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1.
Mov Disord ; 36(4): 948-954, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33253432

RESUMO

BACKGROUND: The clinical diagnosis of Parkinson's disease (PD) requires the presence of parkinsonism and supportive criteria that include a clear and dramatic beneficial response to dopaminergic therapy. Our aim was to test the diagnostic criterion of dopaminergic response by evaluating its association with pathologically confirmed diagnoses in a large population of parkinsonian patients. METHODS: We reviewed clinical data maintained in an electronic medical record from all patients with autopsy data who had been seen in the Movement Disorders Center at Washington University, St. Louis, between 1996 and 2018. All patients with parkinsonism who underwent postmortem neuropathologic examination were included in this analysis. RESULTS: There were 257 unique parkinsonian patients with autopsy-based diagnoses who had received dopaminergic therapy. Marked or moderate response to dopaminergic therapy occurred in 91.2% (166/182) of those with autopsy-confirmed PD, 52.0% (13/25) of those with autopsy-confirmed multiple systems atrophy, 44.4% (8/18) of those with autopsy-confirmed progressive supranuclear palsy, and 1 (1/8) with autopsy-confirmed corticobasal degeneration. Other diagnoses were responsible for the remaining 24 individuals, 9 of whom had a moderate response to dopaminergic therapy. CONCLUSION: A substantial response to dopaminergic therapy is frequent but not universal in PD. An absent response does not exclude PD. In other neurodegenerative disorders associated with parkinsonism, a prominent response may also be evident, but this occurs less frequently than in PD. © 2020 International Parkinson and Movement Disorder Society.


Assuntos
Atrofia de Múltiplos Sistemas , Doença de Parkinson , Transtornos Parkinsonianos , Paralisia Supranuclear Progressiva , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico
2.
Brain ; 133(Pt 12): 3625-34, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20855421

RESUMO

The basal ganglia are thought to be important in the selection of wanted and the suppression of unwanted motor patterns according to explicit rules (i.e. response inhibition). The subthalamic nucleus has been hypothesized to play a particularly critical role in this function. Deep brain stimulation of the subthalamic nucleus in individuals with Parkinson's disease has been used to test this hypothesis, but results have been variable. Based on current knowledge of the anatomical organization of the subthalamic nucleus, we propose that the location of the contacts used in deep brain stimulation could explain variability in the effects of deep brain stimulation of the subthalamic nucleus on response inhibition tasks. We hypothesized that stimulation affecting the dorsal subthalamic nucleus (connected to the motor cortex) would be more likely to affect motor symptoms of Parkinson's disease, and stimulation affecting the ventral subthalamic nucleus (connected to higher order cortical regions) would be more likely to affect performance on a response inhibition task. We recruited 10 individuals with Parkinson's disease and bilateral deep brain stimulation of the subthalamic nucleus with one contact in the dorsal and another in the ventral subthalamic region on one side of the brain. Patients were tested with a Go-No-Go task and a motor rating scale in three conditions: stimulation off, unilateral dorsal stimulation and unilateral ventral stimulation. Both dorsal and ventral stimulation improved motor symptoms, but only ventral subthalamic stimulation affected Go-No-Go performance, decreasing hits and increasing false alarms, but not altering reaction times. These results suggest that the ventral subthalamic nucleus is involved in the balance between appropriate selection and inhibition of prepotent responses in cognitive paradigms, but that a wide area of the subthalamic nucleus region is involved in the motor symptoms of Parkinson's disease. This finding has implications for resolving inconsistencies in previous research, highlights the role of the ventral subthalamic nucleus region in response inhibition and suggests an approach for the clinical optimization of deep brain stimulation of the subthalamic nucleus for both motor and cognitive functions.


Assuntos
Inibição Psicológica , Núcleo Subtalâmico/fisiologia , Idoso , Comportamento/fisiologia , Mapeamento Encefálico , Tomada de Decisões/fisiologia , Discriminação Psicológica , Feminino , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Destreza Motora/fisiologia , Testes Neuropsicológicos , Doença de Parkinson/patologia , Doença de Parkinson/psicologia , Doença de Parkinson/terapia , Desempenho Psicomotor/fisiologia , Núcleo Subtalâmico/patologia
3.
Mov Disord ; 25(15): 2516-23, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20922808

RESUMO

Clinicopathologic studies of Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) commonly reveal abnormal ß-amyloid deposition in addition to diffuse Lewy bodies (α-synuclein aggregates), but the relationship among these neuropathologic features and the development of dementia in these disorders remains uncertain. The purpose of this study was to determine whether amyloid-ß deposition detected by PET imaging with Pittsburgh Compound B (PIB) distinguishes clinical subtypes of Lewy body-associated disorders. Nine healthy controls, 8 PD with no cognitive impairment, 9 PD with mild cognitive impairment, 6 DLB, and 15 PDD patients underwent [(11)C]-PIB positron emission tomography imaging, clinical examination, and cognitive testing. The binding potential (BP) of PIB for predefined regions and the mean cortical BP (MCBP) were calculated for each participant. Annual longitudinal follow-up and postmortem examinations were performed on a subset of participants. Regional PIB BPs and the proportion of individuals with abnormally elevated MCBP were not significantly different across participant groups. Elevated PIB binding was associated with worse global cognitive impairment in participants with Lewy body disorders but was not associated with any other clinical or neuropsychological features, including earlier onset or faster rate of progression of cognitive impairment. These results suggest that the presence of fibrillar amyloid-ß does not distinguish between clinical subtypes of Lewy body-associated disorders, although larger numbers are needed to more definitively rule out this association. Amyloid-ß may modify the severity of global cognitive impairment in individuals with Lewy body-associated dementia.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Encéfalo/metabolismo , Encéfalo/patologia , Cognição , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Corpos de Lewy/metabolismo , Corpos de Lewy/patologia , Doença por Corpos de Lewy/metabolismo , Doença por Corpos de Lewy/patologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Tomografia por Emissão de Pósitrons/métodos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Tiazóis , alfa-Sinucleína/metabolismo
4.
J Neurosci Methods ; 159(2): 300-7, 2007 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-16934332

RESUMO

Levodopa, when combined with a decarboxylase inhibitor, essentially delivers dopamine directly to the brain, with no net effect on brain blood vessels. For future neuroimaging studies of Parkinson disease and Tourette syndrome, we sought to rapidly produce a biologically relevant levodopa concentration in plasma and then maintain that concentration long enough to assess motor, cognitive, emotional, and neuroimaging responses, while minimizing side effects in levodopa-naive individuals. Based on available pharmacokinetic data and a two-compartment model, we designed a decreasing-exponential-rate infusion to meet these goals. This report gives results of double-blind levodopa and placebo infusions in six healthy subjects. Mean plasma levodopa concentrations were within 3% of their 1200 ng/mL target at 20 and 40 min into the infusion, and within 20% between approximately 12 and 90 min. Levodopa significantly reduced serum prolactin and raised serum growth hormone concentrations. Volunteers had no significant side effects.


Assuntos
Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/farmacocinética , Compartimentos de Líquidos Corporais , Levodopa/administração & dosagem , Levodopa/farmacocinética , Modelos Biológicos , Administração Oral , Adulto , Algoritmos , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/sangue , Carbidopa/administração & dosagem , Carbidopa/efeitos adversos , Carbidopa/sangue , Carbidopa/farmacocinética , Dopamina/sangue , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Infusões Intravenosas , Levodopa/efeitos adversos , Levodopa/sangue , Masculino , Medição da Dor , Prolactina/sangue
5.
Psychiatry Res ; 154(2): 181-90, 2007 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-17289354

RESUMO

The basal ganglia and thalamus may play a critical role for behavioral inhibition mediated by prefrontal, parietal, temporal, and cingulate cortices. The cortico-basal ganglia-thalamo-cortical loop with projections from frontal cortex to striatum, then to globus pallidus or to substantia nigra pars reticulata, to thalamus and back to cortex, provides the anatomical substrate for this function. In-vivo neuroimaging studies have reported reduced volumes in the thalamus and basal ganglia in individuals with Tourette Syndrome (TS) when compared with healthy controls. However, patterns of neuroanatomical shape that may be associated with these volume differences have not yet been consistently characterized. Tools are being developed at a rapid pace within the emerging field of computational anatomy that allow for the precise analysis of neuroanatomical shape derived from magnetic resonance (MR) images, and give us the ability to characterize subtle abnormalities of brain structures that were previously undetectable. In this study, T1-weighted MR scans were collected in 15 neuroleptic-naïve adults with TS or chronic motor tics and 15 healthy, tic-free adult subjects matched for age, gender and handedness. We demonstrated the validity and reliability of large-deformation high dimensional brain mapping (HDBM-LD) as a tool to characterize the basal ganglia (caudate, globus pallidus and putamen) and thalamus. We found no significant volume or shape differences in any of the structures in this small sample of subjects.


Assuntos
Gânglios da Base/patologia , Mapeamento Encefálico/instrumentação , Imageamento por Ressonância Magnética , Síndrome de Tourette/patologia , Adulto , Gânglios da Base/anormalidades , Núcleo Caudado/anormalidades , Núcleo Caudado/patologia , Feminino , Globo Pálido/anormalidades , Globo Pálido/patologia , Humanos , Masculino , Núcleo Accumbens/anormalidades , Núcleo Accumbens/patologia , Putamen/anormalidades , Putamen/patologia , Reprodutibilidade dos Testes , Tálamo/anormalidades , Tálamo/patologia
6.
Neuropsychopharmacology ; 30(3): 590-601, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15602502

RESUMO

Some patients with advanced Parkinson's disease (PD) develop dose-related fluctuations in mood. This may reflect alterations in dopamine-influenced brain circuits that mediate emotion. However, there is no available information to localize which dopamine-influenced neurons may be most affected. Eight patients with PD and clinically significant levodopa-related mood fluctuations (mania, depression, or anxiety) were compared to 13 patients with similarly severe PD and fluctuations of motor function but not of mood. Regional cerebral blood flow (rCBF) was measured with positron emission tomography before and after levodopa (in the presence of carbidopa). The rCBF response to levodopa in medial frontal gyrus and posterior cingulate cortex (PCC) significantly differed between mood fluctuators and control patients (corrected p<0.02). Other regions with uncorrected p<0.001 in this comparison were cortical Brodmann areas 22, 40, 13, 11, and 28, hippocampus, and claustrum. The levodopa activation paradigm detected group differences not evident in a comparison of resting rCBF. Abnormalities of dopamine innervation may produce mood fluctuations via effects on PCC, an area strongly linked to mood and anxiety and with known rCBF responsiveness to levodopa or D2-like dopamine receptor agonists. We speculate that mood fluctuations may arise in parkinsonian patients who have abnormal dopaminergic modulation of caudate nucleus, anterior cingulate cortex, or orbital frontal cortex, all of which innervate PCC. The findings require confirmation in larger and better-matched groups.


Assuntos
Afeto/fisiologia , Antiparkinsonianos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Afeto/efeitos dos fármacos , Antiparkinsonianos/efeitos adversos , Feminino , Lateralidade Funcional , Humanos , Levodopa/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/fisiopatologia
7.
Brain Res Cogn Brain Res ; 20(3): 438-48, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15268921

RESUMO

Dopamine has been hypothesized to modulate response inhibition. To test this hypothesis, we used functional magnetic resonance imaging (fMRI) to measure the effects of the dopamine prodrug levodopa on the brain responses to a well-validated response inhibition task (go/no-go, or GNG). Since abnormalities of response inhibition and dopamine have been thought to underlie tics and other symptoms of Tourette syndrome, we studied 8 neuroleptic-naive adults with tic disorders as well as 10 well-matched healthy controls. Subjects were pretreated with the peripheral decarboxylase inhibitor carbidopa, then scanned during GNG and control blocks, both before and during i.v. levodopa infusion. Both groups had similar task performance and task-related regional brain activity before and during levodopa infusion. Levodopa did not affect reaction times or accuracy, so fMRI findings can be interpreted without concern that they simply reflect a performance difference between conditions. Levodopa did affect the magnitude of GNG-related fMRI responses in the right cerebellum and right parietal cortex, significantly reducing both. Pre-levodopa activity in the right cerebellum correlated with reaction times (higher magnitudes associated with faster reaction times), and pre-levodopa activity in the right parietal cortex correlated with false alarm rate (higher magnitudes associated with higher error). In summary, right parietal and cerebellar regions important in mediating specific aspects of the GNG task were modulated by levodopa, suggesting a region-specific role for dopamine in response inhibition.


Assuntos
Dopaminérgicos , Dopamina/fisiologia , Levodopa , Imageamento por Ressonância Magnética , Inibição Neural/efeitos dos fármacos , Síndrome de Tourette/fisiopatologia , Adulto , Carbidopa/efeitos adversos , Carbidopa/sangue , Cerebelo/efeitos dos fármacos , Cerebelo/fisiologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Dopaminérgicos/efeitos adversos , Dopaminérgicos/sangue , Feminino , Humanos , Levodopa/efeitos adversos , Levodopa/sangue , Masculino , Pessoa de Meia-Idade , Inibição Neural/fisiologia , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/fisiologia , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Síndrome de Tourette/diagnóstico
8.
J Neurosci Methods ; 127(1): 19-29, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12865145

RESUMO

Levodopa has several advantages as a pharmacological challenge agent for human neuroscience research. Exogenous levodopa changes striatal neuronal activity and increases extracellular dopamine concentrations, and with adequate inhibition of peripheral metabolism levodopa does not change mean cerebral blood flow. For neuroimaging studies of Parkinson disease (PD) and Tourette syndrome, we sought to rapidly produce a biologically relevant steady-state levodopa concentration and then maintain that concentration for at least an hour. We also wished to minimize side effects, even in individuals without prior levodopa treatment. We designed a two-stage intravenous infusion protocol based on published levodopa pharmacokinetic data. We report results of 125 infusions in 106 subjects, including healthy volunteers, PD patients, and people with chronic tics. At higher doses (target steady-state levodopa concentrations of 2,169 and 1,200 ng/ml), treatment-naive volunteers had unacceptably frequent side effects. The final infusion protocol, with a target steady-state concentration of 600 ng/ml, was well-tolerated (mild nausea in 11% of subjects was the only side effect occurring significantly more than in single-blind saline infusions), produced the desired plasma levodopa concentration (612+/-187 ng/ml, mean+/-S.D.), and produced statistically significant antiparkinsonian benefit (16% mean reduction in a standard rating of parkinsonian motor signs, P<0.0005).


Assuntos
Levodopa/administração & dosagem , Levodopa/sangue , Doença de Parkinson/sangue , Síndrome de Tourette/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbidopa/sangue , Feminino , Humanos , Infusões Intravenosas/métodos , Levodopa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Síndrome de Tourette/tratamento farmacológico
9.
F1000Res ; 2: 150, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24627787

RESUMO

BACKGROUND: Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use.  OBJECTIVE: Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable. METHODS: In 1998-2003 we conducted a four-week, double-blind, placebo-controlled, parallel group, fixed-dose trial of olanzapine (0, 2.5mg, or 5mg) in 23 PD patients with DIP while allowing for clinically realistic dose adjustments of dopaminomimetic mid-study. The primary outcome measures were Brief Psychiatric Rating Scale (BPRS) ratings scored from videotaped interviews after study termination by an observer blinded to dose assignment and to interview timing, and CGI (Clinical Global Impression). The Unified Parkinson's Disease Rating Scale motor subscale (UPDRS) was the primary measure of tolerability. RESULTS: Intention-to-treat analysis found no significant differences among treatment groups in study completion or serious adverse events. However, a disproportionate number of olanzapine vs. placebo subjects reported mild side effects (p<0.04), many citing motor worsening. Fourteen patients completed the study (seven on placebo, two on 2.5mg olanzapine, five on 5mg olanzapine). In study completers, analysis by repeated measures ANOVA revealed no significant difference between olanzapine and placebo groups in BPRS psychosis reduction (p=0.536), parkinsonism (p=0.608), or any other measured parameters (CGI, MMSE, Beck Depression Inventory, Hamilton Depression score, PDQ­39, Schwab-England ADL assessment, and sleep scores). CONCLUSION: This study adds to other evidence that olanzapine is ineffective in treating medication-induced psychosis in Parkinson disease.

10.
Neurology ; 81(6): 520-7, 2013 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-23825179

RESUMO

OBJECTIVE: To use principal component analyses (PCA) of Pittsburgh compound B (PiB) PET imaging to determine whether the pattern of in vivo ß-amyloid (Aß) in Parkinson disease (PD) with cognitive impairment is similar to the pattern found in symptomatic Alzheimer disease (AD). METHODS: PiB PET scans were obtained from participants with PD with cognitive impairment (n = 53), participants with symptomatic AD (n = 35), and age-matched controls (n = 67). All were assessed using the Clinical Dementia Rating and APOE genotype was determined in 137 participants. PCA was used to (1) determine the PiB binding pattern in AD, (2) determine a possible unique PD pattern, and (3) directly compare the PiB binding patterns in PD and AD groups. RESULTS: The first 2 principal components (PC1 and PC2) significantly separated the AD and control participants (p < 0.001). Participants with PD with cognitive impairment also were significantly different from participants with symptomatic AD on both components (p < 0.001). However, there was no difference between PD and controls on either component. Even those participants with PD with elevated mean cortical binding potentials were significantly different from participants with AD on both components. CONCLUSION: Using PCA, we demonstrated that participants with PD with cognitive impairment do not exhibit the same PiB binding pattern as participants with AD. These data suggest that Aß deposition may play a different pathophysiologic role in the cognitive impairment of PD compared to that in AD.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina , Doença de Parkinson/diagnóstico por imagem , Análise de Componente Principal/métodos , Tiazóis , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Ligação Proteica/fisiologia
11.
F1000Res ; 2: 207, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24715957

RESUMO

BACKGROUND: Prior brain imaging and autopsy studies have suggested that structural abnormalities of the basal ganglia (BG) nuclei may be present in Tourette Syndrome (TS). These studies have focused mainly on the volume differences of the BG structures and not their anatomical shapes.  Shape differences of various brain structures have been demonstrated in other neuropsychiatric disorders using large-deformation, high dimensional brain mapping (HDBM-LD).  A previous study of a small sample of adult TS patients demonstrated the validity of the method, but did not find significant differences compared to controls. Since TS usually begins in childhood and adult studies may show structure differences due to adaptations, we hypothesized that differences in BG and thalamus structure geometry and volume due to etiological changes in TS might be better characterized in children. OBJECTIVE: Pilot the HDBM-LD method in children and estimate effect sizes. METHODS: In this pilot study, T1-weighted MRIs were collected in 13 children with TS and 16 healthy, tic-free, control children. The groups were well matched for age.  The primary outcome measures were the first 10 eigenvectors which are derived using HDBM-LD methods and represent the majority of the geometric shape of each structure, and the volumes of each structure adjusted for whole brain volume. We also compared hemispheric right/left asymmetry and estimated effect sizes for both volume and shape differences between groups. RESULTS: We found no statistically significant differences between the TS subjects and controls in volume, shape, or right/left asymmetry.  Effect sizes were greater for shape analysis than for volume. CONCLUSION: This study represents one of the first efforts to study the shape as opposed to the volume of the BG in TS, but power was limited by sample size. Shape analysis by the HDBM-LD method may prove more sensitive to group differences.

12.
J Neuropsychiatry Clin Neurosci ; 14(4): 438-42, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12426412

RESUMO

Parkinson's disease (PD) patients commonly develop fluctuations in their motor responses to levodopa within several years of initiation of treatment; some also develop nonmotor fluctuations. The authors performed a case-control study comparing the frequency of comorbid symptoms in 70 PD patients who experienced clinically apparent mood changes during their motor "on" or "off" states with two control groups with no mood fluctuations. Mood fluctuators had significantly younger age at onset and longer disease duration and were significantly more likely to have dementia, psychosis, clinical depression, and motor complications. This association remained after removing effects of age and disease duration.


Assuntos
Transtornos do Humor/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Hipocinesia/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/diagnóstico , Transtornos do Humor/epidemiologia , Doença de Parkinson/epidemiologia , Doença de Parkinson/psicologia , Índice de Gravidade de Doença , Tremor/epidemiologia
13.
Biol Psychiatry ; 55(9): 916-25, 2004 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15110735

RESUMO

BACKGROUND: Dopamine agonists and antagonists can reduce abnormal movements and vocalizations (tics) in Tourette syndrome (TS); however, dopamine-responsive abnormal function in specific brain regions has not been directly demonstrated in TS. We sought to identify dopamine-modulated brain regions that function abnormally in TS by combining functional magnetic resonance imaging (fMRI), a working memory (WM) task, and infusion of the dopamine prodrug levodopa (while blocking dopamine production outside the brain). METHODS: We obtained complete fMRI data in 8 neuroleptic-naive adults with a chronic tic disorder and in 10 well-matched tic-free control subjects. RESULTS: Different task-sensitive brain regions responded differently to the WM task depending on levodopa status and diagnostic group (analysis of variance [ANOVA], p <.001). Four regions showed interactions with diagnosis (ANOVA, p <.001). In TS subjects, the task induced excessive brain activity in parietal cortex, medial frontal gyrus, and thalamus. Levodopa normalized the excess activity. In left parietal cortex, the degree of normalization was greater in patients with higher levodopa plasma concentrations (n = 6; Spearman's r = -.84, p =.04) and a greater degree of diagnostic confidence of TS (r = -.71, p =.05). CONCLUSIONS: These results are consistent with a dopamine-influenced functional abnormality of brain response in TS and suggest testable hypotheses about the mechanism by which dopamine antagonists and agonists alleviate tics.


Assuntos
Encéfalo/fisiopatologia , Terapia Cognitivo-Comportamental/métodos , Imageamento por Ressonância Magnética , Síndrome de Tourette/fisiopatologia , Síndrome de Tourette/terapia , Adulto , Antiparkinsonianos/uso terapêutico , Encéfalo/irrigação sanguínea , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Índice de Gravidade de Doença , Síndrome de Tourette/diagnóstico
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