Optimal time lags from causal prediction model help stratify and forecast nervous system pathology

Abstract

Traditional clinical approaches diagnose disorders of the nervous system using standardized observational criteria. Although aiming for homogeneity of symptoms, this method often results in highly heterogeneous disorders. A standing question thus is how to automatically stratify a given random cohort of the population, such that treatment can be better tailored to each cluster’s symptoms, and severity of any given group forecasted to provide neuroprotective therapies. In this work we introduce new methods to automatically stratify a random cohort of the population composed of healthy controls of different ages and patients with different disorders of the nervous systems. Using a simple walking task and measuring micro-fluctuations in their biorhythmic motions, we combine non-linear causal network connectivity analyses in the temporal and frequency domains with stochastic mapping. The methods define a new type of internal motor timings. These are amenable to create personalized clinical interventions tailored to self-emerging clusters signaling fundamentally different types of gait pathologies. We frame our results using the principle of reafference and operationalize them using causal prediction, thus renovating the theory of internal models for the study of neuromotor control.

Precision Autism: Genomic Stratification of Disorders Making Up the Broad Spectrum May Demystify Its “Epidemic Rates”

“…In Autism research, when the person has both diagnoses (ASD and a neurological or neuropsychiatric one) the former is coined idiopathic Autism, whereas the latter are called Autism of known etiology. Yet in a random draw of the population, we have identified clusters differentiating subtypes by relying on gait [6,17], voluntary reaches [4,28,43,44] and involuntary head motions [5,7,30,45,46]. I blindly took these genes associated to other disorders of the nervous system (clinically and physiologically defined) and interrogated them in terms of their expression on brain and bodily tissues.…”

“…In Figure 7, I also reveal those genes' expression and SFARI scores for the cardiac (heart left ventricle and the heart atrial appendage), skeletal (muscle skeletal), and smooth muscle (esophagus muscularis and bladder) tissues and for the nerve tibial. The latter is critical to develop kinesthetic reafference and proper gait, known to be disrupted in several of these disorders (autism, PD, FX [17]). Common to all these disorders are well known genes in the Autism literature with SFARI score confidence 1 (e.g., MECP2, AFF2, FOXP1, CREBBP, CACNA1E, CHD7, TRIO and SHANK3, among others.)…”

“…Continuing the blanket approach also misses three important revolutions of the 21st Century: the genomic, the neuroscience and the wearables sensors revolution. The latter brings a level of precision to analyze continuous streams of behaviors beyond the limits of the naked eye, capable of automatically separating geneticbased disorders from natural, simple behaviors like walking and yet uncovering individual stochastic signatures of the person's biorhythms with causal dynamics [17].…”

“…These criteria also remain absent from psychological instruments like the ADOS test, currently used to diagnose different age groups [10,15,16]. However, kinesthetic sensing and motor/vestibular issues define several of the many disorders that today received the Autism diagnosis [17]. Among them are Cerebral Palsy [18,19], Dystonia [20,21], Tourette's Syndrome [22] and obsessive-compulsive disorders (OCD) thought to be related to ADHD [23].…”

“…Despite these caveats explicitly stated on their manuals, children with profound and highly visible motor, kinesthetic sensing and vestibular issues [17] go on to receive the Autism diagnosis that places them on a behavioral modification therapeutic pipeline that does not consider the brain-body physiology [31]. Clearly, there is a contradiction between the somatic-sensory-motor medical-physiological criteria and the social-appropriateness behavioral-psychological criteria explicitly denying the former.…”