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Introduction Functional brain imaging has shown alterations in the basal ganglia, cortex and cerebellum in Parkinson's disease patients. However, few functional imaging studies have tested how these changes evolve over time. Our study aimed to test the longitudinal progression of movement-related functional activity in Parkinson's disease patients. Methods At baseline, 48 Parkinson's disease patients and 16 healthy controls underwent structural and functional magnetic resonance imaging during a joystick motor task. Patients had repeated imaging after 18-months (n = 42) and 36-months (n = 32). T-tests compared functional responses between Parkinson's disease patients and controls, and linear mixed effects models examined longitudinal differences within Parkinson's disease. Correlations of motor-activity with bradykinesia, rigidity and tremor were undertaken. All contrasts used whole-brain analyses, thresholded at Z > 3.1 with a cluster-wise P Results Baseline activation was significantly greater in patients than controls across contralateral parietal and occipital regions, ipsilateral precentral gyrus and thalamus. Longitudinally, patients showed significant increases in cerebellar activity at successive visits following baseline. Task-related activity also increased in the contralateral motor, parietal and temporal areas at 36 months compared to baseline, however this was reduced when controlling for motor task performance. Conclusion We have shown that there are changes over time in the blood-activation level dependent response of patients with Parkinson's disease undertaking a simple motor task. These changes are observed primarily in the ipsilateral cerebellum and may be compensatory in nature.

ObjectiveWe investigated pathological emotionalism in a large cohort of patients that had presented with autoimmune limbic encephalitis(a-LE).Methods38 patients in the post-acute phase of a-LE completed questionnaires probing emotion regula- tion. They all underwent structural/functional MRI post-acutely, along with age- and sex-matched healthy controls. We investigated correlations of questionnaire scores with demographic, clinical, neuropsycho- logical and brain MRI data across patients. We also compared patients with pathological emotionalism and those without, along with healthy controls, on grey matter volume, resting-state functional connec- tivity and activity.ResultsPathological emotionalism was reported by 50% of the patients. It was not associated with depres- sion, impulsiveness, or memory impairment. However, it correlated with abnormalities in specific emotional brain networks: volume reduction in the anterior hippocampus, fusiform gyrus and cerebellum, abnormal hippocampal resting-state functional connectivity with the posteromedial cortex and middle frontal gyrus, and abnormal hemodynamic activity in the fusiform gyrus, inferior parietal lobule, and ventral pons.ConclusionsPathological emotionalism is common following a-LE, is not a manifestation of other neu- ropsychiatric disorders, and reflects abnormalities in networks of emotion regulation including, but not limited to the acute hippocampal focus. This condition provides novel insights into the neural basis of emotion regulation and its dysfunction in disease.christopher.butler@imperial.ac.uk

A central debate in the systems neuroscience of memory concerns whether different medial temporal lobe (MTL) structures support different processes in recognition memory. Using two recognition memory paradigms, we tested a rare patient (MH) with a perirhinal lesion that appeared to spare the hippocampus. Consistent with a similar previous case, MH showed impaired familiarity and preserved recollection. When compared with patients with hippocampal lesions appearing to spare perirhinal cortex, MH showed greater impairment on familiarity and less on recollection. Nevertheless, the hippocampal patients also showed impaired familiarity compared with healthy controls. However, when replacing this traditional categorization of patients with analyses relating memory performance to continuous measures of damage across patients, hippocampal volume uniquely predicted recollection, whereas parahippocampal, rather than perirhinal, volume uniquely predicted familiarity. We consider whether the familiarity impairment in MH and our patients with hippocampal lesions arises from “subthreshold” damage to parahippocampal cortex (PHC). Our data provide the most compelling neuropsychological support yet for dual-process models of recognition memory, whereby recollection and familiarity depend on different MTL structures, and may support a role for PHC in familiarity. Our study highlights the value of supplementing single-case studies with examinations of continuous brain–behavior relationships across larger patient groups.

Background 18F-dopa PET measuring aromatic l-amino acid decarboxylase activity is regarded as the gold standard for evaluating dopaminergic function in Parkinson's disease. Radioligands for dopamine transporters are also used in clinical trials and for confirming PD diagnosis. Currently, it is not clear which imaging marker is more reliable for assessing clinical severity and rate of progression. The objective of this study was to directly compare 18F-dopa with the highly selective dopamine transporter radioligand 11C-PE2I for the assessment of motor severity and rate of progression in PD. Methods Thirty-three mild-moderate PD patients underwent 18F-dopa and 11C-PE2I PET at baseline. Twenty-three were followed up for 18.8 ± 3.4 months. Results Standard multiple regression at baseline indicated that 11C-PE2I BPND predicted UPDRS-III and bradykinesia-rigidity scores (P < 0.05), whereas 18F-dopa Ki did not make significant unique explanatory contributions. Voxel-wise analysis showed negative correlations between 11C-PE2I BPND and motor severity across the whole striatum bilaterally. 18F-Dopa Ki clusters were restricted to the most affected putamen and caudate. Longitudinally, negative correlations were found between striatal Δ11C-PE2I BPND, ΔUPDRS-III, and Δbradykinesia-rigidity, whereas no significant associations were found for Δ18F-dopa Ki. One cluster in the most affected putamen was identified in the longitudinal voxel-wise analysis showing a negative relationship between Δ11C-PE2I BPND and Δbradykinesia-rigidity. Conclusions Striatal 11C-PE2I appears to show greater sensitivity for detecting differences in motor severity than 18F-dopa. Furthermore, dopamine transporter decline is closely associated with motor progression over time, whereas no such relationship was found with aromatic l-amino acid decarboxylase. 11C-PE2I may be more effective for evaluating the efficacy of neuroprotective treatments in PD. © 2017 International Parkinson and Movement Disorder Society

A central debate in the systems neuroscience of memory concerns whether different medial temporal lobe (MTL) structures support different processes or material-types in recognition memory. We tested a rare patient (Patient MH) with a perirhinal lesion that appeared to spare the hippocampus, using two recognition memory paradigms, each run separately with faces, scenes and words. Replicating reports of a previous case, Patient MH showed impaired familiarity and preserved recollection, relative to controls, with no evidence for any effect of material-type. Moreover, when compared with other amnesic patients, who had hippocampal lesions that appeared to spare the perirhinal cortex, Patient MH showed greater impairment on familiarity and less on recollection, forming a double dissociation. However, when replacing this traditional, binary categorization of patients with a parametric analysis that related memory performance to continuous measures of brain damage across all patients, we found a different pattern: while hippocampal damage predicted recollection, it was parahippocampal instead of perirhinal (or entorhinal) cortex volume that predicted familiarity. Furthermore, there was no evidence that these brain-behavior relationships were moderated by material-type, nor by laterality of damage. Thus, while our data provide the most compelling support yet for dual-process models of recognition memory, in which recollection and familiarity depend on different MTL structures, they suggest that familiarity depends more strongly upon the parahippocampal rather than perirhinal cortex. More generally, our study reinforces the need to go beyond single-case and group studies, and instead examine continuous brain-behavior relationships across larger patient groups.

Objective/Aims Autoimmune limbic encephalitis (LE) is commonly associated with cognitive and psychiatric disturbances at the acute stage of the disease, and with residual episodic memory impairment. While behavioural and psychiatric symptoms generally dissipate post-acutely, very little is known about the profile of persistent neuropsychiatric symptoms. In particular, emotional lability represents an elusive entity that may be misdiagnosed as a manifestation of comorbid mood or personality change and can have disabling consequences, due to the stigma attached to the loss of emotional control. We aimed to assess the post-acute profile of emotional lability and its neuroanatomical correlates in LE. Methods We analysed acute neuroradiological reports, clinical notes, scores on post-acute neuropsychological tests and self-administered questionnaires on mood, emotion, and affect (including the Centre for Neurologic Study-Lability Scale; CNS-LS), along with structural MRI and resting-state fMRI datasets in relation to emotional lability in a large cohort of patients (n=36) that had received a neurological diagnosis of LE, presented with focal hippocampal structural abnormalities in the acute phase, and post-acute hippocampal atrophy and thalamic volume reduction. Results Emotional lability was present in 50% of the patients. It was associated with increased tearfulness compared with non-labile patients and healthy controls, whereas no patient presented with labile laughter (CNS-LS). Patients with emotional lability (n=18) did not differ from those without (n=18) in any demographic or clinical details in their acute or post-acute presentation (autoantibodies, immunosuppressive therapy, seizures, antidepressant medication, age at or delay from symptom onset), or in residual depression, anxiety, impulsiveness, memory impairment, or executive dysfunction, or in hippocampal and thalamic volumes. Instead, the presence and extent of emotional lability across patients was associated with reduced resting-state hemodynamic activity in and hippocampal functional connectivity with regions in the inferior and superior parietal lobules. Conclusions We present the first investigation of persistent affective dysregulation in LE. Emotional lability is common following LE, but is not a manifestation of depression, anxiety, impulsiveness, or executive dysfunction. The type of emotional lability seen in LE is semiologically distinct from pseudobulbar affect observed in other neurological diseases. While LE is characterised by focal hippocampal atrophy, functional abnormalities in regions interacting with the hippocampus may provide a more parsimonious explanation of emotional lability than the volume of medial temporal lobe structures. Functional abnormalities in parietal regions supporting perspective taking and social-affective processing may compromise patients’ emotion regulation.

Patients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between patients. We assessed this hypothesis in a uniquely large cohort of patients (n=38) after autoimmune limbic encephalitis, a syndrome associated with focal structural hippocampal pathology. These patients showed impaired recall, recognition and maintenance of new information, and remote autobiographical amnesia. Besides hippocampal atrophy, we observed correlatively reduced thalamic volume, resting-state inter-hippocampal connectivity and activity in posteromedial cortex. Associations of hippocampal volume with recall, recognition, and remote memory were fully mediated by wider network abnormalities, and were only direct in forgetting. Such network abnormalities may explain the variability across studies of amnesia and speak to theoretical debates in memory neuroscience.

BACKGROUND: Measuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored.METHODS: We have conducted a cross-sectional and longitudinal diffusion tensor imaging study in 18 early stage, treated PD patients and 14 age-matched controls. PD patients were scanned on 2 occasions OFF medication, 19.3 months apart (standard deviation = 3.1 months). Longitudinal change of regional nigral and striatal measures of fractional anisotropy and mean diffusivity were calculated using a region-of-interest approach.RESULTS: Region-of-interest analysis demonstrated that at baseline, PD patients and controls did not differ in regard to diffusion indices in any region assessed. A significant difference of nigral fractional anisotropy and mean diffusivity between controls and PD patients at follow-up was detected and confirmed with longitudinal analysis within PD patients. Alterations in striatal regions were not detected in either group or over time.CONCLUSION: Our findings indicate that nigral diffusion measure may be a valuable measure of disease progression. In the future, larger longitudinal studies will confirm whether diffusion indices may serve as sensitive and clinically meaningful measures of disease progression in PD. © 2016 International Parkinson and Movement Disorder Society. (Less)

The locus coeruleus is the site of the earliest pathological changes in many neurodegenerative diseases. Betts et al. describe how in vivo locus coeruleus imaging can be used as a biomarker for noradrenergic dysfunction in neurodegenerative diseases, and outline a strategy for achieving reliable and biologically validated imaging approaches., Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer’s disease, atypical neurodegenerative dementias and Parkinson’s disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.

ObjectiveLimbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment.MethodA cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined.ResultsPatients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531).ConclusionVGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy.

Introduction Dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) patients refers to the compulsive use of dopaminergic replacement therapy and has serious psycho-social consequences. Mechanisms underlying DDS are not clear although has been linked to dysfunctional brain reward networks. Methods With fMRI, we investigate behavioral and neural response to drug-cues in six PD DDS patients and 12 PD control patients in both the ON and OFF medication state. Behavioral measures of liking, wanting and subjectively ‘feeling ON medication’ were also collected. Results Behaviorally, PD DDS patients feel less ON and want their drugs more at baseline compared to PD controls. Following drug-cue exposure, PD DDS patients feel significantly more ON medication, which correlates with significant increases in reward related regions. Conclusions The results demonstrate that exposure to drug-cues increases the subjective feeling of being ‘ON’ medication which corresponds to dysfunctional activation in reward related regions in PD DDS patients. These findings should be extended in future studies. Visual stimuli being sufficient to elicit behavioral response through neuroadaptations could have direct implications to the management of addictive behavior.

We have investigated the role of globus pallidus (GP) serotonergic terminals in the development of levodopa-induced dyskinesias (LIDs) in Parkinson's disease (PD). We studied 12 PD patients without LIDs, 12 PD patients with LIDs, and 12 healthy control subjects. We used (11)C-DASB positron emission tomography (PET), a marker of serotonin transporter availability, and (11)C-raclopride PET to measure changes in synaptic dopamine levels following levodopa administration. PD patients without LIDs showed a significant reduction of GP serotonin transporter binding compared with healthy controls although this was within the normal range in PD patients with LIDs. Levels of GP serotonin transporter binding correlated positively with severity of dyskinesias. (11)C-raclopride PET detected a significant rise in GP synaptic dopamine levels of patients with LIDs after a levodopa challenge but not in patients with a stable response. Our findings indicate that LIDs in PD are associated with higher GP serotonergic function. This increased serotonin function may result in further dysregulation of thalamocortical signals and so promote the expression of dyskinesias.

Posterior cortical atrophy is a neurodegenerative syndrome characterised by progressive disruption of visual and perceptual processing, associated with atrophy in the parieto-occipital cortex. Current diagnostic criteria describe relative sparing of episodic memory function, but recent findings suggest that anterograde memory is often impaired. Whether these deficits extend to remote memory has not been addressed. A large body of evidence suggests that the recollection of an autobiographical event from the remote past coincides with the successful retrieval of visual images. We hypothesised that the profound visual processing deficits in posterior cortical atrophy would result in impaired autobiographical memory retrieval. Fourteen posterior cortical atrophy patients, eighteen typical Alzheimer's disease patients and twenty-eight healthy controls completed the Autobiographical Interview. Autobiographical memory in posterior cortical atrophy was characterised by a striking loss of internal, episodic detail relative to controls and to same extent as typical Alzheimer's disease patients, in conjunction with an increase in external details tangential to the memory described. The memory narratives of posterior cortical atrophy patients showed a specific reduction in spatiotemporal and perceptual detail. Voxel-based morphometry analysis revealed atrophy of the parieto-occipital cortices in posterior cortical atrophy but relatively spared hippocampi bilaterally, compared with characteristic atrophy of the medial temporal lobes in typical Alzheimer's disease. Analysis of brain regions showing posterior cortical atrophy-specific atrophy revealed a correlation between perceptual details in autobiographical memory and grey matter density in the right precuneus. This study demonstrates remote memory impairment in posterior cortical atrophy despite relatively preserved medial temporal lobe structures. The results demonstrate, for the first time, profound autobiographical memory impairment in PCA and suggest that this is driven by the well-recognised deficits in higher-order visual processing. The findings are discussed in the context of posterior parietal contributions to imagery and memory, and the clinical implications of autobiographical memory impairment for diagnostic and management protocols in posterior cortical atrophy., Highlights • Autobiographical memory in PCA shows a striking loss of internal, episodic detail. • Narratives showed a specific reduction in spatiotemporal and perceptual detail. • Loss of perceptual details correlated with grey matter density in the right precuneus. • Impaired autobiographical memory is driven by deficient higher-order visual processing.

The objective of this study was to investigate in vivo the ability of levodopa/carbidopa intestinal gel infusions to produce sustained striatal dopamine levels and to improve clinical outcomes in Parkinson's disease patients.Six advanced Parkinson's disease patients had serial [Mean striatal [Levodopa/carbidopa intestinal gel infusions generate a stable rise in striatal dopamine levels and are associated with improvements in motor manifestations. © 2016 International Parkinson and Movement Disorder Society.

Measuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored.We have conducted a cross-sectional and longitudinal diffusion tensor imaging study in 18 early stage, treated PD patients and 14 age-matched controls. PD patients were scanned on 2 occasions OFF medication, 19.3 months apart (standard deviation = 3.1 months). Longitudinal change of regional nigral and striatal measures of fractional anisotropy and mean diffusivity were calculated using a region-of-interest approach.Region-of-interest analysis demonstrated that at baseline, PD patients and controls did not differ in regard to diffusion indices in any region assessed. A significant difference of nigral fractional anisotropy and mean diffusivity between controls and PD patients at follow-up was detected and confirmed with longitudinal analysis within PD patients. Alterations in striatal regions were not detected in either group or over time.Our findings indicate that nigral diffusion measure may be a valuable measure of disease progression. In the future, larger longitudinal studies will confirm whether diffusion indices may serve as sensitive and clinically meaningful measures of disease progression in PD. © 2016 International Parkinson and Movement Disorder Society.

Background Iron accumulation plays an important role in neurodegeneration in Parkinson’s disease. Susceptibility weighted imaging (SWI) is a high-resolution MR-based imaging technique for quantifying iron depositions in vivo. We hypothesised that high-pass filtered phase imaging may be a useful monitoring tool for longitudinal clinical characterisation of PD, and we sought to investigate the clinical associations of iron depositions in deep grey matter nuclei. Methods We evaluated forty-two PD subjects and six age and gender matched healthy volunteers (HV) longitudinally with high-pass filtered phase imaging at baseline and after 18 months. Average phase shifts (radians) substantia nigra (SN) were analysed using SPIN software. Longitudinal changes of bilateral radians (Δ radians) were calculated by subtracting baseline values from follow up values. Parametric correlations of regional Δ radians were conducted with Δ UPDRS part III, tremor and bradykinesia- rigidity sub-scores. Results PD patients showed significantly higher radians in the SN (p Conclusions High-pass filtered phase imaging offers an interesting monitoring tool to evaluate longitudinal progression of motor severity and could be useful to assess the effect of iron chelation therapies.

Objective Limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex (VGKC-LE) often results in memory impairment with accompanying hippocampal damage thus potentially providing a robust human model of hippocampal amnesia. However, comprehensive characterisation of the neurobehavioural profile of VGKC-LE patients is currently lacking. We aim to provide a detailed description of the clinical outcome of these patients as well as determine whether they are indeed a useful model for hippocampal amnesia studies. Method A group of VGKC-LE patients (n=17) and matched controls underwent clinical interview and extensive neuropsychology testing covering multiple cognitive domains. Structural magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) was acquired in all subjects. Investigation of atrophy profiles was completed via manual delineation of medial temporal lobes (MTL) structures and FreeSurfer cortical parcellation using non-parametric permutation testing. Rs-fMRI data were analysed using both independent component analysis (ICA) and seed-based connectivity analysis (SBCA) to investigate aberrant functional connectivity of the default mode network (DMN) and anterior and posterior memory networks. Associations between memory performance and structure and functional measures were investigated. Results The neuropsychological profile indicates memory function is preferentially affected whereas non-memory function is spared. Moreover, recall memory (recall composite; p Conclusions We have demonstrated that VGKC-LE patients present with persistent memory impairment in line with a previous retrospective study (Butler et al., 2014; JNNP). We also demonstrate that VGKC-LE patients have focal hippocampal atrophy supporting the use of patients with limbic encephalitis as a human model of hippocampal amnesia. However, the presence of hippocampal atrophy alone does not clearly explain the memory deficits. Instead, our data strongly suggest that a functional disturbance at rest is a contributory factor and could explain inconsistencies currently existing in the hippocampal amnesia literature.

Objective Posterior cortical atrophy (PCA) is a syndrome characterised by progressive disruption of visual processing and neurodegeneration in the parieto-occipital cortex. The most common underlying cause is Alzheimer’s pathology. Anterograde memory function and the medial temporal lobes (MTLs) are thought to be relatively preserved. Given that the typical pattern of atrophy in PCA overlaps with brain networks critical for the recollection of personal events, we hypothesised that patients would be impaired on a test of autobiographical memory. Method 14 PCA, 18 Alzheimer’s disease (AD) patients and 28 healthy controls completed the Autobiographical Interview. Results Both PCA and AD patients produced significantly less internal detail relevant to the chosen memories, compared with controls. However, the PCA group also produced a significantly greater amount of unrelated external detail compared with controls and AD. Across the lifespan, PCA and AD again showed similarly poor recall of relevant remote memory details compared with controls, with no temporal gradient evident in either group. Correlational analysis in PCA patients revealed a significant relationship between total external details and the Hayling test of inhibitory control, and a trend towards significance between internal details and visual imagery. Conclusion Our findings suggest that, despite relatively preserved MTL structures, PCA patients have significantly impaired remote memory. We propose that damage to posterior regions of the brain disrupts access to visual information integral to the autobiographical memory trace. Increased provision of external details may be a compensatory strategy due to lack of access to details relevant to episodic memories.

IntroductionDopaminergic neuron loss in substantia nigra (SN) in patients with PD is associated with deposits of iron. Susceptibility weighted imaging (SWI) is a high-resolution MR-based imaging technique for quantifying iron depositions in vivo. SWI may be a robust biomarker for clinical characterization of PD.MethodsForty-two patients with PD were studied with SWI imaging. Average phase shift (radians) and percentage iron deposition of the SN were analysed using SPIN software. SWI data were also compared between PD patients with early (4.0±0.5 PD duration) vs. established PD (7.7±1.9), and according to low (21.2±4.5) vs. high (41.3±8.7) UPDRS-III-assessed motor symptoms severity. Data were interrogated using analysis of covariance (age), relative to healthy controls, and using post hoc univariate tests.ResultsPD patients had higher phase shift values (pConclusionsPD patients show higher levels of deposits of iron in SN compared to healthy controls, and increased iron levels in SN are associated with prolonged disease and increased motor disability