PFC neuronal firing and impairs working memory performance through feedforward, intracellular signaling pathways. Exposure to chronic stress leads to more profound working memory deficits and additional architectural changes in PFC, including dendritic atrophy and spine loss, which can be prevented by inhibition of protein kinase C signaling. fMRI research has extended this research to humans, and confirms that reduced working memory caused by acute stress links to reduced activation of the PFC, and stress increased levels of catecholamines. Imaging studies of medical students undergoing stressful exams have also shown weakened PFC functional connectivity, consistent with the animal studies. The marked effects of stress on PFC structure and function may help to explain how stress can cause or exacerbate mental illness. The more stress in one's life, the lower the efficiency of working memory in performing simple cognitive tasks. Students who performed exercises that reduced the intrusion of negative thoughts showed an increase in their working memory capacity. Mood states (positive or negative) can have an influence on the neurotransmitter dopamine, which in turn can affect problem solving. Effects of alcohol on neurophysiology Excessive alcohol use can result in brain damage which impairs working memory. Alcohol has an effect on the blood-oxygen-level-dependent (BOLD) response. The BOLD response correlates increased blood oxygenation with brain activity, which makes this response a useful tool for measuring neuronal activity. The BOLD response affects regions of the brain such as the basal ganglia and thalamus when performing a working memory task. Adolescents who start drinking at a young age show a decreased BOLD response in these brain regions. Alcohol dependent young women in particular exhibit less of a BOLD response in parietal and frontal cortices when performing a spatial working memory task. Binge drinking, specifically, can also affect one's performance on working memory tasks, particularly visual working memory. Additionally, there seems to be a gender difference in regards to how alcohol affects working memory. While women perform better on verbal working memory tasks after consuming alcohol compared to men, they appear to perform worse on spatial working memory tasks as indicated by less brain activity. Finally, age seems to be an additional factor. Older adults are more susceptible than others to the effects of alcohol on working memory. Genetics Behavioral genetics Individual differences in working-memory capacity are to some extent heritable; that is, about half of the variation between individuals is related to differences in their