A Proposed Human Structural Brain Connectivity Matrix in the Center for Morphometric Analysis Harvard-Oxford Atlas Framework: A Historical Perspective and Future Direction for Enhancing the Precision of Human Structural Connectivity with a Novel Neuroanatomical Typology

Abstract

A complete structural definition of the human nervous system must include delineation of its wiring diagram (e.g., [1]). The complete formulation of the human brain circuit diagram (BCD; [2]) has been hampered by an inability to determine connections in their entirety (i.e., not only pathway stems, but also origins and terminations). From a structural point of view, a neuroanatomic formulation of the BCD should include the origins and terminations of each fiber tract as well as the topographic course of the fiber tract in three dimensions. Classic neuroanatomical studies have provided trajectory information for pathway stems and their speculative origins and terminations [3–7]. We have summarized these studies previously [7] and present them here in a macroscale-level human cerebral structural connectivity matrix. A matrix in the present context is an organizational construct that embodies anatomical knowledge about cortical areas and their connections. This is represented in relation to parcellation units according to the Harvard-Oxford Atlas neuroanatomical framework established by the Center for Morphometric Analysis at Massachusetts General Hospital in the early 2000s, which is based on the MRI volumetrics paradigm of Dr. Verne Caviness and colleagues [8]. This is a classic connectional matrix based mainly on data predating the advent of DTI tractography, which we refer to as the "pre-DTI era" human structural connectivity matrix. In addition, we present representative examples that incorporate validated structural connectivity information from non-human primates and more recent information on human structural connectivity emerging from DTI tractography studies. We refer to this as the "DTI era" human structural connectivity matrix. This newer matrix represents a work in progress and is necessarily incomplete due to the lack of validated human connectivity findings on origins and terminations as well as pathway stems. Importantly, we use a neuroanatomical typology to characterize different types of connections in the human brain, which is critical for organizing the matrices and the prospective database. Although substantial in detail, the present matrices may be assumed to be only partially complete because the sources of data relating to human fiber system organization are limited largely to inferences from gross dissections of anatomic specimens or extrapolations of pathway tracing information from non-human primate experiments [2,9,10]. These matrices, which embody a systematic description of cerebral connectivity, can be used in cognitive and clinical studies in neuroscience and, importantly, to guide research efforts for further elucidating, validating and completing the human brain circuit diagram [2].

Optimization of TMS target engagement: novel evidence based on combined TMS–EEG and dMRI tractography of brain circuitry

“…To minimize these uncertainties, current neuroimaging and neurophysiology technologies can be implemented. More specifically, navigated TMS combined with real-time tractography (Aydogan et al, 2023) helps in detecting the structural cortical and subcortical connectional matrix of the targeted cortical area (Makris et al, 2023a, 2023b). On the other hand, TMS combined with fMRI and high-density electroencephalography (EEG) could be implemented to address the functional signature of the stimulated cortical area (Rosanova et al, 2009b) and its associated functional connectivity.…”

Optimization of TMS target engagement: novel evidence based on combined TMS–EEG and dMRI tractography of brain circuitry

“…To minimize these uncertainties, current neuroimaging and neurophysiology technologies can be implemented. More specifically, navigated TMS combined with real-time tractography (Aydogan et al, 2023) helps in detecting the structural cortical and subcortical connectional matrix of the targeted cortical area (Makris et al, 2023a, 2023b). On the other hand, TMS combined with fMRI and high-density electroencephalography (EEG) could be implemented to address the functional signature of the stimulated cortical area (Rosanova et al, 2009b) and its associated functional connectivity.…”

Neuroanatomy of substantia nigra and ventral tegmental area dopaminergic, and dorsal raphe serotonergic circuits in the human brain using T1-weighted and diffusion magnetic resonance imaging: A morphometric pilot study with estimate of reliability

“…These connections have been described extensively in the experimental animal literature and are detailed in the discussion section. It should be noted that given the paucity of human traditional anatomical studies addressing these structural connections, we followed the paradigm of the Pandya comparative extrapolation principle (Makris et al, 2023b) and the approach of MRI-based brain volumetrics (Caviness et al, 1999; Makris et al, 2023a) as we have adopted in several of our studies. Given the limited literature regarding contralateral structural connectivity of the SN, VTA and DRN in experimental animals and humans, we limited our study to their ipsilateral structural connectomes (e.g., (Nieuwenhuys, 1985)).…”

The Influence of Structural Brain Changes on Cognition in the Context of Healthy Aging: Exploring Mediation Effects Through gBAT—The Graphical Brain Association Tool

“…If a more traditional parcellation of functional connectivity data is required, AICHA or the homotopic functional connectivity atlas is provided (Joliot et al 2015 ). Alternative structure‐based atlases include the Harvard‐Oxford atlas based on macroscopic anatomical landmarks (Makris et al 2023 ), the Julich‐Brain histological atlas based on microstructural properties (Amunts et al 2020 ), and the XTRACT Human Connectome Project probabilistic tractography atlas (Warrington et al 2020 ). Additionally, gBAT offers users the flexibility to incorporate their preferred atlases by simply uploading a custom atlas along with an optional text file detailing the names and tissue categorizations of ROIs.…”

Optimization of TMS target engagement: novel evidence based on combined TMS–EEG and dMRI tractography of brain circuitry

“…To minimize these uncertainties, current neuroimaging and neurophysiology technologies can be implemented. More specifically, navigated TMS combined with real-time tractography (Aydogan et al, 2023) helps in detecting the structural cortical and subcortical connectional matrix of the targeted cortical area (Makris et al, 2023a, 2023b). On the other hand, TMS combined with fMRI and high-density electroencephalography (EEG) could be implemented to address the functional signature of the stimulated cortical area (Rosanova et al, 2009b) and its associated functional connectivity.…”

Neuroanatomy of substantia nigra and ventral tegmental area dopaminergic, and dorsal raphe serotonergic circuits in the human brain using T1-weighted and diffusion magnetic resonance imaging: A morphometric pilot study with estimate of reliability

“…These connections have been described extensively in the experimental animal literature and are detailed in the discussion section. It should be noted that given the paucity of human traditional anatomical studies addressing these structural connections, we followed the paradigm of the Pandya comparative extrapolation principle (Makris et al, 2023b) and the approach of MRI-based brain volumetrics (Caviness et al, 1999; Makris et al, 2023a) as we have adopted in several of our studies. Given the limited literature regarding contralateral structural connectivity of the SN, VTA and DRN in experimental animals and humans, we limited our study to their ipsilateral structural connectomes (e.g., (Nieuwenhuys, 1985)).…”

The Influence of Structural Brain Changes on Cognition in the Context of Healthy Aging: Exploring Mediation Effects Through gBAT—The Graphical Brain Association Tool

“…If a more traditional parcellation of functional connectivity data is required, AICHA or the homotopic functional connectivity atlas is provided (Joliot et al 2015 ). Alternative structure‐based atlases include the Harvard‐Oxford atlas based on macroscopic anatomical landmarks (Makris et al 2023 ), the Julich‐Brain histological atlas based on microstructural properties (Amunts et al 2020 ), and the XTRACT Human Connectome Project probabilistic tractography atlas (Warrington et al 2020 ). Additionally, gBAT offers users the flexibility to incorporate their preferred atlases by simply uploading a custom atlas along with an optional text file detailing the names and tissue categorizations of ROIs.…”

Optimization of TMS target engagement: novel evidence based on combined TMS–EEG and dMRI tractography of brain circuitry

“…To minimize these uncertainties, current neuroimaging and neurophysiology technologies can be implemented. More specifically, navigated TMS combined with real-time tractography (Aydogan et al, 2023) helps in detecting the structural cortical and subcortical connectional matrix of the targeted cortical area (Makris et al, 2023a, 2023b). On the other hand, TMS combined with fMRI and high-density electroencephalography (EEG) could be implemented to address the functional signature of the stimulated cortical area (Rosanova et al, 2009b) and its associated functional connectivity.…”

Neuroanatomy of substantia nigra and ventral tegmental area dopaminergic, and dorsal raphe serotonergic circuits in the human brain using T1-weighted and diffusion magnetic resonance imaging: A morphometric pilot study with estimate of reliability

“…These connections have been described extensively in the experimental animal literature and are detailed in the discussion section. It should be noted that given the paucity of human traditional anatomical studies addressing these structural connections, we followed the paradigm of the Pandya comparative extrapolation principle (Makris et al, 2023b) and the approach of MRI-based brain volumetrics (Caviness et al, 1999; Makris et al, 2023a) as we have adopted in several of our studies. Given the limited literature regarding contralateral structural connectivity of the SN, VTA and DRN in experimental animals and humans, we limited our study to their ipsilateral structural connectomes (e.g., (Nieuwenhuys, 1985)).…”

The Influence of Structural Brain Changes on Cognition in the Context of Healthy Aging: Exploring Mediation Effects Through gBAT—The Graphical Brain Association Tool

“…If a more traditional parcellation of functional connectivity data is required, AICHA or the homotopic functional connectivity atlas is provided (Joliot et al 2015 ). Alternative structure‐based atlases include the Harvard‐Oxford atlas based on macroscopic anatomical landmarks (Makris et al 2023 ), the Julich‐Brain histological atlas based on microstructural properties (Amunts et al 2020 ), and the XTRACT Human Connectome Project probabilistic tractography atlas (Warrington et al 2020 ). Additionally, gBAT offers users the flexibility to incorporate their preferred atlases by simply uploading a custom atlas along with an optional text file detailing the names and tissue categorizations of ROIs.…”