Background and ObjectivesTime orientation is a fundamental cognitive process in which one’s personal sense of time is matched with a universal reference. Assessment of time orientation is a ubiquitous component of neurological mental status examinations and neuropsychological assessments, yet its neural correlates remain unclear. Large bilateral lesions have been associated with deficits in time orientation, but more specific regions of the brain implicated in time disorientation following focal unilateral damage are relatively unknown. The current study investigates the anatomy of time disorientation and its network correlates in patients with focal brain lesions.Methods550 patients with acquired, focal brain lesions participated in this study, identified retrospectively from the Iowa Neurological Patient Registry. Time orientation was assessed 3 months or more after lesion onset using the Benton Temporal Orientation Test (BTOT) was performed 3 months or more after lesion onset, and 39 patients were identified as having chronic impairment in time orientation defined as a score of 3 or worse on the BTOT. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with time disorientation. Performance on a variety of neuropsychological tests was compared between the time oriented and time disoriented group.Results39 patients were identified as having chronic impairment in time orientation. Multivariate lesion-symptom mapping showed that lesions of the posterior cortices were associated with impaired time orientation, including medial temporal lobes, occipitotemporal cortex, and precuneus (r=0.21, p<.001).Individuals with time disorientation tended to have concomitant impairments in memory, visuospatial ability, and naming. Follow-up analyses of individuals with unilateral lesions and those with relatively unimpaired cognition in other domains implicated the precuneus and parahippocampal gyrus in time orientation. Lesion network mapping demonstrated that these regional findings occurred at nodes of the default mode and visual networks. Individuals with time disorientation tended to have concomitant impairments in memory, visuospatial ability, and naming.DiscussionWe interpret these findings as novel evidence for the role of posteromedial cortices extending from the precuneus to the medial temporal lobe in supporting time orientation.

ObjectiveTime orientation is a fundamental cognitive process in which one's personal sense of time is matched with a universal reference. Time orientation is commonly assessed through mental status examination, yet its neural correlates remain unclear. Large lesions have been associated with deficits in time orientation, but the regional anatomy implicated in time disorientation is not well established. The current study investigates the anatomy of time disorientation and its network correlates in patients with focal brain lesions.MethodsTime orientation was assessed 3 months or more after lesion onset using the Benton Temporal Orientation Test (BTOT) in 550 patients with acquired, focal brain lesions, 39 of whom were impaired. Multivariate lesion‐symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with time disorientation. Performance on a variety of neuropsychological tests was compared between the time oriented and time disoriented group.ResultsLesion‐symptom mapping showed that lesions of the precuneus, medial temporal lobes (MTL), and occipito‐temporal cortex were associated with time disorientation (r = 0.264, p < 0.001). Lesion network mapping using normative connectome data demonstrated that these regional findings occurred along a network that includes white and gray matter connecting the precuneus and MTL. There was a strong behavioral and anatomical association of time disorientation with memory impairment, such that the 2 processes could not be fully disentangled.InterpretationWe interpret these findings as novel evidence for a network involving the precuneus and the medial temporal lobe in supporting time orientation. ANN NEUROL 2023

Background and Objectives Approximately 25% of pediatric patients who undergo cerebellar tumor resection develop cerebellar mutism syndrome (CMS). Our group recently showed that damage to the cerebellar outflow pathway is associated with increased risk of CMS. Here, we tested whether these findings replicate in an independent cohort. Methods We evaluated the relationship between lesion location and the development of CMS in an observational study of 56 pediatric patients who underwent cerebellar tumor resection. We hypothesized that individuals that developed CMS after surgery (CMS+), relative to those that did not (CMS-) would have lesions that preferentially intersected with: 1) the cerebellar outflow pathway, and 2) a previously generated 'lesion-symptom map' of CMS. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/). Results We found supporting evidence for both hypotheses. Compared with CMS- patients, CMS+ patients (n=10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen's d=.73, p=.05), and the CMS lesion-symptom map (Cohen's d=1.1, p=.004). Discussion These results strengthen the association of lesion location with risk of developing CMS and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to pediatric cerebellar tumors.

Approximately 25% of pediatric patients who undergo cerebellar tumor resection develop cerebellar mutism syndrome (CMS). Our group recently showed that damage to the cerebellar deep nuclei and superior cerebellar peduncles, which we refer to as the cerebellar outflow pathway, is associated with increased risk of CMS. Here, we tested whether these findings replicate in an independent cohort. We evaluated the relationship between lesion location and the development of CMS in an observational study of 56 pediatric patients who underwent cerebellar tumor resection. We hypothesized that individuals that developed CMS after surgery (CMS+), relative to those that did not (CMS-) would have lesions that preferentially intersected with: 1) the cerebellar outflow pathway, and 2) a previously generated ‘lesion-symptom map’ of CMS. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/). We found supporting evidence for both hypotheses. Compared with CMS- patients, CMS + patients (n = 10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen’s d = .73, p = .05), and the CMS lesion-symptom map (Cohen’s d = 1.1, p = .004). These results strengthen the association of lesion location with risk of developing CMS and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to pediatric cerebellar tumors.