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Relationship between the anterior forebrain mesocircuit and the default mode network in the structural bases of disorders of consciousness.

Lant ND, Gonzalez-Lara LE, Owen AM, Fernández-Espejo D - Neuroimage Clin (2015)

Bottom Line: We found evidence of significant damage to subcortico-cortical and cortico-cortical fibers, which were more severe in vegetative state patients and correlated with clinical severity as determined by Coma Recovery Scale-Revised (CRS-R) scores.Lastly, we found significant damage in all fiber tracts connecting the precuneus with cortical and subcortical areas.Our results suggest a strong relationship between the default mode network - and most importantly the precuneus - and the anterior forebrain mesocircuit in the neural basis of the DOC.

View Article: PubMed Central - PubMed

Affiliation: The Brain and Mind Institute, The University of Western Ontario, London, ON N6A 5B7, Canada.

ABSTRACT
The specific neural bases of disorders of consciousness (DOC) are still not well understood. Some studies have suggested that functional and structural impairments in the default mode network may play a role in explaining these disorders. In contrast, others have proposed that dysfunctions in the anterior forebrain mesocircuit involving striatum, globus pallidus, and thalamus may be the main underlying mechanism. Here, we provide the first report of structural integrity of fiber tracts connecting the nodes of the mesocircuit and the default mode network in 8 patients with DOC. We found evidence of significant damage to subcortico-cortical and cortico-cortical fibers, which were more severe in vegetative state patients and correlated with clinical severity as determined by Coma Recovery Scale-Revised (CRS-R) scores. In contrast, fiber tracts interconnecting subcortical nodes were not significantly impaired. Lastly, we found significant damage in all fiber tracts connecting the precuneus with cortical and subcortical areas. Our results suggest a strong relationship between the default mode network - and most importantly the precuneus - and the anterior forebrain mesocircuit in the neural basis of the DOC.

No MeSH data available.


Related in: MedlinePlus

Spearman correlations of CRS-R scores and composite fiber tract FA values for DOC patients. Sub-Cor: subcortico-cortical composite fiber tract, Cor-Cor: cortico-cortical composite fiber tract.
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f0015: Spearman correlations of CRS-R scores and composite fiber tract FA values for DOC patients. Sub-Cor: subcortico-cortical composite fiber tract, Cor-Cor: cortico-cortical composite fiber tract.

Mentions: Regions of interest (ROIs) were obtained in a semi-automatic way and included subcortical structures and cortical areas. Subcortical structures were the main nodes of the anterior forebrain mesocircuit, as described in Schiff (2008): thalamus, globus pallidus (including both the internal and external subdivisions in a combined ROI), putamen, and caudate nucleus. The putamen and caudate nucleus were considered together as striatum to directly reflect the proposed schema of the anterior forebrain mesocircuit hypothesis (Schiff, 2008, Schiff, 2010). The globus pallidus could not be reliably separated into internal and external segments due to limitations in anatomical resolution. All subcortical structures were defined individually in the left and right hemispheres and fiber tracking was performed to ipsilateral subcortical and cortical structures, as well as midline cortical structures, according to the schematic displayed in Fig. 3. Subcortical masks for each ROI were generated using the Harvard-Oxford Subcortical Structural Atlas (Frazier et al., 2005, Goldstein et al., 2007) on the MNI152 standard brain, and then unwarped to each subject's native space using the FSL linear registration tool, FLIRT (Jenkinson and Smith, 2001, Jenkinson et al., 2002), in a manner consistent with previous work (Fernandez-Espejo et al., 2012). A 2-step registration process within FLIRT (Jenkinson and Smith, 2001, Jenkinson et al., 2002) was used with b = 0 image as low-resolution image, T1 as high resolution image, and the MNI152 1 mm template as the reference image. The inverse of the resulting transformation matrix was applied to each mask to unwarp it to native DTI space in each subject. After registration in native space, each mask was manually corrected in FSL View to ensure a close match with its anatomical boundaries. Because of the close proximity of these subcortical structures, care was taken to ensure that there was no overlap between the masks for each ROI in each subject (e.g. no overlap between globus pallidus and putamen masks). A stereotactic atlas of the basal ganglia and thalamus was used as qualitative visual aid and external reference to help define the appropriate boundaries of each ROI (Morel, 2007). For the thalamus, the transverse plane mean diffusivity (MD) map was used to define the thalamo-ventricular border (medial border of thalamus), and the transverse plane FA map was used to define the border between the thalamus and internal capsule (lateral border of thalamus). After approximate segmentation in the transverse plane, the frontal plane FA map was used to define the shape of the thalamus more precisely. For the caudate, the transverse plane MD map was used to define the border between the caudate and the lateral ventricle, and the transverse plane FA map was used to define the border between the caudate and the internal capsule. The frontal plane FA map was used to define the shape of the caudate more precisely. MD and FA maps failed to provide adequate contrast for accurate delineation of anatomical boundaries of the putamen and globus pallidus. The T1 image acquired for each subject was registered to DTI space using FLIRT (Jenkinson and Smith, 2001, Jenkinson et al., 2002), and then visually inspected to ensure a correct alignment with the FA and MD maps. The boundaries of the unwarped putamen and globus pallidus ROIs were checked against both the registered T1 image and the FA map and manually corrected when necessary. This semi-automated method of subcortical ROI segmentation was chosen over fully automatic segmentation techniques because of the large anatomical variation found in DOC patient brains. Although automatic segmentation tools have been used previously for delineating the thalamus in DOC patients (Fernandez-Espejo et al., 2010, Lutkenhoff et al., 2015), the segmentation tools themselves are built on large collections of manually segmented regions (Patenaude et al., 2011). For consistency in our approaches for cortical and subcortical masking, we used the previously described semi-automatic method for both DOC patients and healthy controls.


Relationship between the anterior forebrain mesocircuit and the default mode network in the structural bases of disorders of consciousness.

Lant ND, Gonzalez-Lara LE, Owen AM, Fernández-Espejo D - Neuroimage Clin (2015)

Spearman correlations of CRS-R scores and composite fiber tract FA values for DOC patients. Sub-Cor: subcortico-cortical composite fiber tract, Cor-Cor: cortico-cortical composite fiber tract.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4660379&req=5

f0015: Spearman correlations of CRS-R scores and composite fiber tract FA values for DOC patients. Sub-Cor: subcortico-cortical composite fiber tract, Cor-Cor: cortico-cortical composite fiber tract.
Mentions: Regions of interest (ROIs) were obtained in a semi-automatic way and included subcortical structures and cortical areas. Subcortical structures were the main nodes of the anterior forebrain mesocircuit, as described in Schiff (2008): thalamus, globus pallidus (including both the internal and external subdivisions in a combined ROI), putamen, and caudate nucleus. The putamen and caudate nucleus were considered together as striatum to directly reflect the proposed schema of the anterior forebrain mesocircuit hypothesis (Schiff, 2008, Schiff, 2010). The globus pallidus could not be reliably separated into internal and external segments due to limitations in anatomical resolution. All subcortical structures were defined individually in the left and right hemispheres and fiber tracking was performed to ipsilateral subcortical and cortical structures, as well as midline cortical structures, according to the schematic displayed in Fig. 3. Subcortical masks for each ROI were generated using the Harvard-Oxford Subcortical Structural Atlas (Frazier et al., 2005, Goldstein et al., 2007) on the MNI152 standard brain, and then unwarped to each subject's native space using the FSL linear registration tool, FLIRT (Jenkinson and Smith, 2001, Jenkinson et al., 2002), in a manner consistent with previous work (Fernandez-Espejo et al., 2012). A 2-step registration process within FLIRT (Jenkinson and Smith, 2001, Jenkinson et al., 2002) was used with b = 0 image as low-resolution image, T1 as high resolution image, and the MNI152 1 mm template as the reference image. The inverse of the resulting transformation matrix was applied to each mask to unwarp it to native DTI space in each subject. After registration in native space, each mask was manually corrected in FSL View to ensure a close match with its anatomical boundaries. Because of the close proximity of these subcortical structures, care was taken to ensure that there was no overlap between the masks for each ROI in each subject (e.g. no overlap between globus pallidus and putamen masks). A stereotactic atlas of the basal ganglia and thalamus was used as qualitative visual aid and external reference to help define the appropriate boundaries of each ROI (Morel, 2007). For the thalamus, the transverse plane mean diffusivity (MD) map was used to define the thalamo-ventricular border (medial border of thalamus), and the transverse plane FA map was used to define the border between the thalamus and internal capsule (lateral border of thalamus). After approximate segmentation in the transverse plane, the frontal plane FA map was used to define the shape of the thalamus more precisely. For the caudate, the transverse plane MD map was used to define the border between the caudate and the lateral ventricle, and the transverse plane FA map was used to define the border between the caudate and the internal capsule. The frontal plane FA map was used to define the shape of the caudate more precisely. MD and FA maps failed to provide adequate contrast for accurate delineation of anatomical boundaries of the putamen and globus pallidus. The T1 image acquired for each subject was registered to DTI space using FLIRT (Jenkinson and Smith, 2001, Jenkinson et al., 2002), and then visually inspected to ensure a correct alignment with the FA and MD maps. The boundaries of the unwarped putamen and globus pallidus ROIs were checked against both the registered T1 image and the FA map and manually corrected when necessary. This semi-automated method of subcortical ROI segmentation was chosen over fully automatic segmentation techniques because of the large anatomical variation found in DOC patient brains. Although automatic segmentation tools have been used previously for delineating the thalamus in DOC patients (Fernandez-Espejo et al., 2010, Lutkenhoff et al., 2015), the segmentation tools themselves are built on large collections of manually segmented regions (Patenaude et al., 2011). For consistency in our approaches for cortical and subcortical masking, we used the previously described semi-automatic method for both DOC patients and healthy controls.

Bottom Line: We found evidence of significant damage to subcortico-cortical and cortico-cortical fibers, which were more severe in vegetative state patients and correlated with clinical severity as determined by Coma Recovery Scale-Revised (CRS-R) scores.Lastly, we found significant damage in all fiber tracts connecting the precuneus with cortical and subcortical areas.Our results suggest a strong relationship between the default mode network - and most importantly the precuneus - and the anterior forebrain mesocircuit in the neural basis of the DOC.

View Article: PubMed Central - PubMed

Affiliation: The Brain and Mind Institute, The University of Western Ontario, London, ON N6A 5B7, Canada.

ABSTRACT
The specific neural bases of disorders of consciousness (DOC) are still not well understood. Some studies have suggested that functional and structural impairments in the default mode network may play a role in explaining these disorders. In contrast, others have proposed that dysfunctions in the anterior forebrain mesocircuit involving striatum, globus pallidus, and thalamus may be the main underlying mechanism. Here, we provide the first report of structural integrity of fiber tracts connecting the nodes of the mesocircuit and the default mode network in 8 patients with DOC. We found evidence of significant damage to subcortico-cortical and cortico-cortical fibers, which were more severe in vegetative state patients and correlated with clinical severity as determined by Coma Recovery Scale-Revised (CRS-R) scores. In contrast, fiber tracts interconnecting subcortical nodes were not significantly impaired. Lastly, we found significant damage in all fiber tracts connecting the precuneus with cortical and subcortical areas. Our results suggest a strong relationship between the default mode network - and most importantly the precuneus - and the anterior forebrain mesocircuit in the neural basis of the DOC.

No MeSH data available.


Related in: MedlinePlus