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These included patients had focal seizure\u2010onset zone, here referred to as a \u201clesion.\u201d The network of brain regions functionally connected to each lesion was identified using whole\u2010brain functional connectivity from a functional magnetic resonance imaging (fMRI) dataset of healthy participants (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091000). Network maps were overlapped to identify regions functionally connected to most lesions. Specificity was evaluated using a case\u2013control design. Therapeutic relevance was assessed using a cohort that underwent deep brain stimulation to the anterior nucleus of the thalamus to improve seizure control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lesion locations for patients with HKS (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200950) and patients without HKS (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200947 for automatisms;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200953 for elementary motor signs) were included. Based on the lesion brain network, the most sensitive and specific region with HKS was the anterior cingulate cortex (ACC) (&gt;90% overlap). Reversed connectivity patterns between the ACC and the whole brain encompassed most lesion locations that caused HKS (47\/50, 94%). In addition, the functional connectivity between ACC and deep brain stimulation sites was associated with improved seizure control (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009.49,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.01) in 27 patients with drug\u2010resistant epilepsy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These findings indicated that HKS might be a symptom of brain network disruption that resulted from lesions in various brain regions commonly connected to ACC, emphasizing the ACC as a potential target for therapeutic intervention in HKS.<\/jats:p>\n                  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