Person: Budson, Andrew
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Budson
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Budson, Andrew
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Publication Cognitive status impacts age-related changes in attention to novel and target events in normal adults.(American Psychological Association (APA), 2007) Daffner, Kirk; Chong, Hyemi; Riis, Jenna; Rentz, Dorene; Wolk, David A.; Budson, Andrew; Holcomb, Phillip J.In this study, the authors investigated the relationship between the cognitive status of normal adults and age-related changes in attention to novel and target events. Old, middle-age, and young subjects, divided into cognitively high and cognitively average performing groups, viewed repetitive standard stimuli, infrequent target stimuli, and unique novel visual stimuli. Subjects controlled viewing duration by a button press that led to the onset of the next stimulus. They also responded to targets by pressing a foot pedal. The amount of time spent looking at different kinds of stimuli served as a measure of visual attention and exploratory activity. Cognitively high performers spent more time viewing novel stimuli than cognitively average performers. The magnitude of the difference between cognitively high and cognitively average performing groups was largest among old subjects. Cognitively average performers had slower and less accurate responses to targets than cognitively high performers. The results provide strong evidence that the link between engagement by novelty and higher cognitive performance increases with age. Moreover, the results support the notion of there being different patterns of normal cognitive aging and the need to identify the factors that influence them.Publication Increased Responsiveness to Novelty is Associated with Successful Cognitive Aging(MIT Press - Journals, 2006) Daffner, Kirk; Ryan, Katherine K.; Williams, Danielle M.; Budson, Andrew; Rentz, Dorene; Wolk, David A.; Holcomb, Phillip J.The animal literature suggests that exposure to more complex, novel environments promotes neurogenesis and cognitive performance in older animals. Studies in humans indicate that participation in intellectually stimulating activities may serve as a buffer against mental decline and help to sustain cognitive abilities. Here, we show that across old adults, increased responsiveness to novel events (as measured by viewing duration and the size of the P3 event-related potential) is strongly linked to better performance on neuropsychological tests, especially those involving attention/executive functions. Cognitively high performing old adults generate a larger P3 response to visual stimuli than cognitively average performing adults. These results suggest that cognitively high performing adults successfully manage the task by appropriating more resources and that the increased size of their P3 component represents a beneficial compensatory mechanism rather than less efficient processing.Publication Patients With Mild Alzheimer's Disease Attribute Conceptual Fluency to Prior Experience(Elsevier BV, 2005) Wolk, David A.; Schacter, Daniel; Berman, Alyssa R.; Holcomb, Phillip J.; Daffner, Kirk; Budson, AndrewPatients with Alzheimer's disease (AD) have been found to be relatively dependent on familiarity in their recognition memory judgments. Conceptual fluency has been argued to be an important basis of familiarity. This study investigated the extent to which patients with mild AD use conceptual fluency cues in their recognition decisions. While no evidence of recognition memory was found in the patients with AD, enhanced conceptual fluency was associated with a higher rate of “Old” responses (items endorsed as having been studied) compared to when fluency was not enhanced. The magnitude of this effect was similar for patients with AD and healthy control participants. Additionally, ERP recordings time-locked to test item presentation revealed preserved modulations thought critical to the effect of conceptual fluency on test performance (N400 and late frontal components) in the patients with AD, consistent with the behavioral results. These findings suggest that patients with mild AD are able to use conceptual fluency in their recognition judgments and the neural mechanisms supporting such processing is maintained.Publication Age-Related Differences in Attention to Novelty Among Cognitively High Performing Adults(Elsevier BV, 2006) Daffner, Kirk; Ryan, Katherine K.; Williams, Danielle M.; Budson, Andrew; Rentz, Dorene; Wolk, David A.; Holcomb, Phillip J.; Ryan, KatherineAge-related differences in attention to novel events were studied in well-matched, cognitively high performing old, middle-aged and young subjects. Event-related potentials were recorded during a visual novelty oddball task in which subjects controlled viewing durations that served as a behavioral measure of attentional allocation. All age groups had a larger P3 amplitude and longer viewing duration to novel than to standard stimuli, with no age-related differences in the magnitude of these effects, indicating old individuals were as engaged by the processing of novelty as younger adults. Old subjects had a larger, more anteriorly distributed P3 component to novels and standards. The increased P3 amplitude differs from prior reports of a diminished P3 response with processes, including aging, that have a potentially deleterious impact on the brain. We hypothesise that cognitively high performing old individuals successfully manage the task by relying on additional neural resources and perhaps more effortful frontal activity than their younger counterparts.Publication Memory and Emotions for the September 11, 2001, Terrorist Attacks in Patients With Alzheimer's Disease, Patients With Mild Cognitive Impairment, and Healthy Older Adults.(American Psychological Association (APA), 2004) Budson, Andrew; Daffner, Kirk; Schacter, Daniel; Simons, Jon; `Sullivan, Alison; Beier, Jonathan; Solomon, Paul; Scinto, LeonardNational traumatic events can produce extremely vivid memories. Using a questionnaire administered during telephone interviews, the authors investigated emotional responses to, and memory for. the September 11, 2001, terrorist attacks in patients with Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and healthy older adults in the initial weeks following the event and again 3-4 months later. There were several notable findings. First, patients with AD showed less memory than patients with MCI and older adults. Second, patients with AD, but not patients with MCI or older adults, appeared to retain more memory for personal versus factual information. Third, patients with AD and older adults did not differ in the intensity of their reported emotional responses to the attacks, whereas patients with MCI reported relatively less intense emotional responses. Last, distortions of memory for personal information were frequent for all participants but were more common in patients with AD.Publication Use of IQ-Adjusted Norms to Predict Progressive Cognitive Decline in Highly Intelligent Older Individuals(American Psychological Association (APA), 2004-01) Huh, Terri J.; Faust, Robert R.; Sperling, Reisa; Daffner, Kirk; Rentz, Dorene; Budson, Andrew; Scinto, Leonard; Sperling, Reisa AnneIdentifying high-functioning older individuals in preclinical phases of Alzheimer's disease (AD) may require more sensitive methods than the standard approach. The authors explored the utility of adjusting for premorbid intelligence to predict progressive cognitive decline or Mild Cognitive Impairment (MCI) in 42 highly intelligent older individuals. When scores were adjusted for baseline IQ, 9 participants had executive impairments, 11 had memory impairments, and 22 scored in the normal range. None were impaired according to standard age norms. Three and a half years later, 9 participants with IQ-adjusted memory impairment declined in naming, visuospatial functioning, and memory; 6 convened to MCI. Three participants with normal memory declined. Implications for using IQ-adjusted norms to predict preclinical AD are discussed.Publication Frontal and Parietal Components of a Cerebral Network Mediating Voluntary Attention to Novel Events(MIT Press - Journals, 2003) Daffner, Kirk; Scinto, L. F. M.; Weitzman, A. M.; Faust, R.; Rentz, Dorene; Budson, Andrew; Holcomb, P. J.Despite the important role that attending to novel events plays in human behavior, there is limited information about the neuroanatomical underpinnings of this vital activity. This study investigated the relative contributions of the frontal and posterior parietal lobes to the differential processing of novel and target stimuli under an experimental condition in which subjects actively directed attention to novel events. Event-related potentials were recorded from well-matched frontal patients, parietal patients, and non-brain-injured subjects who controlled their viewing duration (by button press) of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus, and infrequent, novel visual stimuli. Subjects also responded to target stimuli by pressing a foot pedal. Damage to the frontal cortex resulted in a much greater disruption of response to novel stimuli than to designated targets. Frontal patients exhibited a widely distributed, profound reduction of the novelty P3 response and a marked diminution of the viewing duration of novel events. In contrast, damage to posterior parietal lobes was associated with a substantial reduction of both target P3 and novelty P3 amplitude; however, there was less disruption of the processing of novel than of target stimuli. We conclude that two nodes of the neuroanatomical network for responding to and processing novelty are the prefrontal and posterior parietal regions, which participate in the voluntary allocation of attention to novel events. Injury to this network is indexed by reduced novelty P3 amplitude, which is tightly associated with diminished attention to novel stimuli. The prefrontal cortex may serve as the central node in determining the allocation of attentional resources to novel events, whereas the posterior parietal lobe may provide the neural substrate for the dynamic process of updating one's internal model of the environment to take into account a novel event.Publication Pathophysiology underlying diminished attention to novel events in patients with early AD(Ovid Technologies (Wolters Kluwer Health), 2001) Daffner, Kirk; Rentz, Dorene; Scinto, L. F.M.; Faust, R.; Budson, Andrew; Holcomb, P. J.Background: Patients with mild to moderate AD often are apathetic and fail to attend to novel aspects of their environment. Objective: To investigate the mechanisms underlying these changes by studying the novelty P3 response that measures shifts of attention toward novel events. Methods: While event-related potentials were recorded, mildly impaired AD patients and matched normal controls (NC) viewed line drawings that included a repetitive background stimulus, an infrequent target stimulus, and infrequent novel stimuli. Subjects controlled how long they viewed each stimulus by pressing a button. This served as a measure of their allocation of attention. They also responded to targets by depressing a foot pedal. Patients did not differ from NC in age, education, estimated IQ, or mood but were judged by informants to be more apathetic. Results: P3 amplitude to novel stimuli was significantly smaller for AD patients than NC. However, P3 amplitude to target stimuli did not differ between groups. For NC, P3 response to novel stimuli was much larger than to background stimuli. In contrast, for patients with AD, there was no difference in P3 response to novel vs background stimuli. Although NC spent more time looking at novel than background stimuli, patients with AD distributed their viewing time evenly. Remarkably, for patients with AD, the amplitude of the novelty P3 response powerfully predicted how long they would spend looking at novel stimuli (R2 = 0.52) and inversely correlated with apathy severity. Conclusions: The decreased attention to novel events exhibited by patients with AD cannot be explained by a nonspecific reduction in their attentional abilities. The novelty P3 response is markedly diminished in mild AD, at a time when the target P3 response is preserved. The disruption of the novelty P3 response predicts diminished attention to novel stimuli and is associated with the apathy exhibited by patients with AD.Publication TDP-43 Proteinopathy and Motor Neuron Disease in Chronic Traumatic Encephalopathy(Oxford University Press (OUP), 2010) McKee, Ann C.; Gavett, Brandon E.; Stern, Robert A.; Nowinski, Christopher J.; Cantu, Robert C.; Kowall, Neil; Perl, Daniel P.; Hedley-Whyte, E.; Price, Bruce; Sullivan, Chris; Morin, Peter; Lee, Hyo-Soon; Kubilus, Caroline A.; Daneshvar, Daniel H.; Wulff, Megan; Budson, AndrewEpidemiological evidence suggests that the incidence of amyotrophic lateral sclerosis is increased in association with head injury. Repetitive head injury is also associated with the development of chronic traumatic encephalopathy (CTE), a tauopathy characterized by neurofibrillary tangles throughout the brain in the relative absence of β-amyloid deposits. We examined 12 cases of CTE and, in 10, found a widespread TAR DNA-binding protein of approximately 43 kd (TDP-43) proteinopathy affecting the frontal and temporal cortices, medial temporal lobe, basal ganglia, diencephalon, and brainstem. Three athletes with CTE also developed a progressive motor neuron disease with profound weakness, atrophy, spasticity, and fasciculations several years before death. In these 3 cases, there were abundant TDP-43–positive inclusions and neurites in the spinal cord in addition to tau neurofibrillary changes, motor neuron loss, and corticospinal tract degeneration. The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected. Akin to frontotemporal lobar degeneration with TDP-43 inclusions, in some individuals with CTE, the TDP-43 proteinopathy extends to involve the spinal cord and is associated with motor neuron disease. This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease.Publication Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy After Repetitive Head Injury(Oxford University Press (OUP), 2009) McKee, Ann C.; Cantu, Robert C.; Nowinski, Christopher J.; Hedley-Whyte, E.; Gavett, Brandon E.; Budson, Andrew; Santini, Veronica E.; Lee, Hyo-Soon; Kubilus, Caroline A.; Stern, Robert A.Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed “dementia pugilistica” and more recently, chronic traumatic encephalopathy (CTE). We review the 47 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 professional athletes: one football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, Parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular, patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. CTE is a neuropathologically distinct, slowly progressive tauopathy with a clear environmental etiology.