J Comp Neurol

Although the concept of left-hemispheric lateralization of neural processes during speech production has been known since the times of Broca, its physiological underpinnings still remain elusive. We sought to assess the modulatory influences of a major neurotransmitter, dopamine, on hemispheric lateralization during real-life speaking using a multimodal analysis of functional MRI, intracranial EEG recordings, and large-scale neural population simulations based on diffusion-weighted MRI. We demonstrate that speech-induced phasic dopamine release into the dorsal striatum and speech motor cortex exerts direct modulation of neuronal activity in these regions and drives left-hemispheric lateralization of speech production network. Dopamine-induced lateralization of functional activity and networks during speaking is not dependent on lateralization of structural nigro-striatal and nigro-motocortical pathways. Our findings provide the first mechanistic explanation for left-hemispheric lateralization of human speech that is due to left-lateralized dopaminergic modulation of brain activity and functional networks. This article is protected by copyright. All rights reserved

Differences in Hemodynamics and Rupture Rate of Aneurysms At the Bifurcation of the Basilar and Internal Carotid Arteries

Background and Purpose: Cerebral aneurysms in the posterior circulation are known to have a higher rupture risk than those in the anterior circulation. We sought to test the hypothesis that differences in hemodynamics can explain the difference in rupture rates. MATERIALS AND METHODS: A total of 117 aneurysms, 63 at the tip of the basilar artery (27 ruptured, 36 unruptured, rupture rate 43%) and 54 at the bifurcation of the internal carotid artery (11 ruptured, 43 unruptured, rupture rate 20%) were analyzed with image-based computational fluid dynamics. Several hemodynamic variables were compared among aneurysms at each location and between ruptured and unruptured aneurysms at each location. RESULTS: On average, aneurysms at the basilar tip had more concentrated inflow (P \u3c.001), a larger inflow rate (P \u3c.001), a larger maximum oscillatory shear index (P \u3c.003), more complex flows (P \u3c.033), and smaller areas under low wall shear stress (P \u3c.001) than aneurysms at the bifurcation of the internal carotid artery. In general, ruptured aneurysms had larger inflow concentration (P \u3c.02), larger shear concentration (P \u3c.02), more complex flows (P \u3c.001), and smaller minimum wall shear stress (P \u3c.003) than unruptured aneurysms. CONCLUSIONS: High flow conditions, characterized by large and concentrated inflow jets, complex and oscillatory flow patterns, and wall shear stress distributions with focalized regions of high shear and large regions of low shear, are associated with aneurysm rupture, especially for basilar tip aneurysms. The higher flow conditions in basilar tip aneurysms could explain their increased rupture risk compared with internal carotid bifurcation aneurysms

Identification of Hostile Hemodynamics and Geometries of Cerebral Aneurysms: A Case-Control Study

BACKGROUND AND PURPOSE: Hostile hemodynamic conditions and geometries are thought to predispose aneurysms for instability and rupture. This study compares stable, unstable, and ruptured aneurysms while controlling for location and patient characteristics. MATERIALS AND METHODS: The hemodynamics and geometries of 165 stable, 65 unstable, and 554 ruptured aneurysms were compared. Hemodynamics was modeled using image-based computational fluid dynamics. Case-control pairs were selected matching aneurysm location, patient age, and sex. Paired Wilcoxon tests were used to compare hemodynamic and geometric variables among different aneurysm groups. The pairing was repeated 100 times, and the combined P values were calculated and adjusted for multiple testing. RESULTS: Ruptured aneurysms had lower minimum wall shear stress (P =.03), higher maximum wall shear stress (P =.03), more concentrated (P =.03) and mean oscillatory shear stress (P =.03), higher maximum velocity (P =.03), and more complex flows (vortex core-line length, P=.03) than stable aneurysms. Similarly, unstable aneurysms had more concentrated shear stress (P=.04) and more complex flows (vortex core-line length, P =.04) than stable aneurysms. Compared with stable aneurysms, ruptured aneurysms were larger (size ratio, aneurysm size/vessel size, P =.03), more elongated (aspect ratio, P =.03), and irregular (nonsphericity index, P =.03). Similarly, unstable aneurysms were larger (size ratio, P =.04), more elongated (aspect ratio, P =.04), and irregular (bulge location, P =.04; area-weighted Gaussian curvature; P =.04) than stable aneurysms. No significant differences were found between unstable and ruptured aneurysms. CONCLUSIONS: Unstable and ruptured aneurysms have more complex flows with concentrated wall shear stress and are larger, more elongated, and irregular than stable aneurysms, independent of aneurysm location and patient sex and age

Angioarchitectures and Hemodynamic Characteristics of Posterior Communicating Artery Aneurysms and Their Association with Rupture Status

BACKGROUND AND PURPOSE: Intracranial aneurysms originating at the posterior communicating artery are known to have high rupture risk compared with other locations. We tested the hypothesis that different angioarchitectures (ie, branch point configuration) of posterior communicating artery aneurysms are associated with aneurysm hemodynamics, which in turn predisposes aneurysms to rupture. MATERIALS AND METHODS: A total of 313 posterior communicating artery aneurysms (145 ruptured, 168 unruptured) were studied with image-based computational fluid dynamics. Aneurysms were classified into different angioarchitecture types depending on the location of the aneurysm with respect to parent artery bifurcation. Hemodynamic characteristics were compared between ruptured and unruptured aneurysms, as well as among aneurysms with different angioarchitectures. RESULTS: Angioarchitecture was associated with rupture (P =; .003). Ruptured aneurysms had higher, more concentrated, and more oscillatory wall shear stress distributions (maximum wall shear stress, P\u3c.001; shear concentration index, P\u3c.001; mean oscillatory shear index, P \u3c .001), stronger and more concentrated inflow jets (represented as Q, P \u3c .01; inflow concentration index, P \u3c .001), and more complex and unstable flow patterns (vortex core length, P \u3c .001; proper orthogonal decomposition entropy, P \u3c .001) compared with unruptured aneurysms. These adverse conditions were more common in aneurysms with bifurcation-type angioarchitectures compared with those with lateral or sidewall angioarchitectures. Interestingly, ruptured aneurysms also had lower normalized mean wall shear stress (P \u3c .02) and minimum wall shear stress (P \u3c .002) than unruptured aneurysms. CONCLUSIONS: High-flow intrasaccular hemodynamic characteristics, commonly found in bifurcation-type angioarchitectures, are associated with the posterior communicating artery aneurysm rupture status. These characteristics include strong and concentrated inflow jets, concentrated regions of elevated wall shear stress, oscillatory wall shear stress, lower normalized wall shear stress, and complex and unstable flow patterns

Angioarchitectures and Hemodynamic Characteristics of Posterior Communicating Artery Aneurysms and Their Association with Rupture Status

BACKGROUND AND PURPOSE: Intracranial aneurysms originating at the posterior communicating artery are known to have high rupture risk compared with other locations. We tested the hypothesis that different angioarchitectures (ie, branch point configuration) of posterior communicating artery aneurysms are associated with aneurysm hemodynamics, which in turn predisposes aneurysms to rupture. MATERIALS AND METHODS: A total of 313 posterior communicating artery aneurysms (145 ruptured, 168 unruptured) were studied with image-based computational fluid dynamics. Aneurysms were classified into different angioarchitecture types depending on the location of the aneurysm with respect to parent artery bifurcation. Hemodynamic characteristics were compared between ruptured and unruptured aneurysms, as well as among aneurysms with different angioarchitectures. RESULTS: Angioarchitecture was associated with rupture (P = .003). Ruptured aneurysms had higher, more concentrated, and more oscillatory wall shear stress distributions (maximum wall shear stress, P \u3c .001; shear concentration index, P \u3c .001; mean oscillatory shear index, P \u3c .001), stronger and more concentrated inflow jets (represented as Q, P = .01; inflow concentration index, P \u3c .001), and more complex and unstable flow patterns (vortex core length, P \u3c .001; proper orthogonal decomposition entropy, P \u3c .001) compared with unruptured aneurysms. These adverse conditions were more common in aneurysms with bifurcation-type angioarchitectures compared with those with lateral or sidewall angioarchitectures. Interestingly, ruptured aneurysms also had lower normalized mean wall shear stress (P = .02) and minimum wall shear stress (P = .002) than unruptured aneurysms. CONCLUSIONS: High-flow intrasaccular hemodynamic characteristics, commonly found in bifurcation-type angioarchitectures, are associated with the posterior communicating artery aneurysm rupture status. These characteristics include strong and concentrated inflow jets, concentrated regions of elevated wall shear stress, oscillatory wall shear stress, lower normalized wall shear stress, and complex and unstable flow patterns

Gap junctions on hippocampal mossy fiber axons demonstrated by thin-section electron microscopy and freeze–fracture replica immunogold labeling

Gap junctions have been postulated to exist between the axons of excitatory cortical neurons based on electrophysiological, modeling, and dye-coupling data. Here, we provide ultrastructural evidence for axoaxonic gap junctions in dentate granule cells. Using combined confocal laser scanning microscopy, thin-section transmission electron microscopy, and grid-mapped freeze–fracture replica immunogold labeling, 10 close appositions revealing axoaxonic gap junctions (≈30–70 nm in diameter) were found between pairs of mossy fiber axons (≈100–200 nm in diameter) in the stratum lucidum of the CA3b field of the rat ventral hippocampus, and one axonal gap junction (≈100 connexons) was found on a mossy fiber axon in the CA3c field of the rat dorsal hippocampus. Immunogold labeling with two sizes of gold beads revealed that connexin36 was present in that axonal gap junction. These ultrastructural data support computer modeling and in vitro electrophysiological data suggesting that axoaxonic gap junctions play an important role in the generation of very fast (>70 Hz) network oscillations and in the hypersynchronous electrical activity of epilepsy