PNAS_Commentary_Figure_20210719.pdf
Fig. 1. Integration of subcortical and cortical connections in human consciousness. (A) Tyrosine hydroxylase immunostaining of dopaminergic neurons (brown), counterstained with hematoxylin (blue), in a caudal midbrain tissue section. The human brain specimen was donated by a 53-year-old woman who died of non-neurological causes and whose brainstem histology data provided the basis for the Harvard Ascending Arousal Atlas (reference 22) used by Spindler and colleagues (reference 12). (B) Zoomed-in view of the region indicated by the black rectangle in (A). Dopaminergic ventral tegmental area (VTA) neurons are visualized posterior to the cerebral peduncle (CP), medial to the substantia nigra (SN) and anterior to the decussation of the superior cerebellar peduncles (xSCP). (C) Anterior view of three-dimensional brainstem arousal nuclei, manually traced on an ex vivo MRI dataset from the same brain specimen using histological guidance. (D) A diffusion tractography analysis from an ex vivo MRI scan of a second brain specimen donated by a 60-year-old woman who died of non-neurological causes, as previously described (reference 24). Tracts emanating from the VTA (pink) project diffusely to the cerebral cortex, including the precuneus/posterior cingulate cortex (PCu/PCC). Tracts connecting the PCu/PCC node of the default mode network to the medial prefrontal cortex (mPFC) node via the cingulum bundle (CB) are shown in blue. Collectively, these tractography findings provide a structural correlate for the functional connectivity findings reported by Spindler and colleagues, whereby VTA-PCu/PCC connectivity appears to modulate the DMN. Abbreviations: DR = dorsal raphe; Hy = hypothalamus; IC = inferior colliculus; LC = locus coeruleus; MnR = median raphe; PBC = parabrachial complex; PTg = pedunculotegmental nucleus; SC = superior colliculus. Written informed consent for brain donation was provided by surrogate decision makers, in accordance with an Institutional Review Board-approved protocol.
