Motor noise is rich signal in autism research and pharmacological treatments

Abstract

The human body is in constant motion, from every breath that we take, to every visibly purposeful action that we perform. Remaining completely still on command is a major achievement as involuntary fluctuations in our motions are difficult to keep under control. Here we examine the noise-to-signal ratio of micro-movements present in time-series of head motions extracted from resting-state functional magnetic resonance imaging scans in 1048 participants. These included individuals with autism spectrum disorders (ASD) and healthy-controls in shared data from the Autism Brain Imaging Data Exchange (ABIDE) and the Attention-Deficit Hyperactivity Disorder (ADHD-200) databases. We find excess noise and randomness in the ASD cases, suggesting an uncertain motor-feedback signal. A power-law emerged describing an orderly relation between the dispersion and shape of the probability distribution functions best describing the stochastic properties under consideration with respect to intelligence quotient (IQ-scores). In ASD, deleterious patterns of noise are consistently exacerbated with the presence of secondary (comorbid) neuropsychiatric diagnoses, lower verbal and performance intelligence, and autism severity. Importantly, such patterns in ASD are present whether or not the participant takes psychotropic medication. These data unambiguously establish specific noise-to-signal levels of head micro-movements as a biologically informed core feature of ASD.

Psychotropic Medication Use in Autism Spectrum Disorders May Affect Functional Brain Connectivity

“…RMSD and the number of time points censored also did not correlate with the BRIEF and ADOS-2 RRB scores that were significantly different in the ASD-on compared to ASD-none group. Interestingly, a recent study by Torres et al (47) showed differences in the stochastic nature of motion fluctuations during fMRI scans with psychotropic medication usage in the Autism Brain Imaging Data Exchange cohort (ABIDE; N=1048 including ASD and TD participants, aged 5–60 years). Based on their findings, the authors suggest that psychotropic medications may be related to increased neuromotor symptomatology in individuals with ASDs.…”

The Autism Phenotype

“…Recent work involving 1,048 participants has revealed that excess noise accumulation in involuntary micro-motions of the head (while the person is in resting state) are present in individuals with ASD and ADHD but absent from neuro-typical controls ( Figure 3A). Such excess noise signatures were consistently found regardless of differences in ages, ADOS-severity scores, IQ-levels and levels of social difficulties (Torres and Denisova 2016). For our purposes here note that any excess involuntary micro-motions in these neurodevelopmental disorders is bound to interfere with the ability to remain still on command.…”

Hidden Aspects of the Research-ADOS are Bound to Affect Autism Science

“…Several debates have been published surrounding controversial reliance on the research-grade Autism Diagnostic Observational Schedule (ADOS) [1] for use in scientific Autism research [2]. The field seems to have reached a point whereby some Autism researchers advocate the importance of nervous systems’ biorhythms [3; 4; 5; 6; 7; 8; 9; 10] and the use of biophysical data to adapt tenets of Precision Medicine [11; 12] to a nascent field of Precision Psychiatry [4; 13]. These new developments have led to a surge in the interest to develop digital biomarkers for personalized approaches to diagnose and treat disorders of the nervous systems [14].…”

“…Nevertheless, the biophysical data underlying the types of observed behavior that lead to a diagnosis of Autism, produce empirical outcomes that may not correspond to the theoretical statistical assumptions underlying the analyses that defines the clinical scale used in basic research (Figure 2CD and inset in D). The lack of normality in the distributions of various biophysical parameters of basic electrophysiology appears across several lines of enquiry, spanning from imaging to behavioral physiology [5; 14; 15], but it has not been investigated in research-grade ADOS scores empirically obtained from the adopters of the test in Autism science.…”