The relationship of Asperger's syndrome to autism: a preliminary EEG coherence study

Abstract

Background: It has long been debated whether Asperger's Syndrome (ASP) should be considered part of the Autism Spectrum Disorders (ASD) or whether it constitutes a unique entity. The Diagnostic and Statistical Manual, fourth edition (DSM-IV) differentiated ASP from high functioning autism. However, the new DSM-5 umbrellas ASP within ASD, thus eliminating the ASP diagnosis. To date, no clear biomarkers have reliably distinguished ASP and ASD populations. This study uses EEG coherence, a measure of brain connectivity, to explore possible neurophysiological differences between ASP and ASD.

Methods: Voluminous coherence data derived from all possible electrode pairs and frequencies were previously reduced by principal components analysis (PCA) to produce a smaller number of unbiased, data-driven coherence factors. In a previous study, these factors significantly and reliably differentiated neurotypical controls from ASD subjects by discriminant function analysis (DFA). These previous DFA rules are now applied to an ASP population to determine if ASP subjects classify as control or ASD subjects. Additionally, a new set of coherence based DFA rules are used to determine whether ASP and ASD subjects can be differentiated from each other.

Results: Using prior EEG coherence based DFA rules that successfully classified subjects as either controls or ASD, 96.2% of ASP subjects are classified as ASD. However, when ASP subjects are directly compared to ASD subjects using new DFA rules, 92.3% ASP subjects are identified as separate from the ASD population. By contrast, five randomly selected subsamples of ASD subjects fail to reach significance when compared to the remaining ASD populations. When represented by the discriminant variable, both the ASD and ASD populations are normally distributed.

Conclusions: Within a control-ASD dichotomy, an ASP population falls closer to ASD than controls. However, when compared directly with ASD, an ASP population is distinctly separate. The ASP population appears to constitute a neurophysiologically identifiable, normally distributed entity within the higher functioning tail of the ASD population distribution. These results must be replicated with a larger sample given their potentially immense clinical, emotional and financial implications for affected individuals, their families and their caregivers.

Figure 1

Standard EEG electrode names and positions. Head in vertex view, nose above, left ear to left. EEG electrodes: Z: Midline; FZ: Midline Frontal; CZ: Midline Central; PZ: Midline Parietal; OZ: Midline Occipital. Even numbers, right hemisphere locations; odd numbers, left hemisphere locations: Fp: Frontopolar; F: Frontal; C: Central; T: Temporal; P: Parietal; O: Occipital. The standard 19, 10–20 electrodes are shown as black circles. An additional subset of five, 10–10 electrodes are shown as open circles. Reprinted from Duffy FH and Als H with permission [36].

Figure 2

Coherence loadings: four factors best differentiate Asperger’s syndrome from autism spectrum disorders. EEG coherence factor loadings shown. View from above head, nose at top of each head image, left ear to left of image. Factor number is above each head and peak frequency for factor in Hz is above to right. Lines indicate top 85% coherence loadings per factor. Bidirectional color arrows delineate electrode pairs involved in the displayed factor. Red line = increased coherence in ASP group; blue-green line = decreased coherence in ASP group compared to ASD group. Relevant electrodes (see Figure 1) per factor are shown as black dots. The comparison electrode is shown as a red circle. Background colored areas are regions delineated by original PCA. Involved electrodes: Symbol ‘↔’ connects coherent electrodes for each factor Factor 15: FT9 ↔ TP9, F7, F3, P7 and FT10 ↔ F8; Factor 3: T7 ↔ C3, P3, CZ, OZ Factor 33: T8 ↔ F4 Factor 40: OZ ↔ P3, P7, P4. ASD, Autism Spectrum Disorders; ASP, Asperger’s Syndrome.

Figure 3

Asperger’s syndrome and autism spectrum disorders population distributions. Population distribution histograms are shown for the ASD (green, n = 430) and ASP (red, n = 26) groups. The horizontal axis is the discriminant function value developed to differentiate the ASD and ASP groups on the basis of coherence variables. It varies from −4.0 to +4.0 units. The histograms are formed from bins 0.25 units wide. The populations are both Gaussian in distribution. A smoothed Gaussian distribution is shown above the true histogram data distribution as estimated by Excel software. Discriminant analysis significantly separates the two groups. The ASP population is displayed on an expanded vertical scale. ASD, Autism Spectrum Disorders; ASP, Asperger’s Syndrome.