Cynthia R. Cimino

Bilateral human fetal striatal transplantation in Huntington’s disease

BackgroundTransplanted striatal cells have been demonstrated to survive, grow, establish afferent and efferent connections, and improve behavioral signs in animal models of Huntington’s disease (HD). ObjectiveTo evaluate feasibility and safety and to provide preliminary information regarding the efficacy of bilateral human fetal striatal transplantation in HD. MethodsSeven symptomatic patients with genetically confirmed HD underwent bilateral stereotactic transplantation of two to eight fetal striata per side in two staged procedures. Tissue was dissected from the lateral half of the lateral ventricular eminence of donors 8 to 9 weeks postconception. Subjects received cyclosporine for 6 months. ResultsThree subjects developed subdural hemorrhages (SDHs) and two required surgical drainage. One subject died 18 months after surgery from probable cardiac arrhythmia secondary to severe atherosclerotic cardiac disease. Autopsy demonstrated clearly demarcated grafts of typical developing striatal morphology, with host-derived dopaminergic fibers extending into the grafts and no evidence of immune rejection. Other adverse events were generally mild and transient. Mean Unified HD Rating Scale (UHDRS) motor scores were 32.9 ± 6.2 at baseline and 29.7 ± 7.5 12 months after surgery (p = 0.24). Post-hoc analysis, excluding one subject who experienced cognitive and motor deterioration after the development of symptomatic bilateral SDHs, found that UHDRS motor scores were 33.8 ± 6.2 at baseline and 27.5 ± 5.2 at 12 months (p = 0.03). ConclusionsTransplantation of human fetal striatal cells is feasible and survival of transplanted cells was demonstrated. Patients with moderately advanced HD are at risk for SDH after transplantation surgery.

The orbitomedial frontal syndrome.

An orbitomedial frontal syndrome is proposed, characterized by anosmia, amnesia with confabulation, Go-NoGo deficits, personality change, and hypersensitivity to pain. The orbitomedial frontal syndrome is distinct from the clinical picture that results from dorsolateral frontal damage. Aspects of orbitomedial damage have been discussed previously in isolation, but we argue that recognition of this syndrome in toto is clinically important. It appears to be associated with poor social and vocational adjustment after brain injury, and the co-occurrence of features of the syndrome provides clues to underlying mechanisms for disinhibition and confabulation in frontal lobe patients.

Driving safety in Parkinson's disease

In this study, 39 patients with PD and 25 control subjects without neurologic disease completed testing in a driving simulator. PD patients had more total collisions on the driving simulator than control subjects (t = −3.7, p < 0.01). In PD patients, collisions were associated with Hoehn and Yahr stage (χ2 = 12.4, p = 0.006) and correlated with Unified Parkinson’s Disease Rating Scale score (r = 0.5, p < 0.01).

The independent influence of apathy and depression on cognitive functioning in Parkinson's disease.

OBJECTIVE The purpose of the present study was to examine the independent influence of symptoms of depression and apathy, two of the most common neuropsychiatric symptoms in Parkinsons disease (PD), on executive functioning and memory in PD patients using measures designed to discriminate between these symptoms. METHOD Participants included 68 nondemented, idiopathic PD patients, ages 56-82 years. The Apathy Evaluation Scale-Self-Rating and select items of the Beck Depression Inventory II were used to assess symptoms of apathy and depression, respectively. Cognitive function was assessed using the Wisconsin Card Sorting Test and Hopkins Verbal Learning Test-Revised. Correlations and hierarchical regressions were conducted to investigate the relationships between apathy, depression, and cognitive function. Hierarchical regression analyses were conducted to evaluate the degree of influence of depression and apathy on cognitive function. RESULTS Results revealed that symptoms of apathy, but not depression, were significantly and negatively associated with executive functioning. Immediate memory was significantly and negatively associated with both apathy and depression. However, apathy accounted for additional variance in memory performance after controlling for depression at a level approaching significance. CONCLUSIONS Apathy is not only associated with cognitive impairment, but also with impaired daily functioning, caregiver burden and distress, medication noncompliance, and increased mortality. Differentiating apathy and depression, understanding their unique effects, and appropriately identifying apathy symptoms in patients have robust implications for the development of neuropsychological models of these effects in PD as well as practical implications in guiding improvements to patient care and enhancing quality of life in patients and caregivers.

Hemispheric Lateralization of Perception and Memory for Emotional Verbal Stimuli in Normal Individuals

The purposes of this study were to extend the literature on lateralization of perception of emotional verbal stimuli in normal individuals, including a test of both the right hemisphere and valence models, and to investigate predictions from these models regarding lateralization of memory for emotional verbal stimuli in normal individuals, an area that, to our knowledge, has not been investigated. Seventy-nine undergraduates were presented lateralized positive, negative, and neutral English words and nonwords. Participants were then asked to freely recall the presented words and, after a 20-min delay, to recognize the words. Recognition memory data provided strong support for the valence model. In addition, free-recall and perception data provided partial support for this model. The literature on the lateralization of processing emotional verbal and nonverbal material is discussed.

Alteration of Expected Hemispheric Asymmetries: Valence and Arousal Effects in Neuropsychological Models of Emotion

The relative advantage of the left (LH) over the right hemisphere (RH) in processing of verbal material for most individuals is well established. Nevertheless, several studies have reported the ability of positively and negatively valenced stimuli to enhance and reverse, respectively, the usual LH>RH asymmetry. These studies, however, have used baseline stimuli that differed from emotional stimuli on two dimensions (i.e., valence and verbal/nonverbal nature), creating interpretive difficulties as to whether differences across these conditions are due to differences in valence or the verbal/nonverbal nature of the primes used in the baseline condition. In addition, these studies, along with many others in the literature, have failed to control for potential confounding effects of arousal. Emotional stimuli vary on dimensions of valence as well as arousal and arousal may be asymmetrically presented in the brain therefore contributing to observed asymmetries. Taken together, these considerations underscore the importance of controlling for both valence as well as arousal in any investigation of the effects of emotional stimuli. The objectives of the present study were twofold: (1) to employ an appropriate baseline condition to render emotional stimuli vs. baseline stimuli comparisons meaningful and (2) to examine the extent to which emotional verbal stimuli, equated for arousal level, alter the expected LH>RH asymmetry in a consonant trigram task. Results demonstrated that when LH lateralized consonant trigram presentations were preceded by a positive prime, an enhancement of the expected LH>RH asymmetry was observed. In contrast, when trigram presentations lateralized to the RH were preceded by a negative prime, a complete reversal of the typical asymmetry was found with RH>LH performance. These results are analogous to the pattern of relative hemispheric activations observed for various mood states. Controlling for arousal in studies investigating asymmetries associated with emotional processing may allow more clear interpretation of data intended to test predictions of neuropsychological models of emotion. Moreover, equating stimuli on the dimension of arousal as well as valence may shed more light on conflicting findings with regard to perception vs. expression of emotion.

Cognitively Stimulating Activities: Effects on Cognition across Four Studies with up to 21 Years of Longitudinal Data

Engagement in cognitively stimulating activities has been considered to maintain or strengthen cognitive skills, thereby minimizing age-related cognitive decline. While the idea that there may be a modifiable behavior that could lower risk for cognitive decline is appealing and potentially empowering for older adults, research findings have not consistently supported the beneficial effects of engaging in cognitively stimulating tasks. Using observational studies of naturalistic cognitive activities, we report a series of mixed effects models that include baseline and change in cognitive activity predicting cognitive outcomes over up to 21 years in four longitudinal studies of aging. Consistent evidence was found for cross-sectional relationships between level of cognitive activity and cognitive test performance. Baseline activity at an earlier age did not, however, predict rate of decline later in life, thus not supporting the concept that engaging in cognitive activity at an earlier point in time increases ones ability to mitigate future age-related cognitive decline. In contrast, change in activity was associated with relative change in cognitive performance. Results therefore suggest that change in cognitive activity from ones previous level has at least a transitory association with cognitive performance measured at the same point in time.

The relationship between cigarette smoking and impulsivity: A review of personality, behavioral, and neurobiological assessment

Impulsivity is a multi-dimensional construct that broadly encompasses impaired self-regulation. Studies comparing substance users and non-users, including cigarette smokers, consistently find that users are more impulsive than non-users. However, identifying the role of impulsivity in cigarette smoking initiation, maintenance, and relapse has been challenging because of variation in how impulsivity is defined and whether it is assessed as (1) a stable personality trait, (2) a behavior (either trait or state), or (3) a neurobiological process. Personality and behavioral assessments are typically weakly correlated or uncorrelated, but both types of impulsivity have been related to brain activity in the prefrontal cortex (PFC) and associated areas. This article provides a narrative review of research pertaining to the relationship between impulsivity and cigarette smoking, including smoking initiation, maintenance, and relapse, with respect to these three methods of impulsivity assessment. This review revealed that impulsivity is associated with all stages of tobacco use. Regarding initiation, research involving adolescents suggests that differences between adult smokers and non-smokers in self-reported impulsivity appear to pre-date smoking initiation, whereas behavioral impulsivity has not been as consistently associated with adolescent smoking. Conversely, chronic exposure to nicotine and acute nicotine deprivation may also increase impulsivity. Regarding maintenance and relapse, urgency, an aspect of impulsivity that refers to the tendency to act impulsively when experiencing negative affect, seems to play a particularly important role. In future research, investigators should define impulsivity precisely and provide a rationale for the type of assessment used. Targeting impulsivity reduction may facilitate successful smoking cessation.

Dynamic Associations of Change in Physical Activity and Change in Cognitive Function: Coordinated Analyses of Four Longitudinal Studies

The present study used a coordinated analyses approach to examine the association of physical activity and cognitive change in four longitudinal studies. A series of multilevel growth models with physical activity included both as a fixed (between-person) and time-varying (within-person) predictor of four domains of cognitive function (reasoning, memory, fluency, and semantic knowledge) was used. Baseline physical activity predicted fluency, reasoning and memory in two studies. However, there was a consistent pattern of positive relationships between time-specific changes in physical activity and time-specific changes in cognition, controlling for expected linear trajectories over time, across all four studies. This pattern was most evident for the domains of reasoning and fluency.

Social Activity and Cognitive Functioning Over Time: A Coordinated Analysis of Four Longitudinal Studies

Social activity is typically viewed as part of an engaged lifestyle that may help mitigate the deleterious effects of advanced age on cognitive function. As such, social activity has been examined in relation to cognitive abilities later in life. However, longitudinal evidence for this hypothesis thus far remains inconclusive. The current study sought to clarify the relationship between social activity and cognitive function over time using a coordinated data analysis approach across four longitudinal studies. A series of multilevel growth models with social activity included as a covariate is presented. Four domains of cognitive function were assessed: reasoning, memory, fluency, and semantic knowledge. Results suggest that baseline social activity is related to some, but not all, cognitive functions. Baseline social activity levels failed to predict rate of decline in most cognitive abilities. Changes in social activity were not consistently associated with cognitive functioning. Our findings do not provide consistent evidence that changes in social activity correspond to immediate benefits in cognitive functioning, except perhaps for verbal fluency.