Diffusion MRI Connectometry Research Articles

Understanding Anxiety in Cervical Dystonia: An Imaging Study.

Anxiety may precede motor symptoms in cervical dystonia (CD) and is associated with an earlier onset of dystonia. Our understanding of anxiety in CD is inadequate. To investigate brain networks associated with anxiety in CD. Twenty-six subjects with idiopathic CD underwent MRI Brain without contrast. Correlational tractography was derived using Diffusion MRI connectometry. Quantitative Anisotropy (QA) was used in deterministic diffusion fiber tracking. Correlational tractography was then used to correlate QA with State-Trait Anxiety Inventory (STAI) state (STAI-S) and trait (STAI-T) subscales. Connectometry analysis showed direct correlation between state anxiety and QA in tracts from amygdala to thalamus/ pulvinar bilaterally, and trait anxiety and QA in tracts from amygdala to motor cortex, sensorimotor cortex and parietal association area bilaterally (FDR ≤0.05). Our efforts to map anxiety to brain networks in CD highlight the role of the amygdala in the pathophysiology of anxiety in CD.

Correlation of diffusion tensor tractography with obstructive sleep apnea severity.

Using correlation tractography, this study aimed to find statistically significant correlations between white matter (WM) tracts in participants with obstructive sleep apnea (OSA) and OSA severity. We hypothesized that changes in certain WM tracts could be related to OSA severity. We enrolled 40 participants with OSA who underwent diffusion tensor imaging (DTI) using a 3.0 Tesla MRI scanner. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and quantitative anisotropy (QA)-values were used in the connectometry analysis. The apnea-hypopnea index (AHI) is a representative measure of the severity of OSA. Diffusion MRI connectometry that was used to derive correlational tractography revealed changes in the values of FA, MD, AD, RD, and QA when correlated with the AHI. A false-discovery rate threshold of 0.05 was used to select tracts to conduct multiple corrections. Connectometry analysis revealed that the AHI in participants with OSA was negatively correlated with FA values in WM tracts that included the cingulum, corpus callosum, cerebellum, inferior longitudinal fasciculus, fornices, thalamic radiations, inferior fronto-occipital fasciculus, superior and posterior corticostriatal tracts, medial lemnisci, and arcuate fasciculus. However, there were no statistically significant results in the WM tracts, in which FA values were positively correlated with the AHI. In addition, connectometry analysis did not reveal statistically significant results in WM tracts, in which MD, AD, RD, and QA values were positively or negatively correlated with the AHI. Several WM tract changes were correlated with OSA severity. However, WM changes in OSA likely involve tissue edema and not neuronal changes, such as axonal loss. Connectometry analyses are valuable tools for detecting WM changes in sleep disorders.

Choir singing is associated with enhanced structural connectivity across the adult lifespan.

The global ageing of populations calls for effective, ecologically valid methods to support brain health across adult life. Previous evidence suggests that music can promote white matter (WM) microstructure and grey matter (GM) volume while supporting auditory and cognitive functioning and emotional well-being as well as counteracting age-related cognitive decline. Adding a social component to music training, choir singing is a popular leisure activity among older adults, but a systematic account of its potential to support healthy brain structure, especially with regard to ageing, is currently missing. The present study used quantitative anisotropy (QA)-based diffusion MRI connectometry and voxel-based morphometry to explore the relationship of lifetime choir singing experience and brain structure at the whole-brain level. Cross-sectional multiple regression analyses were carried out in a large, balanced sample (N = 95; age range 21-88) of healthy adults with varying levels of choir singing experience across the whole age range and within subgroups defined by age (young, middle-aged, and older adults). Independent of age, choir singing experience was associated with extensive increases in WM QA in commissural, association, and projection tracts across the brain. Corroborating previous work, these overlapped with language and limbic networks. Enhanced corpus callosum microstructure was associated with choir singing experience across all subgroups. In addition, choir singing experience was selectively associated with enhanced QA in the fornix in older participants. No associations between GM volume and choir singing were found. The present study offers the first systematic account of amateur-level choir singing on brain structure. While no evidence for counteracting GM atrophy was found, the present evidence of enhanced structural connectivity coheres well with age-typical structural changes. Corroborating previous behavioural studies, the present results suggest that regular choir singing holds great promise for supporting brain health across the adult life span.

White matter tracts alterations underpinning reward and conflict processing

BackgroundReinforcement sensitivity theory (RST) is proposed as a neurobiological system that eventually led to emotion and motivation-based constructs of personality. Traditionally segmented into the behavioral activation system (BAS) and the behavioral inhibition system (BIS), RST is commonly used to describe personality and behavior. Although there have been studies linking gray matter alterations with BIS/BAS subscales, the role of white matter (WM) alterations is yet controversial. We aimed to investigate the specific WM tracts associated with BIS/BAS scores. Methods220 healthy participants (mean age = 39.14 ± 20.23, 80 (35.7 %) females) were evaluated using the BIS/BAS questionnaire from the LEMON database. Diffusion MRI connectometry (DMRI) was used to investigate the WM correlates of BIS/BAS subscales in each gender group. Multiple regression models with the covariates of age, handedness, and education were fitted to address the correlation of local connectomes with BIS/BAS components. ResultsDMRI connectometry revealed that the quantitative anisotropy (QA) value of the splenium of the corpus callosum, right cerebellum, middle cerebellar peduncle, and superior cerebellar peduncle, had a significant negative correlation with each BIS/BAS subscale. In contrast, the QA value in the body of the corpus callosum and bilateral cingulum showed a positive correlation with BIS/BAS subscales. ConclusionThe integrity of WM in certain tracts is associated with behavioral activation and inhibition. This finding expands our knowledge of the neural networks associated with risk-taking and reward-seeking behaviors.

Alterations in white matter integrity in cognitively stable Down syndrome correlate with plasma neurofilament light chain: Evidence of early myelin breakdown

AbstractBackgroundAlterations in white matter (WM) integrity occur in adults with DS during the early stage of dementia. These changes may be documented by diffusion tensor imaging wherein increases in radial diffusivity (RD), a marker of dysmyelination or myelin breakdown, occur in commissural and limbic pathways in DS. Neurofilament light chain (NfL) is a support protein within large, myelinated axons specifically within the cerebral white matter and is released into blood following axonal damage and is increased in DS. In this study, we evaluated the association between plasma NfL concentrations and RD.MethodThirty cognitively stable adults with DS from the Alzheimer Disease in Down Syndrome (part of the ABC‐DS) study, (18 M, 12 F: mean age 47.1 years SD 5.2 years), underwent DTI and plasma NfL concentration measurements. Plasma NfL was assayed using the Simoa platform. Diffusion MRI connectometry was conducted using q‐space diffeomorphic reconstruction and a multiple regression model to assess the associations between plasma NfL and white matter radial diffusivity (RD). The Spearman correlation coefficient, and its 95% confidence interval (CI), was used to quantify the monotonic association between plasma NfL and RD.ResultConsistent with our hypothesis, we found positive associations between plasma NfL and RD increases, in several WM higher order association tracts, including the corpus callosum (0.46, 95% CI 0.11‐0.70, p=0.012), the cingulum bundle (L: 0.62, 0.34‐0.80, p<0.001; R: 0.54 0.23‐0.76, p=0.002) and the uncinate fasciculus (L: 0.17, ‐0.20‐0.50, p=0.367; R: 0.51, 0.18‐0.73, p=0.004).ConclusionOur findings support an important link between alterations in WM myelin integrity, particularly of higher order association areas, and axonal degeneration in cognitively stable adults with Down syndrome. These findings support an important role of WM alterations in adults with DS who are at risk for and who develop AD earlier than in sporadic AD cases. WM might provide an important and novel target for intervention. Additional research is needed to understand the underlying neuropathological processes, including the potential contribution of neuronal dysfunction and/or loss to our findings. Acknowledgements: NIH grant U01AG051412. We are grateful to our participants, families, the agencies serving individuals with ID, and our dedicated staff.

Sex Differences are Reflected in Microstructural White Matter Alterations of Musical Sophistication: A Diffusion MRI Study.

Background: The human-specified ability to engage with different kinds of music in sophisticated ways is named “Musical Sophistication.” Herein, we investigated specific white matter (WM) tracts that are associated with musical sophistication and musicality in both genders, separately, using Diffusion MRI connectometry approach. We specifically aimed to explore potential sex differences regarding WM alterations correlated with musical sophistication.Methods: 123 healthy participants [70 (56.9%) were male, mean age = 36.80 ± 18.86 year], who were evaluated for musical sophistication using Goldsmiths Musical Sophistication Index (Gold-MSI) self-assessment instrument from the LEMON database, were recruited in this study. The WM correlates of two Gold-MSI subscales (active engagement and music training) were analyzed. Images were prepared and analyzed with diffusion connectometry to construct the local connectome. Multiple regression models were then fitted to address the correlation of local connectomes with Gold-MSI components with the covariates of age and handedness.Results: a significant positive correlation between WM integrity in the corpus callosum (CC), right corticospinal tract (CST), cingulum, middle cerebellar peduncle (MCP), bilateral parieto-pontine tract, bilateral cerebellum, and left arcuate fasciculus (AF) and both active engagement [false discovery rate (FDR) = 0.008] and music training (FDR = 0.057) was detected in males. However, WM integrity in the body of CC, MCP, and cerebellum in females showed an inverse association with active engagement (FDR = 0.046) and music training (FDR = 0.032).Conclusion: WM microstructures with functional connection with motor and somatosensory areas (CST, cortico-pontine tracts, CC, cerebellum, cingulum, and MCP) and language processing area (AF) have significant correlation with music engagement and training. Our findings show that these associations are different between males and females, which could potentially account for distinctive mechanisms related to musical perception and musical abilities across genders.

Sex differences in microstructural white matter alterations of mathematics anxiety based on diffusion MRI connectometry.

Mathematics Anxiety (MA) is a feeling of stress, tension, and fear in situations engaging with math-related tasks. Herein, we utilized Diffusion Magnetic Resonance Imaging (DMRI) connectometry approach to tracking white matter (WM) fibers with a significant correlation with the severity of MA. A total of 77 healthy adult participants (50 males, mean age ± SD = 26.00 ± 3.54) were included from the Leipzig Study for Mind-Body-Emotion Interactions (LEMON) database. Abbreviated Math Anxiety Scale (AMAS) questionnaire was used for assessing the participant's feelings when facing a math-related activity. DMRI data were prepared and analyzed with the connectometry approach. Multiple regression models were then carried out to examine the correlation of WM microstructural connectivity with AMAS score. DMRI connectometry showed a significant association between AMAS score and increased microstructural connectivity in left arcuate fasciculus (AF), the body of corpus callosum (CC), right cingulum, and left inferior longitudinal fasciculus (ILF) in male participants with moderate effect size false discovery rate (FDR = 0.040). Furthermore, DMRI connectometry in females identified a positive correlation between AMAS score and microstructural connectivity in the genu of CC, right ILF, and bilateral fornices with small-to-moderate effect size (FDR = 0.012) and a negative correlation between AMAS score and microstructural connectivity in the bilateral cingulum with small-to-moderate effect size (FDR = 0.032) Conclusion: Our findings support that structures with functional relation to language processing areas (e.g., AF) or limbic system (cingulum, CC, fornix, and ILF) play a significant role in MA. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Blue-Light Therapy Strengthens Resting-State Effective Connectivity within Default-Mode Network after Mild TBI.

Background:Emerging evidence suggests that post concussive symptoms, including mood changes, may be improved through morning blue-wavelength light therapy (BLT). However, the neurobiological mechanisms underlying these effects remain unknown. We hypothesize that BLT may influence the effective brain connectivity (EC) patterns within the default-mode network (DMN), particularly involving the medial prefrontal cortex (MPFC), which may contribute to improvements in mood.Methods:Resting-state functional MRI data were collected from 41 healthy-controls (HCs) and 28 individuals with mild traumatic brain injury (mTBI). Individuals with mTBI also underwent a diffusion-weighted imaging scan and were randomly assigned to complete either 6 weeks of daily morning BLT (N = 14) or amber light therapy (ALT; N = 14). Advanced spectral dynamic causal modeling (sDCM) and diffusion MRI connectometry were used to estimate EC patterns and structural connectivity strength within the DMN, respectively.Results:The sDCM analysis showed dominant connectivity pattern following mTBI (pre-treatment) within the hemisphere contralateral to the one observed for HCs. BLT, but not ALT, resulted in improved directional information flow (ie, EC) from the left lateral parietal cortex (LLPC) to MPFC within the DMN. The improvement in EC from LLPC to MPFC was accompanied by stronger structural connectivity between the 2 areas. For the BLT group, the observed improvements in function and structure were correlated (at a trend level) with changes in self-reported happiness.Conclusions:The current preliminary findings provide empirical evidence that morning short-wavelength light therapy could be used as a novel alternative rehabilitation technique for mTBI.Trial registry:The research protocols were registered in the ClinicalTrials.gov database (CT Identifiers NCT01747811 and NCT01721356).

Microstructural white matter alterations and personality traits: A diffusion MRI study

Personality traits refer to a set of independent patterns of behaviour, cognition, and emotion. The Big-Five of Personality (NEO-FFI), is one of the most generally recognized taxonomies of personality. The current structural and functional correlates of personality are divergent and inconsistent in some cases, which necessitate further investigation of it. Herein, we aimed to investigate the white matter (WM) microstructural correlates of personality traits using diffusion MRI connectometry. Overall, the main findings of this study were located in different parts of the corpus callosum (CC) and middle cerebellar peduncle (MCP), highlighting the significant role of WM local connectome in the CC and MCP in the regulation of personality traits. Future studies need to validate our results.

White Matter Tract Alterations in Drug-Naïve Parkinson's Disease Patients With Excessive Daytime Sleepiness.

Excessive daytime sleepiness (EDS) is relatively frequent in patients with Parkinson's disease (PD), having a prominent burden on patients' quality of life and causing dangerous events such as motor-vehicle accidents. Previous studies have indicated the role of certain neural tracts in the pathophysiology of sleep disturbances, especially in PD patients. We hypothesized that white matter integrity and connectivity might be altered in patients with PD and EDS. Therefore, this study investigated brain white matter microstructure alterations in patients with Parkinson's disease with EDS (PD-EDS) compared to healthy controls and PD patients without EDS (PD-nEDS). Diffusion MRI connectometry was used to carry out group analysis between PD patients with and without EDS and healthy individuals. EDS in PD patients is associated with decreased connectivity in the left and right fornix, left and right inferior longitudinal fasciculus (ILF), left inferior and middle cerebellar peduncles in comparison to PD-nEDS group. These differences between PD-EDS and PD-nEDS patients reflects microstructural changes with respect to sleep-related circuits, which can pave the way for future investigations considering EDS pathogenesis in Parkinson's disease.

White matter correlates of disease duration in patients with temporal lobe epilepsy: updated review of literature.

Medial temporal lobe epilepsy (mTLE) has been associated with widespread white mater (WM) alternations in addition to mesial temporal sclerosis (MTS). Herein, we aimed to investigate the correlation between disease duration and WM structural abnormalities in mTLE using diffusion MRI (DMRI) connectometry approach. DMRI connectometry was conducted on 24 patients with mTLE. A multiple regression model was used to investigate white matter tracts with microstructural correlates to disease duration, controlling for age and sex. DMRI data were processed in the MNI space using q-space diffeomorphic reconstruction to obtain the spin distribution function (SDF). The SDF values were converted to quantitative anisotropy (QA) and used in further analyses. Connectometry analysis identified impaired white matter QA of the following fibers to be correlated with disease duration: bilateral retrosplenial cingulum, bilateral fornix, right inferior longitudinal fasciculus (ILF), and genu of corpus callosum (CC) (FDR = 0.009). Our results were obtained from DMRI connectometry, which indicates the connectivity and the level of diffusion in nerve fibers rather just the direction of diffusion. Compared to previous studies investigating the correlation between duration of epilepsy and white matter integrity in mTLE patients, we detected broader and somewhat different associations in midline structures and component of limbic system. However, further studies with larger sample sizes are required to elucidate previous and current results.

White matter microstructural differences between right and left mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (mTLE) is a chronic focal epileptic disorder characterized by recalcitrant seizures often necessitating surgical intervention. Identifying the laterality of seizure focus is crucial for pre-surgical planning. We implemented diffusion MRI (DMRI) connectometry to identify differences in white matter connectivity in patients with left and right mTLE relative to healthy control subjects. We enrolled 12 patients with right mTLE, 12 patients with left mTLE, and 12 age/sex matched healthy controls (HCs). We used DMRI connectometry to identify local connectivity patterns of white matter tracts, based on quantitative anisotropy (QA). We compared QA of white matter to reconstruct tracts with significant difference in connectivity between patients and HCs and then between patients with left and right mTLE. Right mTLE patients show higher anisotropy in left inferior longitudinal fasciculus (ILF) and forceps minor and lower QA in genu of corpus callosum (CC), bilateral corticospinal tracts (CSTs), and bilateral middle cerebellar peduncles (MCPs) compared to HCs. Left mTLE patients show higher anisotropy in genu of CC, bilateral CSTs, and right MCP and decreased anisotropy in forceps minor compared to HCs. Compared to patients with right mTLE, left mTLE patients showed increased and decreased connectivity in some major tracts. Our study showed the pattern of microstructural disintegrity in mTLE patients relative to HCs. We demonstrated that left and right mTLE patients have discrepant alternations in their white matter microstructure. These results may indicate that left and right mTLE have different underlying pathologic mechanisms.

Association of olfaction dysfunction with brain microstructure in prodromal Parkinson disease

Although olfaction dysfunction is now considered as an established clinical marker of prodromal Parkinson disease (PD), little is known about the neural underpinnings of olfaction dysfunction in the prodromal phase of PD. The aim of this study was to examine the microstructural association of olfaction in prodromal PD compared to early stage drug-naïve PD patients. Diffusion MRI connectometry was conducted on 18 early PD and 17 prodromal PD patients to investigate the differences in group in terms of altered connectivity, i.e., integrity of white matter tracts, and subsequently to study the correlation of University of Pennsylvania Smell Identification Test (UPSIT) score to white matter integrity in each group using a multiple regression model considering age, sex, RBD, and MoCA, as covariates. Individuals with prodromal PD had significantly higher quantitative anisotropy (QA) comparing with PD patients in bilateral middle cerebellar peduncles and right arcuate fasciculus. Multiple regression analysis in prodromal PD demonstrated positive association between UPSIT score and connectivity in left and right subgenual cingulum, right inferior fronto-occipital fasciculus, left corticospinal tract, left parietopontine, left corticothalamic tract, and the body and the splenium of corpus callosum. These results indicate that PD and prodromal PD patients, which were matched for sex, UPSIT, and MoCA scores, have different white matter fiber architecture. Thus, it is postulated that olfaction dysfunction in prodromal and early clinical phases of PD may involve distinct pathogenesis. Increased network connectivity in prodromal and early PD may suggest the neural compensation.

Microstructural Changes in Patients With Parkinson's Disease Comorbid With REM Sleep Behaviour Disorder and Depressive Symptoms.

The diagnosis of Parkinson's disease (PD) is currently anchored on clinical motor symptoms, which appear more than 20 years after initiation of the neurotoxicity. Extra-nigral involvement in the onset of PD with probable nonmotor manifestations before the development of motor signs, lead us to the preclinical (asymptomatic) or prodromal stages of the disease (various nonmotor or subtle motor signs). REM sleep behavior disorder (RBD) and depression are established prodromal clinical markers of PD and predict worse motor and cognitive outcomes. Nevertheless, taken by themselves, these markers are not yet claimed to be practical in identifying high-risk individuals. Combining promising markers may be helpful in a reliable diagnosis of early PD. Therefore, we aimed to detect neural correlates of RBD and depression in 93 treatment-naïve and non-demented early PD by means of diffusion MRI connectometry. Comparing four groups of PD patients with or without comorbid RBD and/or depressive symptoms with each other and with 31 healthy controls, we found that these two non-motor symptoms are associated with lower connectivity in several white matter tracts including the cerebellar peduncles, corpus callosum and long association fibers such as cingulum, fornix, and inferior longitudinal fasciculus. For the first time, we were able to detect the involvement of short association fibers (U-fibers) in PD neurodegenerative process. Longitudinal studies on larger sample groups are needed to further investigate the reported associations.

High angular resolution diffusion imaging correlates of depression in Parkinson’s disease: a connectometry study

Depression is a significant disabling feature in Parkinson's disease (PD). However, the neuropathology of this comorbidity is still unclear. In fact, few studies have tried to elucidate the neural correlates of depression in PD and have mostly examined specific regions of interest. In this study, we applied diffusion MRI connectometry, a powerful complementary approach to investigate alterations in whole white matter pathways regarding the severity of depressive symptoms. Using a multiple regression model, the correlation of severity of depressive symptoms assessed by the Hospital Anxiety and Depression Scale (HADS) with white matter connectivity was surveyed in 27 non-demented PD patients related to 26 age, sex, and educational level-matched healthy subjects. Results revealed areas, where white matter quantitative anisotropy (QA) was correlated with depression score in PD patients, without any significant association in healthy controls. The analysis showed a significant negative association (false discovery rate < 0.05) between scores on depression subscale of HADS in PD patients and QA of left Cingulum, Genu, and Splenium of the Corpus Callosum, and anterior and posterior limbs of the right internal capsule. This finding might improve our understanding of the neural basis of depression and its severity in PD.

Comprehensive Investigation of White Matter Tracts in Professional Chess Players and Relation to Expertise: Region of Interest and DMRI Connectometry.

Purpose: Expertise is the product of training. Few studies have used functional connectivity or conventional diffusometric methods to identify neural underpinnings of chess expertise. Diffusometric variables of white matter might reflect these adaptive changes, along with changes in structural connectivity, which is a sensitive measure of microstructural changes.Method: Diffusometric variables of 29 professional chess players and 29 age-sex matched controls were extracted for white matter regions based on John Hopkin's Mori white matter atlas and partially correlated against professional training time and level of chess proficiency. Diffusion MRI connectometry was implemented to identify changes in structural connectivity in professional players compared to novices.Result: Compared to novices, higher planar anisotropy (CP) was observed in inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF) and cingulate gyrus, in professional chess players, which correlated with higher RPM score in this group. Higher fractional anisotropy (FA) was observed in ILF, uncinate fasciculus (UF) and hippocampus and correlated with better scores in Raven's progressive matrices (RPM) score and longer duration of chess training in professional players. Consistently, radial diffusivity in bilateral IFOF, bilateral ILF and bilateral SLF was inversely correlated with level of training in professional players. DMRI connectometry analysis identified increased connectivity in bilateral UF, bilateral IFOF, bilateral cingulum, and corpus callosum in chess player's compared to controls.Conclusion: Structural connectivity of major associational subcortical white matter fibers are increased in professional chess players. FA and CP of ILF, SLF and UF directly correlates with duration of professional training and RPM score, in professional chess players.

White Matter Tract Alterations in Drug-Naïve Parkinson's Disease Patients With Impulse Control Disorders.

Impulse control disorders (ICDs) are relatively frequent in patients with Parkinson’s disease (PD), although it is still unclear whether an underlying pathological process plays a significant role in the development of ICD in PD apart from dopaminergic replacement therapy. In this study, we have investigated alterations of white matter tract in drug-naïve PD patients with ICDs via diffusion MRI connectometry. Our results showed that disrupted connectivity in the complex network of dynamic connections between cerebellum, basal ganglia, cortex, and its spinal projections serves as the underlying neuropathology of ICD in PD not interfered with the contribution of dopaminergic replacement therapy. These findings provide the first evidence on involved white matter tracts in the neuropathogenesis of ICD in drug-naïve PD population, supporting the hypothesis that neural disturbances intrinsic to PD may confer an increased risk for ICDs. Future studies are needed to validate the attribution of the impaired corticocerebellar network to impulsivity in PD.

Posterior limb of the internal capsule predicts poor quality of life in patients with Parkinson's disease: connectometry approach.

Psychiatric symptoms and motor impairment are major contributions to the poor quality of life in patients with Parkinson's disease (PD). Here, we applied a novel diffusion-weighted imaging approach, diffusion MRI connectometry, to investigate the correlation of quality of life, evaluated by Parkinson's Disease Questionnaire (PDQ39) with the white matter structural connectivity in 27 non-demented PD patients (disease duration of 5.3±2.9years, H and Y stage=1.5±0.6, UPDRS-III=13.7±6.5, indicating unilateral and mild motor involvement). The connectometry analysis demonstrated bilateral posterior limbs of the internal capsule(PLIC) with increased connectivity related to the higher quality of life (FDR=0.027) in a multiple regression model. The present study suggestsfor the first time a neural basis of the quality of life in PD in the light of major determinants of poor quality of life in these patients: anxiety, depression, apathy and motor impairment. Results in our sample of non-demented PD patients with relatively mild motor impairment and no apparent sign of depression/anxiety also identify a unique and inexplicable association of the PLIC to the quality of life in PD patients.

Microstructural changes in patients with Parkinson disease and REM sleep behavior disorder: depressive symptoms versus non-depressed.

Search for Parkinson's disease (PD) progression biomarkers has led to theidentification of both motor and non-motor symptoms relevant of prodromal PD that could be eye-opening to the spreading underlying Lewy body pathogenesis. One most robust predictor of PD is the REM sleep behavior disorder (RBD), and one most common early non-motor symptom of PD is depression. With RBD, frequently coexisting with clinical depression and both predicting dopamine transmission dysfunction, we aimed to survey structural associates of depressive symptoms in early PD patients with comorbid RBD. Through diffusion MRI connectometry, we tracked fiber differences comparing DWI images obtained from 14 patients with depressive symptoms and 18 without depression from a group with comorbid RBD and PD. DWI images and patients were recruited from the Parkinson's Progression Markers Initiative database. PD-RBD patients with depressive symptoms showed pathways with significantly reduced connectivity in the right cingulum, left and right fornix, left inferior longitudinal fasciculus, right corticospinal tract, left middle cerebellar peduncleand genu of corpus callosum (FDR=0.0228). Diffusivity alteration of the mentioned fibers in depressed, early PD patients with RBD might reflect underlying PD pathology and serve as common structural DWI signatures for early PD diagnosis.

Exploring white matter microstructure and olfaction dysfunction in early parkinson disease: diffusion MRI reveals new insight.

Olfaction dysfunction is considered as a robust marker of prodromal Parkinson disease (PD). Measurement of olfaction function as a screening test is unsatisfactory due to long lead time interval and low specificity for detection of PD. Use of imaging markers might yield more accurate predictive values and provide bases for combined use of imaging and clinical markers for early PD. Diffusion MRI connectometry was conducted on 85 de novo PD patients in and 36 healthy controls to find: first, white matter tracts with significant difference in quantitative anisotropy between PD groups with various degrees of olfaction dysfunction and second, second fibers with correlation with University of Pennsylvania Smell Identification Test (UPSIT) score in each group using a multiple regression analysis considering age, sex, GDS and MoCA score. Local connectomes were determined in seven of all the possible comparisons, correcting for false discovery rate (FDR). PD patients with anosmia and normal olfaction had the highest number of fibers with decreased connectivity in left inferior longitudinal fasciculus, bilateral fornix, bilateral middle cerebellar peduncle (MCP), bilateral cingulum, bilateral corticospinal tract (CST) and body, genu and splenium of corpus callosum (CC) (FDR = 0.0013). In multiple regression analysis, connectivity in the body, genu and splenium of CC and bilateral fornix had significant negative correlation (FDR between 0.019 and 0.083), and bilateral cingulum and MCP had significant positive correlation (FDR between 0.022 and 0.092) with UPSIT score. White matter connectivity in healthy controls could not be predicted by UPSIT score using the same model. The results of this study provide compelling evidence that microstructural degenerative changes in these areas underlie the clinical phenotype of prodromal olfaction dysfunction in PD and that diffusion parameters of these areas might be able to serve as signature markers for early detection of PD. This is the first report that confirms a discriminative role for UPSIT score in identifying PD specific changes in white matter microstructure. Our results open a window to identify microstructural signatures of prodromal PD in white matter.