Where macroscopy fails: going to microscopic architecture

Transcription

1 Where macroscopy fails: going to microscopic architecture Nicola Palomero-Gallagher Institute of Neuroscience and Medicine (INM-1) Research Centre Jülich and Department of Psychiatry, Psychotherapy and Psychosomatics Medical Faculty, RWTH Aachen

2 Does macroscopy fail to provide the anatomical ground truth of borders of cortical areas? No: E.g., delineation of higher visual areas on the fusiform gyrus and prediction of cytoarchitecture by cortical folding patterns Yes: E.g., cortical folding patterns are highly variable at many sites and areal boundaries vary considerably in relation to macroanatomical landmarks

3 Delineation of higher visual areas on the fusiform gyrus Prediction of cytoarchitecture by cortical folding patterns Cortical surface vertex count Cortical surface vertex count Average distance (mm) between boundaries Predictability of cytoarchitectonic borders V1 4a 4p 2 V Agreement between cytoarchitectonically and landmark-based localization of boundaries of V1 FG2 MFS FG1 FG1 MFS FG2 Agreement between functionally and landmarkbased localization of boundaries of V1 Distance (mm) Weiner et al. (2014) The mid-fusiform sulcus: A landmark identifying both cytoarchitectonic and functional divisions of the human fusiform gyrus. Neuroimage 84: Weiner et al. (2016) The cytoarchitecture of domain-specific regions in human high-level visual cortex. Cerebral Cortex, doi: /cercor/bhw361 Fischl B., Rajendran, N., Busa, E., Augustinack, J., Hinds, O., Mohlberg, H., Amunts, K., Zilles, K. (2008) Cortical folding patterns and predicting cytoarchitecture. Cerebral Cortex 18: Hinds et al. (2009) Locating the functional and anatomical boundaries of human primary visual cortex. NeuroImage 46:

4 Cytoarchitectonic boundaries vary independently from sulcal patterns Lack of macroanatomical landmarks 33 25a L 25p orbito-frontal cortex R Amunts, K., Schleicher, A., Bürgel, U., Mohlberg, H., Uylings, H.B.M., Zilles, K. (1999) Broca s region revisited: Cytoarchitecture and intersubject variability. J. Comp. Neurol. 412: Palomero-Gallagher, N., Mohlberg, H., Zilles, K., Vogt, B. (2008) Cytology and receptor architecture of human anterior cingulate cortex. J. Comp. Neurol. 508:

5 Further examples for the lack of landmarks Boundaries of the primary visual cortex V1 Boundaries of the primary motor cortex area 4 Boundaries of the primary somatosensory cortex area 3a Boundaries of the primary somatosensory cortex area 3b Boundaries of the primary somatosensory cortex area 1

6 p-os ips 2 cm V2 V2 p-os ips V Meynert cells in layer IIIc VIa VIa p-os V IV IIIc IVcb IVca IVb IIIab II I I? IVa calcs III? II V1 V1 lins 6

7 cs 3b prcg 3b 3a posg Betz giant cells cs cs

8 Microscopical segregation I II III IVa IVb IVca IVcb V VIa VIb I II IIIa IIIb IIIc Va Vb VIa VIb Primary visual cortex V1 Primary motor cortex area 4 8

9 The cytoarchitectonic map of Brodmann (1909) Based on visual inspection of a single hemisphere Underestimates the number of cortical areas Talairach & Tournoux do not provide Contains borders between areas which cortical do areas not exist (e.g. BA19) Does not provide information on intersubject variability 2D schematic drawing Brodmann, K., Vergleichende Lokalisationslehre der Großhirnrinde in ihren Prinzipien dargestellt auf Grund des Zellbaues. Barth, Leipzig Talairach J & Tournoux P (1988). Co-planar stereotaxic atlas of the human brain. Stuttgart, New York, Thieme 9

10 Identification of cytoarchitectonic borders I II BA17 BA18 III IVa IVb IVc V VIa VIb I II III IV V VIa VIb 10

11 Boundaries between hierarchically higher associative cortical areas are difficult to define by simple visual inspection Bludau, S., Eickhoff, S.B., Mohlberg, H., Caspers, S., Laird, A.R., Fox, P.T., Schleicher, A., Zilles, K., Amunts, K. (2014) Cytoarchitecture, probability maps and functions of the human frontal pole. Neuroimage 93:

12 Are more areas better than less? Discrepancies between published maps of the anterior cingulate cortex Brodmann (1910) 4 areas Vogt & Vogt (1919) von Economo & Koskinas (1925) 23 areas 12 areas Strasburger (1937) 24 areas Sarkissov et al. (1955) Vogt et al. (1995) 17 areas 11 areas

13 supragranular infragranular What are the criteria for cytoarchitectonic mapping? I. molecular II. outer granular I II IIIa Laminar distribution of the packing density of neuronal cell bodies Absolute thickness of cortical layers III. outer pyramidal IV. inner granular V. inner pyramidal VI. polymorphic IIIb IIIc IV Va Vb VIa VIb Proportionate thickness of a layer relative to the other layers and to the total cortical depth Presence of clearly recognizable laminar borders and vertical columns Distribution of cell bodies throughout the layers: homogeneous or clustered Presence of special cell types such as Betz cells Brodmann (1914). Physiologie des Gehirns. In: von Bruns (ed.) Neue Deutsche Chirurgie. Stutgart, Verlag von Ferdinand Enke. pp

14 Quantification of cytoarchitectonic characteristics GLI (Grey Level Index) volume fraction of cell bodies in total brain volume 0% GLI 100% Schleicher, Zilles, Kretschmann (1978) Verhandlungen der Anatomischen Gesellschaft 72,S: Schleicher, Zilles, Wree (1986) Journal of Neuroscience Methods 18: Schleicher & Zilles (1990) Journal of Microscopy 157:

15 GLI (%) GLI (%) Statististical testing of cytoarchitectonic borders a b a b 191 s32 s24a s24b D Cortical depth 0 Cortical depth Mahalanobis distance (D 2 ) = * * * * Profil # Zilles, Schleicher, Palomero-Gallagher, Amunts (2002) In: Brain Mapping: The Methods, Elsevier, pp Palomero-Gallagher, Mohlberg, Zilles, Vogt (2008) Journal of Comparative Neurology 508:

16 Observer-independent and statistically testable mapping of the anterior cingulate cortex 33 25a 25p s24a s24b s32 p24a p24b pv24c pd24cd pd24cv p32 Caudal 32 a24 a a24 b 24 cv 24 cd p24 a p24 b 24 dv 24 dd Rostral Palomero-Gallagher, Mohlberg, Zilles, Vogt (2008) J Comp Neurol 508: Palomero-Gallagher & Zilles (2009) In: Cingulate Neurobiology & Disease. Oxford University Press, pp Palomero-Gallagher, Hoffstaedter, Mohlberg, Eickhoff, Amunts, Zilles (in 16 preparation)

17 The revised map of the anterior cingulate cortex pacc p32 amcc 32 24c d 24c v pd24cd a24b pd24cv a24a p24b p24a pv24c s24a s24b 25 s32 pmcc 24dd 24dv p24b p24a 33 sacc Palomero-Gallagher, Mohlberg, Zilles, Vogt (2008) J Comp Neurol 508: Palomero-Gallagher & Zilles (2009) In: Cingulate Neurobiology & Disease. Oxford University Press, pp

18 Area 32 Interindividual variability in location and size N=1 N=2 0% 100% Palomero-Gallagher, et al. (in preparation) N=10 18

19 Maximum probabilistic maps 32 24dd 24dv 24c d 24c v p24ab a24ab 33 pd24c p32 p24ab pv24c s24a s32 s24b 25 Palomero-Gallagher, et al. (in preparation) 19

20 Functional characterization of ACC areas by means of a metaanalysis of published data based on fmri and own multimodal data Database: Tasks e.g.: Attention Imagination of movements Names Reward task Semantic discrimination Wisconsin Test etc. Functional domains e.g.: Attention Empathy Sadness, fear, anger Language Episodic memory Autonomic control etc.

21 Functional characterization of ACC areas pacc: positive emotions p32: Sadness, fear, anxiety emotion induction Episodic memory Empathy p24: Conflict monitoring Reward tasks Gustatory evaluation pacc p32 p24 sacc: negative emotions, autonomic control s32: Fear Reward tasks s24: Sadness Episodic memory 25: Autonomic control s32 sacc s24 25 Palomero-Gallagher, Eickhoff, Hoffstaedter, Schleicher, Mohlberg, Vogt, Amunts, Zilles (2015). NeuroImage 115:

22 Maximum probability maps and fmri moving dots stationary dots V5 Wilms et al., Anat & Embryol, 2005 and NeuroImage,

23 Summary Macroscopical landmarks are useful in certain brain regions, but not in all Cytoarchitecture provides anatomical ground truth Observer independent mapping is required to decide on reproducible areal boundaries and the true number of cytoarchitectonic areas Cytoarchitectonic probability maps are a useful anatomical basis for the analysis of neuroimaging data

24 Thanks to: Institute of Neuroscience and Medicine, Research Centre Jülich Katrin Amunts Sebastian Bludau Julian Caspers Simon Eickhoff Felix Hoffstaedter Aleksandar Malikovic Hartmut Mohlberg Axel Schleicher Marcus Wilms Karl Zilles Boston University Brent Vogt Stanford University Kalanit Grill-Spector Kevin Weiner Martinos Center for Biomedical Imaging Harvard Medical School Bruce Fischl

25 Thank you for your attention!