Project

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Anatomical and functional segregation within cortico-basal ganglia circuits

English title Anatomical and functional segregation within cortico-basal ganglia circuits
Applicant Draganski Bogdan
Number 135679
Funding scheme Project funding
Research institution Service de Neurologie Département des Neurosciences Cliniques CHUV
Institution of higher education University of Lausanne - LA
Main discipline Neurology, Psychiatry
Start/End 01.01.2012 - 31.10.2015
Approved amount 375'000.00
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Keywords (7)

Parkinson's disease; dopamine; magnetic resonance imaging; neuroanatomy; neural activity; basal ganglia; biomarker

Lay Summary (English)

Lead
Lay summary

Parkinson's disease - the second most common neurodegenerative disorder after Alzheimer's dementia, has a progressive course affecting severely the patients' and family members' quality of life. The fact that neuronal damage and dopamine loss begin 5-10 years before the occurence of first clinical signs underscores the importance of preclinical diagnosis for potential neuroprotective treatment.
The concept of dopamine-related abnormal separation of information flow between functional circuits connecting remote brain areas offers a unified model for Parkinson's disease, characterised by motor, cognitive and motivational/emotional dysfunction. The degree of progressive loss of segregation between information channels at the basal ganglia level can be used as biomarker of preclinical diagnosis and prediction of clinical outcome.

In this project we will use in vivo magnetic resonance imaging next to clinical and behavioural assessment to investigate the interaction between brain anatomy changes and neural activity in functional circuits to:
1. Describe in detail the topography of brain areas corresponding to nodes in specific functional circuits.
2. Estimate the degree of overlap/separation between neural activity in the nodes of the delineated functional circuits.
3. Establish a reliable and accurate biomarker for early detection and clinical outcome prognosis in Parkinson's disease based on generative models combining brain anatomy and function characteristics.

The proposed advanced methods of image analysis will provide information that will directly impact clinical investigation, therapeutic monitoring and would help to unravel pathophysiological aspects of other neurodegenerative disorders associated with loss of dopamine.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Deep brain stimulation of the posterior gyrus rectus region for treatment resistant depression
Accolla E.A., Aust S., Merkl A., Schneider G.-H., Kühn A.A., Bajbouj M., Draganski B. (2016), Deep brain stimulation of the posterior gyrus rectus region for treatment resistant depression, in Journal of Affective Disorders, 194, 33-37.
Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities
D'Angelo Debra, Lebon Sebastien, Chen Qixuan, Martin-Brevet Sandra, Snyder LeeAnne Green, Hippolyte Loyse, Hanson Ellen, Maillard Anne M., Faucett W. Andrew, Mace Aurelien, Pain Aurelie, Bernier Raphael, Chawner Samuel J. R. A., David Albert, Andrieux Joris, Aylward Elizabeth, Baujat Genevieve, Caldeira Ines, Conus Philippe, Ferrari Carrina, Forzano Francesca, Gerard Marion, Goin-Kochel Robin P., Grant Ellen, Hunter Jill V. (2016), Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities, in JAMA PSYCHIATRY, 73(1), 20-30.
Basal ganglia-cortical structural connectivity in Huntington's disease
Novak M.J.U., Seunarine K.K., Gibbard C.R., Mccolgan P., Draganski B., Friston K., Clark C.A., Tabrizi S.J. (2015), Basal ganglia-cortical structural connectivity in Huntington's disease, in Human Brain Mapping, 36(5), 1728-1740.
Computer-based analysis of brain images: how close are we to clinical applications?
Draganski Bogdan (2015), Computer-based analysis of brain images: how close are we to clinical applications?, in CURRENT OPINION IN NEUROLOGY, 28(4), 311-312.
Differential patterns of functional and structural plasticity within and between inferior frontal gyri support training-induced improvements in inhibitory control proficiency
Chavan Camille F., Mouthon Michael, Draganski Bogdan, van der Zwaag Wietske, Spierer Lucas (2015), Differential patterns of functional and structural plasticity within and between inferior frontal gyri support training-induced improvements in inhibitory control proficiency, in HUMAN BRAIN MAPPING, 36(7), 2527-2543.
Sustained enhancements in inhibitory control depend primarily on the reinforcement of fronto-basal anatomical connectivity
Chavan C., Mouthon M., Simonet M., Hoogewoud H.-M., Draganski B., van der Zwaag W., Spierer L. (2015), Sustained enhancements in inhibitory control depend primarily on the reinforcement of fronto-basal anatomical connectivity, in Brain Structure and Function, 1-9.
The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity
Maillard A. M., Ruef A., Pizzagalli F., Migliavacca E., Hippolyte L., Adaszewski S., Dukart J., Ferrari C., Conus P., Maennik K., Zazhytska M., Siffredi V., Maeder P., Kutalik Z., Kherif F., Hadjikhani N., Beckmann J. S., Reymond A., Draganski B., Jacquemont S. (2015), The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity, in MOLECULAR PSYCHIATRY, 20(1), 140-147.
The concept of schizotypy - A computational anatomy perspective
Modenato C., Draganski B. (2015), The concept of schizotypy - A computational anatomy perspective, in Schizophrenia Research: Cognition, 2(2), 89-92.
The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition
Hippolyte L., Maillard A.M., Rodriguez-Herreros B., Pain A., Martin-Brevet S., Ferrari C., Conus P., Mac{é} A., Hadjikhani N., Metspalu A., Reigo A., Kolk A., Männik K., Barker M., Isidor B., Le Caignec C., Mignot C., Schneider L., Mottron L., Keren B., David A., Doco-Fenzy M., G{é}rard M., Bernier R., Goin-Kochel R.P. (2015), The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition, in Biological Psychiatry, 917.
Computational anatomy for studying use-dependant brain plasticity
Draganski B, Kherif F., Lutti A. (2014), Computational anatomy for studying use-dependant brain plasticity, in Front Hum Neurosci, 8, 380.
Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders.
Dukart Juergen, Regen Francesca, Kherif Ferath, Colla Michael, Bajbouj Malek, Heuser Isabella, Frackowiak Richard S, Draganski Bogdan (2014), Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders., in Proceedings of the National Academy of Sciences of the United States of America, 111(3), 1156-61.
Influence of magnetic field strength and image registration strategy on voxel-based morphometry in a study of Alzheimer's disease.
Marchewka Artur, Kherif Ferath, Krueger Gunnar, Grabowska Anna, Frackowiak Richard, Draganski Bogdan, Alzheimer's Disease Neuroimaging Initiative (2014), Influence of magnetic field strength and image registration strategy on voxel-based morphometry in a study of Alzheimer's disease., in Human brain mapping, 35(5), 1865-74.
Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers.
Hippolyte Loyse, Battistella Giovanni, Perrin Aline G, Fornari Eleonora, Cornish Kim M, Beckmann Jacques S, Niederhauser Julien, Vingerhoets François J G, Draganski Bogdan, Maeder Philippe, Jacquemont Sébastien (2014), Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers., in Neurobiology of aging, 1939.
Structural brain plasticity in Parkinson's disease induced by balance training.
Sehm Bernhard, Taubert Marco, Conde Virginia, Weise David, Classen Joseph, Dukart Juergen, Draganski Bogdan, Villringer Arno, Ragert Patrick (2014), Structural brain plasticity in Parkinson's disease induced by balance training., in Neurobiology of aging, 35(1), 232-9.
Widespread age-related differences in the human brain microstructure revealed by quantitative magnetic resonance imaging.
Callaghan Martina F, Freund Patrick, Draganski Bogdan, Anderson Elaine, Cappelletti Marinella, Chowdhury Rumana, Diedrichsen Joern, Fitzgerald Thomas H B, Smittenaar Peter, Helms Gunther, Lutti Antoine, Weiskopf Nikolaus (2014), Widespread age-related differences in the human brain microstructure revealed by quantitative magnetic resonance imaging., in Neurobiology of aging, 1862-1872.
Characterizing aging in the human brainstem using quantitative multimodal MRI analysis.
Lambert Christian, Chowdhury Rumana, Fitzgerald Thomas H B, Fleming Stephen M, Lutti Antoine, Hutton Chloe, Draganski Bogdan, Frackowiak Richard, Ashburner John (2013), Characterizing aging in the human brainstem using quantitative multimodal MRI analysis., in Frontiers in human neuroscience, 7, 462-462.
How early can we predict Alzheimer's disease using computational anatomy?
Adaszewski Stanisław, Dukart Juergen, Kherif Ferath, Frackowiak Richard, Draganski Bogdan, Alzheimer's Disease Neuroimaging Initiative (2013), How early can we predict Alzheimer's disease using computational anatomy?, in Neurobiology of aging, 34(12), 2815-26.
Impact of brain aging and neurodegeneration on cognition: evidence from MRI.
Draganski Bogdan, Lutti Antoine, Kherif Ferath (2013), Impact of brain aging and neurodegeneration on cognition: evidence from MRI., in Current opinion in neurology, 26(6), 640-5.
In vivo assessment of use-dependent brain plasticity--beyond the "one trick pony" imaging strategy.
Draganski Bogdan, Kherif Ferath (2013), In vivo assessment of use-dependent brain plasticity--beyond the "one trick pony" imaging strategy., in NeuroImage, 73, 255.
Relationship between imaging biomarkers, age, progression and symptom severity in Alzheimer's disease.
Dukart Juergen, Mueller Karsten, Villringer Arno, Kherif Ferath, Draganski Bogdan, Frackowiak Richard, Schroeter Matthias L, Alzheimer's Disease Neuroimaging Initiative (2013), Relationship between imaging biomarkers, age, progression and symptom severity in Alzheimer's disease., in NeuroImage. Clinical, 3, 84-94.
Brain tissue properties differentiate between motor and limbic basal ganglia circuits.
Accolla Ettore A, Dukart Juergen, Helms Gunther, Weiskopf Nikolaus, Kherif Ferath, Lutti Antoine, Chowdhury Rumana, Hetzer Stefan, Haynes John-Dylan, Kühn Andrea A, Draganski Bogdan, Brain tissue properties differentiate between motor and limbic basal ganglia circuits., in Human brain mapping.
Disentangling in vivo the effects of iron content and atrophy on the ageing human brain
Lorio S, Lutti A, Kherif F, Ruef A, Dukart J, Chowdhury R, Frackowiak R, Ashburner J, Helms G, Weiskopf N, Draganski B, Disentangling in vivo the effects of iron content and atrophy on the ageing human brain, in Neuroimage, (103C), 280-289.

Collaboration

Group / person Country
Types of collaboration
Abteilung Neurologie, Max-Planck Institute Leipzig - Prof. Villringer Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Wellcome Trust Centre for Neuroimaging Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Neuropsychology and Neurorehabilitation Service - Prof. Stephanie Clarke Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
MR-Forschung in der Neurologie & Psychiatrie, Max-Planck Institut Göttingen Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
EPNS International symposium Talk given at a conference Studying brain plasticity of motor networks 26.05.2015 Wien, Austria Draganski Bogdan;
Guest lecture Max-Planck Institute Talk given at a conference Novel concepts in computational anatomy 11.05.2015 Leipzig, Germany Draganski Bogdan;
Images of the mind Talk given at a conference Computational anatomy - novel insights into brain tissue properties 09.04.2015 Milano, Italy Draganski Bogdan;
Swiss-Japanese Workshop on Ageing Talk given at a conference In vivo histology 18.03.2015 Tokyo, Japan Draganski Bogdan;
Joint ETHZ-UCL workshop Talk given at a conference What can we see and what do we want to see when using in vivo MRI 03.03.2015 Ittingen, Switzerland Draganski Bogdan;
SSN Annual Meeting Talk given at a conference Imaging fingerprints of neurodegenerative disorders 25.01.2014 Bern, Switzerland Draganski Bogdan;
Nencki Institute Translational Research Inauguration Symposium Talk given at a conference Computational anatomy of the brain 14.11.2013 Warsaw, Poland Draganski Bogdan;
5th meeting of the BMBF independent research groups Talk given at a conference In vivo histology using MRI – novel concepts 10.10.2013 Hamburg, Germany Draganski Bogdan;
Workshop “Subthalamic nucleus – anatomy and function”, Society for Neuroscience annual congress, USA Talk given at a conference Quantification of tissue properties in the human sub thalamic nucleus 09.09.2012 New Orleans, United States of America Draganski Bogdan;
Workshop “Quantitative magnetic resonance imaging - Human Brain Mapping annual congress Talk given at a conference Quantification of brain tissue properties 09.06.2012 Beijing, China Draganski Bogdan;
SNG-SSN & SGKN-SSNC Meeting Talk given at a conference Imaging brain tissue properties in movement disorders 03.05.2012 Lugano, Switzerland Draganski Bogdan;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions La semaine du cerveau, Lausanne - Percer les mystères des images Western Switzerland 2014
Talks/events/exhibitions Parkinson Suisse - Séance d'information, Lausanne Western Switzerland 2014
Talks/events/exhibitions La semaine du cerveau, Lausanne - Ce que les images nous apprennent Western Switzerland 2013
Talks/events/exhibitions Parkinson Suisse - Séance d'information, Fribourg Western Switzerland 2013

Associated projects

Number Title Start Funding scheme
159780 The two faces of neuroplasticity - In vivo study of brain plasticity induced by epileptic seizures and electroconvulsive therapy 01.04.2016 Project funding
150828 Development of Advanced Translational High-Field MRI 12.05.2014 R'EQUIP

Abstract

General backgroundParkinson’s disease, acknowledged as the second most common neurodegenerative disorder after Alzheimer’s disease, has a progressive debilitating course featuring motor and non-motor symptoms affecting severely the patients’ quality of life. The fact that neuronal damage begins 5-10 years before occurrence of motor symptoms underscores the importance of preclinical diagnosis for potential neuroprotective treatments. Previous research focused mainly on motor symptoms, however with further sophistication of pharmacological and neurosurgical treatment this concept was challenged by the predominance of cognitive and motivational/emotional dysfunction. Progressive loss of functional segregation within limbic, associative and sensorimotor cortico-basal ganglia circuits offers a unified model of idiopathic Parkinson’s disease (IPD) as clinicopathological entity, which can be used as biomarker of preclinical diagnosis and prediction of clinical outcome.Specific AimsIn this project, we will use in vivo magnetic resonance imaging (MRI) and clinical/behavioural assessment to investigate the interaction between anatomical characteristics and neural activity in limbic, cognitive and sensorimotor basal ganglia-cortex circuits in healthy subjects and IPD patients. The aims of the proposed project are:i.Describe in detail the topography of basal ganglia subregions, corresponding to nodes in specific limbic, associative and sensorimotor cortico-subcortical circuits.ii.Study the interaction between topography characteristics and neural activity in distinct nodes of the cortico-subcortical circuits.iii.Establish the detailed anatomical/functional inferences of cortex-basal ganglia circuitry as biomarkers for early detection and clinical outcome prognosis in IPD.MethodsA key aspect is the proposed well-balanced mixture of established and novel methods for MRI data acquisition, processing and analysis to overcome the limitations of previous work in the field. We build on novel approaches taking advantage of:i.Relaxometry-based quantitative structural MR imaging techniques that we developed for segmentation of the iron-rich basal ganglia, which were previously not detectable in standard T1-weighted MR sequences. ii.Extension of the probabilistic diffusion tractography-based model of cortico-subcortical circuitry we established for studying the topography of basal ganglia circuits with the structures reliably delineated in the previous step - subthalamic nucleus, substantia nigra, hippocampus and amygdala. iii.Coupling the anatomical topography data with neural activity estimation by fMRI using a novel multivariate Bayesian method, to relate structural and functional features of the basal ganglia.Working hypothesisThe hypothesis for the proposed experiment is that IPD will be associated with loss of functional and/or structural segregation within cortico-subcortical loops. Additionally, we hypothesize that the degree of disease progression in IPD patients will have a differential impact on the functional and structural segregation within limbic and associative circuits. By using advanced methods of image analysis, we aim to provide information that will directly impact clinical investigation, therapeutic monitoring and could help in unravelling pathophysiological aspects of other basal ganglia related disorders.
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