Atypical brainstem responses to repeated amplitude-modulated sounds in children diagnosed
with Autism Spectrum Disorders
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1,2
3
1,2
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Cornella M , Leung S ,Hervás A , Costa-Faidella J , Rueda I , Grimm S , Escera C
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Institute for Brain, Cognition and Behavior (IR3C), University of Barcelona, Catalonia-Spain
Cognitive Neuroscience Research Group, Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Spain
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UETD, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues de Llobregat, Barcelona, Spain
Contact: [email protected]
METHODS
Recent studies have shown that the human auditory brainstem can encode
context-dependent information and extract auditory regularities from the
4,5
recent past in order to detect novel events .Therefore, any disruption in the
low level processing of the auditory regularities might propagate to higher
levels and underlie auditory deficits as observed in autism.
The sustained frequency following response (FFR) of the auditory
brainstem reflects the neural phase-locking of brainstem neurons to the
6
continuous acoustic features of a sound .
Aim of the study:
To examine the encoding of acoustic regularities in children
diagnosed with ASD at the level of the auditory brainstem. More
specifically, we focused on how the FFR is modulated by stimulus
repetitions.
Binaural presentation
(alternating polarities)
380 Hz AM
...
100ms
...
...
Time
SOA: 333 ms
Trains of 8,10 or 12 tones
10 carrier frequencies used ranging from 1075 until 2514 Hz
EEG recordings 18 scalp electrodes/A2 reference
Sampling rate: 20 KHz. Filter: 80 Hz highpass
Spectral domain: Multi-tapered FFT 20-90 ms from the start of the FFR.
Analysis was conducted for the first 8 stimulus presentations of a train.
For each participant, data were normalized for SNR (mean amplitude
was divided by the mean of a 100 Hz window before 360 and after 400
Hz)
Repetition effects: FFR responses were
...
collapsed for each position of the train.
...
Only the peak corresponding to the 380 Hz
(frequency of the amplitude modulation)
was analyzed for each position (Cz
...
electrode). Individual mean power
1 2 3 4 ... 8
amplitudes were taken from a 10 Hz
Position in train
window centered at 380 Hz.
...
Children diagnosed with ASD often display atypical processing of auditory
2,3
information, to both simple and complex (e.g. speech) stimuli .
Roving standard paradigm with amplitude modulated tones
Carrier frequency
Autism spectrum disorders are a set of neurodevelopmental disorders that are
characterized by deficits in social communication, narrow interests and
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engagement in repetitive behaviours .
Experimental design
Carrier frequency
INTRODUCTION
Participants:
17 children diagnosed
with ASD (Asperger’s
syndrome or pervasive
developmental disorder,
IQ>90).
17 age and IQ matched
typically developing (TD)
controls
(Age range: 6-12 years)
RESULTS
Repetition effects
Grand-average Frequency Following Responses
TD
-0.2
0.2
-20
130ms
60
Grand average spectra
of the FFRs (all stimuli)
at the AM frequency
(380 Hz)
Normalized power
(SNR)
0
0
0.2
-20
300
130ms
60
300
460
380
Frequency (Hz)
Examples of normalized responses from single participants
1
0.8
0.7
0.7
0.5
0.4
0.3
0.2
0.1
6th+7th
7th+8th
TD
0.8
0.6
5th+6th
0.6
0.5
0.4
0.3
0.2
0.1
0
Position
Position
RMANOVA: Group x Position interaction (p=.037)
Within-subjects contrasts: linear pattern for ASD (p=.002), trend towards a quadratic pattern for TD (p=.051)
> In both groups, FFRs were modulated by stimulus repetitions
> However, the modulation of the responses was different in the ASD group, with power
magnitudes increasing with the number of repetitions
1
0.9
0.9
ASD
Normalized power
0.8
Normalized power
4th+5th
0
0
460
380
Frequency (Hz)
3rd+4th
ASD
Normalized mean power
0
Cz
Normalized power
(SNR)
Cz
Amplitude (µV)
Amplitude (µV)
-0.2
2nd+3rd
1st+2nd
Frequency (Hz)
Normalized mean power
ASD
Position in train
0.7
0.6
0.5
0.4
0.3
0.2
0.1
TD
0.8
0.7
0.6
CONCLUSION
0.5
0.4
0.3
0.2
0.1
0
280 300 320 340 360 380 400 420 440 460 480
0
280 300 320 340 360 380 400 420 440 460 480
Frequency (Hz)
Frequency (Hz)
Position in train
2nd+3rd
1st+2nd
Frequency (Hz)
3rd+4th
4th+5th
5th+6th
6th+7th
7th+8th
> Our findings suggest that regularity encoding (based on stimulus repetitions) in
the auditory brainstem is altered in children with ASD.
> Increased FFR amplitude in ASD children suggests a higher neuronal activation
by each repetition.
> Impaired top down modulation from cortical areas might account for the atypical
responses observed in the ASD group.
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This work is supported by Fundación Alicia Koplowitz, Consolider-Ingenio 2012 (CSD2007-00012), Eranet-Neuron PANS (EUI2009-04086) and the ICREA Academia program.