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Item Acute Ischemic Stroke After Moderate to Severe Traumatic Brain Injury: Incidence and Impact on Outcome(AHA, 2017-07) Kowalski, Robert G.; Haarbauer-Krupa, Juliet K.; Bell, Jeneita M.; Corrigan, John D.; Hammond, Flora M.; Torbey, Michel T.; Hofmann, Melissa C.; Dams-O'Connor, Kristen; Miller, A. Cate; Whiteneck, Gale G.; Physical Medicine and Rehabilitation, School of MedicineBackground and Purpose—Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. Methods—A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Results—Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, −16.8 to −9.7; P<0.001), a 1.9-point increase in Disability Rating Scale (95% confidence interval, 1.3–2.5; P<0.001), and an 18.3-day increase in posttraumatic amnesia duration (95% confidence interval, 13.1–23.4; P<0.001). Conclusions—Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events.Item Assessing Demand for Transparency in Intelligent Systems Using Machine Learning(IEEE, 2018-07) Vorm, Eric S.; Miller, Andrew D.; Human-Centered Computing, School of Informatics and ComputingIntelligent systems offering decision support can lessen cognitive load and improve the efficiency of decision making in a variety of contexts. These systems assist users by evaluating multiple courses of action and recommending the right action at the right time. Modern intelligent systems using machine learning introduce new capabilities in decision support, but they can come at a cost. Machine learning models provide little explanation of their outputs or reasoning process, making it difficult to determine when it is appropriate to trust, or if not, what went wrong. In order to improve trust and ensure appropriate reliance on these systems, users must be afforded increased transparency, enabling an understanding of the systems reasoning, and an explanation of its predictions or classifications. Here we discuss the salient factors in designing transparent intelligent systems using machine learning, and present the results of a user-centered design study. We propose design guidelines derived from our study, and discuss next steps for designing for intelligent system transparency.Item Category fluency in psychometric schizotypy: How altering emotional valence and cognitive load affects performance(Taylor & Francis, 2015) Minor, Kyle S.; Luther, Lauren; Auster, Tracey L.; Marggraf, Matthew P.; Cohen, Alex S.; Department of Psychology, School of ScienceIntroduction. In clinical high-risk populations, category fluency deficits are associated with conversion to psychosis. However, their utility as clinical risk markers is unclear in psychometric schizotypy, a group experiencing schizophrenia-like traits that is at putative high risk for psychosis. Methods. We examined whether introducing affective or cognitive load, two important stress vulnerability markers, altered category fluency performance in schizotypy (n = 42) and non-schizotypy (n = 38) groups. To investigate this question, we developed an experimental paradigm where all participants were administered category fluency tests across baseline, pleasant valence, unpleasant valence, and cognitive load conditions. Results. Compared to the non-schizotypy group, those with schizotypy performed significantly worse in pleasant and unpleasant valence conditions, but not cognitive load or baseline fluency tests. Conclusions. This study demonstrated the role of affect – but not cognitive load – on category fluency in psychometric schizotypy, as group differences only emerged once affective load was introduced. One explanation for this finding is that semantic memory may be unimpaired under normal conditions in psychometric schizotypy, but may be compromised once affective load is presented. Future studies should examine whether fluency deficits – particularly when affect is induced – predict future conversion to psychosis in psychometric schizotypy cohorts.Item Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer’s Disease(IOS, 2015-07) Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J.; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard; Department of Neurological Surgery, IU School of MedicineAbstract Background: The temporal relationship of cognitive deficit and functional impairment in Alzheimer’s disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. Objective: To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Methods: Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. Results: In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Conclusions: Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.Item Cognitive Rehabilitation for Cognitive Dysfunction after Cancer and Cancer Treatment: Implications for Nursing Practice(Elsevier, 2020-02) Von Ah, Diane; Crouch, Adele; School of NursingObjective To provide an overview of cognitive rehabilitation approaches for cognitive dysfunction after cancer and cancer treatment. Data Sources Review and synthesis of empirical articles. Conclusion Cognitive rehabilitation approaches, including cognitive behavioral therapy and cognitive training, for cognitive dysfunction appear feasible to deliver, satisfactory to participants, and have shown promising results in cancer survivors. Future research is needed to address optimal dose, delivery method, access, cost, and the vulnerable aging cancer survivor population. Implications for Nursing Practice Oncology nurses must understand the available evidence and be able to provide information and options to cancer survivors to address cognitive changes after cancer.Item Compared to high and low cannabis use, moderate use is associated with fewer cognitive deficits in psychosis(Elsevier, 2016-12) Martin, Ashley M. Schnakenberg; Bonfils, Kelsey A.; Davis, Beshaun J.; Smith, Elizabeth A.; Schuder, Kelly; Lysaker, Paul H.; Department of Psychiatry, IU School of MedicineLiterature on the relationship of cannabis use and cognition in schizophrenia provides the paradoxical view that cannabis use is sometimes linked with less severe impairment in neurocognition. This paper explored the possibility that this is a reflection of a dose related response between lifetime cannabis use and two forms of cognition, neurocognition and metacognition, in schizophrenia. It was hypothesized that three groups of patients could be differentiated, those with (1) little to no cannabis use with poor levels of cognition, (2) moderate cannabis use and relatively better levels of cognition and (3) high cannabis use with relatively poorer levels of cognition. Sixty-six adults with schizophrenia completed assessments of neurocognition, metacognition and months of lifetime cannabis use. A k-means cluster analysis yielded three distinct groups based on these assessments. The clusters included: (1) low cannabis/poor cognition (n = 34); (2) heavy cannabis/moderately impaired cognition (n = 10); and (3) moderate cannabis/higher cognition (n = 22). Consistent with our hypothesis, participants with high and moderate lifetime cannabis use had lesser impairment of neurocognition and metacognition compared to low lifetime cannabis use. Participants with moderate lifetime cannabis use also had lesser impairment of metacognition compared to low and heavy use. These findings suggest that a dose related relationship exists between cannabis use and cognition. Results could be due to an influence of pre-existing cognitive level on likelihood of lifetime cannabis use, or to an interaction between use and cognitive function.Item Construct Validity of the Multi-Source Interference Task to Examine Attention in Heart Failure(Wolters Kluwer, 2018-11) Jung, Miyeon; Jonides, John; Berman, Marc G.; Northouse, Laurel; Koelling, Todd M.; Pressler, Susan J.; School of NursingBackground Patients with heart failure (HF) are at risk of cognitive dysfunction, including decreased directed attention. Directed attention is critical for performing daily activities including HF self-care by facilitating one to follow instructions or train-of-thought when there are interferences in which presented stimuli are in conflict with one another. The Multi-Source Interference Task (MSIT) is a computerized neuropsychological test that examines the function of the dorsal anterior cingulate cortex, the neurological substrate for directed attention. However, the MSIT has not been used in past HF studies. Objective The purpose of the study was to examine construct validity of the MSIT in HF. Methods Baseline data were obtained from a cognitive intervention study among patients with HF (n = 22) and age- and education-matched healthy adults (n = 20). Construct validity was evaluated using t tests to examine differences between patients with HF and healthy adults and congruent and incongruent MSIT trials. Pearson’s correlations were computed to examine relationships between the MSIT and Trail-Making Test, Stroop Test, and Attentional Function Index. Results Compared with healthy adults, patients with HF demonstrated worse performance (i.e., slower response times and higher error rates) on MSIT. Patients with HF had worse performance on MSIT incongruent trials than congruent trials. Interference z scores of MSIT did not correlate with Trail-Making Tests A and B and Stroop Test interference z scores, but the MSIT interference z scores correlated with perceived attention function measured by Attentional Function Index. Discussion Construct validity of the MSIT was supported, in part, among patients with HF. The MSIT is a sensitive measure of detecting worse directed attention among patients with HF compared with healthy adults. The preliminary findings support the use of the MSIT as a measure of directed attention in HF. Confirmation is warranted for current findings in larger samples.Item Disorders of Consciousness due to Traumatic Brain Injury: Functional Status Ten Years Post-Injury(Mary Ann Liebert, 2018-09-18) Hammond, Flora M.; Giacino, Joseph T.; Nakase Richardson, Risa; Sherer, Mark; Zafonte, Ross D.; Whyte, John; Arciniegas, David B.; Tang, Xinyu; Physical Medicine and Rehabilitation, School of MedicineFew studies have assessed the long-term functional outcomes of patients with a disorder of consciousness due to traumatic brain injury (TBI). This study examined functional status during the first 10 years after TBI among a cohort with disorders of consciousness (i.e., coma, vegetative state, minimally conscious state). The study sample included 110 individuals with TBI who were unable to follow commands prior to inpatient rehabilitation and for whom follow-up data were available at 1, 2, 5, and 10 years post-injury. The sample was subdivided into those who demonstrated command-following early (before 28 days post-injury) versus late (≥ 28 days post-injury or never). Functional Independence Measure (FIM) at 1, 2, 5, and 10 years following TBI was used to measure functional outcomes. Measureable functional recovery occurred throughout the 10-year period, with more than two thirds of the sample achieving independence in mobility and self-care, and about one quarter achieving independent cognitive function by 10 years. Following commands prior to 28 days was associated with greater functional independence at all outcome time-points. Multi-trajectory modeling of recovery of three FIM subscales (self-care, mobility, cognition) revealed four distinct prognostic groups with different temporal patterns of change on these subscales. More than half the sample achieved near-maximal recovery by 1 year post-injury, while the later command-following subgroups recovered over longer periods of time. Significant late functional decline was not observed in this cohort. Among a cohort of patients unable to follow commands at the time of inpatient rehabilitation, a substantial proportion achieved functional independence in self-care, mobility, and cognition. The proportion of participants achieving functional independence increased between 5 and 10 years post-injury. These findings suggest that individuals with disorders of consciousness may benefit from ongoing functional monitoring and updated care plans for at least the first decade after TBI.Item Effect of Epigallocatechin-3-gallate on a pattern separation task and hippocampal neurogenesis in a mouse model of Down syndrome(2015) Stringer, Megan Elizabeth; Goodlett, Charles R.; Roper, Randall J.; Neal-Beliveau, Bethany S.; Grahame, Nicholas J.Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in an array of phenotypes including intellectual disability. Ts65Dn mice, the most extensively studied DS model, have three copies of ~50% of the genes on Hsa21 and display many phenotypes associated with DS, including cognitive deficits. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including CNS development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have shown that a three-week EGCG treatment (~10mg/kg/day) during adolescence normalizes skeletal abnormalities in Ts65Dn mice, yet the same dose did not rescue deficits in the Morris water maze spatial learning task (MWM) or novel object recognition (NOR). Others have reported that An EGCG dose of 2-3 mg per day (90mg/ml) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated deficits in a radial arm maze pattern separation task in Ts65Dn mice. Pattern separation requires differentiation between similar memories acquired during learning episodes; distinguishing between these similar memories is thought to depend on distinctive encoding in the hippocampus. Pattern separation has been linked to functional activity of newly generated granule cells in the dentate gyrus. Recent studies in Ts65Dn mice have reported significant reductions in adult hippocampal neurogenesis, and after EGCG treatment, enhanced hippocampal neurogenesis. Thus, it was hypothesized that Ts65Dn mice would be impaired in the pattern separation task, and that EGCG would alleviate the pattern separation deficits seen in trisomic mice, in association with increased adult hippocampal neurogenesis. At weaning, Ts65Dn mice and euploid littermates were randomly assigned to the water control, or EGCG [0.4 mg/mL], with both treatments yielding average daily intakes of ~50 mg/kg/day. Beginning on postnatal day 75, all mice were trained on a radial arm maze-delayed non-matching-to-place pattern separation task. Euploid mice performed significantly better over training than Ts65Dn mice, including better performance at each of the three separations. EGCG did not significantly alleviate the pattern separation deficits in Ts65Dn mice. After the behavioral testing commenced, animals were given ad libitum food access for five days, received a 100mg/kg injection of BrdU, and were perfused two hours later. Coronal sections through the dorsal hippocampus were processed for BrdU labeling, and cells were manually counted throughout the subgranular zone of the dentate gyrus. The euploid controls had significantly more BrdU labeled cells than Ts65Dn mice, however, EGCG does not appear to increase proliferation of the hippocampal neuroprogenitor cells. This is the first report of deficits in Ts65Dn mice on a pattern separation task. To the extent that pattern separation depends on the functional involvement of newly generated neurons in an adult dentate gyrus, this approach in Ts65Dn mice may help identify more targeted pharmacotherapies for cognitive deficits in individuals with DS.Item Effects of Pre-Collegiate Sport Specialization on Cognitive, Postural, and Psychological Functions: Findings from the NCAA-DoD CARE Consortium(MDPI, 2022-02) Chou, Tsung-Yeh; Caccese, Jaclyn B.; Huang, Yu-Lun; Glutting, Joseph J.; Buckley, Thomas A.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Pasquina, Paul F.; Kaminski, Thomas W.; Psychiatry, School of MedicineBackground: Early sport specialization has been associated with an increased risk of musculoskeletal injuries and unfavorable psychological outcomes; however, it is unknown whether sport specialization is associated with worse cognitive, postural, and psychological functions in first-year collegiate student-athletes. Methods: First-year collegiate multisport (MA) and single-sport (SA) student-athletes were identified using a pre-collegiate sport experience questionnaire. The cognitive, postural, and psychological functions were assessed by the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and Brief Symptom Inventory 18 (BSI-18). Results: MA student-athletes performed higher in cognitive outcomes (e.g., higher ImPACT visual memory composite scores [ß = 0.056, p < 0.001]), but had higher psychological distress (e.g., higher BSI-18 global severity index [ß = 0.057, p < 0.001]) and no difference in postural stability (p > 0.05) than SA student-athletes. Conclusions: This study indicated first-year collegiate athletes with a history of sport specialization demonstrate lower cognitive performance but decreased psychological distress and no differences in static postural stability as compared to their MA counterparts. Future studies should consider involving different health measures to better understand the influence of sport specialization on overall physical and mental health.
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