Hormonal contraceptives and the brain: A systematic review on 60 years of neuroimaging, EEG, and biochemical studies in humans and animals.

Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of hormonal contraception. We systematically review human and animal studies on the brain effects of hormonal contraception which employed neuroimaging techniques such as MRI, PET and EEG, as well as animal studies which reported on neurotransmitter and other brain biochemical effects. We screened 1001 articles and ultimately extracted data from 70, comprising 51 human and 19 animal studies. Of note, there were no animal studies which employed structural or functional MRI, MRS or PET. In summary, our review shows hormonal contraceptive associations with changes in the brain have been documented. Many questions remain and more studies are needed to describe the effects of hormonal contraception on the brain.

Aversive Contexts Reduce Activity in the Ventral Subiculum- BNST Pathway.

Many anxiety disorders can be characterized by abnormalities in detecting and learning about threats, and the inability to reduce fear responses in non-threatening environments. PTSD may be the most representative of context processing pathology, as intrusive memories are experienced in "safe" contexts. The ventral subiculum (vSUB), the main output of the ventral hippocampus, encodes environmental cues and is critical for context processing. The bed nucleus of the stria terminalis (BNST) contributes to anxiety-like behaviors as well as context fear conditioning. Given the important roles of the BNST and the vSUB in these anxiety and fear-related behaviors, and the anatomical connections between the two brain regions, the major aims of this study were to characterize the anatomy and function of the vSUB-BNST pathway. First, using the retrograde tracer cholera toxin, we mapped the topographical arrangement of the vSUB-BNST pathway. Dual retrograde tracing experiments revealed neurons projecting to the BNST and those projecting to the basolateral amygdala are distinct populations. Second, we assessed whether activity in this pathway, as indexed by FOS immunohistochemistry, was modulated by context fear conditioning. Our data reveal less activation of the vSUB-BNST pathway in both males and females in aversive contexts and the greatest activation when animals explored a neutral familiar context. In addition, the vSUB of females contained fewer GABAergic neurons compared to males. These findings suggest that the vSUB-BNST pathway is involved in eliciting appropriate responses to contexts.