Cortical and Subcortical Connections of the Human Claustrum Revealed In Vivo by Constrained Spherical Deconvolution Tractography

Abstract

The claustrum is a thin layer of gray matter that is at the center of an active scientific debate. Recently, Constrained Spherical Deconvolution (CSD) tractography has proved to be an extraordinary tool allowing to track white matter fibers from cortex to cortical and subcortical targets with subvoxel resolution. The aim of this study was to evaluate claustral connectivity in the human brain. Ten normal brains were analyzed by using the High Angular Resolution Diffusion Imaging CSD-based technique. Tractography revealed 4 groups of white matter fibers connecting the claustrum with the brain cortex: Anterior, posterior, superior, and lateral. The anterior and posterior cortico-claustral tracts connected the claustrum to prefrontal cortex and visual areas. The superior tract linked the claustrum with sensory-motor areas, while the lateral pathway connected the claustrum to the auditory cortex. In addition, we demonstrated a claustral medial pathway connecting the claustrum with the basal ganglia, specifically with caudate nucleus, putamen, and globus pallidus. An interesting and exciting new finding was the demonstration of a bilateral connection between claustrum and contralateral cortical areas and a well-represented interclaustral communication with interconnection bundles interspersed within the bulk of the trunk of the corpus callosum. The physiological and pathophysiological relevance of these findings are discussed.

Psychedelics

“…The claustrum theoretically synchronizes cortical areas to accomplish the feat of crossing modalities. Milardi et al (2015) used constrained spherical deconvolution tractography to elucidate the complex relationships between the fiber systems in the claustrum. They detected four groups of white matter fibers connecting the claustrum to the cortex (anterior, posterior, superior, and lateral) and provided a detailed representation of brain areas connected to the claustrum.…”

Synaptic Organization of the Neuronal Circuits of the Claustrum

“…The claustrum, a poorly understood subcortical structure found bilaterally in mammals, including humans, forms connections with almost all regions of the neocortex (Pearson et al, 1982;Sloniewski et al, 1986;Kowianski et al, 1999;Zingg et al, 2014;Milardi et al, 2015). Due in part to its challenging size and location in the brain, studies of the claustrum's functional properties have been limited.…”

Claustrum damage and refractory status epilepticus following febrile illness

“…16 Only in recent years has the scientific community gained a strong interest in the function of the claustrum, mainly with respect to its role in sensory integration and consciousness. [17][18][19][20][21] METHODS Patients and investigations. In a retrospective multicenter study ( -Dec 2013, information including demographic data, clinical features, diagnostic findings, therapeutic interventions, and clinical outcomes of patients fulfilling the following inclusion criteria were acquired: (1) previously healthy adults (.16 years of age) with refractory SE (failed IV treatment with antiepileptic drugs, requiring general anesthesia) 22 ; (2) onset of seizures 0-21 days after a febrile illness; and (3) lacking evidence of infectious agents in CSF.…”

“…Recent advances in neuroanatomy and physiology indicate this subcortical region as a highly relevant hub center in neural synchronization of several (and distant) cortical areas, and, as a consequence, a structure involved in integration of conscious perception. [17][18][19][20][21] Considering these physiologic properties of the claustrum, this structure could also be a key region in promoting the propagation and synchronization of abnormal epileptic activity from several cortical regions. To this point, 2 properties of claustral neurons are relevant.…”

“…First, claustro-cortical fibers connect the claustrum with several cortical areas, including the prefrontal, prepostcentral, posterior parietal, orbitofrontal, and medial temporal cortex. 20,21 Second, the claustrum is constituted by densely packed and tightly interconnected GABAergic interneurons. 17,18 Therefore, the claustrum can potentially bind together and modulate neural activities (epileptic activity in our case) from and to widespread cortical areas.…”