Resting State Functional Magnetic Resonance Imaging Elucidates Neurotransmitter Deficiency in Autism Spectrum Disorder

Resting-state functional magnetic resonance imaging provides dynamic insight into the functional organization of the brains’ intrinsic activity at rest. The emergence of resting-state functional magnetic resonance imaging in both the clinical and research settings may be attributed to recent advancements in statistical techniques, non-invasiveness and enhanced spatiotemporal resolution compared to other neuroimaging modalities, and the capability to identify and characterize deep brain structures and networks. In this report we describe a 16-year-old female patient with autism spectrum disorder who underwent resting-state functional magnetic resonance imaging due to late regression. Imaging revealed deactivated networks in deep brain structures involved in monoamine synthesis. Monoamine neurotransmitter deficits were confirmed by cerebrospinal fluid analysis. This case suggests that resting-state functional magnetic resonance imaging may have clinical utility as a non-invasive biomarker of central nervous system neurochemical alterations by measuring the function of neurotransmitter-driven networks. Use of this technology can accelerate and increase the accuracy of selecting appropriate therapeutic agents for patients with neurological and neurodevelopmental disorders.

[1]  J. Coyle,et al.  Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor coagonist d-serine , 2021, Proceedings of the National Academy of Sciences.

[2]  T. Caffrey,et al.  Toward three-dimensional in vitro models to study neurovascular unit functions in health and disease , 2021, Neural regeneration research.

[3]  E. Morris,et al.  Methods for Quantifying Neurotransmitter Dynamics in the Living Brain With PET Imaging , 2020, Frontiers in Physiology.

[4]  Stephen T. Foldes,et al.  Resting-state functional MRI connectivity impact on epilepsy surgery plan and surgical candidacy: prospective clinical work. , 2020, Journal of neurosurgery. Pediatrics.

[5]  Yong Xu,et al.  The rise and fall of MRI studies in major depressive disorder , 2019, Translational Psychiatry.

[6]  Jeffrey S. Raskin,et al.  Network‐targeted approach and postoperative resting‐state functional magnetic resonance imaging are associated with seizure outcome , 2019, Annals of neurology.

[7]  Stephen T. Foldes,et al.  Resting-state fMRI in disorders of consciousness to facilitate early therapeutic intervention. , 2019, Neurology. Clinical practice.

[8]  G. Northoff,et al.  Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorders , 2019, Molecular Psychiatry.

[9]  Stephen T. Foldes,et al.  Language lateralization with resting-state and task-based functional MRI in pediatric epilepsy. , 2019, Journal of neurosurgery. Pediatrics.

[10]  Stephen T. Foldes,et al.  Subcentimeter epilepsy surgery targets by resting state functional magnetic resonance imaging can improve outcomes in hypothalamic hamartoma , 2018, Epilepsia.

[11]  T. Opladen,et al.  Inherited Disorders of Neurotransmitters: Classification and Practical Approaches for Diagnosis and Treatment , 2018, Neuropediatrics.

[12]  A. Egerton,et al.  The relationship between cortical glutamate and striatal dopamine in first-episode psychosis: a cross-sectional multimodal PET and magnetic resonance spectroscopy imaging study , 2018, The lancet. Psychiatry.

[13]  R. Frye Social Skills Deficits in Autism Spectrum Disorder: Potential Biological Origins and Progress in Developing Therapeutic Agents , 2018, CNS Drugs.

[14]  Dong Pyo Jang,et al.  The Relationship Between Dopamine Neurotransmitter Dynamics and the Blood-Oxygen-Level-Dependent (BOLD) Signal: A Review of Pharmacological Functional Magnetic Resonance Imaging , 2018, Front. Neurosci..

[15]  A. Dagher,et al.  Dopamine Signaling Modulates the Stability and Integration of Intrinsic Brain Networks , 2018, bioRxiv.

[16]  C. Iadecola The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease , 2017, Neuron.

[17]  Charles J. Lynch,et al.  The Default Mode Network in Autism. , 2017, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[18]  Charles G. Minard,et al.  Correlating Resting-State Functional Magnetic Resonance Imaging Connectivity by Independent Component Analysis-Based Epileptogenic Zones with Intracranial Electroencephalogram Localized Seizure Onset Zones and Surgical Outcomes in Prospective Pediatric Intractable Epilepsy Study , 2017, Brain Connect..

[19]  R. Frye,et al.  Folate metabolism abnormalities in autism: potential biomarkers. , 2017, Biomarkers in medicine.

[20]  Justin K. Rajendra,et al.  Functional Connectivity of the Subcallosal Cingulate Cortex And Differential Outcomes to Treatment With Cognitive-Behavioral Therapy or Antidepressant Medication for Major Depressive Disorder. , 2017, The American journal of psychiatry.

[21]  Varina L. Boerwinkle,et al.  Resting-State Functional Connectivity by Independent Component Analysis-Based Markers Corresponds to Areas of Initial Seizure Propagation Established by Prior Modalities from the Hypothalamus , 2016, Brain Connect..

[22]  M. Casanova,et al.  Neuropathological Mechanisms of Seizures in Autism Spectrum Disorder , 2016, Front. Neurosci..

[23]  D. Rossignol,et al.  Identification and Treatment of Pathophysiological Comorbidities of Autism Spectrum Disorder to Achieve Optimal Outcomes , 2016, Clinical medicine insights. Pediatrics.

[24]  Robert M. Sapolsky,et al.  Faculty Opinions recommendation of Stress-related noradrenergic activity prompts large-scale neural network reconfiguration. , 2012 .

[25]  A. Sinclair,et al.  Cerebrospinal fluid and lumbar puncture: a practical review , 2012, Journal of Neurology.

[26]  D. Rossignol,et al.  A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures , 2011, Molecular Psychiatry.

[27]  G. Elliott,et al.  Tetrahydrobiopterin as a novel therapeutic intervention for autism , 2010, Neurotherapeutics.

[28]  P. Hazell,et al.  Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). , 2010, The Cochrane database of systematic reviews.