Lee X. Blonder - US grants

Neuropsychological studies of brain-damaged patients suggest that the right hemisphere (RH) is specialized for behavioral functions that collectively contribute to social interaction and bonding. In particular, patients with right hemisphere damage (RHD) are reported to have abnormalities in emotional facial expression and prosody, attention, arousal, and mood. While these social-emotional disorders of the right hemisphere have ben documented in laboratory assessment, there has been little research examining their effects on natural behavior and interpersonal relations. Given the importance of social cognition in daily interaction, these disorders may prove more disabling for RHD patients and their families than previously thought. The specific aims of this study are a.) to document the extent and evolution of social-emotional and cognitive dysfunction in our population of RHD patients using laboratory measures that have been proven reliable in previous research; and b.) to examine the effects of right versus left hemisphere damage and associated neurobehavioral disorders (documented in laboratory assessment) on spontaneous social interaction and marital relations during the 18 month follow-up period. We will compare patients with unilateral right and left hemisphere infarcts and age and sex-matched control patients with orthopedic disease on laboratory measures of paralinguistic, neuropsychological, and affective function and correlate these results with subjects' performance in studies of spontaneous social interaction. First, judges will rate facial expression and prosody in videotapes of interviews with patients and their spouses. Second, the spouse of each patient will observe and record patient social behavior at regular intervals over the 18 month follow-up period. We will also examine mood and perceptions of marital satisfaction in spouses as a function of presence and side of lesion in the patient. This research will contribute to basic knowledge of the brain regions involved in social behavior, as well as provide clinicians and caregivers with information regarding the effects of these impairments on interpersonal relations during both the acute and chronic phases. In the longterm, this research should contribute to the management of social-emotional and marital disturbance resulting from localized brain damage.

[unreadable] DESCRIPTION (provided by applicant): Depression is a common and potentially serious complication of Parkinson's disease (PD). Studies show that approximately 40 percent of PD patients are depressed. There is evidence that these patients have deficits in verbal fluency, set shifting, confrontation naming, and memory relative to non-depressed PD patients. Despite the widespread toll on emotional health posed by PD, few studies have undertaken a comprehensive examination of the neural underpinnings of Parkinsonian depression. In this project, we will compare depressed versus non-depressed Parkinson patients to a sample of demographically-matched healthy controls using neuropsychological assessment and magnetic resonance imaging (MRI). Our primary hypothesis is that depression in PD is linked to structural and functional abnormality in dorsal and ventral striatum, amygdala, orbitofrontal cortex, medial frontal cortex, and anterior cingulate. Based on this, we predict that in comparisons with non-depressed PD patients, PD patients with depression will show 1.) significant reductions in the volume of the caudate nucleus, orbitofrontal cortex, medial frontal cortex, anterior cingulate, and amygdala; and 2.) reduced activation on cognitive and emotional tasks known to engage these regions. Our secondary hypothesis is that anti-parkinsonian medications, particularly D2/D3 receptor agonists, will result in elevation in mood and increased activation in these brain regions among depressed PD patients during the performance of cognitive and emotional tasks. To delineate the neural substrates of Parkinsonian depression, each patient and control will undergo neuropsychological testing and structural and functional MRI. We will compare regional brain volume in structures associated with depression and patterns of functional MRI activation during working memory and facial affect processing tasks. Neuropsychological testing and fMRI will be performed "on" and "off dopaminergic pharmacotherapy in PD patients and at two similar time points in the unmedicated control group. The research proposed herein will contribute to our understanding of the neural pathways that underlie depression in PD, the relationship of dysphoria to cerebral activation during cognitive and affective processing, and the effects of dopaminergic pharmacotherapy on brain response in prefrontal and limbic regions. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]