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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.

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.

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.

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.

Buspirone is an anxiolytic drug and is a partial agonist for the serotonin 5-HT(1A) receptors as well as possessing low affinity and is an antagonist for the dopamine D(2) autoreceptors, with some evidence of a weak affinity to 5-HT(2) receptors. The underlying mechanism of action of buspirone is not clear; however it is thought that its main pharmacology is mediated via the 5-HT(1A) receptors. Initially developed for use in the treatment of generalised anxiety disorder, it appears that buspirone may be useful in various other neurological and psychiatric disorders, such as attenuating side effects of Parkinson's disease therapy, ataxia, depression, social phobia, and behaviour disturbances following brain injury, and those accompanying Alzheimer's disease, dementia and attention deficit disorder. Considering the potential of this drug to be included in the management of many conditions, thorough and controlled studies are required to elucidate the exact mechanism of action. This review will consider the evidence so far for both the potential underlying mechanisms and its use in various conditions.

Background: Reduplicative paramnesia (RP) is a content-specific delusional misidentification syndrome (DMS) which has received little attention in the research literature relative to other DMS. RP is thought to result from an organic rather than psychiatric cause distinguishing it from other DMS. Our systematic review examines the research literature investigating the prevalence, symptomatology and potential neurologic mechanisms underlying RP. Sampling and Methods: MEDLINE, PsycINFO, and the Cochrane Library were searched (from 1966 to February 10, 2012) with the reference lists of relevant articles examined. Case reports, clinical studies and post-mortem studies focusing on, or referring to, RP were included. Results: There is a paucity of literature regarding the potential mechanisms underlying the psychological, cognitive and neurological aspects of RP. The available literature is limited by the lack of systematic clinical studies and in vivo investigations with current findings remaining only speculative. However, there does appear to be a consensus that RP may have a neurologic rather than psychiatric cause and that right and bifrontal lesions as well as the cognitive dissonance associated with memory, visuospatial and impaired conceptual integration are common factors in RP presentation. Conclusions: This area requires further extensive systematic research with supplementary in vivo data. Current studies suggest that focal lesions within the frontal lobe may account for the onset of RP.

Growing evidence suggests that Parkinson's disease is not solely affecting the dopaminergic system. Results from biochemical, animal,postmortem, and functional imaging studies have revealed that other neurotransmitter systems are affected as well, including the serotonergic system. With the use ofin vivopositron emission tomography functional imaging, it has been shown that serotonergic terminals are affected at a varying, nonlinear degree starting early in the clinical course of Parkinson's disease. Tremor and the majority of nonmotor symptoms do not seem to respond adequately to dopaminergic medication. Recent studies suggest that serotonergic dysfunction has a direct relevance to Parkinson's disease symptoms, the so-called nonmotor symptoms, including depression, fatigue, weight changes, and visual hallucinations. Thesein vivofindings indicate that agents acting on the serotonergic system could help towards alleviating these symptoms. This paper aims to review the current literature and to highlight the need for furtherin vivoinvestigations.

Background: Depression associated with Parkinson disease (PD) has a different symptom profile to endogenous depression. The etiology of depression in PD remains uncertain though abnormal serotonergic neurotransmission could play a role. Objective: To assess with PET serotonergic function via in vivo serotonin transporter (5-HTT) availability in antidepressant-naive patients with PD. Methods: Thirty-four patients with PD and 10 healthy matched control subjects had a clinical battery of tests including the patient-report Beck Depression Inventory–II (BDI-II), the clinician-report Hamilton Rating Scale for Depression (HRSD), and the structured clinical interview for DSM-IV Axis I Disorders (SCID-I). They underwent 11 C-DASB PET, a selective in vivo marker of 5-HTT binding in humans. Results: BDI-II scores correlated with HRSD scores. Ten of 34 patients with PD (29.4%) had BDI-II and HRSD scores above the discriminative cutoff for PD depression though only half of these patients could be classed on SCID-I criteria as having an anxiety/mood disorder. Patients with PD with the highest scores for depression symptoms showed significantly raised 11 C-DASB binding in amygdala, hypothalamus, caudal raphe nuclei, and posterior cingulate cortex compared to low score cases, while 11 C-DASB binding values in other regions were similarly decreased in depressed and nondepressed patients with PD compared to healthy controls. Conclusion: Depressive symptoms in antidepressant-naive patients with PD correlate with relatively higher 5-HTT binding in raphe nuclei and limbic structures possibly reflecting lower extracellular serotonin levels. Our data are compatible with a key role of abnormal serotonergic neurotransmission contributing to the pathophysiology of PD depression and justify the use of agents acting on 5-HTT.

Thirty Parkinson's disease (PD) patients were divided into three equal groups according to their disease duration while 10 normal healthy volunteers matched for age and sex served as a control group. Striatal and extrastriatal serotonergic function was studied with (11)C-DASB PET, a marker of serotonin transporter availability. (11)C-DASB binding was correlated with disease disability and exposure to dopaminergic therapy. We found significant (11)C-DASB binding reductions in striatal, brainstem, and cortical regions in PD but no correlations were evident between (11)C-DASB binding and UPDRS scores, Hoehn &Yahr staging, disease duration and level of exposure to dopaminergic therapy. Our results suggest that progressive non-linear serotonergic dysfunction occurs in PD but it does not determine levels of disability. Additionally, chronic exposure to dopaminergic therapy does not appear to influence SERT binding.

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.

Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson’s disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD.

OBJECTIVE: The underlying pathophysiology of tremor in Parkinson disease (PD) is unclear; however, it is known that tremor does not appear to be as responsive to dopaminergic medication as bradykinesia or rigidity. It is suggested that serotonergic dysfunction could have a role in tremor development.METHODS: Using (11)C-DASB PET, a marker of serotonin transporter binding, and clinical observations, we have investigated function of serotonergic terminals in 12 patients with tremor-predominant and 12 with akinetic-rigid PD. Findings were compared with those of 12 healthy controls.RESULTS: Reductions of (11)C-DASB in caudate, putamen, and raphe nuclei significantly correlated with tremor severity on posture and action, but not with resting tremor. The tremor-predominant group also showed reductions of (11)C-DASB in other regions involved in motor circuitry, including the thalamus and Brodmann areas 4 and 10.CONCLUSIONS: Our findings support a role for serotonergic dysfunction in motor circuitries in the generation of postural tremor in PD.

Hypersexuality with compulsive sexual behaviour is a significant source of morbidity for patients with Parkinson’s disease receiving dopamine replacement therapies. We know relatively little about the pathophysiology of hypersexuality in Parkinson’s disease, and it is unknown how visual sexual stimuli, similar to the portrayals of sexuality in the mainstream mass media may affect the brain and behaviour in such susceptible individuals. Here, we have studied a group of 12 patients with Parkinson’s disease with hypersexuality using a functional magnetic resonance imaging block design exposing participants to both sexual, other reward-related and neutral visual cues. We hypothesized that exposure to visual sexual cues would trigger increased sexual desire in patients with Parkinson’s disease with hypersexuality that would correspond to changes in brain activity in regions linked to dopaminergically stimulated sexual motivation. Patients with Parkinson’s disease with hypersexuality were scanned ON and OFF dopamine drugs, and their results were compared with a group of 12 Parkinson’s disease control patients without hypersexuality or other impulse control disorders. Exposure to sexual cues significantly increased sexual desire and hedonic responses in the Parkinson’s disease hypersexuality group compared with the Parkinson’s disease control patients. These behavioural changes corresponded to significant blood oxygen level-dependent signal changes in regions within limbic, paralimbic, temporal, occipital, somatosensory and prefrontal cortices that correspond to emotional, cognitive, autonomic, visual and motivational processes. The functional imaging data showed that the hypersexuality patients’ increased sexual desire correlated with enhanced activations in the ventral striatum, and cingulate and orbitofrontal cortices. When the patients with Parkinson’s disease with hypersexuality were OFF medication, the functional imaging data showed decreases in activation during the presentation of sexual cues relative to rest. These deactivations were not observed when the patients were ON medication, suggesting that dopamine drugs may release inhibition within local neuronal circuits in the cerebral cortex that may contribute to compulsive sexual behaviour. The findings of this study have implications with respect to the potential influence of cue exposure via exposure to mass media in enhancing libido, which in this group of vulnerable patients can lead to devastating social consequences and occasionally, custodial sentences. Stimulation through exposure to sexual visual cues in patients with Parkinson’s disease with hypersexuality provides a motivational impetus for seeking this reward behaviour through activations and deactivations of cerebral cortex.

Exposure to ambient air pollution has been consistently associated with respiratory and cardiovascular disease. However, the neurological effects of air pollution have received little attention. It is suggested that the components of air pollution, such as particulate matter (PM) and specifically ultrafine particulate matter (UFP), may have the potential to extend beyond pulmonary organs to the central nervous system (CNS) and, ultimately, the brain. The transport mechanisms are not clear, although at least four possible routes have been proposed implicating PM and UFP in neurological disease processes. A limited number of studies have been undertaken to assess the role of PM and UFP in CNS diseases, including migraine, headache, stroke, Alzheimer's disease, and Parkinson's disease. Considering the high prevalence of such CNS diseases, along with the frequent and increasing exposure to ambient air pollution, it is important to highlight possible associations with regards to preventative, monitoring, and control measures. This article aimed to review the literature in relation to translocation routes of PM and UFP and their potential role in neurological disease processes.

Cell therapy studies in patients with Parkinson's disease (PD) have been confined to intrastriatal transplantation of dopamine-rich fetal mesencephalic tissue in efforts to improve motor performance. Although some PD patients receiving the dopamine-rich grafts showed improvements in motor symptoms due to replacement of dopaminergic neurons, they still suffered from nonmotor symptoms including depression, fatigue, visual hallucinations, and sleep problems. Using functional imaging and clinical evaluation of motor and nonmotor symptoms in three PD patients transplanted with intrastriatal fetal grafts 13 to 16 years previously, we assessed whether reestablishment of dopaminergic neuronal networks is sufficient to improve a broad range of symptoms. At 13 to 16 years after transplantation, dopaminergic innervation was restored to normal levels in basal ganglia and preserved in a number of extrabasal ganglia areas. These changes were associated with long-lasting relief of motor symptoms. Then, we assessed the integrity of their serotonergic and norepinephrine neuronal systems using [¹¹C]DASB {[¹¹C]3-amino-4-(2-dimethylaminomethylphenylthio) benzonitrile} positron emission tomography (PET) and ¹⁸F-dopa PET, respectively. ¹⁸F-dopa uptake in the locus coeruleus was within the normal range. In contrast, [¹¹C]DASB uptake in the raphe nuclei and regions receiving serotonergic projections was markedly reduced. These results indicate ongoing degeneration of serotonergic raphe nuclei and their projections to regions involved in the regulation of sleep, arousal, feeding, satiety, mood, and emotion. Our findings indicate that future cell-based therapies using fetal tissue or stem cells in PD patients may require additional grafts of serotonergic neurons to relieve nonmotor symptoms by restoring serotonergic neurotransmission in specific cerebral targets.

More than 50% of patients with Parkinson's disease (PD) are expected to show abnormalities with their weight in a process that starts several years before the diagnosis. The serotonergic (5-HT) system has been proposed to regulate appetite and the 5-HT transporter (SERT) is a key modulator of 5-HT metabolism. Here, we hypothesized that a dysfunctional 5-HT system could be responsible for alterations of weight in PD and we sought to investigate this in vivo. Thirty four PD patients had Body Mass Index (BMI) changes monitored over a 12-month period and one positron emission tomography (PET) brain scan with (11)C-DASB, a selective marker of SERT availability, during their second clinical assessment. Results were compared with those of a group of 10 normal controls. Half (17) of the PD patients showed abnormal BMI changes over the 12-month period; 12 lost while 5 gained weight. PD patients with abnormal BMI changes showed significantly raised (11)C-DASB binding in rostral raphe nuclei, hypothalamus, caudate nucleus and ventral striatum compared to cases with no significant BMI changes. (11)C-DASB binding in other regions was similarly decreased in the PD BMI subgroups compared to normal controls. BMI gainers showed significantly raised (11)C-DASB binding in anterior cingulate cortex (ACC) compared to BMI losers. Our findings suggest that abnormal BMI changes over a 12-month period are linked with relatively raised SERT availability in PD on an overall background of decreased 5-HT function. The regions implicated are the rostral raphe nuclei and its connections to limbic and cognitive areas. It is conceivable that 5-HT agents could help alleviate abnormal changes in BMI in PD.

Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same as in the dyskinesias induced by l-dopa treatment. Using in vivo brain imaging, we show excessive serotonergic innervation in the grafted striatum of two patients with Parkinson's disease, who had exhibited major motor recovery after transplantation with dopamine-rich fetal mesencephalic tissue but had later developed off-medication dyskinesias. The dyskinesias were markedly attenuated by systemic administration of a serotonin [5-hydroxytryptamine (5-HT)] receptor (5-HT(1A)) agonist, which dampens transmitter release from serotonergic neurons, indicating that the dyskinesias were caused by the serotonergic hyperinnervation. Our observations suggest strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson's disease with fetal tissue or stem cells.

Objectives Impulsive-compulsive behaviours (ICBs) in Parkinson's disease (PD) have been anecdotally linked with impaired sleep. The authors investigate measures of sleep in PD patients with and without ICBs, and in healthy controls. Methods The authors compare Parkinsonian features, measures of depression, anxiety and mania, and sleep disturbance in 30 PD patients with ICBs (PD+ICB), 62 PD patients without ICBs (PD−ICB) and 48 healthy controls. Results PD+ICB patients had a younger age of PD onset, took more dopamine replacement therapy (DRT) and had worse sleep, and elevated anxiety, depression and mania scores. Using multiple linear regression analyses, the total anxiety and depression scores, and presence of ICBs were the only variables associated with poorer sleep in PD. Conclusions PD+ICB patients may show enhanced psychomotor effects of DRT that may in turn contribute to poor sleep quality. Sleep disturbance should be specifically queried in PD+ICB patients.

Hoarding is seen in several psychiatric conditions, but has not been specifically assessed in Parkinson's disease (PD). This study investigates hoarding tendency amongst patients with PD, and its association with impulsive-compulsive spectrum behaviors (ICBs). We compare clinical features, measures of hoarding, impulse buying, self-control, obsessive-compulsive symptoms, depression, and anxiety in 39 patients with PD with ICBs (PD + ICB), 61 patients with PD without ICBs (PD - ICB), and 50 healthy controls. A much higher proportion of PD + ICB (27.8%) than PD - ICB (3.5%) were hoarders (P = 0.001). 6% of healthy controls were hoarders. Compulsive shoppers scored higher than other varieties of ICB on excessive acquisition measures. Hoarding correlated positively with impulsive buying, obsessive-compulsive symptoms, PD duration, and negatively with self-control measures. Using multivariate regression analyzes, the presence of ICBs and measures of impulsive buying were the only variables independently associated with hoarding in PD. The association of hoarding with other ICBs and low trait impulse control suggests that excessive hoarding is related to the spectrum of impulsive behaviors in PD.

Levodopa-induced dyskinesias (LIDs) and graft-induced dyskinesias (GIDs) are serious and common complications of Parkinson's disease (PD) management following chronic treatment with levodopa or intrastriatal transplantation with dopamine-rich foetal ventral mesencephalic tissue, respectively. Positron emission tomography (PET) molecular imaging provides a powerful in vivo tool that has been employed over the past 20 years for the elucidation of mechanisms underlying the development of LIDs and GIDs in PD patients. PET used together with radioligands tagging molecular targets has allowed the functional investigation of several systems in the brain including the dopaminergic, serotonergic, glutamatergic, opioid, endocannabinoid, noradrenergic and cholinergic systems. In this article the role of PET imaging in unveiling pathophysiological mechanisms underlying the development of LIDs and GIDs in PD patients is reviewed.