Objective: Neuropsychological assessments should employ scientifically supported instruments to detect bias. To our knowledge, there are no validated measures for assessing bias in informant ratings of personality changes following brain injuries. We report the development of such a measure for the Iowa Scales of Personality Change (ISPC). Method: ISPC personality change ratings were obtained from informants for: (1) 48 Research Registry patients with chronic, focal, ventromedial prefrontal cortex lesions (vmPFC group), and (2) 226 individuals undergoing independent neuropsychological evaluations in the context of litigation (INE group). An "Atypical Change Index" was developed using vmPFC group ISPC data, comprising scales for which extreme changes were rare among vmPFC patients (≤2.5%). We hypothesized that the INE group would have higher Atypical Change Index scores compared to the vmPFC group. To avoid circularity, we used repeated cross-validations to separate the vmPFC group data into "train" sets for identifying scales for the Atypical Change Index, and "test" sets for comparing the Atypical Change Index across vmPFC and INE groups. Results: The INE group had statistically significantly higher Atypical Change Index scores than the vmPFC group (p < .001). One vmPFC patient (2.1% of the group) had an Atypical Change Index score > 1, compared to 64 INE patients (28.3% of the group) with scores > 1. Conclusions: Our findings provide initial support for the potential of the Atypical Change Index to detect bias in informant ratings on the ISPC. Further investigation is required to evaluate the validity of this index.

Patients with damage to the ventromedial prefrontal cortex (vmPFC) classically develop personality disturbances, emotion dysregulation, and social decision-making deficits that have been likened to psychopathic tendencies ("pseudopsychopathy"). These acquired deficits are thought to entail empathy impairments, viz., identifying other people's emotional experiences and caring about their well-being. However, these impairments may be due to either low motivation to empathize or impaired ability to empathize accurately. We examined whether patients with vmPFC lesions (who have been shown previously to have major deficits in empathy accuracy) would exhibit low empathy motivation. We conducted a lesion group comparison study to assess motivation to empathize. The results showed that damage to the vmPFC was not associated with low empathy motivation (including avoidance of affective or cognitive forms of empathy). Specifically, patients with vmPFC lesions did not avoid empathy any more so than comparison groups (participants with damage outside of the vmPFC or participants with no brain damage). Our findings suggest that patients with vmPFC damage may have preserved empathy motivation, at least in an off-line, laboratory task setting, despite their real-world impairments with deploying empathy. More research is needed to examine whether patients with vmPFC lesions would exhibit normal empathy motivation in everyday contexts.

Eating-related disorders such as anorexia nervosa, bulimia nervosa and obesity are associated with high rates of morbidity and mortality in the United States. To investigate the neuroanatomical structures involved in appetite and weight change, we employed lesion symptom mapping. 358 patients with focal brain lesions and appetite ratings were recruited, as well as 48 patients with pre- and post-lesion weight records. Partial least squares regression identified a significant association between patterns of brain damage and appetite change (model R2 = 0.13, P = 0.006), and the relationship between lesion location and weight change was explored using the proportional subtraction method. The right posterior insula was the peak region associated with both decreased appetite and weight loss, providing new insight into the neural correlates of higher-order appetite regulation and weight management.

Background/Objectives: Cognitive impairment can compromise toothbrushing and other oral self-care functions, increasing the risk of oral diseases and related complications. However, how toothbrushing ability declines across stages of cognitive impairment remains unclear. This study aimed to describe functional deficits in toothbrushing among older adults with different levels of cognitive function. Method: Sixty-five older adults (14 cognitively healthy and 51 with documented cognitive impairment) were classified into five cognitive levels based on Standardized Mini-Mental State Examination scores. Participants completed a toothbrushing task as they normally would at home. Performance was videotaped, coded, and evaluated across four domains (task initiation, completion, thoroughness, and quality) with total scores reflecting overall toothbrushing ability. Overall performance, functional deficits, and assistance needs were analyzed in relation to cognitive levels. Results: Participants averaged 76.5 years of age. Toothbrushing ability declined gradually with worsening cognitive impairment, followed by a sharp deterioration at the profound stage (e.g., SMMSE ≤ 5). Compared with cognitively healthy participants (n = 14), those with mild cognitive impairment (MCI, n = 20) or mild (n = 10), moderate (n = 10), or severe dementia (n = 11) lost an average of 3%, 8%, 12%, and 37% of overall toothbrushing ability, respectively. Brushing efficiency declined earlier and more rapidly, decreasing by 13% in MCI and up to 46% in severe dementia (p < 0.001). All participants with MCI or mild dementia completed the task independently, whereas 20% with moderate dementia and 80% with severe dementia required assistance to initiate or complete the task. Conclusions: Overall toothbrushing ability remains relatively preserved until the later stages of cognitive impairment, but brushing quality deteriorates much earlier and quicker. These findings highlight the importance of early caregiver–patient partnerships, functionally tailored oral self-care rehabilitation, and personalized caregiver training to support oral hygiene among older adults with cognitive impairment.

Damage to the amygdala has been linked to impairments in empathy, typically documented as deficits in accurately identifying others' emotional experiences, especially fear. This has led some to theorize that amygdala dysfunction is a core feature of psychopathy. There is growing evidence, however, that motivation to empathize is distinct from empathic accuracy. Moreover, anecdotal observations in patients with amygdala lesions have noted their tendencies to approach, rather than avoid, empathic encounters with strangers, even when the patients have impairments in empathic accuracy. We conducted a novel investigation specifically examining empathy motivation in patients with amygdala damage. We used a free-choice paradigm to assess motivation to empathize. We found that damage to the amygdala was not associated with avoidance of affective or cognitive forms of empathy motivation. Patients with amygdala lesions (n = 21) exhibited similar levels of empathy motivation compared with patients with damage outside the amygdala (n = 22) and healthy individuals with no brain damage (n = 24). These findings suggest that amygdala damage does not necessarily disrupt the motivation to empathize. A potential implication of the findings is that amygdala damage or dysfunction may not be associated with traits such as callousness, apathy or lack of caring that are often linked to psychopathy.

Affective prosody facilitates the communication of emotions by modulating paralinguistic features of speech (e.g., pitch and rhythm). Patients with brain injuries may exhibit impaired expression of affective prosody, referred to as expressive aprosodia, adversely impacting social interactions and quality of life. Despite many previous lesion studies, relatively few studies have investigated neural correlates of expressive aprosodia using a combination of lesion location, as well as associated structural and functional network mapping, within a large patient sample. There is especially a need to advance our understanding of the neurobiology associated with expressive aprosodia in the chronic phase (i.e., > 3 months after lesion onset) given the practical importance of long-term outcomes in regard to social functioning and quality of life. The present study therefore aimed to characterize how expressive aprosodia relates to lesion location and disruption of associated structural and functional brain networks in a large sample of participants with chronic focal brain lesions (N = 673). Using a clinical expert evaluation of prosody and multi-modal lesion mapping, the results showed that expressive aprosodia was most strongly associated with i) lesions affecting right-lateralized fronto-insular-striatal regions, ii) prominent disconnection of right-lateralized cortico-subcortical pathways, and iii) damage to regions exhibiting functional connectivity with subcortical (basal ganglia, thalamus) and cortical ventral attention/salience networks. Overall, these findings are consistent with a previously proposed dorsal stream for expressive aprosodia and provide further insights into the neural architecture whose damage is associated with chronic expressive aprosodia.

Background:Black people are diagnosed with Parkinson's disease (PD) at half the rate as White people. One unexplored possibility to explain this disparity is that practitioners have a racial bias, specifically when appraising motor signs of PD in Black versus White people. Objective:The current study explores whether practitioners have a racial bias when appraising/evaluating Black versus White people with or without hypomimia (a motor sign of PD that results in reduced facial expressivity, which was simulated in this current study). Such bias may cause delays in the diagnosis of PD, which could explain the large racial disparity of the disease in Black versus White people. Methods:A multi-level modeling approach was used to compare practitioners' (N = 175) (1) appraisal of facial expressivity (2) perception of pathology and (3) impression of emotional engagement, in Black versus White people (paid actors) with or without simulated hypomimia. Additional analyses explored the association between these variables and practitioners' demographics. Results:Results show that practitioners rated facial expressivity higher in Black versus White individuals with no hypomimia, t(500.170) = 8.916, p < 0.001, estimate = -13.352. Additionally, more years of patient experience was associated with higher pathology ratings by practitioners, for Black and White people with hypomimia. Conclusion:Although this study did not find a racial bias in practitioners' appraisal of Black versus White people with hypomimia, the results highlight that quantity (i.e., years of experience), and possibly, quality of training could lead to a more accurate evaluation of Black patients with signs of Parkinson's disease, which is a feasible point of intervention.

Training models in clinical neuropsychology have followed the Houston Conference Guidelines for decades. Those Guidelines provided strong emphasis on research training as a core competency for neuropsychologists. The new Minnesota Conference Guidelines (in final stages of development as of this essay) mention that training in the conduct of research is part of the graduate education of neuropsychologists. All four of the current authors were trained in the Iowa-Benton approach to neuropsychology, which is firmly grounded in research training and engagement. We view this not as a prerogative, but as a requirement. Training in clinical neuropsychology should not be "clinical" with a twist of "research" - it should be a healthy admixture of both. Our research training made us better clinical neuropsychologists, and provides a foundation for our teaching, exactly in the spirit that Arthur Benton promoted in his mentoring model. Further, our research experience informs our appraisal and adoption of contemporary trends in the practice of neuropsychology, and proposed new procedures and tests in the Benton Clinic are evaluated through the lens of background research.

Post-stroke cognitive impairment represents a significant clinical challenge, affecting up to 70% of survivors and standing as one of the most critical determinants of patient outcomes. While research has demonstrated that lesion location serves as a powerful predictor of cognitive outcomes, translating these insights into clinical practice faces a fundamental barrier: the current process requires neuroimaging experts to spend several hours manually analyzing each patient's lesions, making it impractical for routine clinical use. Our automated pipeline processes standard clinical MRI sequences, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and anatomical scans, to identify patients at high risk for cognitive impairment based on lesion location. The system was validated using acute clinical data from 114 ischemic stroke patients who underwent comprehensive neuropsychological testing in the chronic phase of stroke. The analysis demonstrated strong predictive performance, where automatically detected lesions in critical left hemisphere white matter regions effectively identified patients who developed significant cognitive impairment (p < 0.0001), with results remaining robust after controlling for confounding variables such as age and lesion volume. The entire analysis pipeline, from raw DICOM data to final prediction, consistently completes in under 10 minutes per patient, representing a dramatic improvement over traditional manual methods that require hours of expert analysis. This efficiency enables rapid processing of large-scale clinical datasets while maintaining accuracy comparable to manual analysis. Our system demonstrates the feasibility of integrating personalized, lesion location-based prognostic information into clinical workflows, potentially transforming acute care decisionmaking and rehabilitation planning across diverse healthcare settings.

Human lesion studies offer one of the most direct routes to investigating the causal relations between brain regions and behavioral outcomes in circumstances where experimental interventions are highly restricted. However, these studies face a major challenge in identifying the right level of granularity at which brain regions and behavioral outcomes should be analyzed to identify the association between lesions to specific brain regions and specific behavioral outcomes. Here we showcase a novel data-driven approach, Causal Feature Learning (CFL), that learns the appropriate level of analysis and the relation between lesion and cognitive impairment at the same time. The method avoids specifying brain regions and specific outcome measures a priori, allowing for the discovery of new cross-cutting lesion-behavior maps. We show that CFL robustly recovers lesion behavior maps in a simulated dataset where Canonical Correlation Analysis fails to provide interpretable results. We then show that CFL recovers known lesion-behavior maps for language deficits and visuospatial processing using a large dataset of lesion subjects, and finally we illustrate how CFL can be used to identify new groupings of outcomes when mapping lesions to depression symptoms.

Lesion-deficit mapping is a premier technique for dissociating neural correlates of cognitive functions. However, the contribution of domain-general cognition (g) to the performance of virtually all complex behavioral tasks may encumber such efforts. This possibility has been largely unexplored. Here, we examined the influence of g in lesion-deficit mapping using a combination of structural equation modeling, lesion-behavior mapping (LBM), and structural (sLNM) and functional (fLNM) lesion network mapping. We modeled latent variables for visuospatial ability, processing speed, language, and anterograde memory among 473 patients with focal brain damage (age range 20-93, 257 men, 216 women), both with and without g-associated variance embedded within each factor. Lesion-deficit maps for domain-specific cognitive abilities were statistically significantly less spatially inter-correlated after partitioning out g (p = 0.010 for LBM; p = 0.003 for sLNM; p = 0.003 for fLNM). Lesion-deficit maps also implicated the existence of distinct neuroanatomy for specific cognitive domains that was, in many cases, only apparent and clearly distinct from lesion-deficit maps of g after partitioning out the influence of g. Overall, our findings suggest that, if left unaccounted for, domain-general cognitive variance could tangibly affect conclusions about the extent to which different cognitive functions rely on distinct neuroanatomy.

Temporal lobe epilepsy surgery is an effective treatment option for patients with drug-resistant epilepsy. However, neurosurgery poses a risk for cognitive deficits-up to one-third of patients have a decline in naming ability following temporal lobe surgery. In this study, we aimed to better understand the neural correlates associated with reduced naming performance after temporal lobe surgery, with the goal of informing surgical planning strategies to mitigate the risk of dysnomia. We retrospectively identified 85 patients who underwent temporal lobe resective surgery (49 left temporal lobe, 36 right temporal lobe) for whom naming ability was assessed before and >3 months post-surgery using the Boston Naming Test. We used multivariate lesion-symptom mapping to identify resection sites associated with naming decline, and we used lesion network mapping to evaluate the broader functional and structural connectivity profiles of resection sites associated with naming decline. We validated our findings in an independent cohort of 59 individuals with left temporal lobectomy, along with repeating all analyses after combining the cohorts. Lesion laterality and location were important predictors of post-surgical naming performance. Naming performance significantly improved after right temporal lobectomy (P = 0.015) while a decrement in performance was observed following left temporal lobectomy (P = 0.002). Declines in naming performance were associated with surgical resection of the left anterior middle temporal gyrus (Brodmann area 21, r = 0.41, P < 0.001), along with a previously implicated basal temporal language area. Resection sites linked to naming decline showed a functional connectivity profile featuring a left-lateralized network closely resembling the extended semantic\default mode network, and a structural connectivity profile featuring major temporo-frontal association white matter tracts coursing through the temporal stem. This extends prior work by implicating the left anterior middle temporal gyrus in naming decline and provides additional support for the role of the previously identified basal temporal language area in naming decline. Importantly, the structural and functional connectivity profiles of these regions suggest they are key nodes of a broader extended semantic network. Together these regional and network findings may help in surgical planning and discussions of prognosis.

Objective:General cognitive ability (g), a latent variable derived from cognitive data, can predict life outcomes (e.g., educational attainment and occupational success) among neurologically healthy individuals. The value of g for predicting post-stroke functional outcomes is unknown. We addressed this gap here. Method:We derived g using exploratory structural equation modeling of 15 neuropsychological tests administered to 112 patients with stroke, 69 of whom also had functional outcome data (42 men; mean age = 53.23 years (SD = 10.54)). We used logistic regressions to compare g and individual tests in terms of their ability to predict the Functional Assessment Measure (FAM) and the Functional Independence Measure (FIM; motor and cognitive subscales) at 12 months post-stroke. Results:g was a statistically significant predictor of FAM (X 2 = 6.86, p = 0.013) and the cognitive (X 2 = 11.48, p = 0.002) but not motor FIM subscale (X 2 = 0.93, p = 0.154). Individual tests varied widely in terms of predictive utility (X 2 range: 0.07-21.03), with the most robust predictors being measures of visuospatial functions. Conclusions:Acute measures of cognition, including g, can predict functional independence 12 months after stroke. g and visuospatial ability measures were the most robust predictors.

Depressive disorders have been consistently associated with elevated levels of mind-wandering and self-focused negative rumination. Separate tracks of research have implicated brain structures within the default mode network (DMN) in both mind-wandering and depression. In this study, we hypothesized that diminished mind-wandering and fewer depressive symptoms would co-occur in individuals with damage to the DMN. To test this hypothesis, we used a k-means clustering algorithm to identify a target group of patients with reduced mind-wandering and fewer depressive symptoms relative to brain-damaged comparison subjects (n = 37 of 68; ps < .001). The anatomical localization of lesions for this target group was predominantly within the medial prefrontal cortex (mPFC). Structural and functional lesion network mapping results revealed that lesions of the target group had significantly greater connectivity with DMN and limbic regions. Taken together, these results suggest that brain injury affecting the mPFC and DMN is associated with both reduced mind-wandering and fewer depressive symptoms. Further investigation of neuroanatomical substrates that mediate a causal relationship between mind-wandering and mood may facilitate the identification of new therapeutic targets for neuromodulation in patients with disorders characterized by maladaptive mind-wandering, such as rumination.

ABSTRACT:Identifying lesion sites associated with central poststroke pain (CPSP) may facilitate targeted screening for early symptoms, possibly even paving the way for preventive measures and earlier treatment initiation. Here, we test the hypothesis that damage to a nociceptive pathway extending from the brainstem to the cerebral cortex, and including white matter tracts, is associated with CPSP. We investigated the lesion locations of 72 patients with CPSP relative to poststroke comparison subjects without pain (n = 123), divided into a discovery and independent validation data set. The study included three main analyses: (1) we compared lesion intersection with our a priori region of interest (ROI) between groups with and without CPSP, (2) we performed lesion-symptom mapping to evaluate whether lesions associated with CPSP localize to the a priori ROI, and (3) we used lesion network mapping to infer the broader structural and functional connectivity patterns associated with CPSP lesions. CPSP lesions overlapped the nociceptive pathway ROI to a greater extent than comparison lesions. Lesion-symptom mapping identified a CPSP-associated region overlapping with the ventrocaudal thalamus and adjacent white matter, which was located mostly within the a priori ROI. Lesion network mapping demonstrated that lesions associated with CPSP disrupt nodes and tracts of the nociceptive pathway ROI. Interestingly, the CPSP lesion network results demonstrated connectivity to intereffector nodes of the primary motor cortex, providing a novel link between CPSP and the somato-cognitive action network. Together, these findings indicate that CPSP can be conceptualized as a lesion-associated network disruption of the nociceptive pathway and somato-cognitive action network.

Background: Our perception of the auditory world allows us to enjoy the richness of music and communicate effectively with others. These everyday processes are disrupted in conditions such as amusia, an inability to perceive music accurately, and misophonia, an intense emotional reaction to common sounds produced by others. We describe a case of acquired, concurrent amusia and misophonia in a 21-year-old right-handed woman following a right posterior insula, posterior temporal, supramarginal cortex, and sensory cortex resection for the treatment of drug-resistant epilepsy. Methods: The patient participated in interviews between 4-8 months post-resection. She completed an extensive testing battery designed to characterize her acquired deficits and increased sensitivity to misophonic triggers. Results: Assessments revealed significant deficits in several domains of music processing, including scale, key, contour, and interval. High levels of misophonia symptom severity and impairment indicated clinically elevated misophonia. The patient performed within the normal range for speech-in-babble perception and music reward despite self-reporting pertinent impairments. Performance on tonal beat perception, musical imagery, memory, and sophistication measures were average. Conclusions: The results from the extensive testing battery highlight the contribution of the resected regions to normal music perception. Additionally, this case represents the first reported instance of acquired misophonia.

Religion and spirituality (R/S) may be associated with better cognitive health, yet most published studies have been conducted in primarily White populations without investigating association variations by gender and race. A cross-sectional analysis of 1041 community-dwelling diverse older adults from the Philadelphia Healthy Brain Aging (PHBA) cohort study was conducted using multiple regression analysis. We examined associations between facets of R/S and total cognitive scores and performed stratification analysis separately by gender and race to explore potential gender- and race-specific variations. Higher non-organizational R/S was associated with lower cognitive scores, while greater religious and spiritual coping was associated with higher cognitive scores, controlling for age, education, chronic conditions, race, and financial constraints. Across gender and race variations, non-organizational R/S was associated with lower cognitive scores in women alone, with no variations across race. Higher religious and spiritual coping was associated with higher cognitive scores in both Black and White women, but not men, while higher religious and spiritual healing was associated with lower cognitive scores in Black women only. Associations between religious and spiritual facets and cognitive health differ across gender and race; longitudinal studies are needed.

Creative solutions are needed to address the well-being of the growing number of individuals living with dementia. Music-based interventions (MBIs) are promising and can be cost-effective; however, empirical evidence for MBIs is limited and published findings have not been widely translated into practice. Here, we describe how we implemented strategies to enhance rigor in a randomized clinical trial of an MBI for persons with dementia. We examined the impact of a singing-based MBI on feelings, emotions, and social engagement, relative to a non-music treatment (verbal discussion), delivered in small group format (25 minutes, 3 times/week for 2 weeks). We implemented National Institutes of Health Behavior Change Consortium strategies regarding: (i) design, (ii) interventionist training, (iii) treatment delivery, (iv) treatment receipt, and (v) treatment skills enactment. We applied the MBI Reporting Criteria including: (i) theoretical framework, (ii) musical content, (iii) dosage, (iv) interventionist, (v) treatment fidelity, (vi) setting, and (vii) delivery unit. We analyzed data with a separate linear mixed model for each dependent variable. 32 older adults with dementia (65-97 years) participated. The MBI yielded significant positive effects on all measured outcomes (all p's < .05). Application of established guidelines enhanced methodological rigor and MBI reproducibility. To support translation of research into practice, clinicians should understand how to implement an MBI reported in research. Our study illustrates practical steps to address the need for improved MBI research in persons with dementia and can provide a model for others to enhance evidence-based practice with this population.

Religious fundamentalism, characterized by rigid adherence to a set of beliefs putatively revealing inerrant truths, is ubiquitous across cultures and has a global impact on society. Understanding the psychological and neurobiological processes producing religious fundamentalism may inform a variety of scientific, sociological, and cultural questions. Research indicates that brain damage can alter religious fundamentalism. However, the precise brain regions involved with these changes remain unknown. Here, we analyzed brain lesions associated with varying levels of religious fundamentalism in two large datasets from independent laboratories. Lesions associated with greater fundamentalism were connected to a specific brain network with nodes in the right orbitofrontal, dorsolateral prefrontal, and inferior parietal lobe. This fundamentalism network was strongly right hemisphere lateralized and highly reproducible across the independent datasets ( r = 0.82) with cross-validations between datasets. To explore the relationship of this network to lesions previously studied by our group, we tested for similarities to twenty-one lesion-associated conditions. Lesions associated with confabulation and criminal behavior showed a similar connectivity pattern as lesions associated with greater fundamentalism. Moreover, lesions associated with poststroke pain showed a similar connectivity pattern as lesions associated with lower fundamentalism. These findings are consistent with the current understanding of hemispheric specializations for reasoning and lend insight into previously observed epidemiological associations with fundamentalism, such as cognitive rigidity and outgroup hostility.