To rise and to fall: functional connectivity in cognitively normal and cognitively impaired patients with Parkinson's disease

Gorges, Martin; Müller, Hans‐Peter; Lulé, Dorothée; Pinkhardt, Elmar H.; Ludolph, Albert C.; Kassubek, Jan

doi:10.1016/j.neurobiolaging.2014.12.026

Cited by 117 publications

(149 citation statements)

References 66 publications

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“…The mechanistic drivers of this remodeling are currently unclear, although it is possible to speculate that homeostatic mechanisms may be activated by alterations in excitability of pMO neurons, including corticospinal motor neurons (Kim et al, 2017). In fact, pathological decrease or increase in the firing properties of vulnerable neuronal subpopulations appears to be a shared phenotype of multiple neurodegenerative conditions (Roselli and Caroni, 2015) and may be one of the driving forces of adaptive cortical remodeling in neurodegeneration (LANDSCAPE Consortium et al, 2015; Rosskopf et al, 2017; Rosskopf et al, 2018). Thus, the combination of the analysis of large-scale projection patterns (enabled by retrograde viral tracing) with chronic manipulation of excitability and firing (such as chemiogenetics; Saxena et al, 2013) may prove fundamental to link functional and structural cortical phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…Preprocessing included (1) spatial upsampling to an 1 × 1×1 mm 3 isogrid (matrix, 256 × 256×256), (2) motion correction using a rigid brain transformation (six degrees of freedom), (3) stereotaxic Montreal Neurological Institute (MNI) normalization (Brett et al, 2002) using a landmark-based deformation approach (Müller and Kassubek, 2013), (4) temporal demeaning and linear detrending, (5) temporal bandpass filter (0.01 < f < 0.08 Hz), and (6) spatial smoothing using a 7 mm 3-dimensional full-width at half maximum (FWHM) Gaussian blur filter (LANDSCAPE Consortium et al, 2016; LANDSCAPE Consortium et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

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Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

Commisso

Ding

Varadi

et al. 2018

eLife

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Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motoneurons in the primary motor cortex (pMO) and in spinal cord. However, the pathogenic process involves multiple subnetworks in the brain and functional MRI studies demonstrate an increase in functional connectivity in areas connected to pMO despite the ongoing neurodegeneration. The extent and the structural basis of the motor subnetwork remodeling in experimentally tractable models remain unclear. We have developed a new retrograde AAV9 to quantitatively map the projections to pMO in the SOD1(G93A) ALS mouse model. We show an increase in the number of neurons projecting from somatosensory cortex to pMO at presymptomatic stages, followed by an increase in projections from thalamus, auditory cortex and contralateral MO (inputs from 20 other structures remains unchanged) as disease advances. The stage- and structure-dependent remodeling of projection to pMO in ALS may provide insights into the hyperconnectivity observed in ALS patients.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

Commisso

Ding

Varadi

et al. 2018

eLife

Self Cite

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“…Although the pathophysiology underlying cognitive deficits in PD remains not entirely clear, efforts should be made to explore the role of the DMN in cognitive dysfunction in PD (Buckner et al, 2008). Previous studies have found that major nodes of the DMN, such as the mPFC and PCC, demonstrated significant dysfunction in PD patients in the resting state (Gorges et al, 2015) and while performing executive tasks (van Eimeren et al, 2009). However, little is known about the changes in DMN connectivity related to cognitive decline in drug-naïve early stage PD patients with MCI.…”

Section: Introductionmentioning

confidence: 99%

Dysfunction of the Default Mode Network in Drug-Naïve Parkinson’s Disease with Mild Cognitive Impairments: A Resting-State fMRI Study

Hou

Yang

Chen

et al. 2016

Front. Aging Neurosci.

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Objective: Cognitive impairments are common in Parkinson’s disease (PD) and can even occur in the early stages. The default mode network (DMN) is highly relevant for cognitive processes; however, it remains largely unknown if changes in the DMN connectivity are related to the cognitive decline in drug-naïve early stage PD patients with a mild cognitive impairment (MCI). This study used resting-state functional MRI (fMRI) to explore the brain connectivity of the DMN in early stage drug-naïve PD patients with MCI.Method: We recruited 32 early stage drug-naïve PD patients and 22 matched healthy controls (HC). Among the PD patients, 14 were classified as having MCI (PD-MCI) and 18 were classified as having unimpaired cognition (PD-CU). The functional integration of the DMN was evaluated by a seed-based correlation approach.Results: The brain connectivity analysis revealed reduced functional connectivity (FC) in both PD subgroups compared with HC. The PD-MCI group showed a significant reduction in FC between the DMN and a set of regions, including the precentral gyrus, middle temporal gyrus, insula, anterior inferior parietal lobule and middle frontal gyrus. Compared to the PD-CU group, the PD-MCI group demonstrated a significantly decreased FC in the middle frontal and middle temporal gyri. Additionally, compared to HC, the PD-MCI group had a significantly decreased FC within the DMN, mainly in the FC between the hippocampal formation and inferior frontal gyrus, between the posterior cingulate cortex and posterior inferior parietal lobule, and between the anterior temporal lobe and inferior frontal gyrus. Compared to the PD-CU group, the only significantly decreased FC within the DMN in the PD-MCI group was between the anterior temporal lobe and inferior frontal gyrus. In all PD patients, the decreased FC between anterior temporal lobe and middle temporal gyrus was positively correlated with attention/working performance, and the reduced FC between the hippocampal formation and inferior frontal gyrus was also positively correlated with memory function.Conclusion: Our findings suggest that an altered DMN connectivity characterizes PD-MCI patients. These findings may be helpful for facilitating the further understanding of the potential mechanisms underlying MCI in PD. However, our results are preliminary, and further investigation is needed.

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“…Increased functional connectivity in cortical, limbic, and basal ganglia-thalamic areas was also observed when comparing cognitively unimpaired patients with PD to healthy controls during resting state fMRI (Gorges et al, 2015). In addition, increased functional connectivity involving shorter-range frontal and temporal regions was found in PD, as compared to controls, and was suggested to represent within-module compensatory mechanisms in response to long-range connectivity reduction (Baggio et al, 2014).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 82%

Alterations in conflict monitoring are related to functional connectivity in Parkinson's disease

Rosenberg‐Katz

Maidan

Jacob

et al. 2016

Cortex

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To rise and to fall: functional connectivity in cognitively normal and cognitively impaired patients with Parkinson's disease

Cited by 117 publications

References 66 publications

Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

Dysfunction of the Default Mode Network in Drug-Naïve Parkinson’s Disease with Mild Cognitive Impairments: A Resting-State fMRI Study

Alterations in conflict monitoring are related to functional connectivity in Parkinson's disease

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