Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor i...Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson's disease and to explore whether there are differences between recognition of different types of emotions in Parkinson's disease. We examined 18 patients with Parkinson's disease(8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson's disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson's disease.展开更多
Parkinson＇s disease （PD） is a neurodegenerative disorder characterized by selective and progressive degeneration, as well as loss of dopaminergic neurons in the substantia nigra. In PD, approximately 60-70% of nigr...Parkinson＇s disease （PD） is a neurodegenerative disorder characterized by selective and progressive degeneration, as well as loss of dopaminergic neurons in the substantia nigra. In PD, approximately 60-70% of nigrostriatal neurons are degenerated and 80% of content of the striatal dopamine is reduced before the diagnosis can be established according to widely accepted clinical diagnostic criteria. This condition describes a stage of disease called ＂prodromal＂, where non-motor symptoms, such as olfactory dysfunction, constipation, rapid eye movement behaviour disorder, depression, precede motor sign of PD. Detection of prodromal phase of PD is becoming an important goal for determining the prognosis and choosing a suitable treatment strategy. In this review, we present some non-invasive instrumental approaches that could be useful to identify patients in the prodromal phase of PD or in an early clinical phase, when the first motor symptoms begin to be apparent. Conventional magnetic resonance imaging （MRI） and advanced MRI techniques, such as magnetic resonance spectroscopy imaging, diffusion-weighted and diffusion tensor imaging and functional MRI, are useful to differentiate early PD with initial motor symptoms from atypical parkinsonian disorders, thus, making easier early diagnosis. Functional MRI and diffusion tensor imaging techniques can show abnormalities in the olfactory system in prodromal PD.展开更多
Regional homogeneity analysis of low-frequency blood oxygenation level-dependent signals from neighboring voxels enables the analysis of local neuronal synchrony. Both structural magnetic resonance imaging and resting...Regional homogeneity analysis of low-frequency blood oxygenation level-dependent signals from neighboring voxels enables the analysis of local neuronal synchrony. Both structural magnetic resonance imaging and resting-state functional magnetic resonance imaging scans were collected from nine Parkinson＇s disease patients with right resting tremor, and from eight age-matched normal controls. Regional homogeneity was compared between Parkinson＇s disease patients and controls. The results revealed that regional homogeneity was increased in several brain regions, including the right precuneus, right superior parietal gyrus, left anterior cingulate cortex, right middle frontal gyrus and right inferior frontal gyrus. Conversely, regional homogeneity was decreased in the cerebellar vermis in Parkinson＇s disease patients compared with healthy controls.展开更多
Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have ...Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.展开更多
Background：Neuroimaging studies have found that functional changes exist in patients with Parkinson＇s disease （PD）.However,the majority of functional magnetic resonance imaging （fMRI） studies in patients with PD...Background：Neuroimaging studies have found that functional changes exist in patients with Parkinson＇s disease （PD）.However,the majority of functional magnetic resonance imaging （fMRI） studies in patients with PD are task-related and cross-sectional.This study investigated the functional changes observed in patients with PD,at both baseline and after 2 years,using resting-state fMRI.It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.Methods：Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI.In addition,20 age-and sex-matched,healthy controls were examined using resting-state fMRI.The fractional amplitude of low-frequency fluctuation （fALFF） approach was used to analyze the fMRI data.Nonlinear registration was used to model within-subject changes over the scanning interval,as well as changes between the patients with PD and the healthy controls.A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.Results：Compared to the control subjects,the patients with PD showed increased fALFF values in the left inferior temporal gyrus,right inferior parietal lobule （IPL） and right middle frontal gyrus.Compared to the baseline in the 2 years follow-up,the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum,right thalamus,right striatum,left superior parietal lobule,left IPL,left precentral gyrus,and left postcentral gyrus （P 〈 0.01,after correction with AlphaSim）.In addition,the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale （UPDRS） motor scores （r =0.5 l,P 〈 0.05,uncorrected） and the change in the UPDRS motor score （r =0.61,P 〈 0.05,uncorrected）.Conclusions：The baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease＇s progression in patients with PD.展开更多
Psychosis is a common non-motor symptom of Parkinson’s disease whose pathogenesis remains poorly understood. Parkinson’s disease in conjunction with psychosis has been shown to induce injury to extracorticospinal tr...Psychosis is a common non-motor symptom of Parkinson’s disease whose pathogenesis remains poorly understood. Parkinson’s disease in conjunction with psychosis has been shown to induce injury to extracorticospinal tracts as wel as within some cortical areas. In this study, Parkinson’s disease patients with psychosis who did not receive antipsychotic treatment and those without psychosis underwent diffusion tensor imaging. Results revealed that in Parkinson’s disease patients with psychosis, damage to the left frontal lobe, bilateral occipital lobe, left cingulated gyrus, and left hippocampal white-matter fibers were greater than damage to the substantia nigra or the globus pal idus. Damage to white-matter fibers in the right frontal lobe and right cingulate gyrus were also more severe than in the globus pal idus, but not the substantia nigra. Damage to frontal lobe and cingulate gyrus white-matter fibers was more apparent than that to occipital or hippocampal fiber damage. Compared with Parkinson’s disease patients without psychosis, those with psychosis had significantly lower fractional anisotropy ratios of left frontal lobe, bilateral occipital lobe, left cingu-lated gyrus, and left hippocampus to ipsilateral substantia nigra or globus pal idus, indicating more severe damage to white-matter fibers. These results suggest that psychosis associated with Par-kinson’s disease is probably associated with an imbalance in the ratio of white-matter fibers be-tween brain regions associated with psychiatric symptoms （frontal lobe, occipital lobe, cingulate gyrus, and hippocampus） and those associated with the motor symptoms of Parkinson’s disease （the substantia nigra and globus pal idus）. The relatively greater damage to white-matter fibers in psychiatric symptom-related brain regions than in extracorticospinal tracts might explain why psy-chosis often occurs in Parkinson’s disease patients.展开更多
We used resting-state fMRI to evaluate longitu- dinal alterations in local spontaneous brain activity in Parkinson＇s disease （PD） over a 2-year period. Data were acquired from 23 PD patients at baseline and follow-...We used resting-state fMRI to evaluate longitu- dinal alterations in local spontaneous brain activity in Parkinson＇s disease （PD） over a 2-year period. Data were acquired from 23 PD patients at baseline and follow-up, and 27 age- and sex-matched normal controls. Regional homogeneity （ReHo） and voxel-based-morphometry （VBM） were used to identify differences in local sponta- neous brain activity and grey matter volume. With disease progression, we observed a progressive decrease in ReHo in the sensorimotor cortex, default-mode network, and left cerebellum, but increased ReHo in the supplementary motor area, bilateral temporal gyrus, and hippocampus. Moreover, there was a significant positive correlation between the rates of ReHo change in the left cerebellum and the rates of change in the Unified Parkinson＇s Disease Rating Scale-III scores. VBM revealed no significant differences in the grey matter volume among the three sets of acquisitions. We conclude that ReHo may be a suitable non-invasive marker of progression in PD.展开更多
Background:Different oscillations of brain networks could carry different dimensions of brain integration.We aimed to investigate oscillation-specific nodal alterations in patients with Parkinson’s disease(PD)across ...Background:Different oscillations of brain networks could carry different dimensions of brain integration.We aimed to investigate oscillation-specific nodal alterations in patients with Parkinson’s disease(PD)across early stage to middle stage by using graph theory-based analysis.Methods:Eighty-eight PD patients including 39 PD patients in the early stage(EPD)and 49 patients in the middle stage(MPD)and 36 controls were recruited in the present study.Graph theory-based network analyses from three oscillation frequencies(slow-5:0.01–0.027 Hz;slow-4:0.027–0.073 Hz;slow-3:0.073–0.198 Hz)were analyzed.Nodal metrics(e.g.nodal degree centrality,betweenness centrality and nodal efficiency)were calculated.Results:Our results showed that(1)a divergent effect of oscillation frequencies on nodal metrics,especially on nodal degree centrality and nodal efficiency,that the anteroventral neocortex and subcortex had high nodal metrics within low oscillation frequencies while the posterolateral neocortex had high values within the relative high oscillation frequency was observed,which visually showed that network was perturbed in PD;(2)PD patients in early stage relatively preserved nodal properties while MPD patients showed widespread abnormalities,which was consistently detected within all three oscillation frequencies;(3)the involvement of basal ganglia could be specifically observed within slow-5 oscillation frequency in MPD patients;(4)logistic regression and receiver operating characteristic curve analyses demonstrated that some of those oscillation-specific nodal alterations had the ability to well discriminate PD patients from controls or MPD from EPD patients at the individual level;(5)occipital disruption within high frequency(slow-3)made a significant influence on motor impairment which was dominated by akinesia and rigidity.Conclusions:Coupling various oscillations could provide potentially useful information for large-scale network and progressive oscillation-specific nodal alterations were observed in PD patients across early to middle stages.展开更多
文摘Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson's disease and to explore whether there are differences between recognition of different types of emotions in Parkinson's disease. We examined 18 patients with Parkinson's disease(8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson's disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson's disease.
文摘Parkinson＇s disease （PD） is a neurodegenerative disorder characterized by selective and progressive degeneration, as well as loss of dopaminergic neurons in the substantia nigra. In PD, approximately 60-70% of nigrostriatal neurons are degenerated and 80% of content of the striatal dopamine is reduced before the diagnosis can be established according to widely accepted clinical diagnostic criteria. This condition describes a stage of disease called ＂prodromal＂, where non-motor symptoms, such as olfactory dysfunction, constipation, rapid eye movement behaviour disorder, depression, precede motor sign of PD. Detection of prodromal phase of PD is becoming an important goal for determining the prognosis and choosing a suitable treatment strategy. In this review, we present some non-invasive instrumental approaches that could be useful to identify patients in the prodromal phase of PD or in an early clinical phase, when the first motor symptoms begin to be apparent. Conventional magnetic resonance imaging （MRI） and advanced MRI techniques, such as magnetic resonance spectroscopy imaging, diffusion-weighted and diffusion tensor imaging and functional MRI, are useful to differentiate early PD with initial motor symptoms from atypical parkinsonian disorders, thus, making easier early diagnosis. Functional MRI and diffusion tensor imaging techniques can show abnormalities in the olfactory system in prodromal PD.
基金the Science and Technology Planning Project of Guangdong Province, China, No. 2008B080703041
文摘Regional homogeneity analysis of low-frequency blood oxygenation level-dependent signals from neighboring voxels enables the analysis of local neuronal synchrony. Both structural magnetic resonance imaging and resting-state functional magnetic resonance imaging scans were collected from nine Parkinson＇s disease patients with right resting tremor, and from eight age-matched normal controls. Regional homogeneity was compared between Parkinson＇s disease patients and controls. The results revealed that regional homogeneity was increased in several brain regions, including the right precuneus, right superior parietal gyrus, left anterior cingulate cortex, right middle frontal gyrus and right inferior frontal gyrus. Conversely, regional homogeneity was decreased in the cerebellar vermis in Parkinson＇s disease patients compared with healthy controls.
文摘Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.
文摘Background：Neuroimaging studies have found that functional changes exist in patients with Parkinson＇s disease （PD）.However,the majority of functional magnetic resonance imaging （fMRI） studies in patients with PD are task-related and cross-sectional.This study investigated the functional changes observed in patients with PD,at both baseline and after 2 years,using resting-state fMRI.It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.Methods：Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI.In addition,20 age-and sex-matched,healthy controls were examined using resting-state fMRI.The fractional amplitude of low-frequency fluctuation （fALFF） approach was used to analyze the fMRI data.Nonlinear registration was used to model within-subject changes over the scanning interval,as well as changes between the patients with PD and the healthy controls.A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.Results：Compared to the control subjects,the patients with PD showed increased fALFF values in the left inferior temporal gyrus,right inferior parietal lobule （IPL） and right middle frontal gyrus.Compared to the baseline in the 2 years follow-up,the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum,right thalamus,right striatum,left superior parietal lobule,left IPL,left precentral gyrus,and left postcentral gyrus （P 〈 0.01,after correction with AlphaSim）.In addition,the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale （UPDRS） motor scores （r =0.5 l,P 〈 0.05,uncorrected） and the change in the UPDRS motor score （r =0.61,P 〈 0.05,uncorrected）.Conclusions：The baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease＇s progression in patients with PD.
基金supported by the Applied Basic Research Foundation of Yunnan Province in China,No.2009CD193
文摘Psychosis is a common non-motor symptom of Parkinson’s disease whose pathogenesis remains poorly understood. Parkinson’s disease in conjunction with psychosis has been shown to induce injury to extracorticospinal tracts as wel as within some cortical areas. In this study, Parkinson’s disease patients with psychosis who did not receive antipsychotic treatment and those without psychosis underwent diffusion tensor imaging. Results revealed that in Parkinson’s disease patients with psychosis, damage to the left frontal lobe, bilateral occipital lobe, left cingulated gyrus, and left hippocampal white-matter fibers were greater than damage to the substantia nigra or the globus pal idus. Damage to white-matter fibers in the right frontal lobe and right cingulate gyrus were also more severe than in the globus pal idus, but not the substantia nigra. Damage to frontal lobe and cingulate gyrus white-matter fibers was more apparent than that to occipital or hippocampal fiber damage. Compared with Parkinson’s disease patients without psychosis, those with psychosis had significantly lower fractional anisotropy ratios of left frontal lobe, bilateral occipital lobe, left cingu-lated gyrus, and left hippocampus to ipsilateral substantia nigra or globus pal idus, indicating more severe damage to white-matter fibers. These results suggest that psychosis associated with Par-kinson’s disease is probably associated with an imbalance in the ratio of white-matter fibers be-tween brain regions associated with psychiatric symptoms （frontal lobe, occipital lobe, cingulate gyrus, and hippocampus） and those associated with the motor symptoms of Parkinson’s disease （the substantia nigra and globus pal idus）. The relatively greater damage to white-matter fibers in psychiatric symptom-related brain regions than in extracorticospinal tracts might explain why psy-chosis often occurs in Parkinson’s disease patients.
基金supported by the 13th Five-year Plan for National Key Research and Development Program of China (2016YFC1306600)the 12th Five-year Plan for National Science and Technology Supporting Program of China (2012BAI10B04)the National Natural Science Foundation of China (81571654, 81371519, and 81301190)
文摘We used resting-state fMRI to evaluate longitu- dinal alterations in local spontaneous brain activity in Parkinson＇s disease （PD） over a 2-year period. Data were acquired from 23 PD patients at baseline and follow-up, and 27 age- and sex-matched normal controls. Regional homogeneity （ReHo） and voxel-based-morphometry （VBM） were used to identify differences in local sponta- neous brain activity and grey matter volume. With disease progression, we observed a progressive decrease in ReHo in the sensorimotor cortex, default-mode network, and left cerebellum, but increased ReHo in the supplementary motor area, bilateral temporal gyrus, and hippocampus. Moreover, there was a significant positive correlation between the rates of ReHo change in the left cerebellum and the rates of change in the Unified Parkinson＇s Disease Rating Scale-III scores. VBM revealed no significant differences in the grey matter volume among the three sets of acquisitions. We conclude that ReHo may be a suitable non-invasive marker of progression in PD.
基金This work was supported by the 13th Five-year Plan for National Key Research and Development Program of China(Grant No.2016YFC1306600)the Fundamental Research Funds for the Central Universities of China(Grant No.2017XZZX001-01)+3 种基金the 12th Five-year Plan for National Science and Technology Supporting Program of China(Grant No.2012BAI10B04)the National Natural Science Foundation of China(Grant Nos.81571654,81371519 and 81701647)the Cooperative Project by Ministry of Health and Provincial Department(Grant No.2016149022)the Projects of Medical and Health Technology Development Program in Zhejiang Province(Grant No.2015KYB174).
文摘Background:Different oscillations of brain networks could carry different dimensions of brain integration.We aimed to investigate oscillation-specific nodal alterations in patients with Parkinson’s disease(PD)across early stage to middle stage by using graph theory-based analysis.Methods:Eighty-eight PD patients including 39 PD patients in the early stage(EPD)and 49 patients in the middle stage(MPD)and 36 controls were recruited in the present study.Graph theory-based network analyses from three oscillation frequencies(slow-5:0.01–0.027 Hz;slow-4:0.027–0.073 Hz;slow-3:0.073–0.198 Hz)were analyzed.Nodal metrics(e.g.nodal degree centrality,betweenness centrality and nodal efficiency)were calculated.Results:Our results showed that(1)a divergent effect of oscillation frequencies on nodal metrics,especially on nodal degree centrality and nodal efficiency,that the anteroventral neocortex and subcortex had high nodal metrics within low oscillation frequencies while the posterolateral neocortex had high values within the relative high oscillation frequency was observed,which visually showed that network was perturbed in PD;(2)PD patients in early stage relatively preserved nodal properties while MPD patients showed widespread abnormalities,which was consistently detected within all three oscillation frequencies;(3)the involvement of basal ganglia could be specifically observed within slow-5 oscillation frequency in MPD patients;(4)logistic regression and receiver operating characteristic curve analyses demonstrated that some of those oscillation-specific nodal alterations had the ability to well discriminate PD patients from controls or MPD from EPD patients at the individual level;(5)occipital disruption within high frequency(slow-3)made a significant influence on motor impairment which was dominated by akinesia and rigidity.Conclusions:Coupling various oscillations could provide potentially useful information for large-scale network and progressive oscillation-specific nodal alterations were observed in PD patients across early to middle stages.
