Abnormal structural and functional brain connectivity in gray matter heterotopia

Abstract

Summary Purpose Periventricular nodular heterotopia (PNH) is a malformation of cortical development associated with epilepsy and dyslexia. Evidence suggests that heterotopic gray matter can be functional in brain malformations and that connectivity abnormalities may be important in these disorders. We hypothesized that nodular heterotopia develop abnormal connections and systematically investigated the structural and functional connectivity of heterotopia in patients with PNH. Methods Eleven subjects were studied using diffusion tensor tractography and resting-state functional connectivity MRI with bold oxygenation level-dependent (BOLD) imaging. Fiber tracks with a terminus within heterotopic nodules were visualized to determine structural connectivity, and brain regions demonstrating resting-state functional correlations to heterotopic nodules were analyzed. Relationships between these connectivity results and measures of clinical epilepsy and cognitive disability were examined. Key Findings A majority of heterotopia (69%) showed structural connectivity to discrete regions of overlying cortex, and almost all (96%) showed functional connectivity to these regions (mean peak correlation coefficient 0.61). Heterotopia also demonstrated connectivity to regions of contralateral cortex, other heterotopic nodules, ipsilateral but nonoverlying cortex, and deep gray matter structures or the cerebellum. Subjects with the longest durations of epilepsy had a higher degree of abnormal functional connectivity (p=0.036). Significance Most heterotopic nodules in PNH are structurally and functionally connected to overlying cortex, and the strength of abnormal connectivity is higher among those with the longest durations of epilepsy. Along with prior evidence that cortico-cortical tract defects underlie dyslexia in this disorder, the current findings suggest that altered connectivity is likely a critical substrate for neurological dysfunction in brain malformations.

Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography

“…For display purposes, an additional tractogram was also generated with 100,000 tracks for each participant using the exact same processing constraints. From a technical perspective, this whole brain tractography approach allowed us to avoid potential sources of error inherent in 'seed to target' region-of-interest-based tractography approaches where assessment of structural connectivity, and comparison to control subjects, is complicated by the absence in control subjects of structures corresponding to the ectopic clusters of neurons (27)(28)(29)(30)(31)(32). ( inferior-superior).…”

Repetitive transcranial magnetic stimulation for the treatment of refractory epilepsy

“…A further elucidation of the networks associated with epilepsy, connecting deep or multiple foci with neocortical areas, would be of major interest and allow targeted network stimulation compared to non-targeted vertex stimulation in patients without a superficial EF. Pioneering work revealed abnormal structural and functional connectivity between deep heterotopic gray matter nodules and discrete regions of overlying cortex in patients with periventricular heterotopia [63]. A TMS-EEG study in these patients confirmed the presence of cortical hyperexcitability that was specifically linked to the cortical regions with aberrant connectivity to the heterotopic nodules [64].…”

Morphometric changes in subcortical structures of the central auditory pathway in mice with bilateral nodular heterotopia

“…Furthermore, it is known that early disruption of cortical development is capable of reorganizing the brain and altering connectivity [12][13][14][15][16][17]54]. Therefore, it is likely that alterations in reciprocal corticothalamic/thalamocortical interactions as well as structural dysgenesis in other central auditory pathway structures (e.g., MGN, inferior colliculous, cochlear nucleus) may also be present.…”