{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:56:12Z","timestamp":1790906172847,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NeuroSci"],"abstract":"<jats:p>Charles Bonnet syndrome (CBS) is characterized by complex visual hallucinations in visually impaired individuals who maintain intact cognitive function. Despite significant progress in understanding this condition, the precise neural mechanisms underlying CBS remain incompletely understood. This review synthesizes current evidence regarding the pathophysiology of CBS, with particular emphasis on emerging neurobiological models that extend beyond simple cortical hyperexcitability. Recent neuroimaging, neurophysiological, and computational modeling studies suggest that CBS hallucinations may arise from complex interactions among deafferentation-induced neural plasticity, neurotransmitter imbalances, and altered functional connectivity within visual processing hierarchies. The evidence increasingly points toward a model involving desynchronization between bottom-up and top-down visual processing pathways, rather than mere hyperexcitability of deafferented visual cortex. This integrated perspective has important implications for both the theoretical understanding of visual perception and the development of targeted therapeutic interventions.<\/jats:p>","DOI":"10.3390\/neurosci7020031","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T09:45:12Z","timestamp":1772531112000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond Hyperexcitability: A Review of Neural Mechanisms in Charles Bonnet Syndrome"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7424-2386","authenticated-orcid":false,"given":"Eric","family":"Altieri","sequence":"first","affiliation":[{"name":"Neuro.Vis.U.S. Laboratory, University of Padova, 35131 Padova, Italy"},{"name":"University Centre for Clinical Psychological Services (SCUP), University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5187-9225","authenticated-orcid":false,"given":"Luca","family":"Battaglini","sequence":"additional","affiliation":[{"name":"Neuro.Vis.U.S. Laboratory, University of Padova, 35131 Padova, Italy"},{"name":"University Centre for Clinical Psychological Services (SCUP), University of Padova, 35131 Padova, Italy"},{"name":"Department of General Psychology, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1001\/archopht.123.3.349","article-title":"Complex Visual Hallucinations in the Visually Impaired: A structured history-taking approach","volume":"123","author":"Menon","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.survophthal.2007.06.012","article-title":"Charles Bonnet, His Life, and His Syndrome","volume":"52","author":"Terao","year":"2007","journal-title":"Surv. Ophthalmol."},{"key":"ref_3","unstructured":"Bonnet, C. (1760). Essai Analytique sur les Facult\u00e9s de L\u2019ame, Chez le freres C. & A. Philibert."},{"key":"ref_4","first-page":"667","article-title":"Le Syndrome de Charles Bonnet: Hallucinations Visuelles Des Viellards sans Dificience Mentale","volume":"125","year":"1967","journal-title":"Ann. Med. Psychol. Paris"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1001\/archneur.1971.00490050102009","article-title":"Phantom Vision","volume":"25","author":"Cohn","year":"1971","journal-title":"Arch. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/ICU.0b013e328329b643","article-title":"Charles Bonnet Syndrome: A Review","volume":"20","author":"Schadlu","year":"2009","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_7","first-page":"25158414211034715","article-title":"An Overview of Psychological and Social Factors in Charles Bonnet Syndrome","volume":"13","author":"Jones","year":"2021","journal-title":"Ther. Adv. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.31887\/DCNS.2007.9.2\/dffytche","article-title":"Visual Hallucinatory Syndromes: Past, Present, and Future","volume":"9","author":"Ffytche","year":"2007","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e002009","DOI":"10.1136\/bmjophth-2024-002009","article-title":"From Research to Action: Ecommendations for Charles Bonnet Syndrome Care and Policy","volume":"10","author":"Jones","year":"2025","journal-title":"BMJ Open Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1093\/fampra\/cmy006","article-title":"Family Physician Awareness of Charles Bonnet Syndrome","volume":"35","author":"Gordon","year":"2018","journal-title":"Fam. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111282","DOI":"10.1016\/j.brainresbull.2025.111282","article-title":"The Prevalence of Charles-Bonnet Syndrome in Ophthalmic Patients: A Systematic Review and Meta-Analysis","volume":"223","author":"Christoph","year":"2025","journal-title":"Brain Res. Bull."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6793","DOI":"10.21037\/aes-21-37","article-title":"Prevalence of Charles Bonnet Syndrome in Low Vision: A Systematic Review and Meta-Analysis","volume":"7","author":"Subhi","year":"2022","journal-title":"Ann. Eye Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/S0140-6736(96)90869-7","article-title":"Visual Hallucinations in Psychologically Normal People: Charles Bonnet\u2019s Syndrome","volume":"347","author":"Teunisse","year":"1996","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/S0039-6257(02)00414-9","article-title":"Complex Visual Hallucinations in the Visually Impaired: The Charles Bonnet Syndrome","volume":"48","author":"Menon","year":"2003","journal-title":"Surv. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1080\/09286580801939320","article-title":"Charles Bonnet Syndrome in Age-Related Macular Degeneration: The Nature and Frequency of Images in Subjects with End-Stage Disease","volume":"15","author":"Khan","year":"2008","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/brain\/99.4.719","article-title":"Simple Formed Hallucinations Confined to the Area of a Specific Visual Field Defect","volume":"99","author":"Lance","year":"1976","journal-title":"Brain"},{"key":"ref_17","first-page":"421","article-title":"Charles Bonnet Syndrome","volume":"82","author":"Yacoub","year":"2011","journal-title":"Optom.-J. Am. Optom. Assoc."},{"key":"ref_18","first-page":"360","article-title":"Charles Bonnet Syndrome: Case Presentation and Literature Review","volume":"80","author":"Kester","year":"2009","journal-title":"Optom.-J. Am. Optom. Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1017\/S0033291700046584","article-title":"The Charles Bonnet Syndrome in Perspective","volume":"12","author":"Jenner","year":"1982","journal-title":"Psychol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/j.1442-9071.2008.01814.x","article-title":"Butterflies and Black Lacy Patterns: The Prevalence and Characteristics of Charles Bonnet Hallucinations in an Australian Population","volume":"36","author":"Vukicevic","year":"2008","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1001\/archneur.63.4.598","article-title":"Visual Hallucinations During Visual Recovery After Central Retinal Artery Occlusion","volume":"63","author":"Tan","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1532-5415.1987.tb01321.x","article-title":"Visual Hallucinations in Sane People: Charles Bonnet Syndrome","volume":"35","author":"Rosenbaum","year":"1987","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1136\/jnnp.73.5.535","article-title":"The Neural Basis of Charles Bonnet Hallucinations: A Hypothesis","volume":"73","author":"Burke","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1093\/brain\/121.10.1819","article-title":"Complex Visual Hallucinations. Clinical and Neurobiological Insights","volume":"121","author":"Manford","year":"1998","journal-title":"Brain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1017\/S0140525X05000130","article-title":"Why People See Things That Are Not There: A Novel Perception and Attention Deficit Model for Recurrent Complex Visual Hallucinations","volume":"28","author":"Collerton","year":"2005","journal-title":"Behav. Brain Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Marr, D. (2010). Vision: A Computational Investigation into the Human Representation and Processing of Visual Information, MIT Press.","DOI":"10.7551\/mitpress\/9780262514620.001.0001"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/3738","article-title":"The Anatomy of Conscious Vision: An fMRI Study of Visual Hallucinations","volume":"1","author":"Ffytche","year":"1998","journal-title":"Nat. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nn878","article-title":"Critical Periods for Experience-Dependent Synaptic Scaling in Visual Cortex","volume":"5","author":"Desai","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrn1327","article-title":"Homeostatic Plasticity in the Developing Nervous System","volume":"5","author":"Turrigiano","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.neuron.2012.06.030","article-title":"Adult Visual Cortical Plasticity","volume":"75","author":"Gilbert","year":"2012","journal-title":"Neuron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1152\/jn.1965.28.6.1029","article-title":"Comparison of the Effects of Unilateral and Bilateral Eye Closure on Cortical Unit Responses in Kittens","volume":"28","author":"Wiesel","year":"1965","journal-title":"J. Neurophysiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Reichert, D.P., Seri\u00e8s, P., and Storkey, A.J. (2013). Charles Bonnet Syndrome: Evidence for a Generative Model in the Cortex?. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1003134"},{"key":"ref_33","first-page":"25158414241280201","article-title":"Neurochemistry and Functional Connectivity in the Brain of People with Charles Bonnet Syndrome","volume":"16","author":"Bridge","year":"2024","journal-title":"Ther. Adv. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Piarulli, A., Annen, J., Kupers, R., Laureys, S., Martial, C., Piarulli, A., Annen, J., Kupers, R., Laureys, S., and Martial, C. (2021). High-Density EEG in a Charles Bonnet Syndrome Patient during and without Visual Hallucinations: A Case-Report Study. Cells, 10.","DOI":"10.3390\/cells10081991"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/00004850-200411000-00008","article-title":"Treatment of Typical Charles Bonnet Syndrome with Donepezil","volume":"19","author":"Ukai","year":"2004","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/BF00407835","article-title":"Visual Hallucinations as Release Phenomena","volume":"188","author":"Cogan","year":"1973","journal-title":"Albrecht Von Graefes Arch. F\u00fcr Klin. Exp. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1016\/j.cub.2018.08.058","article-title":"Stimulus-Driven Cortical Hyperexcitability in Individuals with Charles Bonnet Hallucinations","volume":"28","author":"Painter","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1017\/S0140525X12000477","article-title":"Whatever next? Predictive Brains, Situated Agents, and the Future of Cognitive Science","volume":"36","author":"Clark","year":"2013","journal-title":"Behav. Brain Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hohwy, J. (2013). The Predictive Mind, Oxford University Press.","DOI":"10.1093\/acprof:oso\/9780199682737.001.0001"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1177\/0269881106075275","article-title":"Charles Bonnet Syndrome: Successful Treatment of Visual Hallucinations Due to Vision Loss with Selective Serotonin Reuptake Inhibitors","volume":"21","author":"Lang","year":"2007","journal-title":"J. Psychopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00415-024-12741-2","article-title":"Visual Cortical Activity in Charles Bonnet Syndrome: Testing the Deafferentation Hypothesis","volume":"272","author":"Collerton","year":"2025","journal-title":"J. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"103041","DOI":"10.1016\/j.nicl.2022.103041","article-title":"Investigation of Structural Brain Changes in Charles Bonnet Syndrome","volume":"35","author":"Firbank","year":"2022","journal-title":"NeuroImage Clin."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Martial, C., Larroque, S.K., Cavaliere, C., Wannez, S., Annen, J., Kupers, R., Laureys, S., and Perri, C.D. (2019). Resting-State Functional Connectivity and Cortical Thickness Characterization of a Patient with Charles Bonnet Syndrome. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0219656"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrn2536","article-title":"Perceiving Is Believing: A Bayesian Approach to Explaining the Positive Symptoms of Schizophrenia","volume":"10","author":"Fletcher","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"111683","DOI":"10.1016\/j.brainresbull.2025.111683","article-title":"Understanding the Charles Bonnet Syndrome: An Updated Review","volume":"234","author":"Christoph","year":"2026","journal-title":"Brain Res. Bull."},{"key":"ref_46","first-page":"25158414241294177","article-title":"Are Depression, Anxiety and Loneliness Associated with Visual Hallucinations in Younger Adults with Charles Bonnet Syndrome?","volume":"16","author":"Walker","year":"2024","journal-title":"Ther. Adv. Ophthalmol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1136\/bjophthalmol-2014-304920","article-title":"Negative Outcome Charles Bonnet Syndrome","volume":"98","author":"Cox","year":"2014","journal-title":"Br. J. Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1017\/S1041610213000719","article-title":"Escitalopram for Antipsychotic Nonresponsive Visual Hallucinosis: Eight Patients Suffering from Charles Bonnet Syndrome","volume":"25","author":"Bergman","year":"2013","journal-title":"Int. Psychogeriatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/j.ophtha.2022.06.041","article-title":"Transcranial Direct Current Stimulation in the Treatment of Visual Hallucinations in Charles Bonnet Syndrome: A Randomized Placebo-Controlled Crossover Trial","volume":"129","author":"Schumacher","year":"2022","journal-title":"Ophthalmology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s10072-005-0455-0","article-title":"Olanzapine Therapy in Hallucinatory Visions Related to Bonnet Syndrome","volume":"26","author":"Milano","year":"2005","journal-title":"Neurol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1136\/jnnp.70.6.813","article-title":"Charles Bonnet\u2019s Syndrome: Complete Remission of Complex Visual Hallucinations Treated by Gabapentin","volume":"70","author":"Paulig","year":"2001","journal-title":"J. Neurol. Neurosurg. Psychiatry"}],"container-title":["NeuroSci"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-4087\/7\/2\/31\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T11:48:17Z","timestamp":1772538497000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-4087\/7\/2\/31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["neurosci7020031"],"URL":"https:\/\/doi.org\/10.3390\/neurosci7020031","relation":{},"ISSN":["2673-4087"],"issn-type":[{"value":"2673-4087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]}}}