Nicholas T. Bott

Pictionary-based fMRI paradigm to study the neural correlates of spontaneous improvisation and figural creativity.

A novel game-like and creativity-conducive fMRI paradigm is developed to assess the neural correlates of spontaneous improvisation and figural creativity in healthy adults. Participants were engaged in the word-guessing game of PictionaryTM, using an MR-safe drawing tablet and no explicit instructions to be “creative”. Using the primary contrast of drawing a given word versus drawing a control word (zigzag), we observed increased engagement of cerebellum, thalamus, left parietal cortex, right superior frontal, left prefrontal and paracingulate/cingulate regions, such that activation in the cingulate and left prefrontal cortices negatively influenced task performance. Further, using parametric fMRI analysis, increasing subjective difficulty ratings for drawing the word engaged higher activations in the left pre-frontal cortices, whereas higher expert-rated creative content in the drawings was associated with increased engagement of bilateral cerebellum. Altogether, our data suggest that cerebral-cerebellar interaction underlying implicit processing of mental representations has a facilitative effect on spontaneous improvisation and figural creativity.

Cross-species translation of the Morris maze for Alzheimer’s disease

Analogous behavioral assays are needed across animal models and human patients to improve translational research. Here, we examined the extent to which performance in the Morris water maze - the most frequently used behavioral assay of spatial learning and memory in rodents - translates to humans. We designed a virtual version of the assay for human subjects that includes the visible-target training, hidden-target learning, and probe trials that are typically administered in the mouse version. We compared transgenic mice that express human amyloid precursor protein (hAPP) and patients with mild cognitive impairment due to Alzheimers disease (MCI-AD) to evaluate the sensitivity of performance measures in detecting deficits. Patients performed normally during visible-target training, while hAPP mice showed procedural learning deficits. In hidden-target learning and probe trials, hAPP mice and MCI-AD patients showed similar deficits in learning and remembering the target location. In addition, we have provided recommendations for selecting performance measures and sample sizes to make these assays sensitive to learning and memory deficits in humans with MCI-AD and in mouse models. Together, our results demonstrate that with careful study design and analysis, the Morris maze is a sensitive assay for detecting AD-relevant impairments across species.

Changes in Brain Activation Associated with Spontaneous Improvization and Figural Creativity After Design-Thinking-Based Training: A Longitudinal fMRI Study

Creativity is widely recognized as an essential skill for entrepreneurial success and adaptation to daily-life demands. However, we know little about the neural changes associated with creative capacity enhancement. For the first time, using a prospective, randomized control design, we examined longitudinal changes in brain activity associated with participating in a five-week design-thinking-based Creative Capacity Building Program (CCBP), when compared with Language Capacity Building Program (LCBP). Creativity, an elusive and multifaceted construct, is loosely defined as an ability to produce useful/appropriate and novel outcomes. Here, we focus on one of the facets of creative thinking-spontaneous improvization. Participants were assessed pre- and post-intervention for spontaneous improvization skills using a game-like figural Pictionary-based fMRI task. Whole-brain group-by-time interaction revealed reduced task-related activity in CCBP participants (compared with LCBP participants) after training in the right dorsolateral prefrontal cortex, anterior/paracingulate gyrus, supplementary motor area, and parietal regions. Further, greater cerebellar-cerebral connectivity was observed in CCBP participants at post-intervention when compared with LCBP participants. In sum, our results suggest that improvization-based creative capacity enhancement is associated with reduced engagement of executive functioning regions and increased involvement of spontaneous implicit processing.

Frontotemporal dementia: diagnosis, deficits and management.

Frontotemporal dementia (FTD) is a progressive neurologic syndrome with diverse clinical presentations and attendant underlying pathologies. Psychiatric prodrome, neuropsychiatric symptoms and language difficulties are common in FTD, but the diversity of presentation raises unique diagnostic challenges that can significantly impact patient care and counsel for caregivers regarding clinical status and prognosis. While neuropsychiatric symptom measures are helpful, more sensitive assessments delineating the specific behavioral and linguistic deficits accompanying FTD are needed. Comprehensive clinical assessment in combination with evaluation of language, socio-emotional functioning, cognition and neuroimaging aid in accurate and early diagnosis and treatment planning. In what follows, we review each of the FTD syndromes, highlight current research investigating the cognitive, behavioral and socio-emotional deficits observed with this disease, address common diagnostic challenges and summarize best practices associated with management of FTD.

Sensitive measures of executive dysfunction in non-demented Parkinson's disease *

BACKGROUND We examined the sensitivity of different executive function measures for detecting deficits in Parkinsons disease patients without dementia. METHODS Twenty-one non-demented PD subjects and 21 neurologically healthy controls were administered widely used clinical executive functioning measures as well as the NIH EXAMINER battery, which produces Cognitive Control, Working Memory, and Verbal Fluency scores, along with an overall Executive Composite score, using psychometrically matched scales. RESULTS No significant differences between groups were observed on widely used clinical measures. The PD patients scored lower than controls on the EXAMINER Executive Composite, Cognitive Control, and Working Memory Scores. CONCLUSIONS The NIH EXAMINER Executive Composite and Cognitive Control Scores are sensitive measures of executive dysfunction in non-demented PD, and may be more sensitive than several widely used measures. Results highlight the importance of careful test selection when evaluating for mild cognitive impairment in PD.

Cotard Delusion in the Context of Schizophrenia: A Case Report and Review of the Literature

Background: The Cotard delusion (CD) is one of a variety of narrowly defined monothematic delusions characterized by nihilistic beliefs about the body’s existence or life itself. The presence of CD within the context of schizophrenia is rare (<1%), and remains understudied. Case: ‘Mr. C’ is a 58-year-old veteran with a prior diagnosis of schizophrenia, who presented with CD in the context of significant depression, suicidal ideation, violence, and self-harm behavior. He perseverated in his belief that he was physically dead and possessed by demons for several weeks. This delusion was reinforced by his religious belief that life was an attribute of God, and by inference, he as a human, was dead. His condition gradually improved over the course of treatment with Divalproex and quetiapine with discussions about the rationale for his belief. Upon discharge, Mr. C. demonstrated awareness of his fixation on death and an ability to redirect himself. Discussion: This case highlights the need to better understand the co-occurrence of CD in schizophrenia, their differentiation, the increased risk of violence and self-harm behavior in this presentation, and how specific events and religious factors can influence delusional themes of CD. Pharmacotherapy and aspects of cognitive-behavioral therapy may be effective in ameliorating these symptoms in CD.

Web Camera Based Eye Tracking to Assess Visual Memory on a Visual Paired Comparison Task

Background: Web cameras are increasingly part of the standard hardware of most smart devices. Eye movements can often provide a noninvasive “window on the brain,” and the recording of eye movements using web cameras is a burgeoning area of research. Objective: This study investigated a novel methodology for administering a visual paired comparison (VPC) decisional task using a web camera.To further assess this method, we examined the correlation between a standard eye-tracking camera automated scoring procedure [obtaining images at 60 frames per second (FPS)] and a manually scored procedure using a built-in laptop web camera (obtaining images at 3 FPS). Methods: This was an observational study of 54 clinically normal older adults.Subjects completed three in-clinic visits with simultaneous recording of eye movements on a VPC decision task by a standard eye tracker camera and a built-in laptop-based web camera. Inter-rater reliability was analyzed using Siegel and Castellans kappa formula. Pearson correlations were used to investigate the correlation between VPC performance using a standard eye tracker camera and a built-in web camera. Results: Strong associations were observed on VPC mean novelty preference score between the 60 FPS eye tracker and 3 FPS built-in web camera at each of the three visits (r = 0.88–0.92). Inter-rater agreement of web camera scoring at each time point was high (κ = 0.81–0.88). There were strong relationships on VPC mean novelty preference score between 10, 5, and 3 FPS training sets (r = 0.88–0.94). Significantly fewer data quality issues were encountered using the built-in web camera. Conclusions: Human scoring of a VPC decisional task using a built-in laptop web camera correlated strongly with automated scoring of the same task using a standard high frame rate eye tracker camera.While this method is not suitable for eye tracking paradigms requiring the collection and analysis of fine-grained metrics, such as fixation points, built-in web cameras are a standard feature of most smart devices (e.g., laptops, tablets, smart phones) and can be effectively employed to track eye movements on decisional tasks with high accuracy and minimal cost.

Developing Novel Methods to Assess Long-Term Sustainability of Creative Capacity Building and Applied Creativity

Creativity, the ability to create novel and useful outcomes, has been widely recognized as an essential skill for both entrepreneurial and every-day success. Given the vital import of creativity in our everyday lives, our research proposes to examine the impact and sustainability of creative capacity building using targeted training. In this chapter, we provide (a) a summary of behavioral results of creative capacity enhancement following 5-weeks of targeted training; (b) an unique experimental design to examine the long-term (after 1 year) sustainability of creative capacity building and the effect of a “booster-shot” of creativity training; and (c) preliminary insights and proposed work on the newly developed Design Test of Creativity Thinking (DTCT) to assess applied creativity. Altogether, we anticipate that our work will provide valuable insights into creative capacity building and assessment.

Individualized Acute Medical Care for Cognitively Impaired Individuals: A Call Always to Pause Before Hospitalization

Staying “mentally sharp” was recently identified as American retirees’ number one health priority. For those living with mild cognitive impairment (MCI) and dementia, the lack of disease-modifying treatment precludes this goal. Worse, delivery of health care through hospitalization drives and accelerates cognitive decline for those at risk. Although most frail elderly adults experience posthospitalization disability, those with MCI and dementia are at greatest risk of permanent functional and cognitive losses. A health systems-wide intervention that addresses the unique needs of this population and offers cognitively protective medical care is needed. Acute illness combined with hospitalization is common and poses a significant risk of delirium that often results in permanent cognitive and functional losses. An estimated 66% of community-dwelling persons with dementia are hospitalized at least once a year. Considering the 56% risk of delirium from hospitalization, upwards of one in three community-dwelling individuals with dementia will experience some degree of accelerated cognitive decline from hospitalization per year. Although we deliver care with the best of intentions, the health system fails to appreciate cognitive impairment as chronic organ failure and thus does not take proper steps to protect brains in the same manner it protects other organs. Electronic decision support and safety checklists mitigate iatrogenic injury in a myriad of other organ failure scenarios. Imaging studies with contrast cannot be ordered until creatinine is assessed in individuals with chronic renal disease. Hepatotoxic medications require pharmacy override in individuals with sepsis with chronic liver failure. Surgeons require an international normalized ratio before taking a person with cirrhosis to the operating room. All these cases underscore how our health system recognizes the harm of interventions in the context of underlying organ failure, yet for neurodegenerative disease—chronic brain failure—we ignore what is arguably the greatest known threat: hospitalization. No evidence suggests that cognitively impaired individuals are warned of hospitalization threats or that health systems appreciate the connection between dementia, delirium, and permanent cognitive and functional deterioration. There are well-established protections against the hazards of hospitalization; considering the critical nature of the problem, these alternatives remain vastly underused. Hospitalization comes in two varieties: unplanned and planned. Hospital at Home can safely treat acute medical illness that necessitates hospitalization in nearly one-third of cases of older adults with certain acute medical illnesses. Better sleep, encouraged ambulation, and familiar surroundings are a few of the many reasons why Hospital at Home averts delirium and subsequent decline. Hospital at Home advocates often champion the lower costs, greater patient satisfaction, and better medical outcomes, including significant mortality benefit (20% risk reduction at 6 months, number needed to treat = 50) of this alternate treatment venue. The paramount benefit of avoiding iatrogenic cognitive decline from hospitalization is particularly compelling in cognitively impaired individuals. Cognitively impaired individuals are also prone to the phenomenon of “social admission,” wherein they arrive in the emergency department for unclear reasons and are hospitalized because they are judged “unsafe” for return home—despite no medical justification. Models of emergency department–based geriatric case management exist, but they have not been widely disseminated. Although it may be difficult to return people to their origin (assuming safety evaluations), the reflexive admission should be viewed as a last resort after thoroughly exhausting alternatives. This may disrupt emergency department workflow with prolonged visits, but no individual should be subjected to the gauntlet of hospitalization simply because it was the easiest exit for social disposition problems. For the remainder of individuals for whom inpatient hospitalization is unavoidable because of illness severity or treatment complexity, it is well validated that inpatient delirium prevention mitigates acute or chronic brain failure (delirium superimposed on dementia). Multifactorial interventions such as the Hospital Elder Life Program (HELp) and individualized hospital Acute Care for Elders Units succeed at reducing iatrogenic harm in cognitively impaired individuals. Despite conclusive evidence, these interventions show marginal dissemination and adoption. Multiple barriers may explain this paradox, including institutional culture that normalizes delirium as the “cost of doing business,” underappreciation of the effects of delirium superimposed on dementia, and the perceived difficulty funding these programs. Just as we never secondguess the protocols that place individuals with neutropenia in reverse isolation (regardless of expenses in contact garments and a private room), enacting similar systems for cognitively impaired individuals could make cognitively minded care the standard of care.

Device-Embedded Cameras for Eye Tracking–Based Cognitive Assessment: Validation With Paper-Pencil and Computerized Cognitive Composites

Background As eye tracking-based assessment of cognition becomes more widely used in older adults, particularly those at risk for dementia, reliable and scalable methods to collect high-quality data are required. Eye tracking-based cognitive tests that utilize device-embedded cameras have the potential to reach large numbers of people as a screening tool for preclinical cognitive decline. However, to fully validate this approach, more empirical evidence about the comparability of eyetracking-based paradigms to existing cognitive batteries is needed. Objective Using a population of clinically normal older adults, we examined the relationship between a 30-minute Visual Paired Comparison (VPC) recognition memory task and cognitive composite indices sensitive to a subtle decline in domains associated with Alzheimer disease. Additionally, the scoring accuracy between software used with a commercial grade eye tracking camera at 60 frames per second (FPS) and a manually scored procedure used with a laptop-embedded web camera (3 FPS) on the VPC task was compared, as well as the relationship between VPC task performance and domain-specific cognitive function. Methods A group of 49 clinically normal older adults completed a 30-min VPC recognition memory task with simultaneous recording of eye movements by a commercial-grade eye-tracking camera and a laptop-embedded camera. Relationships between webcam VPC performance and the Preclinical Alzheimer Cognitive Composite (PACC) and National Institutes of Health Toolbox Cognitive Battery (NIHTB-CB) were examined. Inter-rater reliability for manually scored tests was analyzed using Krippendorff’s kappa formula, and we used Spearman’s Rho correlations to investigate the relationship between VPC performance scores with both cameras. We also examined the relationship between VPC performance with the device-embedded camera and domain-specific cognitive performance. Results Modest relationships were seen between mean VPC novelty preference and the PACC (r=.39, P=.007) and NIHTB-CB (r=.35, P=.03) composite scores, and additional individual neurocognitive task scores including letter fluency (r=.33, P=.02), category fluency (r=.36, P=.01), and Trail Making Test A (–.40, P=.006). Robust relationships were observed between the 60 FPS eye tracker and 3 FPS webcam on both trial-level VPC novelty preference (r=.82, P<.001) and overall mean VPC novelty preference (r=.92 P<.001). Inter-rater agreement of manually scored web camera data was high (kappa=.84). Conclusions In a sample of clinically normal older adults, performance on a 30-minute VPC task correlated modestly with computerized and paper-pencil based cognitive composites that serve as preclinical Alzheimer disease cognitive indices. The strength of these relationships did not differ between camera devices. We suggest that using a device-embedded camera is a reliable and valid way to assess performance on VPC tasks accurately and that these tasks correlate with existing cognitive composites.