Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, NY 10461 USA.
Gizely N
GN
Andrade
Department of Neurology, Rett Syndrome Center, Montefiore Medical Center & Albert Einstein College of Medicine, Bronx, NY 10467 USA.
Aleksandra
A
Djukic
Department of Pediatrics, The Sheryl and Daniel R. Tishman Cognitive Neurophysiology Laboratory, Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, NY 10461 USA ; Department of Neurology, Columbia University Medical Center, New York, NY 10032 USA.
Hans-Peter
HP
Frey
Department of Pediatrics, The Sheryl and Daniel R. Tishman Cognitive Neurophysiology Laboratory, Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, NY 10461 USA ; The Dominic P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461 USA.
Sophie
S
Molholm
AEP; Auditory evoked potential; EEG; ERP; Event-related potential; Females; High-density electrical mapping; MECP2; MMN; Mismatch negativity