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Principal Investigator: Richard Ryan Darby
Organization: VANDERBILT UNIVERSITY MEDICAL CENTER
Fiscal Year: 2024
Award: $159,438
Funding agency: National Institute on Aging
ABSTRACT: Antisocial behavior is common in patients with frontotemporal dementia (FTD). These behaviors
result in significant morbidity and can lead to crimes in extreme cases. Yet despite being one of the most
challenging and problematic symptoms to manage clinically, the mechanisms leading to antisocial behavior in
FTD are unknown, and treatments remain limited. The goal of the current proposal is to determine the
cognitive and neural mechanisms leading to antisocial behavior in FTD. Understanding these
mechanisms will have a major impact on FTD patients by improving clinical evaluations to monitor the onset
and progression of antisocial behaviors, helping to develop novel pharmacologic and neuromodulatory
treatment strategies, and informing legal and ethical treatment of FTD patients who commit crimes. In Aim 1 I
will examine the neural mechanisms and the hypothesis that FTD patients with antisocial behavior will have
atrophy in a pre-defined network of brain regions I identified in patients with antisocial behaviors caused by
focal brain lesions. I will test this hypothesis using a new neuroimaging method I recently developed and
validated called atrophy network mapping that uses the human connectome and single-subject atrophy maps
to localize neurological symptoms to brain networks rather than an isolated region. In Aim 2 I will examine the
cognitive mechanisms and the hypothesis that FTD patients with antisocial behavior have specific impairments
in moral decision-making. My long-term goal is to use multimodal neuroimaging and decision-making tasks to
better understand the mechanisms leading to antisocial behavior and other behavioral problems in dementia
patients. To achieve this goal, a training plan is proposed to learn additional research skills in functional
neuroimaging methods (Training goal 1) and the neuropsychology of social decision-making (Training Goal 2).
Additional training in leadership, biostatistics, and grant-writing will prepare me to achieve independence
(Training goal 3). A mentorship team of experts has been assembled to help me achieve these training goals,
consisting of Dr. Daniel Claassen (primary mentor), a behavioral neurologists who studies reward-based
decision-making and functional neuroimaging in patients with neurodegenerative disorders; Dr. David Zald (co-
primary mentor), a neuropsychologist and cognitive neuroscientist who uses functional neuroimaging to study
decision-making in aging and antisocial behavior; and Dr. Bennett Landman (co-mentor), a neuroimager who
develops computational methods to study neuroimaging changes in aging. The team will also include Dr.
Hakmook Kang (collaborator), a biostatistician with expertise in neuroimaging, Dr. Catherine Chang, a
neuroimager with expertise in functional connectivity, and Dr. Katherine Rankin (external consultant), a
neuropsychologist with expertise in psychometric assessments of social and emotional processing in FTD.
Terms: <AD dementia><Acquired brain injury><Address><Affective><Aging><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Amentia><Amygdala><Amygdaloid Body><Amygdaloid Nucleus><Amygdaloid structure><Atrophic><Atrophy><Behavior><Behavioral><Behavioral Symptoms><Biometrics><Biometry><Biostatistics><Brain><Brain Injuries><Brain Mapping><Brain Nervous System><Brain region><Clinical Evaluation><Clinical Management><Clinical Testing><Clinical Trials><Clinical assessments><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Complex><Computing Methodologies><Crime><Decision Making><Degenerative Neurologic Disorders><Delusions><Dementia><Disturbance in cognition><Emotional><Encephalon><Ethics><Executive Dysfunction><Executive Function Deficit><Executive Impairment><Frontal Temporal Dementia><Frontotemporal Dementia><Future><Goals><Grant><Human><Impaired cognition><Impairment><Investigators><Knowledge><Laws><Leadership><Learning><Legal><Lesion><Link><Location><Maps><Measures><Memory Deficit><Memory impairment><Mentors><Mentorship><Methods><Modern Man><Monitor><Morals><Morbidity><Morbidity - disease rate><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neuranatomies><Neuranatomy><Neuroanatomies><Neuroanatomy><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Neurologic Manifestations><Neurologic Signs and Symptoms><Neurologic Symptoms><Neurological Manifestations><Neurological Signs and Symptoms><Neurologist><Neuropsychologies><Neuropsychology><Outcome Measure><Patients><Performance><Policies><Primary Senile Degenerative Dementia><Problem behavior><Process><Psychometrics><Reaction><Research><Research Personnel><Researchers><Rewards><Severities><Social Behavior><Standardization><Stealing><Symptoms><Task Performances><Techniques><Testing><Theft><Training><Use of New Techniques><Violence><Work><Writing><amygdaloid nuclear complex><anti social><antisocial><antisocial behavior><behavioral problem><brain atrophy><brain damage><brain-injured><cerebral atrophy><clinical test><cognitive dysfunction><cognitive loss><computational methodology><computational methods><computer based method><computer methods><computing method><connectome><cortical atrophy><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><effective intervention><effective therapy><effective treatment><ethical><front temporal dementia><frontal lobe dementia><frontotemporal lobar dementia><frontotemporal lobe degeneration associated with dementia><improved><man><measurable outcome><memory dysfunction><moral><multi-modal neuro-imaging><multi-modal neuroimaging><multimodal neuro-imaging><multimodal neuroimaging><network dysfunction><neural><neural control><neural imaging><neural manifestation><neural mechanism><neural regulation><neuro-imaging><neurodegenerative illness><neuroimaging><neurological imaging><neuromechanism><neuromodulation><neuromodulatory><neuropsychiatric symptom><neuropsychologic><neuroregulation><novel><outcome measurement><pharmacologic><prevent><preventing><primary degenerative dementia><psychopathic personality><psychopathy><research clinical testing><response><senile dementia of the Alzheimer type><skills><social><social norm><sociobehavior><sociobehavioral><treatment strategy><violent><violent behavior>