Non-depressed Parkinson's Disease Patients Research Articles

Altered functional-structural coupling may predict Parkinson's patient's depression.

We aimed to elucidate the neurobiological basis of depression in Parkinson's disease and identify potential imaging markers for depression in patients with Parkinson's disease. We recruited 43 normal controls (NC), 46 depressed Parkinson's disease patients (DPD) and 56 non-depressed Parkinson's disease (NDPD). All participants underwent routine T2-weighted, T2Flair, and resting-state scans on the same 3.0T magnetic resonance imaging (MRI) scanner at our hospital. Pre-processing includes calculating surface-based Regional Homogeneity (2DReHo) and cortical thickness. Then we defined the correlation coefficient between 2DReHo and cortical thickness as the functional-structural coupling index. Between-group comparisons were conducted on the Fisher's Z-transformed correlation coefficients. To identify specific regions of decoupling, the 2DReHo for each participant were divided by cortical thickness at each vertex, followed by threshold-free cluster enhancement (TFCE) multiple comparison correction. Binary logistic regression analysis was performed with DPD as the dependent variable, and significantly altered indicators as the independent variables. Receiver operating characteristic curves were constructed to compare the diagnostic performance of individual predictors and combinations using R and MedCalc software. DPD patients exhibited a significantly lower whole-brain functional-structural coupling index than NDPD patients and NC. Abnormal functional-structural coupling was primarily observed in the left inferior parietal lobule and right primary and early visual cortices in DPD patients. Receiver operating characteristic analysis revealed that the combination of cortical functional-structural coupling, surface-based ReHo, and thickness had the best diagnostic performance, achieving a sensitivity of 65% and specificity of 77.7%. This is the first study to explore the relationship between functional and structural changes in DPD patients and evaluate the diagnostic performance of these altered correlations to predict depression in Parkinson's disease patients. We posit that these changes in functional-structural relationships may serve as imaging biomarkers for depression in Parkinson's disease patients, potentially aiding in the classification and diagnosis of Parkinson's disease. Additionally, our findings provide functional and structural imaging evidence for exploring the neurobiological basis of depression in Parkinson's disease.

Atrophy patterns in hippocampus and amygdala subregions of depressed patients with Parkinson's disease

We aimed to explore the subregional atrophy patterns of the amygdala and hippocampus in Parkinson's disease (PD) with depression and their correlation with the severity of the depressive symptom. MRI scans were obtained for 34 depressed PD patients (DPD), 22 nondepressed PD patients (NDPD), and 28 healthy controls (HC). Amygdala and hippocampal subregions were automatically segmented, and the intergroup volume difference was compared. The relationships between the volumes of the subregions and depression severity were investigated. Logistic analysis and Receiver operator characteristic curve were used to find independent predictors of DPD. Compared with the HC group, atrophy of the bilateral lateral nucleus, left accessory basal nucleus, right cortical nucleus, right central nucleus, and right medial nucleus subregions of the amygdala were visible in the DPD group, while the right lateral nucleus subregion of the amygdala was smaller in the DPD group than in the NDPD group. The DPD group showed significant atrophy in the left molecular layer, left GC-DG, left CA3, and left CA4 subregions compared with the HC group for hippocampal subregion volumes. Also, the right lateral nuclei volume and disease duration were independent predictors of DPD. To sum up, DPD patients showed atrophy in multiple amygdala subregions and left asymmetric hippocampal subregions. The decreased amygdala and hippocampal subregion volumes were correlated with the severity of depressive symptoms. The volume of right lateral nuclei and disease duration could be used as a biomarker to detect DPD.

Cortical gyrification pattern of depression in Parkinson's disease: a neuroimaging marker for disease severity?

Although the study of the neuroanatomical correlates of depression in Parkinson's Disease (PD) is gaining increasing interest, up to now the cortical gyrification pattern of PD-related depression has not been reported. This study was conducted to investigate the local gyrification index (LGI) in PD patients with depression, and its associations with the severity of depression. LGI values, as measured using FreeSurfer software, were compared between 59 depressed PD (dPD), 27 non-depressed PD (ndPD) patients and 43 healthy controls. The values were also compared between ndPD and mild-depressed PD (mi-dPD), moderate-depressed PD (mo-dPD) and severe-depressed PD (se-dPD) patients as sub-group analyses. Furthermore, we evaluated the correlation between LGI values and depressive symptom scores within dPD group. Compared to ndPD, the dPD patients exhibited decreased LGI in the left parietal, the right superior-frontal, posterior cingulate and paracentral regions, and the LGI values within these areas negatively correlated with the severity of depression. Specially, reduced gyrification was observed in mo-dPD and involving a larger region in se-dPD, but not in mi-dPD group. The present study demonstrated that cortical gyrification is decreased within specific brain regions among PD patients with versus without depression, and those changes were associated with the severity of depression. Our findings suggested that cortical gyrification might be a potential neuroimaging marker for the severity of depression in patients with PD.

Autophagy markers, cognitive deficits and depressive symptoms in Parkinson's disease.

Depressive symptoms are common in Parkinson's disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients.A total of 163 PD patients aged 50-80years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively.There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = -0.002, t = -2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = -0.001, t = -2.452, p = 0.017).LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall.

Altered Functional Connectivity of Ventral Striatum Subregions in De-novo Parkinson’s Disease with Depression

Although various studies have reported a high prevalence of depression among Parkinson's disease (PD) patients, the pathophysiological mechanism of depression in PD (DPD) is still unclear. The core region of the reward network, the ventral striatum (VS), is critical in the occurrence and development of DPD. This study aimed to explore the altered functional connectivity (FC) of VS subregions in DPD. We recruited 20 DPD patients, 37 non-depressed PD (NDPD) patients, and 41 healthy controls (HC) matched in age, gender, and years of education. The patients' diagnosis with PD was de-novo. We then used resting-state functional magnetic resonance imaging to detect the FC differences of VS subregions among these groups. The FC between the left ventral caudate (vCa_L) and the left middle occipital gyrus (MOG.L) was significantly increased in DPD than in NDPD patients or HC. Compared with HC, NDPD patients exhibited significantly increased FCs between bilateral ventromedial putamen and the left paracentral lobule, the right ventromedial putamen (vmPu_R), and the right precentral gyrus, the vmPu_R, and the left precuneus. Besides, a significant negative correlation was found between the FC values of the vCa_L with the MOG.L and the HAMD-17 scores in the DPD group. The hyperconnectivity between vCa_L and the MOG.L might be viewed as a compensatory mechanism for depression in the early stage of PD. This study provides new insight into the neural mechanism of depression in the early stage of PD and contributes to explore the potential neuroimaging markers for DPD.

Improving Self-Awareness of Motor Symptoms in Patients With Parkinson's Disease by Using Mindfulness - A Study Protocol for a Randomized Controlled Trial.

ObjectiveThis study aims to increase self-awareness in patients with Parkinson’s disease (PD) using a newly developed mindfulness-based intervention, tailored for the specific needs of PD patients. Its impact on self-awareness and patients’ daily lives is currently being evaluated.BackgroundRecently, the phenomenon of impaired self-awareness for motor symptoms (ISAm) and some non-motor symptoms has been described in PD. ISAm can negatively influence patients’ daily lives, e.g., by affecting therapy adherence, and is therefore the main focus of this study. The main goal is the development of IPSUM (“Insight into Parkinson’s Disease Symptoms by using Mindfulness”), a PD-specific intervention for increasing patients’ mindfulness and thereby reducing ISAm.MethodsThe effectiveness of IPSUM is evaluated by comparison of an intervention group with a waitlist-control group. A pre-post design with an additional 8-week follow-up measurement is applied, resulting in three measurement points: before, directly after and 8 weeks after completing the intervention protocol. In total, up to 180 non-depressed PD patients without severe cognitive impairment (non-demented) will be included. The primary outcome is a quantitative score for measuring ISAm. Secondary outcome measures are affective changes, neuropsychological performance and self-awareness of cognition. At pre- and post-measurement an fMRI scan is performed to connect behavioral and neurobiological findings. At post- and follow-up-measurement each patient will take part in a semi-structured interview to explore IPSUM’s impact on self-awareness and patients’ everyday lives.ResultsThe conception of the intervention protocol is finished, the resulting 8-week program is presented in detail. It has successfully been tested in the first group of patients, their feedback so far was quite promising. Recruitment is ongoing and a first interim analysis will be performed once 30 patients have completed IPSUM.ConclusionFor the first time, the intervention protocol of IPSUM has successfully been tested in a group of PD patients. As the study goes on, more quantitative data is collected for statistical analyses to evaluate its effectiveness. More qualitative data is collected to evaluate feasibility and effectiveness. We hope for this intervention to be capable of reducing the patients’ ISAm and improving their quality of life on many levels.

Damaged Insula Network Contributes to Depression in Parkinson's Disease.

BackgroundDepression is common in patients with Parkinson’s disease (PD). Our previous studies suggest that depressed PD patients have altered insula structures. It is, however, still unknown whether the altered structures cause disruption of insula functional networks, further contributing to depression in PD.MethodsIn the present study, 17 depressed PD patients, 17 non-depressed PD patients, and 17 normal controls were enrolled. All subjects went through neurological and psychiatric clinical assessments. Resting-state functional magnetic resonance imaging and seed-based insula functional analyses were performed to examine the insula functional connectivity alterations in PD patients.ResultsWe found that compared with normal controls, PD patients exhibited significantly decreased insula functional connectivity widely across the whole brain. Compared with non-depressed PD patients, depressed patients showed further decreased functional connectivity in the middle frontal gyrus and inferior parietal lobe. Furthermore, connectivity between the left anterior insula and middle frontal gyrus was positively correlated with the cognitive scale score.ConclusionThese results suggest that insula networks were severely damaged in PD patients, and that the disrupted connection between the salience network and executive control network might contribute to depression in PD.

New insights into facial emotion recognition in Parkinson's disease with and without mild cognitive impairment from visual scanning patterns

BackgroundRecognizing emotional facial expressions is crucial for social interactions. Cognitive impairment and oculomotor abnormalities are common features of Parkinson's disease (PD) which may contribute to the performance in facial emotion recognition (FER) in PD. ObjectiveThe aim of this study was to analyze eye movement behavior during a facial emotion recognition (FER) task with respect to cognitive state in PD patients and healthy controls. MethodsEye movements of 24 non-demented, non-depressed PD patients (12 with intact cognitive functions and 12 with Mild Cognitive Impairment (MCI) according to MDS task force criteria level 2), and 12 age-, sex and education-matched healthy controls were recorded during visual exploration of 28 emotional (happiness, surprise, disgust, anger, fear and sadness) and neutral faces. Participants were asked to identify the displayed emotion out of a sevenfold multiple choice question. ResultsPD-MCI patients showed reduced FER with specific impairment of anger recognition. Although the scanned area of PD patients with intact cognition was significantly restricted, they did not differ in FER from healthy subjects. While healthy subjects and cognitively intact PD patients scanned faces with preference for mouth and eyes, patients with PD-MCI tended to look at the center of the face and spent significantly less time fixating the mouth. ConclusionsIneffective visual exploration may contribute to impaired emotion recognition in PD. Visual scanning of emotional faces is altered in PD even in the absence of cognitive impairment. The progression to PD-MCI may result in further deterioration of scanning behavior and FER impairment.

Cognitive correlates of “pure apathy” in Parkinson's disease

IntroductionPrevious studies exploring the association between apathy and cognitive deficits in Parkinson's disease (PD) employed scales and questionnaires for apathy, which did not control for the possible confounding effect of motor symptoms. Here we investigated the cognitive correlates of “pure apathy” by the Dimensional Apathy Scale, which allows us to assess apathy minimizing the influence of motor symptoms. MethodsConsecutive PD outpatients referred to our centre were screened. All participants underwent a neuropsychological battery to assess verbal memory, executive functions and visuospatial abilities, apathy and depressive symptoms. ResultsWe enrolled 56 non-depressed and non-demented PD patients, of whom 28 were apathetic and 28 were not. The two groups did not differ on demographic and clinical aspects; apathetic PD patients performed worse than non-apathetic PD patients on the part A, B and B-A of Trail Making Test and the interference task of Stroop test. No significant differences were found on memory and perceptual visuospatial tasks. ConclusionsOur results demonstrated that “pure apathy” is associated with more severe executive dysfunctions such as alteration of set-shifting and inhibitory control, which are mediated by prefrontal cortex and subcortical regions (i.e. basal ganglia). Our findings also supported the hypothesis that co-occurrence of apathy and executive deficits may be the epiphenomenon of damage in prefrontal-striatal cortical circuitries connecting dorsolateral prefrontal cortex, anterior cingulate cortex and basal ganglia.

Altered resting-state voxel-level whole-brain functional connectivity in depressed Parkinson's disease

BackgroundDepression is one of the most common non-motor symptoms in Parkinson's disease (PD), but its pathogenesis is still not very clear. Recently, degree centrality, a voxel-level whole-brain functional connectivity (FC) analysis of resting-state functional magnetic resonance imaging, has provided the most promising way to explore the neural network mechanisms underlying depressed PD. MethodsDegree centrality, voxel-wise image and clinical symptoms correlation and secondary seed-based FC analyses were performed in twenty-seven drug-naïve, early stage depressed PD patients, 27 non-depressed PD patients and 27 healthy controls (HCs) to reveal voxel-level whole-brain FC changes in depressed PD. ResultsCompared with the HCs, depressed PD and non-depressed PD patients shared similar brain degree centrality abnormalities mainly in the basal ganglia, insular cortex, motor cortices, default mode network, prefrontal gyrus and the cerebellum. However, compared with non-depressed PD, depressed PD showed degree centrality abnormalities in the right middle prefrontal gyrus, anterior cingulate cortices, supplementary motor cortices and cerebellum lobule VI. The right middle prefrontal gyrus degree centrality abnormalities were correlated with the clinical depression severity, and using it as a seed, a secondary seed-based FC analysis further revealed the FC changes in the anterior cingulate cortices and the cerebellum lobule VI. ConclusionsOur findings revealed that dysfunction in extensive brain areas were involved in depressed PD, and among these regions, the right middle prefrontal gyrus, anterior cingulate cortices and the cerebellum may pose as pathogenesis hubs underlying depressed PD.

Mechanisms Underlying Dopamine-Induced Risky Choice in Parkinson's Disease With and Without Depression (History).

Patients with Parkinson’s disease (PD) are often treated with dopaminergic medication. Dopaminergic medication is known to improve both motor and certain nonmotor symptoms, such as depression. However, it can contribute to behavioral impairment, for example, by enhancing risky choice. Here we characterize the computational mechanisms that contribute to dopamine-induced changes in risky choice in PD patients with and without a depression (history). We adopt a clinical–neuroeconomic approach to investigate the effects of dopaminergic medication on specific components of risky choice in PD. Twenty-three healthy controls, 21 PD patients with a depression (history), and 22 nondepressed PD patients were assessed using a well-established risky choice paradigm. Patients were tested twice: once after taking their normal dopaminergic medication and once after withdrawal of their medication. Dopaminergic medication increased a value-independent gambling propensity in nondepressed PD patients, while leaving loss aversion unaffected. By contrast, dopaminergic medication effects on loss aversion were associated with current depression severity and with drug effects on depression scores. The present findings demonstrate that dopaminergic medication increases a value-independent gambling bias in nondepressed PD patients. Moreover, the current study raises the hypothesis that dopamine-induced reductions in loss aversion might underlie previously observed comorbidity between depression and medication-related side effects in PD, such as impulse control disorder.

Impaired long contact white matter fibers integrity is related to depression in Parkinson's disease.

Depression is one of the most common nonmotor symptoms in Parkinson's disease (PD). But the pathogenesis is still unclear. Studies have shown that depression in PD is closely related to the white matter abnormalities, but the number of studies is still very small and lack of whole brain white matter lesions study. In this study, we investigated whole brain white matter integrity in 31 depressed PD patients and 37 nondepressed PD patients by diffusion tensor imaging. There was no difference in age, gender, age of onset, disease duration, Hoehn-Yahr scale, Unified Parkinson's Disease Rating Scale scores-III, and Mini-Mental State Examination scores between the two groups. The only difference was the Hamilton Depression Rating Scale. Depressed PD patients showed reduced fractional anisotropy values in the left anterior corona radiata, left posterior thalamic radiation, left cingulum, left superior longitudinal fasciculus, left sagittal stratum (including inferior longitudinal fasciculus and inferior fronto-occipital fasciculus), and left uncinate fasciculus. In patients with depression, the Hamilton Depression Rating Scale (HDRS) was negatively correlated with the FA value in the left cingulum (r=-0.712, P=.032) and left superior longitudinal fasciculus (r=-0.699, P=.025). This study suggested depression in PD was related to impaired white matter integrity especially the long contact fibers in the left hemisphere. These findings may be helpful for further understanding the potential mechanisms underlying depression in PD.

Reward learning deficits in Parkinson's disease depend on depression.

Depression is one of the most common and debilitating non-motor symptoms of Parkinson's disease (PD). The neurocognitive mechanisms underlying depression in PD are unclear and treatment is often suboptimal. We investigated the role of striatal dopamine in reversal learning from reward and punishment by combining a controlled medication withdrawal procedure with functional magnetic resonance imaging in 22 non-depressed PD patients and 19 PD patients with past or present depression. PD patients with a depression (history) exhibited impaired reward v. punishment reversal learning as well as reduced reward v. punishment-related BOLD signal in the striatum (putamen) compared with non-depressed PD patients. No effects of dopaminergic medication were observed. The present findings demonstrate that impairments in reversal learning from reward v. punishment and associated striatal signalling depend on the presence of (a history of) depression in PD.

Facial Emotion Recognition and Expression in Parkinson's Disease: An Emotional Mirror Mechanism?

Background and aimParkinson’s disease (PD) patients have impairment of facial expressivity (hypomimia) and difficulties in interpreting the emotional facial expressions produced by others, especially for aversive emotions. We aimed to evaluate the ability to produce facial emotional expressions and to recognize facial emotional expressions produced by others in a group of PD patients and a group of healthy participants in order to explore the relationship between these two abilities and any differences between the two groups of participants.MethodsTwenty non-demented, non-depressed PD patients and twenty healthy participants (HC) matched for demographic characteristics were studied. The ability of recognizing emotional facial expressions was assessed with the Ekman 60-faces test (Emotion recognition task). Participants were video-recorded while posing facial expressions of 6 primary emotions (happiness, sadness, surprise, disgust, fear and anger). The most expressive pictures for each emotion were derived from the videos. Ten healthy raters were asked to look at the pictures displayed on a computer-screen in pseudo-random fashion and to identify the emotional label in a six-forced-choice response format (Emotion expressivity task). Reaction time (RT) and accuracy of responses were recorded. At the end of each trial the participant was asked to rate his/her confidence in his/her perceived accuracy of response.ResultsFor emotion recognition, PD reported lower score than HC for Ekman total score (p<0.001), and for single emotions sub-scores happiness, fear, anger, sadness (p<0.01) and surprise (p = 0.02). In the facial emotion expressivity task, PD and HC significantly differed in the total score (p = 0.05) and in the sub-scores for happiness, sadness, anger (all p<0.001). RT and the level of confidence showed significant differences between PD and HC for the same emotions. There was a significant positive correlation between the emotion facial recognition and expressivity in both groups; the correlation was even stronger when ranking emotions from the best recognized to the worst (R = 0.75, p = 0.004).ConclusionsPD patients showed difficulties in recognizing emotional facial expressions produced by others and in posing facial emotional expressions compared to healthy subjects. The linear correlation between recognition and expression in both experimental groups suggests that the two mechanisms share a common system, which could be deteriorated in patients with PD. These results open new clinical and rehabilitation perspectives.

Non-demented Parkinson's disease patients with apathy show decreased grey matter volume in key executive and reward-related nodes.

Apathy is a common but poorly understood neuropsychiatric disturbance in Parkinson's disease (PD). In a recent study using event-related brain potentials we demonstrated impaired reward processing and compromised mesocortico-limbic pathways in PD patients with clinical symptoms of apathy. Here we aimed to further investigate the involvement of reward circuits in apathetic PD patients by assessing potential differences in brain structure. Using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) we quantified grey matter volume (GMV) in a sample of 18 non-demented and non-depressed PD patients with apathy, and 18 matched non-apathetic patients. Both groups were equivalent in terms of sociodemographic characteristics, disease stage, cognitive performance and L-Dopa equivalent daily dose. Apathetic patients showed significant GMV loss in cortical and subcortical brain structures. Various clusters of cortical GMV decrease were found in the parietal, lateral prefrontal cortex, and orbitofrontal cortex (OFC). The second largest cluster of GMV loss was located in the left nucleus accumbens (NAcc), a subcortical structure that is a key node of the human reward circuit. Isolated apathy in our sample is explained by the combined GMV loss in regions involved in executive functions, and cortical and subcortical structures of the mesolimbic reward pathway. The correlations observed between apathy and cognition suggests apathy as a marker of more widespread brain degeneration even in a sample of non-demented PD patients.

Brain perfusion alterations in depressed patients with Parkinson's disease.

Although Parkinson's disease (PD) is frequently accompanied by depression, brain perfusion deficits in PD with depression remain unclear. This study aimed to assess alterations in regional cerebral blood flow (rCBF) in depressed PD patients using 99mTc hexamethyl-propylene-amine-oxime single-photon emission computed tomography (SPECT). Among 78 patients with PD, 35 patients were classified into the depressed PD group, while the rest (43 patients) was assigned to the nondepressed PD group based on the scores of the Geriatric Depressive Scale (GDS). All participants underwent brain SPECT imaging. The voxel-wise whole-brain analysis and region-of-interest (ROI) analysis of the limbic areas were conducted to compare rCBF between the depressed and nondepressed PD groups. The depressed PD patients demonstrated higher GDS scores than nondepressed patients, whereas between-group differences in the PD severity and cognitive function were not significant. Perfusion in the left cuneus was increased, while that in the right superior temporal gyrus and right medial orbitofrontal cortex was reduced in the depressed PD patients as compared with nondepressed PD patients. In addition, the ROI analysis demonstrated rCBF decreases in the amygdala, anterior cingulate cortex, hippocampus, and parahippocampal gyrus in the depressed PD group. A positive correlation was found between the GDS scores and rCBF in the left cuneus cluster in the depressed PD patients. This study identified the regional pattern of brain perfusion that distinguished depressed from nondepressed PD patients. Hyperperfusion in the occipital areas and hypoperfusion in the fronto-temporo-limbic regions may be potential imaging biomarkers for depression in PD.

Altered directional connectivity between emotion network and motor network in Parkinson's disease with depression.

Depression is common in patients with Parkinson's disease (PD), which can make all the other symptoms of PD much worse. It is thus urgent to differentiate depressed PD (DPD) patients from non-depressed PD (NDPD).The purpose of the present study was to characterize alterations in directional brain connectivity unique to Parkinson's disease with depression, using resting state functional magnetic resonance imaging (rs-fMRI).Sixteen DPD patients, 20 NDPD patients, 17 patients with major depressive disorder (MDD) and 21 healthy control subjects (normal controls [NC]) underwent structural MRI and rs-fMRI scanning. Voxel-based morphometry and directional brain connectivity during resting-state were analyzed. Analysis of variance (ANOVA) and 2-sample t tests were used to compare each pair of groups, using sex, age, education level, structural atrophy, and/or HAMD, unified PD rating scale (UPDRS) as covariates.In contrast to NC, DPD showed significant gray matter (GM) volume abnormalities in some mid-line limbic regions including dorsomedial prefrontal cortex and precuneus, and sub-cortical regions including caudate and cerebellum. Relative to NC and MDD, both DPD and NDPD showed significantly increased directional connectivity from bilateral anterior insula and posterior orbitofrontal cortices to left inferior temporal cortex. As compared with NC, MDD and NDPD, alterations of directional connectivity in DPD were specifically observed in the pathway from bilateral anterior insula and posterior orbitofrontal cortices to right basal ganglia.Resting state directional connectivity alterations were observed between emotion network and motor network in DPD patients after controlling for age, sex, structural atrophy. Given that these alterations are unique to DPD, it may provide a potential differential biomarker for distinguishing DPD from NC, NDPD, and MDD.

Behavioural and neuroimaging correlates of impaired self-awareness of hypo- and hyperkinesia in Parkinson's disease

IntroductionAnosognosia or impaired self-awareness of motor symptoms (ISAm) has been rarely investigated in Parkinson's disease (PD). We here studied the relationship between ISAm during periods with and without dopaminergic medication (ON- and OFF-state), and clinical, neuropsychological, and neuroimaging data to further elucidate behavioural aspects and the neurobiological underpinnings of ISAm. MethodsThirty-one right-handed, non-demented, non-depressed PD patients were included. ISAm was evaluated using a recently developed scale that assesses awareness of dyskinesia, resting tremor, and bradykinesia. The test was applied during both ON- and OFF-states. Multiple correlation analyses between ISAm and behavioural data were conducted. In addition, imaging of glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was performed to investigate the neural basis of ISAm. A multiple regression approach was applied to investigate metabolism alterations related to ISAm. ResultsIn the OFF-state, higher ISAm was associated with left-sided disease onset, older age, and shorter disease duration. Concerning FDG-PET data, there was a significant negative correlation between higher OFF-state ISAm and decreased glucose metabolism in the right inferior frontal gyrus (IFG). In the ON-state, ISAm was not significantly correlated with clinical or behavioural data. However, there was a significant correlation between higher ISAm and an increased metabolism in the bilateral medial frontal gyrus, left IFG, right superior frontal gyrus and right precentral gyrus. ConclusionThe results support the role of the right hemisphere in awareness of motor symptoms in the OFF-state. In the ON-state, dopaminergic medication and dyskinesia influence ISAm and relate to metabolism changes in bilateral frontal regions.

Cortical abnormalities in Parkinson’s disease patients and relationship to depression: A surface-based morphometry study

Depression is a common occurrence in patients with Parkinson's disease (PD). Brain deficits may be the underlying cause of depression in PD. In the present study, we investigated whether morphometric alterations contribute to depression in PD. Seventeen depressed PD patients, 17 non-depressed PD patients and 45 normal controls were enrolled in the study. All subjects went through neurological and psychiatric clinical assessments. T1 weighted magnetic resonance imaging and surface-based morphometric analyses were performed to examine morphometric abnormalities in PD patients and their relationship to depression. We found that compared with normal controls, PD patients exhibited significantly decreased cortical thickness in the left precentral gyrus and the right postcentral gyrus extending to the middle frontal gyrus. Compared with non-depressed PD patients, depressed patients showed significantly increased cortical areas in the orbitofrontal regions and insula, which may imply white matter atrophy in these areas. The results of orbitofrontal and insula white matter atrophy are consistent with our previous finding that white matter integrity and functional connectivity are damaged in these regions in depressed PD patients, confirming their contribution to depression in PD.

The pons and human affective processing — Implications for Parkinson's disease

Affective processing determines how we react to stimuli, interact with the surroundings and perceive the world. It shapes our behaviour. In their article in this issue of EBioMedicine, Lee et al. (Lee et al., 2015) shed light on the involvement of the pons in affective processing in healthy volunteers. The authors report the findings of experiments where they showed images to adult women. The images consisted of visual stimuli containing a positive, neutral or negative affective charge. They conducted blood-oxygen-level dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) to determine brain metabolism during the visualising and subsequent emotional processes. Specifically, they analysed task-based BOLD signals, tested small-world connectivity and examined resting-state functional and diffusion tensor imaging (DTI) structural connectivity. They discovered that showing positive visual stimuli results in activation of a pontine region, possibly the caudal raphe nuclei. A significant functional connectivity was found between the pons and cortico-sub-cortical structures involved in affective processing, encompassing the caudate nucleus, thalamus, hippocampus, amygdala, as well as the cingulate, insular and frontal cortices. The authors conclude that their findings indicate that the pons forms a network with “cortico-limbic-striatal” systems to mediate one's affective state after seeing emotionally-charged images. Whereas Lee et al.'s study was conducted in a sample of subjects without prior neuro-psychiatric history, as pointed out by the authors, their results suggest that the pons might play a role in affective/mood disorders. Depressive and related disorders are a category of mood disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). It is noteworthy that depression is encountered in several neuro-degenerative diseases, such as Parkinson's disease (PD). What do the findings of Lee et al. might mean for PD patients? In PD, the pons degenerates, encompassing serotonin (5-HT)-producing raphe nuclei (Halliday et al., 1990). The role of 5-HT in mood and affect has been well-documented (Berger et al., 2009). As many as 30–40% of PD patients are afflicted by depressive symptoms (Aarsland et al., 2009). Tallying this to the results of Lee et al., it becomes plausible that dysfunctional pontine structures might play a role in mood disorders in PD. Several in vivo imaging studies have examined the raphe 5-HT transporter in PD, via either positron emission tomography (PET) or single-photon emission computed tomography (SPECT) modalities. However, as these PET and SPECT studies were designed to study the 5-HT transporter function, they would, at most, provide only indirect assessment of the pons per se. Moreover, several of these were conducted in non-depressed patients (Guttman et al., 2007, Politis et al., 2010a) or focussed on other regions of interest, e.g. the midbrain (Haapaniemi et al., 2001, Berding et al., 2003). Two studies are worth discussing here, as they assessed the 5-HT transporter binding in the caudal raphe nuclei, which are located in the pons. In a recent SPECT study encompassing 345 early, drug-naive male and female PD patients, there was no correlation between raphe (rostral and caudal) 5-HT transporter binding and depression (Qamhawi et al., 2015). In contrast, in a PET study encompassing PD patients with and without depression and healthy controls, caudal raphe nuclei 5-HT transporter binding was lower in non-depressed PD patients when compared to depressed PD patients and healthy controls, while no difference was encountered between depressed PD patients and controls (Politis et al., 2010b). It should be noted that the PD patients from this last study were more advanced than those from the first study and were not drug-naive, thus making the PD populations from the two studies difficult to compare. The fate of 5-HT transporter located in the caudal raphe nuclei therefore appears unclear in PD and possibly varies according to disease progression and medication intake. Nevertheless, the second study suggests that 5-HT transporter binding is higher in depressed PD patients compared to depressed patients; how does that relate to the increased metabolic activity found by Lee et al. in the pons in their study needs to be further investigated. In summary, Lee et al.'s results point out that the pons might be involved in affective processing of visual stimuli. Their study refines the understanding of affective processing and has implications to better understand the networks underlying affective processing in the physiological state. It also provides a new neuro-anatomical substrate to investigate in neuro-degenerative conditions where there are affective/mood disorders such as PD.