The Role of Glutamate in Language and Language Disorders - Evidence from ERP and Pharmacologic Studies

• Published in: Neuroscience and biobehavioral reviews Vol. 119; pp. 217 - 241
• Main Authors: Li, Wentao, Kutas, Marta, Gray, John A., Hagerman, Randi H., Olichney, John M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.12.2020
• Subjects: Alzheimer's Disease; Aphasia; Event-Related Potentials; Fragile X Syndrome; Fragile X-associated Tremor/Ataxia Syndrome; Glutamate Neurotransmission; Glutamic Acid; Humans; Language; Pharmacology; Stroke Aphasia; Tremor; Language; Stroke Aphasia; Alzheimer's Disease; Event-Related Potentials; Pharmacology; Glutamate Neurotransmission; Fragile X-associated Tremor/Ataxia Syndrome
• ISSN: 0149-7634; 1873-7528; 1873-7528
• DOI: 10.1016/j.neubiorev.2020.09.023

•L-Glutamate neurotransmission likely plays a physiologic role in the regulation of language access, comprehension, and production.•NMDA, AMPA, and mGlu Receptor dysregulation is implicated in the pathogenesis of Alzheimer’s Disease, FXTAS, and Stroke, and may contribute to language dysfunction in these diseases.•Memantine, a selective NMDA receptor antagonist, improves language function in Alzheimer’s Disease, FXTAS, and Post-Stroke Aphasia patients based on patient report and language-battery tests.•Memantine normalizes language-related ERPs (closer to healthy-controls) in post-stroke aphasia and FXTAS patients.•Ketamine, another NMDAR receptor antagonist, affects language-related ERPs in non-aphasic subjects. Current models of language processing do not address mechanisms at the neurotransmitter level, nor how pharmacologic agents may improve language function(s) in seemingly disparate disorders. L-Glutamate, the primary excitatory neurotransmitter in the human brain, is extensively involved in various higher cortical functions. We postulate that the physiologic role of L-Glutamate neurotransmission extends to the regulation of language access, comprehension, and production, and that disorders in glutamatergic transmission and circuitry contribute to the pathogenesis of neurodegenerative diseases and sporadic-onset language disorders such as the aphasic stroke syndromes. We start with a review of basic science data pertaining to various glutamate receptors in the CNS and ways that they may influence the physiological processes of language access and comprehension. We then focus on the dysregulation of glutamate neurotransmission in three conditions in which language dysfunction is prominent: Alzheimer’s Disease, Fragile X-associated Tremor/Ataxia Syndrome, and Aphasic Stroke Syndromes. Finally, we review the pharmacologic and electrophysiologic (event related brain potential or ERP) data pertaining to the role glutamate neurotransmission plays in language processing and disorders.