Posterior Putamen Research Articles

Efficiency of 123I-ioflupane SPECT as the marker of basal ganglia damage in acute methanol poisoning: 6-year prospective study

Context Investigate whether 123I-ioflupane SPECT (DaT SPECT) has the potential as a marker of basal ganglia damage in acute methanol poisoning. Methods Prospective, single-centre, cohort study of patients with confirmed methanol poisoning was conducted. DaT SPECT was performed twice with semi-quantification using DaTQUANTTM and MRI-based volumetry was calculated. Specific binding ratios (SBR) of striatum, caudate nucleus, and putamen were correlated with laboratory parameters of outcome, volumetric data, and retinal nerve fibres layer (RNFL) thickness measurements. Results Forty-two patients (mean age 46.3 ± 4.2 years; 8 females), including 15 with MRI-detected putamen lesions (group I) and 27 patients with intact putamen (group II), underwent DaT SPECT. Volumetry was calculated in 35 of the patients assessed. SBR values for the left putamen correlated with putamen volume (r = 0.665; p < 0.001). Decreased bilateral SBR values were determined for the striatum and the putamen, but not for the nucleus caudate, in group I (p < 0.05). Significant correlation was observed between the SBR of the posterior putamen and arterial blood pH (r = 0.574; p < 0.001) and other toxicological parameters of severity of poisoning/outcome including serum lactate, glucose, and creatinine concentrations (p < 0.05). The SBR of the posterior putamen positively correlated with the global RNFL thickness (p < 0.05). ROC analysis demonstrated a significant discriminatory ability of SBR of the posterior putamen with AUC = 0.753 (95%CI 0.604–0.902; p = 0.007). The multivariate regression model demonstrated that arterial blood pH, age, and gender were the most significant factors associated with SBR of the posterior putamen. Conclusion DaT SPECT demonstrates significant potential for the diagnosis of methanol-induced basal ganglia damage.

Right Posterior Insula and Putamen Volume Mediate the Effect of Oxytocin Receptor Polygenic Risk for Autism Spectrum Disorders on Reward Dependence in Healthy Adults.

Much evidence indicates the influence of the oxytocin receptor (OXTR) gene on autism spectrum disorders (ASDs), a set of disorders characterized by a range of deficits in prosocial behaviors, which are closely related to the personality trait of reward dependence (RD). However, we do not know the effect of the OXTR polygenic risk score for ASDs (OXTR-PRSASDs) on RD and its underlying neuroanatomical substrate. Here, we aimed to investigate associations among the OXTR-PRSASDs, gray matter volume (GMV), and RD in two independent datasets of healthy young adults (n = 450 and 540). We found that the individuals with higher OXTR-PRSASDs had lower RD and significantly smaller GMV in the right posterior insula and putamen. The GMV of this region showed a positive correlation with RD and a mediation effect on the association between OXTR-PRSASDs and RD. Moreover, the correlation map between OXTR-PRSASDs and GMV showed spatial correlation with OXTR gene expression. All results were highly consistent between the two datasets. These findings highlight a possible neural pathway by which the common variants in the OXTR gene associated with ASDs may jointly impact the GMV of the right posterior insula and putamen and further affect the personality trait of RD.

Shared functional neural substrates in Parkinson's disease and drug-induced parkinsonism: association with dopaminergic depletion

While drug-induced parkinsonism (DIP) is mainly caused by blockage of the dopaminergic pathway, multiple neurotransmitter systems besides the dopaminergic system are involved in Parkinson’s disease (PD). Therefore, alterations found in both DIP and PD might be manifestations of dopaminergic dysfunction. To prove this hypothesis, we aimed to define the areas commonly involved in DIP and PD and determine whether the overlapping areas were associated with the dopaminergic system. 68 PD patients, 69 DIP patients and 70 age-and sex-matched controls underwent resting-state functional MRI (rsfMRI). Regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF were calculated and compared. Afterwards, we compared mean rsfMRI values extracted from the overlapping areas with uptake quantitatively measured on dopamine transporter (DAT) images and neuropsychological test results. Compared to the controls, both PD and DIP patients revealed altered rsfMRI values in the right insular cortex, right temporo-occipital cortex, and cerebellum. Among them, decreased ALFF in the right insular cortex and decreased ReHo in the right occipital cortex were correlated with decreased DAT uptake in the caudate as well as executive, visuospatial, and language function. Increased ReHo in the cerebellum was also correlated with decrease DAT uptake in the posterior and ventral anterior putamen, but not with cognitive function. In conclusion, the insular cortex, occipital cortex, and cerebellum were commonly affected in both PD and DIP patients and might be associated with altered dopaminergic modulation.

Structural and functional brain alterations in patients with idiopathic rapid eye movement sleep behavior disorder

ObjectiveTo investigate structural and functional alterations in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) compared with healthy controls. MethodsTwenty-seven patients with polysomnography-confirmed iRBD and 33 healthy subjects were recruited. All subjects underwent a 3-tesla structural and resting-state functional magnetic resonance imaging (fMRI) examination. Voxel-based morphometry (VBM) analysis was performed to assess grey matter alterations between groups. The amplitude of low-frequency fluctuations (ALFF) was calculated and then compared to measure differences in spontaneous brain activity. Correlations were performed to explore associations between imaging metrics and clinical characteristics in iRBD patients. ResultsCompared with healthy controls, patients with iRBD had decreased grey matter volume in the frontal, temporal, parietal, occipital cortices as well as increased grey matter volume in cerebellum posterior lobe, putamen, and thalamus. Patients with iRBD also exhibited increased ALFF values in the right parahippocampal gyrus. Olfaction correlated with ALFF value changes in occipital cortices. ConclusionsPatients with iRBD had widespread decreases of grey matter volume. Increases of grey matter volume in cerebellum, putamen, and thalamus may suggest a compensatory effect, while the altered ALFF values in parahippocampal gyrus and occipital cortices may play a role in the underlying process of neurodegeneration in this disorder.

Ioflupane 123I (DAT scan) SPECT identifies dopamine receptor dysfunction early in the disease course in progressive apraxia of speech

To describe 123I-FP-CIT (DAT scan) SPECT findings in progressive apraxia of speech (PAOS) patients and to compare those findings with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). PAOS is a neurodegenerative syndrome in which patients present with apraxia of speech, a motor speech disorder affecting programming and planning of speech. Patients with PAOS predictably develop Parkinsonism. DAT scan is a neuroimaging tool that assesses the integrity of presynaptic dopamine transporters in striatum and is usually abnormal in PSP and CBS. As part of an NIH-funded grant, we performed a DAT scan on 17 PAOS patients early in the disease course. DaTQUANT software was used to quantify uptake in the left and right caudate and anterior/posterior putamen, with striatum to background ratios (SBRs). The PAOS cohort was compared to 15 PSP and 8 CBS patients. Five PAOS patients (29%) showed abnormalities in at least one striatal region on DAT scan. When the five PAOS patients with abnormal DAT were compared to the PSP and CBS patients, the only difference observed was lower uptake in the posterior putamen in PSP (p = 0.03). There were no differences is putamen/caudate ratio or in symmetry of uptake, across all groups. There was also no difference in MDS-UPDRS-III scores between PAOS patients with and without abnormal DAT scans (p = 0.56). Abnormal DAT scan is observed early in the disease course in approximately 30% of PAOS patients, with striatal abnormalities similar to those in PSP and CBS.

Chronic Neuroleptic-Induced Parkinsonism Examined With Positron Emission Tomography.

Neuroleptic drug-induced parkinsonism (NIP) is a leading cause of parkinsonism, particularly in aging. Based on abnormal dopamine transporter scan results, individuals displaying chronic NIP are often diagnosed with Lewy-body Parkinson's disease (PD), but this assumption needs further substantiation. To quantitate the profile of striatal dopaminergic nerve terminal density in NIP relative to PD. We used the positron emission tomography ligand [11 C](+)-dihydrotetrabenazine targeting vesicular monoamine transporter type 2 (VMAT2) binding sites and collected various clinical parameters (motor ratings, olfaction, polysomnography to document rapid eye movement sleep muscle activity, quantitative sensory testing for pain thresholds) possibly predicting binding results in patients older than age 50 living with schizophrenia spectrum disorders under long-term stable antipsychotic drug treatment, with (N = 11) or without (N = 11) chart documention of chronic NIP, and compared them to healthy volunteers (N = 11) and others medicated for PD (N = 12). Striatal VMAT2 binding was dichotomous in the NIP group between those with spared (N = 5) or low (N = 6) PD-like values. Striatal binding reduction in the low VMAT2-NIP group was asymmetric without the gradient of maximal involvement in the posterior putamen typical of PD. Anosmia was the only nonmotor parameter measured matching the abnormal striatal VMAT2 binding status. These preliminary observations suggest that striatal VMAT2 binding is abnormal in a fraction of chronic NIP cases and differs in spatial distribution from PD. The possibility of a drug-induced axonopathy and resultant synaptopathy, as well as the evolution of the binding deficit, warrant further longitudinal studies in a large cohort. © 2020 International Parkinson and Movement Disorder Society.

Which Effects on Neuroanatomy and Path-Integration Survive? Results of a Randomized Controlled Study on Intensive Balance Training.

Balancing is a complex task requiring the integration of visual, somatosensory and vestibular inputs. The vestibular system is linked to the hippocampus, a brain structure crucial for spatial orientation. Here we tested the immediate and sustained effects of a one-month-long slackline training program on balancing and orientation abilities as well as on brain volumes in young adults without any prior experience in that skill. On the corrected level, we could not find any interaction effects for brain volumes, but the effect sizes were small to medium. A subsequent within-training-group analysis revealed volumetric increments within the somatosensory cortex and decrements within posterior insula, cerebellum and putamen remained stable over time. No significant interaction effects were observed on the clinical balance and the spatial orientation task two months after the training period (follow-up). We interpret these findings as a shift away from processes crucial for automatized motor output towards processes related to voluntarily controlled movements. The decrease in insular volume in the training group we propose to result from multisensory interaction of the vestibular with the visual and somatosensory systems. The discrepancy between sustained effects in the brain of the training group on the one hand and transient benefits in function on the other may indicate that for the latter to be retained a longer-term practice is required.

Confirmation of 123I-FP-CIT SPECT Quantification Methods in Dementia with Lewy Bodies and Other Neurodegenerative Disorders.

Our rationale was to conduct a retrospective study comparing 3 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) SPECT quantitative methods in patients with neurodegenerative syndromes as referenced to neuropathologic findings. Methods:123I-FP-CIT-SPECT and neuropathologic findings among patients with neurodegenerative syndromes from the Mayo Alzheimer Disease Research Center and Mayo Clinic Study of Aging were examined. Three 123I-FP-CIT SPECT quantitative assessment methods-MIMneuro, DaTQUANT, and manual region-of-interest creation on a workstation-were compared with neuropathologic findings describing the presence or absence of Lewy body disease (LBD). Striatum-to-background ratios (SBRs) generated by DaTQUANT were compared with the calculated SBRs of the manual method and MIMneuro. The left and right SBRs for caudate, putamen, and striatum were evaluated with the manual method. For DaTQUANT and MIMneuro, the left, right, total, and average SBRs and z scores for whole striatum, caudate, putamen, anterior putamen, and posterior putamen were calculated. Results: The cohort included 24 patients (20 [83%] male, mean age for all patients at death, 75.4 ± 10.0 y). The antemortem clinical diagnoses were Alzheimer disease dementia (n = 6), probable dementia with Lewy bodies (n = 12), mixed Alzheimer disease dementia and probable dementia with Lewy bodies (n = 1), Parkinson disease with mild cognitive impairment (n = 2), corticobasal syndrome (n = 1), idiopathic rapid-eye-movement sleep behavior disorder (n = 1), and behavioral-variant frontotemporal dementia (n = 1). Seventeen (71%) had LBD. All 3 123I-FP-CIT SPECT quantitative methods had an area under the receiver-operating-characteristics curve ranging from more than 0.93 to up to 1.000 (P < 0.001) and showed excellent discrimination between LBD and non-LBD patients in each region assessed (P < 0.001). There was no significant difference between the accuracy of the regions in discriminating the 2 groups, with good discrimination for both caudate and putamen. Conclusion: All 3 123I-FP-CIT SPECT quantitative methods showed excellent discrimination between LBD and non-LBD patients in each region assessed, using both SBRs and z scores.

Dopaminergic Depletion, β-Amyloid Burden, and Cognition in Lewy Body Disease.

We aimed to determine the association between striatal dopaminergic depletion, cerebral β-amyloid deposition, and cognitive dysfunction in Lewy body disease (LBD). This cross-sectional study recruited 48 LBD patients (30 with dementia, 18 with mild cognitive impairment) and 15 control subjects from a university-based hospital. We measured the striatal dopamine transporter (DAT) activity and regional β-amyloid burden using N-(3-[18 F]fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography (PET) and 18 F-florbetaben (FBB) PET, respectively. The relationship between striatal FP-CIT uptake, regional cortical FBB uptake, and cognitive function scores was evaluated using path analyses. We also investigated the effects of striatal FP-CIT uptake and cortical FBB uptake on the interval between motor symptom and dementia onset. Reduced striatal FP-CIT uptake was associated with increased FBB uptake in the posterior cortical regions, most prominently in the occipital cortices. Reduced FP-CIT uptake in the anterior putamen was associated with visuospatial dysfunction with mediation of increased occipital FBB uptake. Reduced FP-CIT uptake in the posterior putamen and an increased parietal FBB uptake were independently associated with memory dysfunction. Reduced striatal FP-CIT uptake was associated with attention, language, and frontal/executive dysfunction, independent of amyloid deposition. Increased FBB uptake, especially in the parietal cortex, was associated with earlier onset of dementia. Our results suggest that occipital β-amyloid deposition may contribute to the association between striatal dopaminergic depletion and visuospatial dysfunction in LBD patients. Although the effects of reduced DAT activity are more prominent than those of β-amyloid burden on cognitive dysfunction, the latter affects the onset of cognitive dysfunction. ANN NEUROL 2020;87:739-750.

The neurobehavioral mechanisms of motivational control in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) poses debilitating impairments in the neurobehavioral systems governing reward-related processes—key to the control of motivated behaviors. Individuals with ADHD may rely on a motivational control system that favors cue-driven habits—rooted in the posterior putamen—over caudate and prefrontal cortex-driven goal-directed behaviors. We examined the neurobehavioral correlates of motivational control in ADHD. Twenty-five adults with ADHD and 25 neurotypicals underwent fMRI while training on two stimulus–response–outcome associations. A devaluation procedure followed, whereby they were selectively satiated on one of the snack outcomes, decreasing its value. A subsequent extinction test determined outcome-sensitivity (i.e., whether responses towards devalued snack diminished). Despite behavioral similarities, the ADHD group displayed a distinct neural signature marked by enhanced posterior putamen activation as a function of training. This region also displayed diminished functional connectivity with the dorsal anterior cingulate cortex, which is associated with top-down control. Our whole-brain analysis yielded ADHD-specific posterior putamen and opercular/insular cortex activity over the course of training—regions associated with stimulus-sensitivity and maladaptively rigid behaviors, respectively. Neural comparisons also identified hyper-recruitment of the hippocampus in the ADHD group. These results highlight corticostriatal discrepancies in ADHD, possibly serving as a biomarker of the disorder.

The Relationship Between the Striatal Dopaminergic Neuronal and Cognitive Function With Aging

Both cognitive function and striatal dopamine function decline by normal aging. However, the relationship among these three factors remains unclear. The aim of this study was to elucidate the association among age-related changes in the striatal dopamine transporter (DAT) and cognitive function in healthy subjects. The 30 healthy volunteers were enrolled in this research, the age ranged from 41 to 82 (64.5 ± 11.5, mean ± SD). All subjects were scanned with both T1-weighted magnetic resonance imaging (MRI) and 123I-FP-CIT single-photon emission computed tomography (SPECT) images. The Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) was used to evaluate cognitive function. Six spherical regions of interest (ROI) using 10 mm in diameter on the caudate nucleus, anterior putamen and posterior putamen were manually drawn on MRI image which was applied onto SPECT image. The relationship between striatal occipital ratio (SOR) values and WAIS-III subscore were analyzed by multiple regression analysis. Subscores which was significant were further analyzed by path analyses. Full intelligence quotient (IQ), verbal IQ, verbal comprehension were all positively correlated with age-adjusted striatal DAT binding (P < 0.01). Multiple regression analyses revealed that the coding digit symbol correlated with all striatal regions except for the left caudate (P < 0.04). Picture completion and right caudate, similarities and left caudate also showed a positive correlation (P < 0.04). Path analysis found that the right caudate and picture completion; the left caudate and similarities were correlated independently from age, whereas the models of coding digit symbol were not significant. These results suggest that age-based individual diversity of striatal DAT binding was associated with verbal function, and the caudate nucleus plays an important role in this association.

The effect of distress on the balance between goal-directed and habit networks in obsessive-compulsive disorder

The classical cognitive-behavioral theory of obsessive-compulsive disorder (OCD) holds that compulsions are performed to reduce distress that is evoked by obsessions, whereas a recent neuroscience-inspired theory suggests that compulsivity results from a disbalance between goal-directed and habit-related neural networks. To bridge these theories, we investigated whether the balance between goal-directed and habit networks in patients with OCD was affected during psychological distress. Twenty-three OCD patients and twenty-three healthy controls participated in a controlled stress induction paradigm using the socially evaluated cold-pressor test in a crossover design. Stress responses were evaluated through cortisol levels, blood pressure, and anxiety ratings. Functional connectivity of the caudate nucleus and posterior putamen was assessed using seed region analysis of resting-state functional magnetic resonance imaging data, which are hubs of the goal-directed and habit network, respectively. Stress induction increased blood pressure and psychological stress measures across groups and resulted in blunted cortisol responses in patients. Furthermore, patients showed a blunted reduction in connectivity between the caudate nucleus and precuneus during psychological distress, which was positively correlated with compulsivity but not obsession severity. The posterior putamen showed no significant group differences in distress-induced connectivity. These results suggest that compulsivity in OCD is associated with altered connectivity between the goal-directed and default mode networks during psychological distress.

Sex-dependent association of urate on the patterns of striatal dopamine depletion in Parkinson's disease.

The aim was to investigate the relationship between the serum urate (UA) levels and patterns of striatal dopamine depletion in patients with de novo Parkinson's disease (PD). In all, 167 de novo PD patients who underwent 18 F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane positron emission tomography scans were enrolled. After quantifying dopamine transporter (DAT) availability in each striatal subregion, sex-dependent patterns of striatal dopamine depletion were analysed by measuring (i) dopamine depletion in the other striatal subregions and posterior putamen (intersubregional ratio, ISR) and (ii) the interhemispheric asymmetry of dopamine depletion in the posterior putamen (asymmetric ratio, AR). The interaction analysis revealed a significant interaction effect of sex and serum UA levels on the ISR but not on the AR. The ISR was negatively correlated with the serum UA levels in all patients with PD (r=-0.156, P=0.045), and this association was more prominent in male PD patients (r=-0.422, P<0.001). However, no significant association between the AR and serum UA levels was found in any of the patients. In addition, serum UA levels were significantly associated with DAT availability in the posterior putamen on both the more affected side (r=0.312, P=0.005) and the less affected side (r=0.312, P=0.005) only in male PD patients. The present study demonstrated the potentially close sex-specific relationship between the serum UA levels and the anterior-posterior gradient of DAT patterns, suggesting a sex-specific protective effect of UA on nigrostriatal dopaminergic neurons in de novo PD.

Network degeneration in Parkinson's disease: multimodal imaging of nigro-striato-cortical dysfunction.

The spreading hypothesis of neurodegeneration assumes an expansion of neural pathologies along existing neural pathways. Multimodal neuroimaging studies have demonstrated distinct topographic patterns of cerebral pathologies in neurodegeneration. For Parkinson's disease the hypothesis so far rests largely on histopathological evidence of α-synuclein spreading in a characteristic pattern and progressive nigrostriatal dopamine depletion. Functional consequences of nigrostriatal dysfunction on cortical activity remain to be elucidated. Our goal was to investigate multimodal imaging correlates of degenerative processes in Parkinson's disease by assessing dopamine depletion and its potential effect on striatocortical connectivity networks and cortical metabolism in relation to parkinsonian symptoms. We combined 18F-DOPA-PET, 18F-fluorodeoxyglucose (FDG)-PET and resting state functional MRI to multimodally characterize network alterations in Parkinson's disease. Forty-two patients with mild-to-moderate stage Parkinson's disease and 14 age-matched healthy control subjects underwent a multimodal imaging protocol and comprehensive clinical examination. A voxel-wise group comparison of 18F-DOPA uptake identified the exact location and extent of putaminal dopamine depletion in patients. Resulting clusters were defined as seeds for a seed-to-voxel functional connectivity analysis. 18F-FDG metabolism was compared between groups at a whole-brain level and uptake values were extracted from regions with reduced putaminal connectivity. To unravel associations between dopaminergic activity, striatocortical connectivity, glucose metabolism and symptom severity, correlations between normalized uptake values, seed-to-cluster β-values and clinical parameters were tested while controlling for age and dopaminergic medication. Aside from cortical hypometabolism, 18F-FDG-PET data for the first time revealed a hypometabolic midbrain cluster in patients with Parkinson's disease that comprised caudal parts of the bilateral substantia nigra pars compacta. Putaminal dopamine synthesis capacity was significantly reduced in the bilateral posterior putamen and correlated with ipsilateral nigral 18F-FDG uptake. Resting state functional MRI data indicated significantly reduced functional connectivity between the dopamine depleted putaminal seed and cortical areas primarily belonging to the sensorimotor network in patients with Parkinson's disease. In the inferior parietal cortex, hypoconnectivity in patients was significantly correlated with lower metabolism (left P = 0.021, right P = 0.018). Of note, unilateral network alterations quantified with different modalities corresponded with contralateral motor impairments. In conclusion, our results support the hypothesis that degeneration of nigrostriatal fibres functionally impairs distinct striatocortical connections, disturbing the efficient interplay between motor processing areas and impairing motor control in patients with Parkinson's disease. The present study is the first to reveal trimodal evidence for network-dependent degeneration in Parkinson's disease by outlining the impact of functional nigrostriatal pathway impairment on striatocortical functional connectivity networks and cortical metabolism.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

Striatal dopamine deficits play a key role in the pathogenesis of Parkinson's disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson’s disease

BackgroundResting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson’s disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. ObjectivesTo examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. MethodsWe assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using 11C-PE2I PET in thirty-four PD patients at baseline. Of these, twenty PD patients were rescanned after 19.9 ± 3.8 months. A seed-based approach was used to analyze resting-state fMRI data. 11C-PE2I binding potential (BPND) was calculated for each participant. PD patients were assessed for disease severity. ResultsAt baseline, PD patients with greater dopaminergic deficits, as measured with 11C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. ConclusionsOur findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression.

Effect of various blood glucose levels on regional FDG uptake in the brain.

Objective(s):Studies have mainly assessed the effect of hyperglycemia on 18F-fluorodeoxyglucose (FDG) uptake in the brain. In this study, we assessed the FDG uptake of the brain not only in normo- and hyperglycemia but also in hypoglycemia to compare the effect of various blood glucose levels on regional FDG uptake in the brain.Methods:This retrospective study was conducted on whole-body FDG positron emission tomography/computed tomography (PET/CT) images including the brain. The inclusion criteria included adult patients with no known history of diseases or symptoms affecting the brain, lack of abnormal brain findings on both PET and CT images, no image artifacts, and lack of any factors affecting brain FDG uptake. Maximum standardized uptake values (SUVmax) were measured in the lateral and medial frontal, temporal, parietal, and occipital cortices, lateral cerebellar cortex, posterior cingulate cortex, caudate nucleus, putamen, thalamus, brain stem (BS), and scalp in patients with normal (91-100 mg/dl), low (61-70 mg/dl), and high (171-200 mg/dl) blood glucose (BG) levels. Mean SUVmax of the brain regions for each BG range was calculated and statistically analyzed.Results:In all BG levels, FDG uptake was at the highest level in the lateral frontal cortex and lowest level in the medial temporal cortex (MTC) and BS. The SUVmax in all assessed brain regions was significantly lower in hyperglycemia (P<0.001). However, this value was not significantly different in hypoglycemia (P>0.05) as compared to that in normoglycemia. At the BG range of 171-200 mg/dl, hyperglycemia-induced reduction in regional SUVmax had a range of 55.9-63.7% (60%±2.4%). This reduction was below 60% in the MTC, cerebellum, and BS and above 60% in other regions. Scalp activity was lower in hyperglycemia (P<0.001) and not different in hypoglycemia (P>0.05) as compared to normoglycemia.Conclusion:The FDG uptake appears to be at the highest level in the lateral frontal cortex and the lowest level in the MTC and BS in normo-, hypo-, and hyperglycemia. Hyperglycemia-induced reduction in FDG uptake was approximately the same as that in various regions of the brain. However, the MTC, cerebellum, and BS may be slightly less affected than the other regions. Hypoglycemia does not seem to have a significant effect on FDG uptake in the brain.

Intrastriatal gradient analyses of 18F-FDOPA PET scans for differentiation of Parkinsonian disorders.

L -3,4-dihydroxy-6-18F-fluorophenylalanine (18F-DOPA PET may be used to distinguish subjects with Parkinsonism fromthose with symptoms not originating from impaired dopaminergic transmission. However, it is not routinely utilized to discriminate Idiopathic Parkinson's disease (IPD) from Atypical Parkinsonian Disorders (APD). We investigated the potential of FDOPA PET to discriminate between IPD and APD, with a focus on the anterior-to-posterior decline in het striatum, considered to be more specific for IPD. 18F-DOPA PET data from a total of 58 subjects were retrospectively analyzed. 28 subjects had idiopathic Parkinson's disease (14 male, 14 female; age at scan 61 +- 11,5), 13 atypical Parkinsonian disease (7 male, 6 females; age at scan: 69,6 +- 6,4) and 17 were controls (6 male, 11 female; age at scan 65,3 +-8,6). Regional striatal-to-occipital ratio's (RSOR's) were calculated, as well as multiple in-line VOI's from the caudate nucleus to the posterior part of the putamen. The linearity of anteroposterior decline was determined by a linear regression fit and associated R squared values. ROC curves were calculated to assess the diagnostic performance of these measurements. Data contralateral to the clinically most affected side were used for analysis. ROC curve analysis for differentiation between controls and Parkinsonism patients showed the highest AUC for the caudate nucleus-to-posterior putamen ratio (AUC=0.930; p<0.00) and for the R squared value for the linear regression fit (AUC=0.948; p=0.006). For discrimating IPD from APD, the highest AUC was found for the caudate nucleus-to-anterior putamen ratio (0.824; p<0.001) CONCLUSIONS: Subregional analysis of the striatum in F-DOPA PET scans may provide additional diagnostic information in patients screened for a presynaptic dopaminergic deficit. A more linear decrease from the head of the caudate nucleus to the posterior putamen was present in patients with IPD, although this feature did not have additional diagnostic value over the RSOR analysis.

Olfactory dysfunction correlates with putaminal dopamine turnover in early de novo Parkinson's disease.

Although olfactory dysfunction is one of the most well-established prodromal symptoms in Parkinson's disease (PD), its correlation with clinical disease progression or dopaminergic dysfunction still remains unclear. We here evaluated the association of striatal dopamine metabolism and olfactory function in a homogenous cohort of 30 patients with early untreated de novo PD. Striatal dopamine metabolism was assessed by the extended 18Fluorodopa PET scanning protocol to measure 18Fluorodopa uptake (Kocc) and the effective dopamine distribution volume ratio (EDVR) as the inverse of dopamine turnover. Olfactory function was estimated by the "Sniffin' Sticks" test including odor threshold (T), discrimination (D) and identification (I) assessment. We detected moderate correlations of the EDVR in the posterior putamen with the TDI composite score (r = 0.412; p = 0.024; Pearson's correlation test) and the odor identification score (r = 0.444; p = 0.014). These correlations were confirmed by multivariate regression analyses using age, sex, symptom duration and disease severity as measured by UPDRSIII motor score as candidate covariates. No other associations were observed between olfaction measures and Kocc and EDVR in all striatal regions. Together, olfactory dysfunction in early PD is not correlated with striatal 18Fluorodopa uptake as a measure for dopaminergic degeneration, but with putaminal dopamine turnover as a marker for dopaminergic presynaptic compensatory processes in early PD. These results should be treated as hypothesis generating and require confirmation by larger multicenter studies.

Across-vendor standardization of semi-LASER for single-voxel MRS at 3T.

The semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence provides single-shot full intensity signal with clean localization and minimal chemical shift displacement error and was recommended by the international MRS Consensus Group as the preferred localization sequence at high- and ultra-high fields. Across-vendor standardization of the sLASER sequence at 3 tesla has been challenging due to the B1 requirements of the adiabatic inversion pulses and maximum B1 limitations on some platforms. The aims of this study were to design a short-echo sLASER sequence that can be executed within a B1 limit of 15 μT by taking advantage of gradient-modulated RF pulses, to implement it on three major platforms and to evaluate the between-vendor reproducibility of its perfomance with phantoms and in vivo. In addition, voxel-based first and second order B0 shimming and voxel-based B1 adjustments of RF pulses were implemented on all platforms. Amongst the gradient-modulated pulses considered (GOIA, FOCI and BASSI), GOIA-WURST was identified as the optimal refocusing pulse that provides good voxel selection within a maximum B1 of 15 μT based on localization efficiency, contamination error and ripple artifacts of the inversion profile. An sLASER sequence (30 ms echo time) that incorporates VAPOR water suppression and 3D outer volume suppression was implemented with identical parameters (RF pulse type and duration, spoiler gradients and inter-pulse delays) on GE, Philips and Siemens and generated identical spectra on the GE 'Braino' phantom between vendors. High-quality spectra were consistently obtained in multiple regions (cerebellar white matter, hippocampus, pons, posterior cingulate cortex and putamen) in the human brain across vendors (5 subjects scanned per vendor per region; mean signal-to-noise ratio > 33; mean water linewidth between 6.5 Hz to 11.4 Hz). The harmonized sLASER protocol is expected to produce high reproducibility of MRS across sites thereby allowing large multi-site studies with clinical cohorts.