Predictors of normal and abnormal outcome in clinical brain dopamine transporter imaging

Brain dopamine transporter (DAT) imaging with [123I]FP-CIT SPECT can be used to evaluate the integrity of the mesostriatal dopaminergic system in patients with clinically uncertain parkinsonism. To evaluate whether scanning a patient is clinically necessary, it is vital to understand possible factors that affect the scanning result. Therefore, we investigated an unselected sample of 538 consecutively scanned patients from a 6-year period, and the demographic data and indications for DAT SPECT were recorded. After scanning, the patients were divided into groups according to the scanning outcome. Multivariate binary logistic regression analyses were performed to investigate whether the pre-imaging variables had independent associations with the outcome of the scan. Three hundred and three (56.3 %) patients had abnormal scans showing a dopaminergic deficit. The independent factors associated with abnormal scans were older age (p = 0.002), asymmetry of motor symptoms (p = 0.005) and shorter symptom duration (p p = 0.004), whereas the possibility of medication-induced parkinsonism was associated with a higher probability of a normal scan (35.4 %, p = 0.036). The probability of an abnormal outcome in clinical brain DAT imaging increases with known risk factors of neurodegenerative parkinsonism. However, a long duration of uncertain motor symptoms and suspicion of medication-induced parkinsonism are associated with a higher probability of a normal outcome. The findings reflect epidemiological factors in parkinsonism together with referral biases that may be used to improve the clinical use of DAT imaging.</p

Beyond volume : A surface-based approach to bilingualism-induced grey matter changes

Bilingualism is a sustained experience associated with structural changes in cortical grey matter (GM) morphology. Apart from a few studies, a dominant method used to assess bilingualism-induced GM changes has been the voxel-based morphometry (VBM) analysis. While VBM is sensitive to GM volume/density differences in general, it cannot be used to identify whether the observed difference is due to relative changes in, e.g., cortical thickness, area or folding, as it uses a single combined measure of them all. Here, we used surface-based analysis (SBA) approach to investigate whether early acquisition of a second language (L2) affects the cortical GM morphology relative to late L2 acquisition. More specifically, our aim was to test a hypothesis that early acquisition of two languages induces GM changes that are predominantly surface area-driven, while late acquisition is supposedly characterised with primarily thickness-driven changes. To this end, several surface-based measures were concurrently compared between the groups. In line with the hypothesis, the results revealed that early bilingual experience is associated with significantly extended cortical surface area over the left pars opercularis and the right superior temporal gyrus. Contrary to our expectations, however, we found no evidence supporting the postulated association between late L2 acquisition and increased cortical thickness. Nevertheless, our study highlights the importance of including cortical surface measures when investigating bilingualism related GM modulations.Peer reviewe

Lesion network localization of free will

Our perception of free will is composed of a desire to act (volition) and a sense of responsibility for our actions (agency). Brain damage can disrupt these processes, but which regions are most important for free will perception remains unclear. Here, we study focal brain lesions that disrupt volition, causing akinetic mutism (n = 28), or disrupt agency, causing alien limb syndrome (n = 50), to better localize these processes in the human brain. Lesion locations causing either syndrome were highly heterogeneous, occurring in a variety of different brain locations. We next used a recently validated technique termed lesion network mapping to determine whether these heterogeneous lesion locations localized to specific brain networks. Lesion locations causing akinetic mutism all fell within one network, defined by connectivity to the anterior cingulate cortex. Lesion locations causing alien limb fell within a separate network, defined by connectivity to the precuneus. Both findings were specific for these syndromes compared with brain lesions causing similar physical impairments but without disordered free will. Finally, our lesion-based localization matched network localization for brain stimulation locations that disrupt free will and neuro-imaging abnormalities in patients with psychiatric disorders of free will without overt brain lesions. Collectively, our results demonstrate that lesions in different locations causing disordered volition and agency localize to unique brain networks, lending insight into the neuroanatomical substrate of free will perception

Survival in Parkinson's disease in relation to striatal dopamine transporter binding

Objective: To investigate whether dopamine transporter (DAT) binding, as measured with single photon emission computed tomography (SPECT), can be used to predict mortality in patients with Parkinson's disease (PD). Methods: A total of 162 patients with PD and abnormal [I-123]FP-CIT SPECT were clinically followed for a median of 5.8 years. A multivariate Cox regression model was used to investigate survival with the independent predictors of age, gender, severity of motor impairment, levodopa-equivalent daily dose of medication, presence of cognitive defects, and putaminal specific binding ratio (SBR) of [I-123]FP-CIT. In addition, associations between striatal and extrastriatal SBRs and survival were investigated using voxel-based analyses.Results: The overall mortality was 25.9%, and the Kaplan-Meier estimate for mortality was 36%. Older age (P< 0.001), presence of cognitive defects (P = 0.001), and more severe motor symptom severity (P = 0.002) were significantly associated with increased mortality. No associations were found between putaminal DAT binding and survival (P = 0.99). There were no significant differences in SBRs in any striatal or extrastriatal region between survivors and non-survivors, and no associations were found between SBRs and scan-to-death intervals among non-survivors.Conclusions: Unlike the severity of motor and cognitive symptoms, the level of striatal dopaminergic defect in DAT SPECT does not predict mortality in PD. Although presynaptic dopaminergic functional imaging may have value as a diagnostic tool, the clinical symptom-based characteristics are superior for predicting lifespan. (c) 2017 Elsevier Ltd. All rights reserved

Ventral striatal dopaminergic defect is associated with hallucinations in Parkinson's disease

ConclusionsLow striatal DAT function may predispose PD patients to VHs, and the regional distribution of the findings suggests a particular role of the ventral striatum. This is in line with non-PD research that has implicated ventral striatal dysfunction in psychosis.</p

Electric field-navigated transcranial magnetic stimulation for chronic tinnitus: a randomized, placebo-controlled study

Objective: Repetitive transcranial magnetic stimulation (rTMS) may alleviate tinnitus. We evaluated effects of electric field (E-field) navigated rTMS targeted according to tinnitus pitch. No controlled studies have investigated anatomically accurate E-field-rTMS for tinnitus. Design: Effects of E-field-rTMS were evaluated in a prospective randomised placebo-controlled 6-month follow-up study on parallel groups. Patients received 10 sessions of 1Hz rTMS or placebo targeted to the left auditory cortex corresponding to tonotopic representation of tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3 and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100) for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap Inventory (THI). Study sample: Thirty-nine patients (mean age 50.3 years). Results: The mean tinnitus intensity (F-3=15.7, p<0.0001), annoyance (F-3=8.8, p=0.0002), distress (F-3=9.1, p=0.0002) and THI scores (F-4=13.8, p<0.0001) decreased in both groups over time with non-significant differences between the groups. After active rTMS, 42% and 37% of the patients showed excellent response at 1 and 3 months against 15% and 10% in the placebo group (p=0.082 and p=0.065). Conclusions: Despite the significant effects of rTMS on tinnitus, differences between active and placebo groups remained non-significant, due to large placebo-effect and wide inter-individual variation

Visual versus automated analysis of [I-123]FP-CIT SPECT scans in parkinsonism

The clinical evaluation of dopamine transporter (DAT) SPECT scans typically relies on visual analysis in combination with an automated semi-quantitative method. The interpretation of the results may be difficult in cases that show disagreement between the two methods on the borderline of abnormality. The frequency and clinical characteristics of such cases are unclear. Automated semi-quantitative analyses and independent visual analyses by two experienced nuclear medicine physicians and four inexperienced raters were performed for 120 patients with clinically uncertain parkinsonism scanned with brain [I-123]FP-CIT SPECT. Agreement was evaluated with kappa statistics. The clinical characteristics of patients who had discrepant findings between the two analysis methods were investigated. The expert raters outperformed nonexperts in terms of agreement between visual and automated analyses (kappa = 0.66, 0.72 vs. 0.23-0.54) and between raters (kappa = 0.81 vs. 0.44-0.63). Twelve patients showed discrepant findings between the visual and automated analyses. These patients were older compared to other patients (p = 0.023), had 17.6 % lower mean striatal tracer binding compared to normal scans (p = 0.003) and 62.7 % higher compared to abnormal scans (p < 0.001). After a minimum of 4.5 years of clinical follow-up, none of these patients developed neurodegenerative parkinsonism. Clinical DAT SPECT scans show discrepancies between visual and automated analyses in 10 % of cases. The patients with discrepant findings are older, show normal to slightly abnormal tracer binding, and importantly, do not develop neurodegenerative parkinsonism syndromes. Visual analyses by experienced raters are reliable, but the diagnostic accuracy in discrepant cases can be improved by an automated method

Psychiatric (Axis I) and personality (Axis II) disorders and subjective psychiatric symptoms in chronic tinnitus

Objective: Chronic tinnitus has been associated with several psychiatric disorders. Only few studies have investigated these disorders using validated diagnostic interviews. The aims were to diagnose psychiatric and personality disorders with structured interviews, to assess self-rated psychiatric symptoms and elucidate temporal relations between psychiatric disorders and tinnitus. Design: Current and lifetime DSM-IV diagnoses of axis-I (psychiatric disorders) and axis-II (personality disorders) were assessed using structured clinical interviews (SCID-I and -II). Current subjective psychiatric symptoms were evaluated via self-rating instruments: the Symptom Check List-90 (SCL-90), the Beck Depression Inventory, and the Dissociative Experiences Scale (DES). Study sample: 83 patients (mean age 51.7, 59% men) with chronic, disturbing tinnitus and a median Tinnitus Handicap Inventory score of 32. Results: The rates of lifetime and current major depression were 26.5% and 2.4%. The lifetime rate of obsessive-compulsive personality disorder (type C) was 8.4%. None of the patients had cluster B personality disorder or psychotic symptoms. The SCL-90 subscales did not differ from the general population, and median DES score was low, 2.4. Conclusions: Tinnitus patients are prone to episodes of major depression and often also have obsessive-compulsive personality features. Psychiatric disorders seem to be comorbid or predisposing conditions rather than consequences of tinnitus.Clinical trial reference: ClinicalTrials.gov (ID NCT 01929837).</p