THE STUDY OF BRAIN MORPHOLOGY

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1 1/12 THE STUDY OF BRAIN MORPHOLOGY Neuorecomics the functional brain

2 1/13 Basic Principle: the functional brain Vascular Anatomy Functional Anatomy Morphological Anatomy Microscopic Brain Anatomy at Cortical level The Neuro Vascular Unit Frontal lobe Anterior Cerebral Artery Parietal lobe synapse capillary Middle Cerebral Artery Silvian Fissure Posterior Cerebral ArteryOccipital lobe Temporal lobe Brodmann Areas astrocyte M. Ellisman and E. Bushong. A protoplasmic astrocyte (green) enveloping the cell body and the processes of a neuron (red). Nicola J. Nature :

3 The Function of Neurovascular Unit in Adult Age COX PhLA2 PGE2 mnos NO PSD nnos NO GLU Aminoacidic transporters AMPAr Glucose (Magistretti TINS 2008, Sestini S CML Science 2007) NMDAr PSD mglu Post-synaptic protein nnos Nitrox. syntetasis

4 The Study of Dopaminergic Transmission with Bio-molecular Neuroimaging

5 THE STUDY OF THE BRAIN FUNCTION in vivo The Study of Dopaminergic Transmission with Molecular Neuroimaging Radioligand: generic formula Bio-marker component Radioactive component Dopaminergic Radioligand: FP-CIT (I-N-ω-fluoropropyl-2-β-carbometossi-3-β-(4-iodo-fenil)-nortropano)

6 The Study of Dopaminergic Transmission with Molecular Neuroimaging Procedure Striatal Uptake Striatal Uptake Abnormal Normal

7 The Study of Dopaminergic Transmission with Molecular Neuroimaging Permission from L. Farde, Karolinska Institute Permission from L. Farde, Karolinska Institute

8 THE STUDY OF THE BRAIN Transmission FUNCTION in vivo The Study of Dopaminergic with Molecular Neuroimaging Permission from L. Farde, Karolinska Institute

9 The Study of Synaptic Function with Molecular Neuroimaging ECD PASSIVE DIFFUSION Esterase M Esterase cytosol ECD -> ECM -> EC -> IDROPHILIC C. COX PhLA2 PGE2 mnos NO HMPAO GLU reduct. red-ox state PSD nnos IDROPHILIC C. ECD HMPAO GLU Trasportatori aminoacidici AMPAr Glucosio 99mTc-HMPAO 18FDG NO 99mTc-ECD NMDAr PSD mglu Proteine post-sinaptiche nnos Nitrossido sintetasi 18FDG

10 The Study of Synaptic Function with Molecular Neuroimaging LUIS SOKOLOFF Noto che la trasmissione sinaptica è caratterizzata da una elevata richiesta energetica e che tale richiesta è soddisfatta dal catabolismo ossidativo del glucosio, Sokoloff dimostrò che: il consumo di glucosio negli astrociti presenta una relazione lineare con l intensità della trasmissione sinaptica

11 The Study of Synaptic Function with Molecular Neuroimaging Ma Luis andò oltre Se conoscere come funziona il cervello significa fotografare il funzionamento della sinapsi, se il funzionamento della sinapsi ha una relazione lineare con il consumo di glucosio, allora se riesco a fotografare il metabolismo del glucosio io so come funziona la sinapsi Sokoloff unì al glucosio una molecola radioattiva il C11, iniettò il C11-Deossi Glucosio in un vaso del ratto prima e della scimmia dopo, sacrificò l animale e fece delle auto-radiografie per vedere dove era andato a finire il C11-Glucosio

12 The Study of Synaptic Function with Molecular Neuroimaging AD PD

13 The Study of Synaptic Function with Molecular Neuroimaging Molecular Neuroimaging is different from morphological MRI surface projection 100% 0% 5 SD 0 right laterale aspect left laterale aspect

14 The Study of Synaptic Function with Molecular Neuroimaging Molecular Neuroimaging is different from functional MRI Il 95% della Energia viene consumata quando il cervello è teoricamente a riposo ovvero quando i neuroni comunicano continuamente e svolgono quel ruolo che si chiama plasticità sinaptica -> FDG-PET: METABOLISMO NEURONALE BASALE delle singole aree funzionali e nei network di trasmissione Il 5% viene consumato durante attivazione a seguito di task specifici -> fmri: picchi di attivazione metabolica Glucose Metabolism with PET Functional MRI

15 The Study of Functional Brain with Molecular Neuroimaging THE VOXEL BASED WORLD

16 The Study of Functional Brain with Molecular Neuroimaging in: NEUROECONOMY

17 The Study of Functional Brain with Molecular Neuroimaging A large number of brain areas are involved (metglu) in higher cognitive function and neuro-modulation in economic decision making Striatum Superior parietal lobule, Precuneus, Posterior Cingulate Cortex Superior parietal lobule, Precuneus, Posterior Cingulate Cortex Premotor Cortex, Dorsolateral Pre-frontal Cortex Ventromedial Pre-frontal, Dorsomedial Pre-frontal Cortex Premotor Cortex Amygdala and several neurotransmission systems, mainly dopa- and sero- toninergic

18 The Study of Functional Brain with Molecular Neuroimaging 1. Cooperation Interaction -> decision making 2. High Resting State Activity Sestini S et. al Current Radioph 2015

19 The Study of Functional Brain with Molecular Neuroimaging Brain Areas with High Resting State Activity within the Default Mode Network DMN Task Sestini S et. al Current Radioph 2015 Brain Areas with High Resting State Activity outside the Default Mode Network DMN Task +

20 The Study of Functional Brain with Molecular Neuroimaging Brain Areas with High Resting State Activity within the Default Mode Network DMN Task - Sestini S et. al Current Radioph 2015 Brain Areas with High Resting State Activity outside the Default Mode Network DMN Task +

21 The Study of Functional Brain with Molecular Neuroimaging Brain Areas with High Resting State Activity within the Default Mode Network DMN Task - Brain Areas with High Resting State Activity outside the Default Mode Network DMN Task + h 1,5 mm l 0,5 mm = neurons and synapses Sestini S et. al Current Radioph 2015

22 The Study of Functional Brain with Molecular Neuroimaging Brain Pathologies Stressful Behaviour strike the synapse DMN

23 The Study of Functional Brain with Molecular Neuroimaging Meditation as well as any relaxing brain activity may increase cognitive performances even in the long term (neuroplasticity) R. Davidson BMJ Newber E et al. Percept Mot Skills 2003; Marchand WR Word J Radiol 2014

24 Grazie per l attenzione