The visual kinetic depth effect is altered with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) often have visual-perceptual disorders. The goal of this study was to learn if they can develop a three dimensional (3D) percept that depends on the kinetic depth effect; that is, the viewer's ability to spatially integrate over time images that are moving along many trajectories. METHODS: Sixteen patients with PD and 12 healthy matched controls were presented with stimuli that were comprised of a circular region of randomly placed dots that moved as orthographic projections of a sphere. With a normal kinetic depth effect, the Training stimuli appear as an opaque rotating ball and the Test stimuli appear as a rotating transparent ball. RESULTS: Whereas all controls and all PD patients reported seeing the Training stimuli as a rotating ball, the patients with PD were significantly less likely to report the Test stimuli appearing as a 3D "ball" than were the healthy participants. Instead, seven PD patients often reported these bidirectional stimuli appeared "flat." CONCLUSIONS: This study has revealed that some patients with PD have impaired spatio-temporal integration of bidirectional visual motions, but the mechanism accounting for this loss, as well as why only some patients had this deficit, needs further study. When the driver of a moving vehicle fixates upon a stationary target in the surroundings, bidirectional retinal image motions may occur. Failure to perceive 3D structure in such moving scenes can be plausibly suspected to contribute to adverse events such as auto accidents.

A full-brain, bootstrapped analysis of diffusion tensor imaging robustly differentiates Parkinson disease from healthy controls.

There is a compelling need for early, accurate diagnosis of Parkinson's disease (PD). Various magnetic resonance imaging modalities are being explored as an adjunct to diagnosis. A significant challenge in using MR imaging for diagnosis is developing appropriate algorithms for extracting diagnostically relevant information from brain images. In previous work, we have demonstrated that individual subject variability can have a substantial effect on identifying and determining the borders of regions of analysis, and that this variability may impact on prediction accuracy. In this paper we evaluate a new statistical algorithm to determine if we can improve accuracy of prediction using a subjects left-out validation of a DTI analysis. Twenty subjects with PD and 22 healthy controls were imaged to evaluate if a full brain diffusion tensor imaging-fractional anisotropy (DTI-FA) map might be capable of segregating PD from controls. In this paper, we present a new statistical algorithm based on bootstrapping. We compare the capacity of this algorithm to classify the identity of subjects left out of the analysis with the accuracy of other statistical techniques, including standard cluster-thresholding. The bootstrapped analysis approach was able to correctly discriminate the 20 subjects with PD from the 22 healthy controls (area under the receiver operator curve or AUROC 0.90); however the sensitivity and specificity of standard cluster-thresholding techniques at various voxel-specific thresholds were less effective (AUROC 0.72-0.75). Based on these results sufficient information to generate diagnostically relevant statistical maps may already be collected by current MRI scanners. We present one statistical technique that might be used to extract diagnostically relevant information from a full brain analysis.

Reliability analysis of the resting state can sensitively and specifically identify the presence of Parkinson disease.

Parkinson disease (PD) is characterized by a number of motor and behavioral abnormalities that could be considered deficits of a "no task" or "resting" state, including resting motor findings and defects in emerging from a resting state (e.g., resting tremor, elevated resting tone, abulia, akinesia, apathy). PET imaging, and recently, the MRI technique of continuous arterial spin labeling (CASL) have shown evidence of changes in metabolic patterns in individuals with PD. The purpose of this study was to learn if the presence of PD could be "predicted" based on resting fluctuations of the BOLD signal. Participants were 15 healthy controls, 14 subjects with PD, and 1 subject who presented as a control but later developed PD. The amplitude of the low frequency fluctuation (ALFF) was used as an index of brain activity level in the resting state. Participants with PD using this index showed a reliable decrease in activity in a number of regions, including the supplementary motor cortex, the mesial prefrontal cortex, the right middle frontal gyrus, and the left cerebellum (lobule VII/VIII) as well as increased activity in the right cerebellum (lobule IV/V). Using a cross validation approach we term "Reliability Mapping of Regional Differences" (RMRD) to analyze our sample, we were able to reliably distinguish participants with PD from controls with 92% sensitivity and 87% specificity. Our "pre-diagnostic" subject segregated in our analysis with the PD group. These results suggest that resting fMRI should be considered for development as a biomarker and analytical tool for evaluation of PD.

Apathy, depression, and motor symptoms have distinct and separable resting activity patterns in idiopathic Parkinson disease.

Apathy and depression are heterogeneous syndromes with symptoms that overlap clinically. This clinical overlap leads to problems with classification and diagnosis in clinical populations. No functional imaging study has attempted to separate brain regions altered in apathy from those altered in depression in a clinical population. Parkinson disease (PD) is a disorder in which apathy and depression co-exist in a single population. We evaluate the relationship between apathy, depression, and motor severity of disease in PD, focusing on the relationship between these factors and the amplitude of the low frequency fluctuation (ALFF) in the resting state. We first evaluated if the resting ALFF signal is a reliable measure for our clinical question. For this, we develop and introduce a cross validation approach we term the "Regional Mapping of Reliable Differences" (RMRD) method to evaluate reliability of regions of interest deemed "significant" by standard voxel-wise techniques. Using this approach, we show that the apathy score in this sample is best predicted by ALFF signal in the left supplementary motor cortex, the right orbitofrontal cortex, and the right middle frontal cortex, whereas depression score is best predicted by ALFF signal in the right subgenual cingulate. Disease severity was best predicted by ALFF signal in the right putamen. A number of additional regions are also statistically (but not reliably) correlated with our neuropsychological measures and disease severity. Our results support the use of resting fMRI as a means to evaluate neuropsychiatric states and motor disease progression in Parkinson disease, and the clinical and epidemiologic observation that apathy and depression are distinct pathological entities. Our finding that "significance" and "reliability" are dissociated properties of regions of interest identified as significant using standard voxel-wise techniques suggests that including reliability analyses may add useful scientific information in neurobehavioral research.

Bilateral restless legs affecting a phantom limb, treated with dopamine agonists.

BACKGROUND: Restless legs syndrome (RLS) is a common condition characterised by unpleasant sensations deep inside the legs, which usually occurs at rest and especially at night. These sensations are accompanied by an urge to move the limb, and movements result in a temporary relief of the symptoms. The pathophysiology of RLS is not completely known, especially the role of afferent feedback. An individual with a below the knee amputation who developed restless legs in his real and phantom limbs is reported. METHODS AND RESULTS: A 54-year-old man with a left leg amputation 22 years ago developed RLS, primarily at night, that met the International RLS Study Group's criteria for RLS. This RLS, however, involved both his real and phantom lower limbs. Movement and phantom movements, as well as treatment with dopamine agonists, relieved this symptom in both the real and amputated limbs. However, creating an image of the limb moving without "moving" the limb did not improve the uncomfortable sensations in either limb. CONCLUSIONS: That restless legs can occur simultaneously in a phantom as well as a real limb and that the perception of movement in a phantom limb as well as dopaminergic treatment improved the symptoms provides further support for the important role of central nervous system dysfunction in the development of this disorder.

Turning off artistic ability: the influence of left DBS in art production.

BACKGROUND: The influence of Parkinson's disease (PD) as well as deep brain stimulation (DBS) on visual-artistic production of people who have been artists is unclear. We systematically assessed the artistic-creative productions of a patient with PD who was referred to us for management of a left subthalamic region (STN) DBS. The patient was an artist before her disease started, permitting us to analyze changes in her artistic-creative production over the course of the illness and during her treatment with DBS. METHODS: We collected her paintings from four time periods: Time 1 (Early Pre-Presymptomatic), Time 2 (Later Presymptomatic), Time 3 (Symptomatic), and Time 4 (DBS Symptomatic). A total of 59 paintings were submitted to a panel of judges, who rated the paintings on 6 different artistic qualities including: aesthetics, closure, evocative impact, novelty, representation, technique. RESULTS: Aesthetics and evocative impact significantly declined from Time 2 to Time 4. Representation and technique indicated a curvilinear relationship, with initial improvement from Time 1 to Time 2 followed by a decline from Time 2 to Time 4. CONCLUSIONS: These results suggest that left STN/SNR-DBS impacted artistic performances in our patient. The reason for these alterations is not known, but it might be that alterations of left hemisphere functions induce a hemispheric bias reducing the influence the right hemisphere which is important for artistic creativity. The left hemisphere itself plays a critical role in artistic creativity and DBS might have altered left hemisphere functions or altered the mesolimbic system which might have also influenced creativity. Future studies will be required to learn how PD and DBS influence creativity.

Creativity in Parkinson's disease as a function of right versus left hemibody onset.

OBJECTIVE: Creativity is heavily dependent on divergent thinking and divergent thinking appears to be strongly dependent on fontal lobe function. Since patients with Parkinson's disease (PD) often have evidence of frontal lobe dysfunction we wanted to learn if these patients have a reduction of creativity, as well as learning if the side of onset (right versus left) influences the type (verbal versus visuospatial) of decrement in creativity. DESIGN: Participants of this study were patients with right (RHO) or left (LHO) onset PD as well as matched controls. All subjects were given the Abbreviated Torrance Test of Creative Thinking for Adults (ATTA), a widely used test to assess creativity that examines Fluency, Originality, Flexibility and Elaboration. Subjects were also assessed with the Controlled Word Association Test (COWAT). RESULTS/CONCLUSIONS: When compared to controls the patients with RHO, but not LHO, had a decrease of verbal creative fluency. Patients with PD often have a decrease on the COWAT, but performance on the COWAT did not differ between the RHO and the LHO patients. This suggests that patients with PD who have RHO have a decrease in verbal creativity and this decrement does not appear to be related to decreased fluency.

Artistic creativity and DBS: a case report.

BACKGROUND: Deep brain stimulation (DBS) is a treatment for patients with Parkinson's disease (PD) who are not adequately controlled with medications. An artist reported changes in her artistic creativity and art appreciation when treated with left DBS. We sought to study her artistic productions and her appreciation of art while both "on" and "off" left DBS. METHODS: A 69-year-old right-handed woman with an approximate 20-year history of PD was referred to us for management of a left subthalamic region nucleus (STN) DBS placed at another institution 4 years prior. In Experiment 1 we had her rate several dimensions (Evocative Impact, Aesthetics, Novelty, Technique, Closure and Representation) of another artist's paintings. In Experiment 2, we tested her with the Abbreviated Torrance Test (of creativity) for Adults (ATTA). During testing the patient remained on her dopaminergic medication, but was tested on and off left DBS. RESULTS: On the judgment task while "on" left DBS, versus "off" DBS, there were significant reductions in her appreciation of artistic Closure and Technique. When "off" DBS her ATTA creativity index was above average, but when switched "on" her creativity index was below average. CONCLUSIONS: These results suggest the possibility that left ventral STN/SNR DBS reduces creativity as well as appreciation of art. The reason for these alterations is not known, but might be related to enhanced activation of the left hemisphere and reciprocal deactivation of the right hemisphere which mediates both visuospatial skills and global attention, both of which are important in artistic creativity and appreciation.

An ambulatory persistence power curve: motor planning affects ambulatory persistence in Parkinson's disease.

BACKGROUND/OBJECTIVES: When performing activity associated with walking, the amount of walking a person does often will depend on their plans. This study was designed to evaluate the relationship between motor planning and ambulatory persistence in participants with Parkinson's disease (PD) and to see if ambulatory persistence was related to the ability to perform activities of daily living (ADL). METHODS: 20 individuals with idiopathic PD were recruited to perform the Trail making Test (a test of motor planning) and to wear a step activity monitor for 48h. The measurement of persistence of an ambulatory event consisted of the number of steps taken during an event and an ambulatory event was defined as continuous ambulation (taking step) without pausing for 3 or more seconds. The resumption of taking step (ambulation) after 3 or more seconds counted as a new ambulatory event. UPDRS-motor and ADL scale were also obtained. ANALYSIS AND RESULTS: The cumulative percentage of the total ambulatory events at each number of steps was plotted for each subject which when plotted could be described as a sigmoid curve. We found that this sigmoidal curve defined by the equation y=x(n)/(k(n)+x(n)), fit the data well, where k represents a constant specific to each subject, x represents the number of steps during each ambulatory event, and y represents the projected percentage of movement events containing x number of steps or less. (Root Mean Square Error (RMSE)=0.02, R(2)=0.98). Trail making test part A was highly associated with the constant k (R=-0.74, p<0.001). The constant k was also highly associated with the UPDRS ADL subscale (R=-0.81, p=0.0001). A forward bivariate regression model including Part A of the Trail making test, and the UPDRS-ADL subscale predicted 66% of the variability of the constant k. The overall number of steps taken per day, and the UPDRS motor subscale did not contribute to the model. CONCLUSIONS: Defective motor planning in Parkinson's disease as measured by poor performance on a Trail making test is associated with a measurable alteration in ambulatory persistence, and altered ambulatory persistence, quantified by our proposed model parameter, correlates highly with the UPDRS ADL score. Thus, cognitive-motor planning defects might be a major source of disability in PD. We suggest that in future clinical practice gait tests can be used in order to quantify short-term planning ability in neurodegenerative diseases.

Aceruloplasminaemia with progressive atrophy without brain iron overload: treatment with oral chelation.

BACKGROUND: Hereditary aceruloplasminaemia is a disorder of iron metabolism that is characterised by iron accumulation in the brain and other visceral organs. In previously reported cases, individuals with the disorder were noted to have evidence of iron accumulation in the brain. Oral chelating agents have not been used in neurological diseases of iron metabolism. METHODS: A 54-year-old woman who presented with ataxia, lower extremity spasticity and chorea was evaluated for evidence of the source of neurological dysfunction. RESULTS: Blood studies revealed no detectable ceruloplasmin. Marked iron overload was defined by a liver biopsy, which showed a variegated pattern consistent with a primary cause of iron overload. Review of MRI scans showed progressive brain atrophy without visible iron accumulation occurring over a 5-year period. The history suggested that neurodegeneration was coincident with aggressive oral iron replacement. Oral chelation improved many symptoms. CONCLUSIONS: Our findings in this patient suggest that disorders of iron transport such as aceruloplasminaemia can be a cause of neurological symptoms such as chorea and cognitive decline, as well as progressive neurodegeneration in the absence of visible iron on MRI scans. We found that oral iron chelation was effective at improving symptoms.

Presentation, etiology, and outcome of stroke in pregnancy and puerperium.

PURPOSE: The purpose of this study was to evaluate the presentation, timing, etiology, and outcome of ischemic stroke (IS), hemorrhagic stroke (HS), and cerebral venous thrombosis (CVT) occurring during pregnancy and puerperium at 3 Indianapolis hospitals. METHODS: Medical records of patients with a stroke during pregnancy and the puerperium were identified by using International Classification of Diseases (ICD 9) codes and a computerized records database. The records were available from 1992 to 1999 at 2 of the hospitals and from 1994 to 1999 at the third hospital. The records were retrospectively reviewed for presentation, treatment, etiology, and outcome. The sample included all cases of IS, HS, and CVT occurring in our pregnant population and included events up to 12 weeks postpartum. RESULTS: Thirty-six patients were identified, including 21 with IS, 11 with HS, and 4 patients with CVT. The majority of events (89%) occurred in the third trimester and postpartum period, and 16 of 36 (44%) events occurred in postpartum week 1. Of the 8 African American patients in our study, 5 had HS (63%), whereas 18 of the 25 white patients (72%) had IS. A definable cause was identified in 72% of IS and 82% of HS. Some causes of IS include pre-eclampsia or eclampsia (13%), cardioembolism (23%), and a diverse array of other causes, include hypercoagulable states, thrombotic thrombocytopenic purpura (TTP), cerebral vasculitis, cerebrovascular mucormycosis, and migrainous infarction. Pre-eclampsia/eclampsia (37%) and ruptured atriovenous malformation (AVM) (36%) were the primary causes of HS. None of the cases of CVT had a clear etiology other than the pregnant or puerperal state, although risk factors included systemic lupus erythematosus (negative antiphospholipid antibodies and lupus anticoagulant) in 1 patient and dehydration in a second. Hypertensive disorders of pregnancy were the most common comorbid conditions in both IS and HS, affecting 45% of those with IS and 64% of patients with HS. IS presented with focal deficits (76%), whereas HS tended to present with an altered level of consciousness (73%) and headache (64%). All patients with CVT (4/4) presented with a headache, and 2 of 4 patients presented with an altered level of consciousness. The majority of patients with HS were discharged to nursing homes or rehabilitation centers (63%), whereas 73% of patients with IS and 3 of 4 patients with CVT were discharged home. Only 1 death occurred in our study, because of a brain herniation after a massive hemispheric IS. CONCLUSION: The etiology of stroke in pregnancy and the puerperium is diverse. Strokes are most likely to occur in the third trimester and postpartum period and cluster in the first postpartum week.