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In this retrospective study, we aimed to evaluate the effects of the neurotrophic compound Cerebrolysin on executive, cognitive, and functional performance in patients with traumatic brain injury (TBI) with a highly severe disability level. A total of 44 patients were included in the study, with 33 patients in the control group and 11 patients in the interventional group who received intravenous infusions of 30 mL Cerebrolysin. Both groups received standard rehabilitation therapy following the rehabilitation protocol for patients with TBI at Hospital Clínico Mutual de Seguridad. Functional and cognitive scales were evaluated at baseline, at four months, and at the endpoint of the intervention therapy at seven months (on average). The results revealed a significant improvement in the Cerebrolysin-treated group compared to the control group. Specifically, patients who received Cerebrolysin showed a moderate residual disability and a significant reduction in the need for care. Concerning the promising results and considering the limitations of the retrospective study design, we suggest that randomized controlled studies be initiated to corroborate the positive findings for Cerebrolysin in patients with moderate to severe brain trauma.

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Introduction: Finding a non-invasive and repeatable tool has been recommended to make an accurate diagnosis of Alzheimer's disease (AD) and Parkinson's disease (PD). Methods: 70 volunteers participated in three groups: 24 with mild dementia of AD, 24 in the first and second stages of PD, and 22 healthy controls. After valuing the scores of cognitive tests, the salivary levels of phosphorylated tau (p-tau), total alpha-synuclein (α-syn), and beta-amyloid 1-42 (Aß) proteins have been evaluated. Finally, the cutoff points, receiver operating characteristic (ROC), sensitivity, and specificity have been calculated to find accurate and detectable biomarkers. Results: Findings showed that the salivary level of Aß was higher in both PD (p < 0.01) and AD (p < 0.001) patients than in controls. Moreover, the level of α-syn in both PD and AD patients was similarly lower than in controls (p < 0.05). However, the level of p-tau was only higher in the AD group than in the control (p < 0.01). Salivary Aß 1-42 level at a 60.3 pg/ml cutoff point revealed an excellent performance for diagnosing AD (AUC: 0.81). Conclusion: Evaluation of p-tau, α-syn, and Aß 1-42 levels in the saliva of AD and PD patients could help the early diagnosis. The p-tau level might be valuable for differentiation between AD and PD. Therefore, these hopeful investigations could be done to reduce the usage of invasive diagnostic methods, which alone is a success in alleviating the suffering of AD and PD patients. Moreover, introducing accurate salivary biomarkers according to the pathophysiology of AD and PD should be encouraged.

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Background: Although homeostasis of the cardiovascular system is regulated by the cerebral cortex via the autonomic nervous system, the role of abnormal brain functional connectivity (FC) networks in patients with cardiac dysfunction remains unclear. Here, we report thalamus-based FC alterations and their relationship with clinical characteristics in patients with coronary heart disease (CHD). Methods: We employed resting-state functional magnetic resonance imaging (rs-fMRI) to acquire imaging data in twenty-six patients with CHD alongside sixteen healthy controls (HCs). Next, we performed a thalamus-based FC analysis to profile abnormal FC patterns in the whole brain. Subsequently, the mean time series of the brain regions that survived in the FC analysis were used to determine correlations with clinical parameters in patients with CHD. Results: We found no statistically significant differences in demographic and clinical data between patients with CHD and HCs. Patients with CHD showed decreased FC patterns between bilateral thalami and left hemisphere, encompassing supplementary motor area, superior frontal gyrus, superior parietal gyrus, inferior parietal gyrus, middle cingulate cortex, lingual gyrus and calcarine sulcus. Conclusions: These findings not only have implications in clarifying the relationship between cerebral functional imbalance and cardiovascular system, but also provide valuable insights to guide future evaluation and management of cardiac autonomic regulation via the brain-heart axis.

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Objectives: Regular Baduanjin exercise training has been shown to be beneficial to the physical and cognitive health of older adults, but the underlying mechanisms remain to be investigated. This study examined the influence of Baduanjin on cerebral hemodynamics in community-dwelling older adults with cognitive frailty. Design: Randomized controlled trial. Methods: A total of 102 eligible participants were randomly allocated into the Baduanjin exercise intervention group (BEG) or usual physical activity control group (CG) for 24 weeks. Cerebral hemodynamic parameters of bilateral middle/anterior cerebral artery and basilar artery, cognitive ability and physical frailty were assessed using Transcranial Doppler (TCD), Montreal Cognitive Assessment (MoCA) and Edmonton Frailty Scale (EFS) at baseline and 24 weeks post-intervention. Results: After 24 weeks intervention, the changes in peak systolic velocity (PSV), mean blood flow velocity (MBFV), and end diastolic velocity (EDV) in the right middle cerebral artery and basilar artery were better in the BEG than in the CG; the increase in MoCA scores and the decrease in EFS scores were significantly higher in the BEG than in the CG. Moreover, the interaction of exercise and time on those variables showed obvious significance. Conclusions: The 24 weeks Baduanjin exercise training had a positive beneficial effect on cerebral blood flow in community-dwelling older adults with cognitive frailty. This may be a potential mechanism by which Baduanjin exercise improves the cognitive frailty in older adults. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800020341. Date of registration: December 25, 2018, http://www.chictr.org.cn/showproj.aspx?proj=29846.

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Background: Reliable estimates of frequency, severity and associated factors of both fatigue and cognitive impairment after COVID-19 are needed. Also, it is not clear whether the two are distinct sequelae of COVID-19 or part of the same syndrome." Methods: In this prospective multicentre study, frequency of post-COVID fatigue and cognitive impairment were assessed in n = 969 patients (535 [55%] female) ≥6 months after SARS-CoV-2 infection with the FACIT-Fatigue scale (cut-off ≤30) and Montreal Cognitive Assessment (≤25 mild, ≤17 moderate impairment) between November 15, 2020 and September 29, 2021 at University Medical Center Schleswig-Holstein, Campus Kiel and University Hospital Würzburg in Germany. 969 matched non-COVID controls were drawn from a pre-pandemic, randomised, Germany-wide population survey which also included the FACIT-Fatigue scale. Associated sociodemographic, comorbid, clinical, psychosocial factors and laboratory markers were identified with univariate and multivariable linear regression models. Findings: On average 9 months after infection, 19% of patients had clinically relevant fatigue, compared to 8% of matched non-COVID controls (p < 0.001). Factors associated with fatigue were female gender, younger age, history of depression and the number of acute COVID symptoms. Among acute COVID symptoms, altered consciousness, dizziness and myalgia were most strongly associated with long-term fatigue. Moreover, 26% of patients had mild and 1% had moderate cognitive impairment. Factors associated with cognitive impairment were older age, male gender, shorter education and a history of neuropsychiatric disease. There was no significant correlation between fatigue and cognitive impairment and only 5% of patients suffered from both conditions. Interpretation: Fatigue and cognitive impairment are two common, but distinct sequelae of COVID-19 with potentially separate pathophysiological pathways. Funding: German Federal Ministry of Education and Research (BMBF).

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AIMS: To evaluate neurocognitive performance, daily activity and quality of life (QoL), other than usual oncologic outcomes, among patients with brain metastasis ≥5 (MBM) from solid tumors treated with Stereotactic Brain Irradiation (SBI) or Whole Brain Irradiation (WBI). METHODS: This multicentric randomized controlled trial will involve the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, known primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) score ≥ 20/30, Barthel Activities of Daily Living score ≥ 90/100, to be submitted to SBI by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBI (control arm). The primary endpoints are neurocognitive performance, QoL and autonomy in daily-life activities variations, the first one assessed by MoCa Score and Hopkins Verbal Learning Test-Revised, the second one through the EORTC QLQ-C15-PAL and QLQ-BN-20 questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatment rate, acute and late toxicities, changing of KPS. It will be considered significant a statistical difference of at least 30% between the two arms (statistical power of 80% with a significance level of 95%). DISCUSSION: Several studies debate what is the decisive factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiation effect on clinically healthy brain tissue or intracranial tumor burden? The answer to this question may come from the recent technological advancement that allows, in a context of a significant time saving, improved patient comfort and minimizing radiation dose to off-target brain, a selective treatment of MBM simultaneously, otherwise attackable only by WBI. The achievement of a local control rate comparable to that obtained with WBI remains the fundamental prerequisite. TRIAL REGISTRATION: NCT number: NCT04891471.

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BACKGROUND AND PURPOSE: There is sufficient evidence to support vitamin D's noncalcemic effects and the role of vitamin D deficiency in the development of a wide range of neurological disorders. This study aimed to evaluate whether serum 25(OH)D and 1,25(OH) 2 D could be used as biomarkers to differentiate between healthy subjects (HS), multiple system atrophy (MSA) and Parkinson's disease (PD) patients of both genders. METHODS: A total of 107 subjects were included in this study, divided into three groups: 1- HS (n = 61), 2- MSA patients (n = 19), and 3- PD patients (n = 27). The patients were assessed using UMSARS II, UPDRS III, H&Y, MMSE and MoCA rating scales. The levels of 25(OH)D and 1,25(OH) 2 D in serum were determined using the radioimmunoassay technique. RESULTS: The levels of 25(OH)D and 1,25(OH) 2 D in HS were 26.85 +/- 7.62 ng/mL and 53.63 +/- 13.66 pg/mL respectively. 25(OH)D levels were lower in both MSA and PD by 61% and 50%, respectively (P = 0.0001 vs. HS). 1,25(OH) 2 D levels were lower in MSA by 29%(P = 0.001 vs HS). There was a correlation between 25(OH)D and 1,25(OH) 2 D in MSA and PD, but not in HS. 1,25(OH) 2 D regressed with MMSE (ß = 0.476, P = 0.04, R 2 = 0.226) in MSA, and with UPDRS III (ß = -0.432, P = 0.024, R 2 = 0.187) and MoCA (ß = 0.582, P = 0.005,R 2 = 0.279) in PD. 25(OH)D displayed considerable differentiative strength between HS and MSA (Wald = 17.123, OR = 0.586, P = 0.0001; AUC = 0.982, sensitivity and Youden index = 0.882, P = 0.0001) and PD (Wald = 18.552, OR = 0.700, P = 0.0001; AUC = 0.943, sensitivity = 0.889, YI = 0.791, P = 0.0001). 1,25(OH) 2 D distinguished MSA from PD (Wald 16.178, OR = 1.117, P = 0.0001; AUC = 0.868, sensitivity = 0.926, Youden index =0.632, P = 0.0001). H&Y exhibited the highest sensitivity, AUC, and significant distinguishing power between MSA and PD. CONCLUSIONS: Serum 25(OH)D and 1,25(OH) 2 D could be useful biomarkers for MSA and PD. 25(OH)D and H&Y provided the highest sensitivity and group classification characteristics.

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BACKGROUND: Neuroinflammation has long been theorized to arise from exposures to fine particulate matter and to be modulated when individuals experience chronic stress, both of which are also though to cause cognitive decline in part as a result of neuroinflammation. OBJECTIVES: Hypothesizing that neuroinflammation might be linked to experiences at the World Trade Center (WTC) events, this study explored associations between glial activation and neuropsychological measures including post-traumatic stress disorder (PTSD) symptom severity and WTC exposure duration. METHODS: Translocator protein 18-kDa (TSPO) is overexpressed by activated glial cells, predominantly microglia and astrocytes, making TSPO distribution a putative biomarker for neuroinflammation. Twenty WTC responders completed neuropsychological assessments and in vivo PET brain scan with [18F]-FEPPA. Generalized linear modeling was used to test associations between PTSD, and WTC exposure duratiioni as the predictor and both global and regional [18F]-FEPPA total distribution volumes as the outcomes. RESULT: Responders were 56.0 â€‹± â€‹4.7 years-old, and 75% were police officers on 9/11/2001, and all had at least a high school education. Higher PTSD symptom severity was associated with global and regional elevations in [18F]-FEPPA binding predominantly in the hippocampus (d â€‹= â€‹0.72, P â€‹= â€‹0.001) and frontal cortex (d â€‹= â€‹0.64, P â€‹= â€‹0.004). Longer exposure duration to WTC sites was associated with higher [18F]-FEPPA binding in the parietal cortex. CONCLUSION: Findings from this study of WTC responders at midlife suggest that glial activation is associated with PTSD symptoms, and WTC exposure duration. Future investigation is needed to understand the important role of neuroinflammation in highly exposed WTC responders.

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OBJECTIVE: To determine the adequacy of the Brief Interview for Mental Status (BIMS) compared with other screening tools in identifying individuals with limitations in functional cognition and instrumental activities of daily living (IADL). DESIGN: Cross-sectional observational study. SETTING: Midsized midwestern city. PARTICIPANTS: We assessed a convenience sample of community dwelling individuals (N=197) aged 55 years and older who were living independently. MAIN OUTCOME MEASURES: Participant scores on the BIMS, Mini-Cog, Menu Task, and Montreal Cognitive Assessment (MoCA) were compared with the Performance Assessment of Self-Care Skills Checkbook Balancing and Shopping tasks (PCST), which are known to predict impairment in complex IADLs associated with a diagnosis of mild cognitive impairment. Multiple logistic regression analyses controlling for participant demographics, as well as sensitivity and specificity, were computed for each screening measure using the PCST as the criterion measure. RESULTS: The Mini-Cog, Menu Task, and MoCA identified 25.89%, 32.49%, and 47.21% more individuals, respectively, as impaired than the BIMS. In multiple logistical regression analyses, the BIMS correctly identified 58% of those impaired on the PCST. However, each of the alternate screening measures correctly identified at least 70% of individuals as impaired on the PCST. CONCLUSIONS: In this community sample, the BIMS was insensitive to subtle impairments with the potential to compromise community living, suggesting that the BIMS may be inappropriate for use outside nursing home settings.

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Introduction: Carotid plaque burden is a strong predictor of stroke risk, and preventing stroke reduces the risk of dementia. Treating carotid plaque burden markedly reduces the risk of stroke. Methods: Among patients age 65-80 years attending a stroke prevention clinic, we identified those with a carotid plaque burden in the top 20% of Total Plaque Area (High TPA) and the bottom 20% (Low TPA) and performed cognitive tests: The Montreal Cognitive Assessment test (MoCA), the WAIS-III Digit Symbol-Coding Test (DSST) and Trail-Making Test (TMT) part A and B. Results: There were 31 patients recruited; 11 Low TPA (5 men) and 20 High TPA (17 men), p = 0.04. TPA was 35 ± 25 mm2 in the Low TPA vs.392 ± 169 mm2 in the High TPA group (0.0001). Patients with a high plaque burden had significantly worse performance on all the cognitive tests, all p< 0.05. Discussion: A high carotid plaque burden identifies patients at risk of cognitive impairment. Because carotid plaque burden is treatable, and treating it markedly reduces the risk of stroke, we suggest that measurement of plaque burden is a useful tool for both prediction of cognitive impairment, and prevention of dementia.

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INTRODUCTION: Depressive and neurocognitive disorders are debilitating conditions that account for the leading causes of years lived with disability worldwide. However, there are no biomarkers that are objective or easy-to-obtain in daily clinical practice, which leads to difficulties in assessing treatment response and developing new drugs. New technology allows quantification of features that clinicians perceive as reflective of disorder severity, such as facial expressions, phonic/speech information, body motion, daily activity, and sleep. METHODS: Major depressive disorder, bipolar disorder, and major and minor neurocognitive disorders as well as healthy controls are recruited for the study. A psychiatrist/psychologist conducts conversational 10-min interviews with participants ≤10 times within up to five years of follow-up. Interviews are recorded using RGB and infrared cameras, and an array microphone. As an option, participants are asked to wear wrist-band type devices during the observational period. Various software is used to process the raw video, voice, infrared, and wearable device data. A machine learning approach is used to predict the presence of symptoms, severity, and the improvement/deterioration of symptoms. DISCUSSION: The overall goal of this proposed study, the Project for Objective Measures Using Computational Psychiatry Technology (PROMPT), is to develop objective, noninvasive, and easy-to-use biomarkers for assessing the severity of depressive and neurocognitive disorders in the hopes of guiding decision-making in clinical settings as well as reducing the risk of clinical trial failure. Challenges may include the large variability of samples, which makes it difficult to extract the features that commonly reflect disorder severity. TRIAL REGISTRATION: UMIN000021396, University Hospital Medical Information Network (UMIN).

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INTRODUCTION: We reviewed the literature on interventions for patients with medically refractory chronically occluded internal carotid artery (COICA) to assess the risks and/or benefits after recanalization via an endovascular technique (ET) or hybrid surgery (HS, i.e., ET plus carotid endarterectomy). METHODS: A systematic search of the electronic databases was performed. Patients with COICA were classified into 4 different categories according to Hasan et al classification. RESULTS: Eighteen studies satisfied the inclusion criteria. Only 6 studies involved an HS procedure. We identified 389 patients with COICA who underwent ET or HS; 91% were males. The overall perioperative complication rate was 10.1% (95% confidence interval [CI]: 7.4%-13.1%). For types A and B, the successful recanalization rate was 95.4% (95% CI: 86.5%-100%), with a 13.7% (95% CI: 2.3%-27.4%) complication rate. For type C, the success rate for ET was 45.7% (95% CI: 17.8%-70.7%), with a complication rate of 46.0% (95% CI: 20.0%-71.4%) for ET and for the HS technique 87.6% (95% CI: 80.9%-94.4%), with a complication rate of 14.0% (95% CI: 7.0%-21.8%). For type D, the success rate of recanalization was 29.8% (95% CI: 7.8%-52.8%), with a 29.8% (95% CI: 6.1%-56.3%) complication rate. Successful recanalization resulted in a symmetrical perfusion between both cerebral hemispheres, resolution of penumbra, normalization of the mean transit time, and improvement in Montreal Cognitive Assessment (MoCA) score (ΔMoCA = 9.80 points; P = 0.004). CONCLUSIONS: Type A and B occlusions benefit from ET, especially in the presence of a large penumbra. Type C occlusions can benefit from HS. Unfortunately, we did not identify an intervention to help patients with type D occlusions. A phase 2b randomized controlled trial is needed to confirm these findings.

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Objectives: Covert stroke is a complication of coronary artery bypass graft surgery that is increasingly recognized as a serious problem. In noncardiac surgery settings, covert stroke is associated with the development of delirium, long-term cognitive decline, and future clinical stroke. Therefore, we sought to determine the feasibility of conducting a large, prospective cohort study of the influence of covert stroke on neurocognitive outcomes in patients undergoing coronary artery bypass graft surgery. Methods: NeuroVISION Cardiac pilot was a prospective cohort study enrolling patients aged ≥21 years undergoing isolated coronary artery bypass graft surgery to receive diffusion-weighted magnetic resonance imaging of the brain after surgery to identify patients with covert stroke. Patients were screened for postoperative delirium in-hospital and were administered questionnaires of cognitive and global function (once before and twice after surgery). Regional cerebral oxygen saturation was recorded during surgery using near-infrared spectroscopy. Results: Between March 27, 2017, and February 11, 2018, 50 of 66 patients enrolled (76%) completed the brain magnetic resonance imaging (1 patient per week). Among the 49 patients included in the analysis, 19 (39%; 95% confidence interval, 26%-53%) experienced perioperative covert stroke and 3 (6%) had a clinical stroke within 30 days of surgery. Postoperative delirium occurred in 5 (26%) patients with covert stroke and in 3 (10%) patients who did not experience covert stroke. Conclusions: The NeuroVISION Cardiac pilot study established the feasibility of conducting a large, prospective cohort study of the determinants and consequences of covert stroke in patients undergoing coronary artery bypass graft surgery.

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INTRODUCTION: Parkinson's disease patients are usually characterized by body motor dysfunction due to dopaminergic reduction in the central nervous system. Freezing of gait is a motor disorder that affects certain Parkinson's disease patients. However, it is hypothesized that non-motor functions mediated by the cholinergic system are also involved in developing freezing of gait. Visual information processing speed, or inspection time is independent of the motor response, and can be used a reliable measure of the cholinergic system integrity. OBJECTIVE: Inspection time can be used to investigate whether Parkinson's disease patients with freezing of gait symptoms have a larger impairment in cholinergic mediated functions than those patients who have no freezing of gait symptoms and healthy controls. METHODS: The inspection time was determined by a simple length discrimination task. Twenty-two Parkinson's disease patients with freezing of gait, 25 Parkinson's disease patients without freezing of gait, and 25 aged matched healthy controls participated in the study. RESULTS: Based on the log values of IT score, Parkinson's disease patients with freezing of gait symptoms had statistically significant slower inspection times (mean of 1.793 ms) than Parkinson's disease patients without freezing of gait (mean of 1.655 ms) and healthy controls (mean of 1.523 ms). Inspection times for the Parkinson's disease patients without FOG symptoms were also significantly slower than healthy controls. CONCLUSION: The results of this study support the hypothesis that the cholinergic system integrity is affected more in Parkinson's disease patients with freezing of gait symptoms.

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OBJECTIVES: To examine the role of the hippocampus in stress regulation in older adults with amnestic mild cognitive impairment (aMCI). METHODS: This study combined resting-state functional MRI, structural MRI, self-reported chronic stress exposure, and an electrocardiography-based acute stress protocol to compare aMCI group (n = 17) to their cognitively healthy counterparts (HC, n = 22). RESULTS: For the entire sample, there was a positive correlation between chronic stress exposure and acute stress regulation. The aMCI group showed significantly smaller volumes in the right hippocampus than HC. The two groups did not differ in chronic stress exposure or acute stress regulation. In the HC group, the left hippocampal connectivity with inferior parietal lobe was significantly correlated with both the chronic stress and acute stress. In the aMCI group, the left hippocampal connectivity with both the right insula and the left precentral gyrus was significantly correlated to chronic stress exposure and acute stress regulation. Additionally, the left hippocampal connectivity with right insula significantly mediated the relationship between chronic stress exposure and acute stress regulation in aMCI group. CONCLUSIONS: Extra hippocampal networks may be recruited as compensation to attend the maintenance of relatively normal stress regulation in aMCI by alleviating the detrimental effects of chronic stress exposure on acute stress regulation.

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OBJECTIVE: Our objective was to (1) evaluate the linguistic and cultural acceptability of a Spanish translation of the Ohio State University traumatic brain injury identification method (OSU TBI-ID) and (2) to assess the usability and acceptability of a tablet-based version of this instrument in a cohort of Spanish-dominant older adults. SETTING: University clinical research center and local community center. PARTICIPANTS: Community-dwelling Spanish-dominant adults age 50 years or older without dementia residing in the Bay Area of California (N=22). DESIGN: Cross-sectional cohort study. MAIN OUTCOME MEASURES: Qualitative assessment of linguistic or cultural acceptability of a Spanish translation of the OSU TBI-ID as well as usability or acceptability of a tablet-based self-administered version of this instrument. RESULTS: The Spanish translation had high linguistic and cultural acceptability and was further optimized based on participant feedback. Cognitive interviews to review survey wording revealed high levels of homogeneity in the clinical definitions and synonyms given by participants-for example, results for the clinical term "Quedó Inconsciente/Pérdida (temporal) de la conciencia" (To be unconscious/[Temporary] loss of consciousness) used in the survey included "perder el conocimiento" (loss of consciousness), "knockeado" (knocked out), "No es que esté dormida, porque está inconsciente, pero su corazón está todavía palpitando" (it's not that they're sleeping, because they're unconscious, but their heart is still palpitating). The tablet interface had low observer-based usability, revealing that participants with <13 years of education (n=6) had more difficulty using the tablet which could be improved with minor changes to the coding of the application and minimal in-person technology support. Acceptability of the tool was low among all but 1 participant. CONCLUSION: This linguistically optimized Spanish translation of the OSU TBI-ID is recommended for use as a semistructured interview among Spanish-dominant older adults. Although the tablet-based instrument may be used by interviewers as an efficient electronic case report form among older adults, further research is needed, particularly among older adults with varying levels of education, to validate this instrument as a self-administered survey.

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We investigated the effect of acute levodopa administration on movement-related cortical oscillations and movement velocity in Parkinson's disease (PD). Patients with PD on and off medication and age- and sex-matched healthy controls performed a ballistic upper limb flexion movement as fast and accurately as possible while cortical oscillations were recorded with high-density electroencephalography. Patients off medication were also studied using task-based functional magnetic resonance imaging (fMRI) using a force control paradigm. Percent signal change of functional activity during the force control task was calculated for the putamen and subthalamic nucleus (STN) contralateral to the hand tested. We found that patients with PD off medication had an exaggerated movement-related beta-band (13-30 Hz) desynchronization in the supplementary motor area (SMA) compared to controls. In PD, spectral power in the beta-band was correlated with movement velocity. Following an acute dose of levodopa, we observed that the beta-band desynchronization in the SMA was reduced in PD, and was associated with increased movement velocity and increased voltage of agonist muscle activity. Further, using fMRI we found that the functional activity in the putamen and STN in the off medication state, was related to how responsive that cortical oscillations in the SMA of PD were to levodopa. Collectively, these findings provide the first direct evaluation of how movement-related cortical oscillations relate to movement velocity during the ballistic phase of movement in PD and demonstrate that functional brain activity in the basal ganglia pathways relate to the effects of dopaminergic medication on cortical neuronal oscillations during movement.

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SPG11 mutations are the major cause of autosomal recessive Hereditary Spastic Paraplegia. The disease has a wide phenotypic variability indicating many regions of the nervous system besides the corticospinal tract are affected. Despite this, anatomical and phenotypic characterization is restricted. In the present study, we investigate the anatomical abnormalities related to SPG11 mutations and how they relate to clinical and cognitive measures. Moreover, we aim to depict how the disease course influences the regions affected, unraveling different susceptibility of specific neuronal populations. We performed clinical and paraclinical studies encompassing neuropsychological, neuroimaging, and neurophysiological tools in a cohort of twenty-five patients and age matched controls. We assessed cortical thickness (FreeSurfer software), deep grey matter volumes (T1-MultiAtlas tool), white matter microstructural damage (DTI-MultiAtlas) and spinal cord morphometry (Spineseg software) on a 3 T MRI scan. Mean age and disease duration were 29 and 13.2 years respectively. Sixty-four percent of the patients were wheelchair bound while 84% were demented. We were able to unfold a diffuse pattern of white matter integrity loss as well as basal ganglia and spinal cord atrophy. Such findings contrasted with a restricted pattern of cortical thinning (motor, limbic and parietal cortices). Electromyography revealed motor neuronopathy affecting 96% of the probands. Correlations with disease duration pointed towards a progressive degeneration of multiple grey matter structures and spinal cord, but not of the white matter. SPG11-related hereditary spastic paraplegia is characterized by selective neuronal vulnerability, in which a precocious and widespread white matter involvement is later followed by a restricted but clearly progressive grey matter degeneration.

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•Understanding of the phenotypic heterogeneity of Parkinson's disease is needed.•Gender and genetics determine manifestation and progression of Parkinson's disease.•Altered emotion processing in Parkinson's disease is specific to male patients.•This is influenced by endocrinal and genetic factors in both genders.•This finding may impact the diagnosis and treatment of emerging clinical features.

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Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age- and sex-matched healthy controls (HCs) using PET imaging with [18F]fallypride, a high affinity D2/3 receptor ligand, to measure striatal and extrastriatal D2/3 nondisplaceable binding potential (BPND). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BPND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D2/3 receptors, where reduced BPND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.

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