Originally released in May 2025, this conversation is being re-released as part of a selection of guest interviews from the podcast archive.

Video: https://youtu.be/SjOKEX_KO3A?si=fYsl9tS0sVUAhozL

Dr. Richard Frye, MD, PhD, returns to discuss leucovorin, folate metabolism, and the growing research examining their relationship with autism. Dr. Frye is a child neurologist and autism researcher with extensive work investigating metabolic and physiological differences associated with neurodevelopmental disorders.

We explore why folate is so important to the brain, how folate crosses the blood-brain barrier, cerebral folate deficiency, folate receptor alpha autoantibodies, and the biological mechanisms that led researchers to investigate leucovorin in autism. Dr. Frye also walks through clinical research examining leucovorin and verbal communication, discusses why some individuals may respond differently than others, and explains the connections among folate metabolism, neurotransmitters, methylation, mitochondrial function, and neurodevelopment.

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0:00 Dr. Richard Frye

0:58 Daylight Computer Company

5:17 Chroma Light Devices

8:27 History of Leucovorin; low risk, high reward; Folate Receptor Alpha (FRa)

10:25 Blood Brain Barrier; Folate; CSF (cerebral spinal fluid)

14:04 DNA, RNA; MTHFR (Methylenetetrahydrofolate reductase)

17:34 Cerebral Folate deficiency; BH4, Placenta & Womb

23:35 Folate deficiency & Autism

26:21 Clinical Studies & Data

29:28 Folate & Mitochondria; Cerebral Folate Antibodies; White Matter Findings (!)

34:45 Cerebral Folate deficiency & Ranges; Autistic Phenotypes: Language, Communication, & Behaviors

40:45 Language & Communication; Self-Injurious Behaviors; Hyperactivity, Agitation; Treatment duration

42:53 Folate Autoantibodies & Maternal Health & Markers

45:30 Studies & Behavioral outcomes; inflammation & thyroid findings

46:58 Neural development; Language connections, white matter tracts & distal connections

48:53 Leucovorin for different severity/levels of Autism; Spinal Bifida

51:08 Preparing for pregnancy

53:50 Transgenerational aspects of Folate Autoantibodies Research; Prenatal Care & Awareness

59:32 Guidance & Support

Originally released in September 2024, this conversation is being re-released as part of a selection of guest interviews from the podcast archive.

Video: https://youtu.be/_wsDkv-dkEU?si=uTaUav5v7YfZBsaO

In this episode, I speak with Dr. Richard Frye, MD, PhD, a child neurologist and autism researcher whose work examines the metabolic and physiological systems associated with neurodevelopmental disorders. Dr. Frye received his MD and PhD in Physiology and Biophysics from Georgetown University and has published extensively on autism, mitochondrial function, metabolism, and related areas of medicine.

We explore mitochondria far beyond their familiar description as the “powerhouse of the cell,” including their roles in energy production, metabolism, oxidative stress, immune function, and sensing changes in the environment. Dr. Frye explains mitochondrial dysfunction, the citric acid cycle, the electron transport chain, biomarkers of mitochondrial function, and the complex relationship among mitochondria, inflammation, and cellular health. We also discuss autism, environmental influences, light, photobiomodulation, and emerging research.

Dr, Richard Frye https://drfryemdphd.com

Rossingnol Medical Center Facebook https://www.facebook.com/RossignolMedicalCenter

Neurobiology of Disease 2024 paper https://www.sciencedirect.com/science/article/pii/S0969996124001190?via%3Dihub

BE ON THE LOOKOUT FOR CHROMA'S NEW LIGHTS!!!

Elevate How You Navigate with Len & a free call https://elevatehowyounavigate.com

MAYU Water, use "autism" for 10% off at https://mayuwater.com

Daylight Computer Company, use "autism" for $50 off at https://buy.daylightcomputer.com/autism

Daylight Kids (!!!) https://kids.daylightcomputer.com/autism ‪

Chroma Light Devices, use "autism" for 10% discount at https://getchroma.co/?ref=autism

0:00 Dr. Richard Frye

6:13 Intro into mitochondria & energy production, various disease & dysfunction

11:16 Mitochondrial DNA, sensitivity, and the roles with epigenetics

16:16 Biomarkers of mitochondrial dysfunction, delicate delivery (space and time) into the electron transport chain

20:58 Cytochrome C Oxidase (complex IV); Carnitine, Fat, and Creatine

26:57 Molecules connected to aging & cellular respiration, environemental signals implicating mitochondria

30:26 Terrible Trio: oxidative stress, mitochondria dysfunction, immune/inflammation, DAMPS & inflammation

34:29 Environmental risks for the Embryo, overreactivity of mitochondria (200%) and physiological insults and regression

42:50 Tryptophan (aromatic amino acid), NAD, and Gastrointestinal biosynthesis

45:52 Light as an environmental change factoring into the Autistic Phenotype, Infant Tree and Adult Tree examples; Vitamin D (skin & brain are connected through Neuroectoderm)

54:54 Future Research

Originally released in April 2025, this conversation is being re-released as part of a selection of guest interviews from the podcast archive.

In this episode, I speak with Dr. Reza Shadmehr of Johns Hopkins University about the cerebellum and one of the brain's most fundamental problems: how do we learn to control our movements accurately? With a background spanning electrical engineering, robotics, biomedical engineering, and neuroscience, Dr. Shadmehr has spent his career investigating the computations that allow the brain to learn, predict, and control movement.

We discuss internal models, motor learning and memory, prediction, sensory feedback, error correction, Purkinje cells, and how the cerebellum helps distinguish the sensory consequences of our own actions from information coming from the outside world. We also explore reward and effort, eye and tongue movements, research with marmosets, sensory processing, and the possible relevance of cerebellar function beyond movement, including cognition and autism. The conversation reveals the cerebellum as much more than a structure for coordination. It is deeply involved in learning what to expect and using those predictions to make behavior accurate.

Shadmehr Lab: http://shadmehrlab.org

Publications: http://shadmehrlab.org/publications

YT Videos (Very Good !): https://www.youtube.com/@shadmehrlab1352

BE ON THE LOOKOUT FOR CHROMA'S NEW LIGHTS!!!

Elevate How You Navigate with Len & a free call https://elevatehowyounavigate.com

MAYU Water, use "autism" for 10% off at https://mayuwater.com

Daylight Computer Company, use "autism" for $50 off at https://buy.daylightcomputer.com/autism

Daylight Kids (!!!) https://kids.daylightcomputer.com/autism ‪

Chroma Light Devices, use "autism" for 10% discount at https://getchroma.co/?ref=autism

00:00 Reza Shadmehr

02:26 Daylight Computer Company, use "autism" for $25 discount

06:45 Chroma Light Devices- Lights Designed for Humans, use "autism" for 10% discount

9:54 Reza's journey into Biomedical Engineering & Neuroscience

16:26 Understanding the Cerebellum; 3 primary functions

22:07 Neuronal Communication & Purkinje Cells; Sensory and Interneurons

25:41 Cerebellum, eyes, and Autistic phenotype; Mesencephalon & other connections

28:13 Excitation/Inhibition (E/I) balance; Video examples & Movement deficiencies

29:29 Layers of the Cerebellum

34:08 E/I & Brain function

36:30 Learning & Memory in the Cerebellum

39:54 Dysfunction & Brain Compensation

41:57 Basal Ganglia and Cerebellum

43:48 Internal Calculators & Prediction

49:42 Reward & Movement & Accuracy

52:52 Movement control; Eye movements

55:56 Purkinje Cells & Tongue movements; deceleration

59:47 Understanding Language of the Cerebellum

1:01:58 Future of Cerebellar Technology