Dedifferentiation of caudate functional connectivity and striatal dopamine transporter density predict memory change in normal aging.

Age-related changes in striatal function are potentially important for predicting declining memory performance over the adult life span. Here, we used fMRI to measure functional connectivity of caudate subfields with large-scale association networks and positron emission tomography to measure striatal dopamine transporter (DAT) density in 51 older adults (age 65-86 years) who received annual cognitive testing for up to 7 years (mean = 5.59, range 2-7 years). Analyses showed that cortical-caudate functional connectivity was less differentiated in older compared with younger adults (n = 63, age 18-32 years). Unlike in younger adults, the central lateral caudate was less strongly coupled with the frontal parietal control network in older adults. Older adults also showed less "decoupling" of the caudate from other networks, including areas of the default network (DN) and the hippocampal complex. Contrary to expectations, less decoupling between caudate and the DN was not associated with an age-related reduction of striatal DAT, suggesting that neurobiological changes in the cortex may drive dedifferentiation of cortical-caudate connectivity. Reduction of specificity in functional coupling between caudate and regions of the DN predicted memory decline over subsequent years at older ages. The age-related reduction in striatal DAT density also predicted memory decline, suggesting that a relation between striatal functions and memory decline in aging is multifaceted. Collectively, the study provides evidence highlighting the association of age-related differences in striatal function to memory decline in normal aging.

A voxel-based analysis of brain activity in high-order trigeminal pathway in the rat induced by cortical spreading depression.

Cortical spreading depression (SD) is a self-propagating wave of depolarization that is thought to be an underling mechanism of migraine aura. Growing evidence demonstrates that cortical SD triggers neurogenic meningeal inflammation and contributes to migraine headaches via subsequent activation of trigeminal afferents. Although direct and indirect evidence shows that cortical SD activates the trigeminal ganglion (peripheral pathway) and the trigeminal nucleus caudalis (TNC, the first central site of the trigeminal nociceptive pathway), it is not yet known whether cortical SD activates the high-order trigeminal nociceptive pathway in the brain. To address this, we induced unilateral cortical SD in rats, and then examined brain activity using voxel-based statistical parametric mapping analysis of FDG-PET imaging. The results show that approximately 40h after the induction of unilateral cortical SD, regional brain activity significantly increased in several regions, including ipsilateral TNC, contralateral ventral posteromedial (VPM) and posterior thalamic nuclei (Po), the trigeminal barrel-field region of the primary somatosensory cortex (S1BF), and secondary somatosensory cortex (S2). These results suggest that cortical SD is a noxious stimulus that can activate the high-order trigeminal nociceptive pathway even after cortical SD has subsided, probably due to prolonged meningeal inflammation.

Post-embedding immunogold labeling of gamma-aminobutyric acid in lamina II of the spinal trigeminal subnucleus pars caudalis: I. A qualitative study.

This study examines the normal synaptic organization of the feline spinal trigeminal nucleus pars caudalis (PC). A primary goal of this study is to identify and characterize the synaptic complexes within PC based on their specific neurotransmitter content. Post-embedding immunogold techniques are utilized with electron microscopy to determine the ultrastructural localization of gamma-aminobutyric acid (GABA) immunoreactivity within lamina II of PC. The colloidal gold particles (10 nm) are randomly distributed over immunoreactive (IR) profiles without preference toward membranous or cytoplasmic regions. GABA immunoreactivity occurs on small unmyelinated axons, on terminals which form synaptic contacts, and on some vesicle-containing dendrites. The GABA-IR terminals form symmetric (type II) contracts onto unlabeled somata and dendrites of various sizes, and onto other unlabeled axon terminals. The GABA-IR terminal in axo-axonic complexes is presynaptic to a round vesicle-containing terminal, which itself may form a type I asymmetric contact onto an unlabeled dendrite or soma. A proportion of vesicle-containing dendrites show GABA-immunoreactivity and are post-synaptic to unlabeled terminals with round vesicles. Other, but far fewer, vesicle-containing dendrites are GABA negative and postsynaptic to GABA-IR terminals. In summary, the findings are consistent with the localization of GABA in intrinsic neurons, and may be associated with presynaptic and postsynaptic inhibition within nociceptive related pathways.

Increased right caudate nucleus size in obsessive-compulsive disorder: detection with magnetic resonance imaging.

Magnetic resonance images were used to measure the volume of the head of the caudate nucleus in 20 patients with obsessive-compulsive disorder and 16 normal control subjects. The obsessive-compulsive patients showed a significant increase in the volume of the right side of the head of the caudate nucleus compared with that of control subjects. This finding was not correlated with demographic, psychopathological, or clinical characteristics.