Ventromedial prefrontal cortex damage alters resting blood flow to the bed nucleus of stria terminalis.

The ventromedial prefrontal cortex (vmPFC) plays a key role in modulating emotional responses, yet the precise neural mechanisms underlying this function remain unclear. vmPFC interacts with a number of subcortical structures involved in affective processing, including the amygdala, hypothalamus, periaqueductal gray, ventral striatum, and bed nucleus of stria terminalis (BNST). While a previous study of non-human primates shows that vmPFC lesions reduce BNST activity and anxious behavior, no such causal evidence exists in humans. In this study, we used a novel application of magnetic resonance imaging (MRI) in neurosurgical patients with focal, bilateral vmPFC damage to determine whether vmPFC is indeed critical for modulating BNST function in humans. Relative to neurologically healthy subjects, who exhibited robust rest-state functional connectivity between vmPFC and BNST, the vmPFC lesion patients had significantly lower resting-state perfusion of the right BNST. No such perfusion differences were observed for the amygdala, striatum, hypothalamus, or periaqueductal gray. This study thus provides unique data on the relationship between vmPFC and BNST, suggesting that vmPFC serves to promote BNST activity in humans. This finding is relevant for neural circuitry models of mood and anxiety disorders.

Functional MRI of the amygdala and bed nucleus of the stria terminalis during conditions of uncertainty in generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a common psychiatric disorder characterized by constant worry or anxiety over every day life activities and events. The neurobiology of the disorder is thought to involve a wide cortical and subcortical network that includes but is not limited to the amygdala and the bed nucleus of the stria terminalis (BNST). These two regions have been hypothesized to play different roles in stress and anxiety; the amygdala is thought to regulate responses to brief emotional stimuli while the BNST is thought to be involved in more chronic regulation of sustained anxiety. In this study, we exposed medication-free GAD patients as well as non-anxious controls to a gambling game where one of the conditions involved non-contingent monetary loss. This condition of high uncertainty was intended to elicit a stressful response and sustained anxiety. Functional MRI scans were collected simultaneously to investigate BOLD activity in the amygdala and BNST during performance of this task. Compared to controls, we found that GAD patients demonstrated decreased activity in the amygdala and increased activity in the BNST. Skin conductance measures showed a consistent early versus late effect within block where GAD patients demonstrated higher arousal than controls late in the task blocks. Based on these results, we hypothesize that GAD patients disengage the amygdala and its response to acute stress earlier than non-anxious controls making way for the BNST to maintain a more sustained response. Future studies are needed to investigate the temporal dynamics of activation and deactivation in these regions.

Galanin immunoreactivity in mouse basal forebrain: sex differences and discrete projections of galanin-containing cells beyond the blood-brain barrier.

The distribution of galanin-immunoreactive (GAL-IR) cell bodies in the basal forebrain of mice was investigated. The overall pattern of staining for GAL in the area of brain analyzed was similar to that reported in other species with noticeable variations. Distinctive groups of GAL-IR cells were present in the bed nucleus of stria terminalis (BNST), supraoptic nucleus, retrochiasmatic supraoptic nucleus (SOR), magnocellular paraventricular nucleus, arcuate nucleus (ARC) and the nucleus circularis which is one of the cell groups belonging to the accessory magnocellular system. Comparison of the number of GAL-IR cells between the sexes indicated sexual dimorphism in the BNST, SOR and the ARC. As compared with female mice, the mean number of GAL-IR cells/section in the BNST and the SOR was higher and that in the ARC was lower in the males. Unlike in rats, the preoptic area contained mostly scattered GAL-IR cell bodies. Intraperitoneal injection of the retrograde tracer fluoro-gold in male mice resulted in uptake of fluoro-gold by selective GAL-IR cell groups in the basal forebrain suggesting that only some of these cell groups may project outside the blood-brain barrier whereas others may be involved in intracerebral neural transmission.

Extent of survival and vascularization of adult superior cervical sympathetic or nodose ganglia transplanted into the septal nuclei or choroid fissure of adult rats.

Adult superior cervical sympathetic ganglia were auto-transplanted, and adult nodose ganglia were homografted into the septal nuclei or the choroid fissure of adult Wistar rats. At times from 4 h to 9 weeks after operation, the distribution of surviving transplanted neurons was compared with the development of the transplant vascularization, as visualized by transcardial Indian ink filling of the host vascular system. Within 24 h, the ganglionic neurons and Schwann cells of the interior of the transplants in both sites were necrotic. The surviving neurons and Schwann cells formed a shell, occupying those areas of the transplant periphery which were in direct contact with the host circulation. Occasional ink-filled vessels were evident at this time in transplants in the choroid fissure, but there were none in the septal nuclei, where vessels did not appear until the next day. Blood vessels reached the centre of the ganglia by 3-4 days in the choroid fissure and one week in the septal nuclei, the finest diameter capillaries forming last. At longer survivals there was a slow loss of neurons, notable between 1 and 2 months, and leading progressively (especially in the septal transplantation site) to the disappearance of all but a very small number of ganglionic neurons. The general findings were similar for both types of ganglion, and in both sites, but the initial cell loss was much greater for both types of ganglia in the septum (over 90%) as compared with about a 50% loss in the choroid fissure. The initial rapid cell loss was probably a result of ischaemia. The subsequent, slow progressive loss may be associated with failure to make or receive neuronal connections, or the absence of appropriate growth factors.