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Mutant huntingtin affects corticogenesis, cell migration, and differentiation. Cortical changes are reminiscent of focal cortical dysplasia, a malformation of cortical development that leads to hyperexcitability and epilepsy. Striatal development also is affected by the mutation. In animal models, recent studies provide additional evidence that neuronal morphology and intrinsic and electrophysiological properties deviate from normal development. Some changes indicate delayed development of cortical pyramidal neurons, while a subtype of striatal projection neuron displays a transient accelerated maturation. However, the brain is able to compensate for early abnormalities and, during a variable latent period, brain function appears normal. Eventually, homeostatic mechanisms begin to fail, resulting in the emergence of HD symptoms. The realization that neurodevelopment in HD is abnormal offers new insights and opens new avenues for early treatment. In this review, we present a brief summary of imaging and morphological studies from human carriers of the HD mutation followed by a more in-depth examination of recent findings in genetic animal models.<\/jats:p>","DOI":"10.1177\/18796397251366891","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T07:03:02Z","timestamp":1755586982000},"page":"190-200","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Abnormal neurodevelopment predisposes to cortical hyperexcitability in Huntington's disease"],"prefix":"10.1177","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5953-6692","authenticated-orcid":false,"given":"Carlos","family":"Cepeda","sequence":"first","affiliation":[{"name":"IDDRC, Jane and Terry Semel Institute for Neuroscience &amp; Human Behavior, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Barry","sequence":"additional","affiliation":[{"name":"IDDRC, Jane and Terry Semel Institute for Neuroscience &amp; Human Behavior, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M","family":"Holley","sequence":"additional","affiliation":[{"name":"IDDRC, Jane and Terry Semel Institute for Neuroscience &amp; Human Behavior, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq280"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-200394"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603871113"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0715-14.2014"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0477-7"},{"key":"e_1_3_3_7_2","article-title":"Abnormal brain development in huntington\u2019 disease is recapitulated in the zQ175 knock-in mouse model","volume":"1","author":"Zhang C","year":"2020","unstructured":"Zhang C, Wu Q, Liu H, et al. 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