{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:33:08Z","timestamp":1790947988082,"version":"4.1.0"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SA 1723\/5\u20131"],"award-info":[{"award-number":["SA 1723\/5\u20131"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinician Scientist Program of the University of Leipzig Medical Faculty"},{"name":"University of Leipzig Medical Faculty","award":["990101\u2013113"],"award-info":[{"award-number":["990101\u2013113"]}]},{"DOI":"10.13039\/100000913","name":"James S. 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Based on case studies reporting various lesions locations, PLC has been conceptualized as dysfunction in a cortico-limbic-subcortico-thalamo-ponto-cerebellar network.<\/jats:p>\n                  <jats:p>To test whether the heterogeneous lesion locations are indeed linked in a common network, we applied \u2018lesion network-symptom-mapping\u2019 to 70 focal lesions identified in a systematic literature search for case reports of PLC. In lesion network-symptom-mapping normative connectome data (resting state functional MRI, n\u2009=\u2009100) is used to identify the brain regions that are likely affected by diaschisis based on the lesion locations. With lesion network-symptom-mapping we were able to identify a common network specific for PLC when compared with a control cohort (n\u2009=\u2009270). This bilateral network is characterized by positive connectivity to the cingulate and temporomesial cortices, striatum, hypothalamus, mesencephalon and pons, and negative connectivity to the primary motor and sensory cortices. In the most influential pathophysiological model of PLC, a centre for the control and coordination of facial expressions, respiration and vocalization in the periaqueductal grey is assumed, which is controlled via two pathways: an emotional system that exerts excitatory control of the periaqueductal grey descending from the temporal and frontal lobes, basal ganglia and hypothalamus; and a volitional system descending from the lateral premotor cortices that can suppress laughter or crying.<\/jats:p>\n                  <jats:p>To test whether the positive and negative PLC subnetworks identified in our analyses can indeed be related to an emotional system and a volitional system, we identified lesions causing emotional (n\u2009=\u200915) or volitional facial paresis (n\u2009=\u200946) in a second literature search. Patients with emotional facial paresis show preserved volitional movements but cannot trigger emotional movements in the affected hemiface, while the reverse is true for volitional facial paresis. Importantly, these lesions map differentially onto the PLC subnetworks: the \u2018positive PLC subnetwork\u2019 is part of the emotional system and the \u2018negative PLC subnetwork\u2019 overlaps with the volitional system for the control of facial movements.<\/jats:p>\n                  <jats:p>Based on this network analysis we propose a two-hit model of PLC: a combination of direct lesion and indirect diaschisis effects cause PLC through the loss of inhibitory cortical control of a dysfunctional emotional system.<\/jats:p>","DOI":"10.1093\/brain\/awab224","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T07:08:44Z","timestamp":1623740924000},"page":"3264-3276","source":"Crossref","is-referenced-by-count":42,"title":["Pathological laughter and crying: insights from lesion network-symptom-mapping"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-9212","authenticated-orcid":false,"given":"Julian","family":"Klingbeil","sequence":"first","affiliation":[{"name":"Language and Aphasia Laboratory, Department of Neurology, University of Leipzig Medical Centre, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5089-1214","authenticated-orcid":false,"given":"Max","family":"Wawrzyniak","sequence":"additional","affiliation":[{"name":"Language and Aphasia Laboratory, Department of Neurology, University of Leipzig Medical Centre, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-2498","authenticated-orcid":false,"given":"Anika","family":"Stockert","sequence":"additional","affiliation":[{"name":"Language and Aphasia Laboratory, Department of Neurology, University of Leipzig Medical Centre, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max-Lennart","family":"Brandt","sequence":"additional","affiliation":[{"name":"Language and Aphasia Laboratory, Department of Neurology, University of Leipzig Medical Centre, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4750-2994","authenticated-orcid":false,"given":"Hans-Ralf","family":"Schneider","sequence":"additional","affiliation":[{"name":"Language and Aphasia Laboratory, Department of Neurology, University of Leipzig Medical Centre, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Metelmann","sequence":"additional","affiliation":[{"name":"Language and Aphasia Laboratory, Department of Neurology, University of Leipzig Medical Centre, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Saur","sequence":"additional","affiliation":[{"name":"Language and Aphasia Laboratory, Department of Neurology, University of Leipzig Medical Centre, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"issue":"7","key":"2021120109194811600_awab224-B1","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1586\/ern.11.68","article-title":"Pseudobulbar affect: The spectrum of clinical presentations, etiologies and treatments","volume":"11","author":"Miller","year":"2011","journal-title":"Expert Rev Neurother"},{"issue":"5","key":"2021120109194811600_awab224-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1092852900026602","article-title":"The differential diagnosis of pseudobulbar affect (PBA). 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