Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome

Abstract

The cerebral nuclei form the ventral division of the cerebral hemisphere and are thought to play an important role in neural systems controlling somatic movement and motivation. Network analysis was used to define global architectural features of intrinsic cerebral nuclei circuitry in one hemisphere (association connections) and between hemispheres (commissural connections). The analysis was based on more than 4,000 reports of histologically defined axonal connections involving all 45 gray matter regions of the rat cerebral nuclei and revealed the existence of four asymmetrically interconnected modules. The modules form four topographically distinct longitudinal columns that only partly correspond to previous interpretations of cerebral nuclei structure-function organization. The network of connections within and between modules in one hemisphere or the other is quite dense (about 40% of all possible connections), whereas the network of connections between hemispheres is weak and sparse (only about 5% of all possible connections). Particularly highly interconnected regions (rich club and hubs within it) form a topologically continuous band extending through two of the modules. Connection path lengths among numerous pairs of regions, and among some of the network's modules, are relatively long, thus accounting for low global efficiency in network communication. These results provide a starting point for reexamining the connectional organization of the cerebral hemispheres as a whole (right and left cerebral cortex and cerebral nuclei together) and their relation to the rest of the nervous system. behavior | connectomics | mammal | neural connections | neuroinformatics T he paired adult vertebrate cerebral hemispheres are differentiations of the embryonic neural tube's endbrain (telencephalic) vesicle, which in turn forms a ventral nonlaminated part, the cerebral nuclei, and then a dorsal laminated part, the cerebral cortex (1-3). In mammals the largest parts of the cerebral nuclei by volume are the caudoputamen (striatal) and globus pallidus (pallidal). Together, they are commonly regarded as the endbrain parts of the basal ganglia (3), which play an important role in controlling skeletomuscular (somatic) movements and in the etiology of movement disorders (4).A major shift in thinking about the basal ganglia occurred with the recognition that certain ventral parts of the cerebral nuclei display the same basic circuit organization, but involve different parts of a cerebral cortex to cerebral nuclei to thalamus to cerebral cortex loop (5). This finding led to an expanded view of the basal ganglia, with dorsal and ventral striatopallidal subsystems involved primarily in movement (dorsal) and motivational functionality (ventral) (6). Complete expansion of the view was then proposed on the basis of connectional, gene expression, embryological, and functional evidence (7). It was hypothesized that the entire cerebral cortex, cerebral nuclei, and thalamus can be divided into four basic subsystems involving dorsal, vent...

Macroscale intrinsic network architecture of the hypothalamus

“…Centrality Metrics and Additional Network Attributes. In addition to MRCC analysis, we investigated hypothalamic network properties using four common network centrality metrics (measures that indicate the dominance/"importance" of each node in the network): degree, strength, betweenness, and closeness (8)(9)(10). The centrality metric of degree measures the number of input (in-degree) or output (out-degree) connections for each network node (here, each gray matter region); strength represents the total weight of each node's macroconnections; and the related centrality measures of betweenness and closeness take account of the shortest path between nodes and are considered to provide an indication of node centrality with respect to information flow.…”

“…More generally, we have demonstrated how data-driven network modeling approaches can be employed as hypothesis-generating tools, with selected examples provided by interrogation of an updated model of the intrahypothalamic network, and we hope this encourages further investigation of the multiple intrahypothalamic subnetworks described here. Thus far, we have investigated macroscale subconnectomes for the cerebral hemispheres (8)(9)(10) and for the hypothalamus (this study). Future investigations will be aided by a more comprehensive understanding of the network architecture of the nervous system.…”

“…We investigated two additional network properties: the attributes of "small-world" and "rich-club." Previously, we investigated these for macroscale cerebral hemisphere subconnectomes (8)(9)(10). The small-world attribute is characteristic of networks with clustered nodes connected via short paths, whereas rich-club, in network theory parlance, refers to a group (subgraph) of well-connected network nodes that are also densely connected with one another.…”

“…Using data-driven approaches, we recently investigated the macroscale network of the cerebral hemispheres (8) and their principle parts: the cerebral cortex (9) and cerebral nuclei (10). This led to novel network models for two of the four major divisions of the forebrain that play an essential role in the cognitive control of behavior.…”

“…This is complemented with comparative analysis of gene markers associated with inhibitory [glutamic acid decarboxylase 65 (GAD65)] and excitatory [vesicular glutamate transporter 2 (VGLUT2)] neurotransmission. Network analysis is based on a weighted and directed connection matrix (for all 130 hypothalamic gray matter regions; 65 on each side), which is a macroscale intrahypothalamic subconnectome, and follows a strategy we have employed previously (8)(9)(10). on the same side (ipsilateral) or opposite sides (contralateral) of the hypothalamus.…”