A Comparison of Parent Reports, the Mental Synthesis Evaluation Checklist (MSEC) and the Autism Treatment Evaluation Checklist (ATEC), with the Childhood Autism Rating Scale (CARS).

This study compares two parent reports, the Mental Synthesis Evaluation Checklist (MSEC) and the Autism Treatment Evaluation Checklist (ATEC), with the Childhood Autism Rating Scale (CARS). The ATEC consists of four subscales, as follows: (1) expressive language, (2) sociability, (3) sensory awareness, and (4) health. The MSEC is complementary to the ATEC in measuring complex language comprehension. The parents of 143 autistic children, from 2 to 22 years of age (mean 6.7 ± 5.1 years), completed the MSEC and the ATEC questionnaires and a clinician assessed their CARS score. The CARS score correlated strongly with all parent reports, the complex language comprehension MSEC (r = 0.60, p < 0.0001), expressive language (r = 0.66, p < 0.0001), sociability (r = 0.58, p < 0.0001), sensory awareness (r = 0.71, p < 0.0001), and health (r = 0.53, p < 0.0001), as well as the total ATEC score (r = 0.75, p < 0.0001). The strongest correlation was between the CARS score and the composite of all five parent-reported scores (total ATEC + MSEC, r = 0.77, p < 0.0001). These results suggest a high fidelity of the MSEC and ATEC parent reports and especially of their composite score, total ATEC + MSEC.

Dietary Factors Impact Developmental Trajectories in Young Autistic Children.

PURPOSE: The purpose of this research was to investigate the impact of dietary factors on developmental trajectories in young autistic children. METHODS: A gluten-free and casein-free diets, as well as six types of food (meat and eggs, vegetables, uncooked vegetables, sweets, bread, and "white soft bread that never molds") were investigated observationally for up to three years in 5,553 children 2 to 5 years of age via parent-report measures completed within a mobile application. Children had a parent-reported diagnosis of Autism Spectrum Disorder (ASD); 78% were males; the majority of participants resided in the USA. Outcome was monitored on five orthogonal subscales: Language Comprehension, Expressive Language, Sociability, Sensory Awareness, and Health, assessed by the Autism Treatment Evaluation Checklist (ATEC) (Rimland & Edelson, 1999) and Mental Synthesis Evaluation Checklist (MSEC) (Arnold & Vyshedskiy, 2022; Braverman et al., 2018). RESULTS: Consumption of fast-acting carbohydrates - sweets, bread, and "white soft bread that never molds" - was associated with a significant and a consistent Health subscale score decline. On the contrary, a gluten-free diet, as well as consumption of meat, eggs, and vegetables were associated with a significant and consistent improvement in the Language Comprehension score. Consumption of meat and eggs was also associated with a significant and consistent improvement in the Sensory Awareness score. CONCLUSION: The results of this study demonstrate a strong correlation between a diet and developmental trajectories and suggest possible dietary interventions for young autistic children.

A Feasibility Study of AlzLife 40 Hz Sensory Therapy in Patients with MCI and Early AD.

Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) are debilitating diseases that affect millions of individuals and have notoriously limited treatment options. One emerging therapy, non-invasive 40 Hz sensory therapy delivered through light and sound has previously shown promise in improving cognition in Alzheimer Disease (AD) rodent models. Small studies in humans have proven safe and tolerable, however exploration of feasibility and utility is limited. The purpose of this study is to examine the feasibility of this treatment in a human population through a smart tablet application that emits light and sound waves at 40 Hz to the user over the span of 1 h a day. Confirmation of entrainment of 40 Hz stimulation in the cerebral cortex was performed via EEG. 27 preliminary subjects with subjective cognitive complaints, Mild Cognitive Impairment, or AD were enrolled in the study; 11 participants completed 6 months of therapy. Of those that discontinued treatment, other health issues and difficulties with compliance were the most common causes. Participants were followed with Montreal Cognitive Assessment (MOCA) and Boston Cognitive Assessment (BOCA). For participants with subjective cognitive complaints, 2 of the 4 had improved MOCA score and 1 of 4 had improved BOCA score. For the participant with MCI, his MOCA score improved. For AD participants, 2 out of 6 had improved MOCA score and 3 of the 6 stayed stable, while 3 of 6 BOCA score improved. 4 of 11 participants specifically increased their MOCA scores in the Memory Index section. Of the 8 participants/caregivers able to speak to perceived usefulness of the study, 6 spoke to at least some level of benefit. Of these 6, 2 enrolled with subjective cognitive complaint, 1 had MCI, and 3 had AD. The therapy did not have reported side effects. However, those who did not finish the study experienced issues obtaining and operating a smart tablet independently as well as complying with the therapy. Overall, further exploration of this treatment modalities efficacy is warranted.

Combinatorial Language parent-report Scores Differ Significantly Between Typically Developing Children and Those with Autism Spectrum Disorders.

Prefrontal synthesis (PFS) is a component of constructive imagination. It is defined as the process of mentally juxtaposing objects into novel combinations. For example, to comprehend the instruction "put the cat under the dog and above the monkey," it is necessary to use PFS in order to correctly determine the spatial arrangement of the cat, dog, and monkey with relation to one another. The acquisition of PFS hinges on the use of combinatorial language during early childhood development. Accordingly, children with developmental delays exhibit a deficit in PFS, and frequent assessments are recommended for such individuals. In 2018, we developed the Mental Synthesis Evaluation Checklist (MSEC), a parent-reported evaluation designed to assess PFS and combinatorial language comprehension. In this manuscript we use MSEC to identify differences in combinatorial language acquisition between ASD (N = 29,138) and neurotypical (N = 111) children. Results emphasize the utility of the MSEC in distinguishing language deficits in ASD from typical development as early as 2 years of age (p < 0.0001).

Parent-Reported Assessment Scores Reflect the ASD Severity Level in 2- to 7-Year-Old Children.

We investigated the relationship between parent-reported assessments and autism spectrum disorder (ASD) severity level. Parents evaluated 9573 children with ASD on five subscales-combinatorial receptive language, expressive language, sociability, sensory awareness, and health-using the Autism Treatment Evaluation Checklist (ATEC) and Mental Synthesis Evaluation Checklist (MSEC). The scores in every subscale improved with age, and there were clear differences between the three diagnostic categories. The differences between mild and moderate ASD, and moderate and severe ASD reached statistical significance in each subscale and in every age group in children 3 years of age and older. These findings demonstrate a consistent relationship between children's diagnoses and their assessments and provide evidence in support of the reliability of parent-report evaluations for ASD. Additionally, this is the first investigation of the relationship between ASD severity level and the ATEC/MSEC scores for the age range from 2 to 7 years.

Boston cognitive assessment (BOCA) - a comprehensive self-administered smartphone- and computer-based at-home test for longitudinal tracking of cognitive performance.

Longitudinal cognitive testing is essential for developing novel preventive interventions for dementia and Alzheimer's disease; however, the few available tools have significant practice effect and depend on an external evaluator. We developed a self-administered 10-min at-home test intended for longitudinal cognitive monitoring, Boston Cognitive Assessment or BOCA. The goal of this project was to validate BOCA. BOCA uses randomly selected non-repeating tasks to minimize practice effects. BOCA evaluates eight cognitive domains: 1) Memory/Immediate Recall, 2) Combinatorial Language Comprehension/Prefrontal Synthesis, 3) Visuospatial Reasoning/Mental rotation, 4) Executive function/Clock Test, 5) Attention, 6) Mental math, 7) Orientation, and 8) Memory/Delayed Recall. BOCA was administered to patients with cognitive impairment (n = 50) and age- and education-matched controls (n = 50). Test scores were significantly different between patients and controls (p < 0.001) suggesting good discriminative ability. The Cronbach's alpha was 0.87 implying good internal consistency. BOCA demonstrated strong correlation with Montreal Cognitive Assessment (MoCA) (R = 0.90, p < 0.001). The study revealed strong (R = 0.94, p < 0.001) test-retest reliability of the total BOCA score one week after participants' initial administration. The practice effect tested by daily BOCA administration over 10 days was insignificant (ß = 0.03, p = 0.68). The effect of the screen size tested by BOCA administration on a large computer screen and re-administration of the BOCA to the same participant on a smartphone was insignificant (ß = 0.82, p = 0.17; positive ß indicates greater score on a smartphone). BOCA has the potential to reduce the cost and improve the quality of longitudinal cognitive tracking essential for testing novel interventions designed to reduce or reverse cognitive aging. BOCA is available online gratis at www.bocatest.org .

Novel linguistic evaluation of prefrontal synthesis (LEPS) test measures prefrontal synthesis acquisition in neurotypical children and predicts high-functioning versus low-functioning class assignment in individuals with autism.

In order to grasp the difference between "the cat on the mat" and "the mat on the cat," understanding the words and the grammar is not enough. Rather it is essential to visualize the cat and the mat together to appreciate their relations. This type of imagination, which involves juxtaposition of mental objects is conducted by the prefrontal cortex and is therefore called Prefrontal Synthesis (PFS). PFS acquisition has a strong experience-dependent critical period putting children with language delay in danger of never acquiring PFS and, consequently, not mastering complex language comprehension. In typical children, the timeline of PFS acquisition correlates with vocabulary expansion. Conversely, atypically developing children may learn many words but never acquire PFS. In these individuals, intelligence tests based on vocabulary assessment may miss the profound deficit in PFS. Accordingly, we developed a test specific for PFS - Linguistic Evaluation of Prefrontal Synthesis or LEPS - and administered it to 50 neurotypical children, age 4.1 ± 1.3 years and to 23 individuals with impairments, age 16.4 ± 3.0 years. All neurotypical children older than 4 years received the LEPS score 7/10 or greater indicating good PFS ability. Among individuals with impairments only 39% received the LEPS score 7/10 or greater. LEPS was 90% correct in predicting high-functioning vs. low-functioning class assignment in individuals with impairments.

The Boston cognitive assessment: Psychometric foundations of a self-administered measure of global cognition.

Objective: The Boston Cognitive Assessment (BoCA) is a novel, computerized, self-administered assessment of global cognition. This work sought to establish the validity and reliability of the BoCA. Method: Two studies were conducted. The first study used a sample of 43 outpatients from a clinic in eastern Massachusetts to evaluate the content validity and internal consistency of the BoCA. The second study used a sample of 38 patients seen at an outpatient specialty neurological clinic to evaluate the BoCA's test-retest reliability after one week. Results: In the first study, participants without cognitive diagnoses scored significantly higher on both the BoCA and the Telephone Interview for Cognitive Status (TICS) compared to those with mild Neurocognitive Disorders. Correlational analyses revealed moderate correlations between several of the BoCA tasks and measures of related abilities. Exploratory factor analysis of the BoCA tasks revealed one robust factor accounting for a plurality (i.e., 42%) of variance in participant scores. The BoCA demonstrated good internal consistency (α = 0.79) and strong correlations (r = 0.80, p < 0.01) with the TICS. The second study revealed strong (r = 0.89, p < 0.001) test-retest reliability of the total BoCA score one week after participants' initial administration. Conclusions: This work provides evidence of the BoCA's psychometric properties as a self-administered screener of global cognition, and supports its implementation in clinical practice and future studies. Clinical implications, future directions, and limitations are discussed.

Watching Videos and Television Is Related to a Lower Development of Complex Language Comprehension in Young Children with Autism.

The effect of passive video and television watching duration on 2- to 5-year-old children with autism was investigated in the largest and the longest observational study to date. Parents assessed the development of 3227 children quarterly for three years. Longer video and television watching were associated with better development of expressive language but significantly impeded development of complex language comprehension. On an annualized basis, low TV users (low quartile: 40 min or less of videos and television per day) improved their language comprehension 1.4 times faster than high TV users (high quartile: 2 h or more of videos and television per day). This difference was statistically significant. At the same time, high TV users improved their expressive language 1.3 times faster than low TV users. This difference was not statistically significant. No effect of video and television watching duration on sociability, cognition, or health was detected.

Imagination in Autism: A Chance to Improve Early Language Therapy.

Children with autism often have difficulties in imaginative play, Theory of Mind, and playing out different scenarios in their minds. Research shows that the root of these problems may be the voluntary imagination network that involves the lateral prefrontal cortex and its long frontoposterior connections to the temporal-parietal-occipital area. Previously disconnected visuospatial issues (stimulus overselectivity and tunnel vision) and language issues (lack of comprehension of spatial prepositions and complex recursive sentences) may be explained by the same voluntary imagination deficit. This review highlights the new insights into the mechanism of voluntary imagination, its difference from involuntary imagination, and its unusually strong critical period. Clearer developmental terminology and a better understanding of voluntary imagination have the potential to facilitate communication between therapists and parents, and improve therapy outcomes in children.

Novel Prefrontal Synthesis Intervention Improves Language in Children with Autism.

Prefrontal synthesis (PFS) is defined as the ability to juxtapose mental visuospatial objects at will. Paralysis of PFS may be responsible for the lack of comprehension of spatial prepositions, semantically-reversible sentences, and recursive sentences observed in 30 to 40% of individuals with autism spectrum disorder (ASD). In this report we present data from a three-year-long clinical trial of 6454 ASD children age 2 to 12 years, which were administered a PFS-targeting intervention. Tablet-based verbal and nonverbal exercises emphasizing mental-juxtaposition-of-objects were organized into an application called Mental Imagery Therapy for Autism (MITA). The test group included participants who completed more than one thousand exercises and made no more than one error per exercise. The control group was selected from the rest of participants by a matching procedure. Each test group participant was matched to the control group participant by age, gender, expressive language, receptive language, sociability, cognitive awareness, and health score at first evaluation using propensity score analysis. The test group showed a 2.2-fold improvement in receptive language score vs. control group (p < 0.0001) and a 1.4-fold improvement in expressive language (p = 0.0144). No statistically significant change was detected in other subscales not targeted by the exercises. These findings show that language acquisition improves after training PFS and that a further investigation of the PFS-targeting intervention in a randomized controlled study is warranted.

Longitudinal Epidemiological Study of Autism Subgroups Using Autism Treatment Evaluation Checklist (ATEC) Score.

Here we report the results of the subgroup analyses of an observational cohort of children whose parents completed the Autism Treatment Evaluation Checklist (ATEC) over the period of several years. A linear mixed effects model was used to evaluate longitudinal changes in ATEC scores within different patient subgroups. All groups decreased their mean ATEC score over time indicating improvement of symptoms, however there were significant differences between the groups. Younger children improved more than the older children. Children with milder ASD improved more than children with more severe ASD in the Communication subscale. There was no difference in improvement between females vs. males. One surprising finding was that children from developed English-speaking countries improved less than children from non-English-speaking countries.

Development of the Mental Synthesis Evaluation Checklist (MSEC): A Parent-Report Tool for Mental Synthesis Ability Assessment in Children with Language Delay.

Mental synthesis is the conscious purposeful process of synthesizing novel mental images from objects stored in memory. Mental synthesis ability is essential for understanding complex syntax, spatial prepositions, and verb tenses. In typical children, the timeline of mental synthesis acquisition is highly correlated with an increasing vocabulary. Children with Autism Spectrum Disorder (ASD), on the other hand, may learn hundreds of words but never acquire mental synthesis. In these individuals, tests assessing vocabulary comprehension may fail to demonstrate the profound deficit in mental synthesis. We developed a parent-reported Mental Synthesis Evaluation Checklist (MSEC) designed to assess mental synthesis acquisition in ASD children. The psychometric quality of MSEC was tested with 3715 parents of ASD children. Internal reliability of the 20-item MSEC was good (Cronbach's alpha >0.9). MSEC exhibited adequate test⁻retest reliability; good construct validity, supported by a positive correlation with the Autism Treatment Evaluation Checklist (ATEC) Communication subscale; and good known group validity reflected by the difference in MSEC scores for children of different ASD severity levels. The MSEC questionnaire is copyright-free and can be used by researchers as a complimentary subscale for the ATEC evaluation. We hope that the addition of MSEC will make the combined assessment more sensitive to small steps in a child's development. As MSEC does not rely on productive language, it may be an especially useful tool for assessing the development of nonverbal and minimally verbal children.

Autism Treatment Evaluation Checklist (ATEC) Norms: A "Growth Chart" for ATEC Score Changes as a Function of Age.

Most early-intervention Autism Spectrum Disorder (ASD) clinical trials are limited by the availability of psychometric technicians who assess each child's abilities before and after therapeutic intervention. If parents could administer regular psychometric evaluations of their children, then the cost of clinical trials will be reduced, enabling longer clinical trials with the larger number of participants. The Autism Treatment Evaluation Checklist (ATEC) was designed nearly two decades ago to provide such a tool, but the norms on the longitudinal changes in ATEC in the "treatment as usual" population were lacking. Here we report the norms of the observational cohort who voluntarily completed ATEC evaluations over the period of four years from 2013 to 2017.

Pendelluft in chronic obstructive lung disease measured with lung sounds.

Objective. The phenomenon of pendelluft was described over five decades ago. In patients with regional variations in resistance and elastance, gas moves at the beginning of inspiration out of some alveoli into others. Gas moves in the opposite direction at the end of inspiration. The objective of this study was to apply the method of lung sounds mapping, which is known to provide regional information about gas flow, to study pendelluft in COPD patients. Methods. A 16-channel lung sound analyzer was used to collect sounds from patients with COPD (n = 90) and age-matched normals (n = 90). Pendelluft at the beginning of inspiration is expected to result in vesicular sounds leading the tracheal sound by a few milliseconds. Pendelluft at the end of inspiration is expected to result in vesicular sounds lagging the tracheal sound. These lead and lag times were calculated for the 14 chest wall sites. Results. The lead time was significantly longer in COPD patients: 123 ± 107 ms versus 48 ± 59 ms in controls (P < 0.0001). The lag time was also significantly longer in COPD patients: 269 ± 249 ms in COPD patients versus 147 ± 124 ms in controls (P < 0.0001). When normalized by the duration of the inspiration at the trachea, the lead was 14 ± 13% for COPD versus 4 ± 5% for controls (P < 0.0001). The lag was 28 ± 25% for COPD versus 13 ± 12% for controls (P < 0.0001). Both lead and lag correlated moderately with the GOLD stage (correlation coefficient 0.43). Conclusion. Increased lead and lag times in COPD patients are consistent with the phenomenon of pendelluft as has been observed by other methods.

Crackle Pitch Rises Progressively during Inspiration in Pneumonia, CHF, and IPF Patients.

Objective. It is generally accepted that crackles are due to sudden opening of airways and that larger airways produce crackles of lower pitch than smaller airways do. As larger airways are likely to open earlier in inspiration than smaller airways and the reverse is likely to be true in expiration, we studied crackle pitch as a function of crackle timing in inspiration and expiration. Our goal was to see if the measurement of crackle pitch was consistent with this theory. Methods. Patients with a significant number of crackles were examined using a multichannel lung sound analyzer. These patients included 34 with pneumonia, 38 with heart failure, and 28 with interstitial fibrosis. Results. Crackle pitch progressively increased during inspirations in 79% of all patients. In these patients crackle pitch increased by approximately 40 Hz from the early to midinspiration and by another 40 Hz from mid to late-inspiration. In 10% of patients, crackle pitch did not change and in 11% of patients crackle pitch decreased. During expiration crackle pitch progressively decreased in 72% of patients and did not change in 28% of patients. Conclusion. In the majority of patients, we observed progressive crackle pitch increase during inspiration and decrease during expiration. Increased crackle pitch at larger lung volumes is likely a result of recruitment of smaller diameter airways. An alternate explanation is that crackle pitch may be influenced by airway tension that increases at greater lung volume. In any case improved understanding of the mechanism of production of these common lung sounds may help improve our understanding of pathophysiology of these disorders.

Crackle pitch and rate do not vary significantly during a single automated-auscultation session in patients with pneumonia, congestive heart failure, or interstitial pulmonary fibrosis.

OBJECTIVE: To determine the variability of crackle pitch and crackle rate during a single automated-auscultation session with a computerized 16-channel lung-sound analyzer. METHODS: Forty-nine patients with pneumonia, 52 with congestive heart failure (CHF), and 18 with interstitial pulmonary fibrosis (IPF) performed breathing maneuvers in the following sequence: normal breathing, deep breathing, cough several times; deep breathing, vital-capacity maneuver, and deep breathing. From the auscultation recordings we measured the crackle pitch and crackle rate. RESULTS: Crackle pitch variability, expressed as a percentage of the average crackle pitch, was small in all patients and in all maneuvers: pneumonia 11%, CHF 11%, pulmonary fibrosis 7%. Crackle rate variability was also small: pneumonia 31%, CHF 32%, IPF 24%. Compared to the first deep-breathing maneuver (100%), the average crackle pitch did not significantly change following coughing (pneumonia 100%, CHF 103%, IPF 100%), the vital-capacity maneuver (pneumonia 100%, CHF 92%, IPF 104%), or during quiet breathing (pneumonia 97%, CHF 100%, IPF 104%). Similarly, the average crackle rate did not change significantly following coughing (pneumonia 105%, CHF 110%, IPF 90%) or the vital-capacity maneuver (pneumonia 102%, CHF 101%, IPF 99%). However, during normal breathing the crackle rate was significantly lower in the patients with pneumonia (74%, P < .001) and significantly higher in the patients with IPF (147%, P < .05) than it was during deep breathing. In patients with CHF the average crackle rate during normal breathing was not significantly different from that during the first deep-breathing maneuver (108%). CONCLUSIONS: Crackle pitch and rate were surprisingly stable in all 3 conditions. Neither crackle pitch nor crackle rate changed significantly from breath to breath or from one deep-breathing maneuver to another, even when the maneuvers were separated by cough or the vital-capacity maneuver. The observation that crackle rate is a reproducible measurement during one automated-auscultation session suggests that crackle rate can be used to follow the course of cardiopulmonary illnesses such as pneumonia, IPF, and CHF.

Mechanism of inspiratory and expiratory crackles.

OBJECTIVE: Although crackles are frequently heard on auscultation of the chest of patients with common cardiopulmonary disorders, the mechanism of production of these sounds is inadequately understood. The goal of this research was to gain insights into the mechanism of crackle generation by systematic examination of the relationship between inspiratory and expiratory crackle characteristics. METHODS: Patients with a significant number of both inspiratory and expiratory crackles were examined using a multichannel lung sound analyzer. These patients included 37 with pneumonia, 5 with heart failure, and 13 with interstitial fibrosis. Multiple crackle characteristics were calculated for each crackle, including frequency, amplitude, crackle transmission coefficient, and crackle polarity. RESULTS: Spectral, temporal, and spatial characteristics of expiratory and inspiratory crackles in these patients were found to be similar, but two characteristics were strikingly different: crackle numbers and crackle polarities. Inspiratory crackles were almost twice as numerous as expiratory crackles (n = 3,308 vs 1,841) and had predominately negative polarity (76% of inspiratory crackles vs 31% of expiratory crackles). CONCLUSION: These observations are quantitatively consistent with the so-called stress-relaxation quadrupole hypothesis of crackle generation. This hypothesis holds that expiratory crackles are caused by sudden airway closure events that are similar in mechanism but opposite in sign and far less energetic than the explosive opening events that generate inspiratory crackles. We conclude that the most likely mechanism of crackle generation is sudden airway closing during expiration and sudden airway reopening during inspiration.

Transmission of crackles in patients with interstitial pulmonary fibrosis, congestive heart failure, and pneumonia.

OBJECTIVE: Patients with interstitial pulmonary fibrosis (IPF) often have diffusely abnormal findings on chest radiographs, making it difficult to detect evidence of superimposed congestive heart failure (CHF) or pneumonia. The goal of this study was to determine whether the crackles of IPF differed in their transmission and frequency from crackles of CHF and pneumonia in the hope of improving diagnosis and monitoring of these patients. METHODS: A multichannel lung sound analyzer was used to collect 20-s samples of sound from 25 patients with pneumonia, 17 patients with CHF, and 19 patients with IPF. We calculated a crackle transmission coefficient (CTC) by quantifying the distance a crackle spreads using a technique that cross-correlated the signal containing the highest amplitude crackle with the corresponding signal on all other ipsilateral channels: CTC, 0% = no transmission; CTC, 100% = equal transmission to all channels. RESULTS: Both the CTC and the crackle frequency in IPF were statistically different from that in CHF and pneumonia (p < 0.0001). The CTC averaged 24 +/- 5% for pneumonia, 25 +/- 8% for CHF, and 14 +/- 4% for IPF. The crackle frequency averaged 302 +/- 47 Hz for pneumonia, 311 +/- 62 Hz for CHF, and 462 +/- 50 Hz for IPF (+/- SD). CONCLUSION: These differences in CTC and crackle frequency offer the promise of helping guide treatment in IPF patients.