The amplitude of fNIRS hemodynamic response in the visual cortex unmasks autistic traits in typically developing children

Abstract

Autistic traits represent a continuum dimension across the population, with autism spectrum disorder (ASD) being the extreme end of the distribution. Accumulating evidence shows that neuroanatomical and neurofunctional profiles described in relatives of ASD individuals reflect an intermediate neurobiological pattern between the clinical population and healthy controls. This suggests that quantitative measures detecting autistic traits in the general population represent potential candidates for the development of biomarkers identifying early pathophysiological processes associated with ASD. Functional near-infrared spectroscopy (fNIRS) has been extensively employed to investigate neural development and function. In contrast, the potential of fNIRS to define reliable biomarkers of brain activity has been barely explored. Features of non-invasiveness, portability, ease of administration, and low-operating costs make fNIRS a suitable instrument to assess brain function for differential diagnosis, follow-up, analysis of treatment outcomes, and personalized medicine in several neurological conditions. Here, we introduce a novel standardized procedure with high entertaining value to measure hemodynamic responses (HDR) in the occipital cortex of adult subjects and children. We found that the variability of evoked HDR correlates with the autistic traits of children, assessed by the Autism-Spectrum Quotient. Interestingly, HDR amplitude was especially linked to social and communication features, representing the core symptoms of ASD. These findings establish a quick and easy strategy for measuring visually-evoked cortical activity with fNIRS that optimize the compliance of young subjects, setting the background for testing the diagnostic value of fNIRS visual measurements in the ASD clinical population.

Conflict of interest statement

The authors declare no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1. Visual stimulation and experimental paradigm.

A Representative frame of baseline grey screen (upper row, stimulus ‘off’) and reversing checkerboard (lower row, stimulus ‘on’) for RS condition. The small black square indicates the fixation point. B Representative frame of low-contrast (20%) grey-scale baseline animated cartoon (upper row, stimulus ‘off’) and blended checkerboard-cartoon (lower row, stimulus ‘on’) for Cartoon-Fixed (CF) and Cartoon Chosen (CC) conditions. C Representative HDR in the occipital cortex during the stimulus ‘off’ (upper row) and stimulus ‘on’ activation phase (lower row) according to the output of nirsLAB software. The Look Up table is reported under the images. D Experimental protocol showing that the cycles of visual stimulation were structured in blocks of 40 trials (20 trials with the reversing checkerboard and 20 trials with the ‘mock’ stimulus) for a total duration of 10 min.

Fig. 2. HDR was reliably detected in adults using both RS and blended RS-animated cartoons.

For all panels, values in the y-axis are multiplied for 10^4. A On the left, the average time course for THb (green line), OHb (red line), and DHb (blue line) in response to the Radial Simulus (RS) are shown. The three plots on the right depict the average peak response to the stimulus (S) vs. the blank (B) across all the adult subjects. The stimulus-driven signal was significantly different from the blank for all the conditions (t-test, p < 0.001 for all comparisons). B Same plots as above for the Cartoon Fixed (CF) condition. On the left, the average time course of the evoked HDR is depicted. On the right, the graphs showed that the HDR amplitude was significantly higher in response to S with respect to B for THb, OHb, and DHb (t-test, p < 0.001 for all comparisons). C Cartoon Chosen (CC) condition. Also in this case the S elicited significantly higher responses for THb, OHb, and DHb with respect to the B (t-test, p < 0.001 for all comparisons). D Comparison among different visual stimulations shows no differences in evoked amplitudes for THb, whereas a significant difference was detected between RS and CC for OHb (One-way RM ANOVA, p < 0.01, post hoc BH-FDR, RS vs. CC p < 0.01) and a more complex pattern of differences emerged for DHb (One-way RM ANOVA, p < 0.001, post hoc BH-FDR, RS vs. CF p < 0.01, RS vs. CC p < 0.001, CF vs CC p < 0.05). E No differences of evoked responses were detected with different contrast levels of the baseline movie (L: low, M: medium, H: high). For statistical metrics and details, refer to Table S1. Data are shown as average ± s.e.m. * p < 0.05; ** p < 0.01; *** p < 0.001.

Fig. 3. HDR signal was reliably detected in children using blended RS-animated cartoons with low and high contrast.

For all panels, values in the y-axis are multiplied for 10^4. A On the left, the average time course for THb (green line), OHb (red line), and DHb (blue line) in response to high-contrast (80%) blended RS-animated cartoons is shown (CH1). On the right, the graphs represent the average amplitude of the evoked HDR following the stimulus (S) and the blank (B). A significantly different response to S with respect to the B was detectable for all metrics (t-test, p < 0.001 for all comparisons). B The average time course of the HDR to low-contrast (20%) blended RS-animated cartoons is shown (CL1). Here, the baseline cartoon is the same as the experiment described in panel (A), but a different part of the movie was used. THb, OHb, and DHb showed a significantly higher deflection to the S with respect to the B in this condition as well (t-test, p < 0.001 for all comparisons). C On the left, the average time course of HDR following the second low-contrast blended RS-animated cartoon selected by the subject (CL2). On the right, the analysis of peak amplitudes revealed significantly higher responses during S compared to B for THb, OHb, and DHb (t-test, p < 0.001 for all comparisons). D Comparison among different contrast levels of the baseline cartoon revealed no differences in the amplitude of HDR. E Response amplitudes for low-contrast blended RS-animated cartoons in adults and children. More specifically, we compared the response to CF condition of adults with CL1 condition for children. The average amplitude of HDR was significantly higher in children (t-test, p < 0.001 for THb, p < 0.05 for OHb, p < 0.01 for DHb). For statistical metrics and details, refer to Table S1. Data are shown as average ± s.e.m. * p < 0.05; ** p < 0.01; *** p < 0.001.

Fig. 4. Correlation between HDR and AQ scores.

For all panels, values in the x-axis are multiplied for 10^4. The ρ (rho) index in each plot indicates the Spearman correlation value. Correlation between HDR and AQ scores in adults, for amplitudes obtained using RS (A), CF (B), and CC (C). No significant correlations were detected for adult participants. Correlation between HDR and AQ scores in children, for amplitudes obtained using high (D), and low (E) contrast baseline cartoons. A significant correlation was found between THb and AQ scores for both high- and low-contrast blended stimuli (p < 0.05 for both cases). Circles are individual values; lines represent the linear regression model fit and shaded regions are the 95% CI.

Fig. 5. Correlation between HDR and AQ subscales in children.

For all panels, values in the x-axis are multiplied for ×10^4. The ρ (rho) index in each plot indicates the Spearman correlation value. A, B Correlations between HDR and AQ Social Skills (AQ_S) subscale. A significant correlation between THb and AQ_S was detected using both high- (A) and low-contrast blended stimuli (B; p < 0.05 for both cases). In addition, OHb recorded in response to the low-contrast blended RS-cartoon was significantly correlated with AQ_S (B; p < 0.05). C, D Correlations between HDR and AQ Communication (AQ_C) subscale. THb amplitude in response to the high-contrast blended RS-cartoon was significantly correlated with AQ_C (p < 0.05). Circles are individual values; lines represent the linear regression model fit and shaded regions are the 95% CI.