The medial forebrain bundle (MFB), is a neural pathway containing fibers from the basal olfactory regions, the periamygdaloid region and the septal nuclei, as well as fibers from brainstem regions, including the ventral tegmental area and nigrostriatal pathway. Anatomy The MFB passes through the lateral hypothalamus and the basal forebrain in a rostral-caudal direction. The MFB has its main projections to these regions of Brodmann areas (BA) 8, 9, 10, 11, 11m. The superior frontal region of MFB projects to BA 8, 9, 10; the rostral middle frontal projects to dorsolateral prefrontal cortex (BA 9, 10); lateral orbitofrontal of MFB shows its projections to nucleus accumbens septi (NAC) and ventral striatum as subcortical reward associated structures. It contains both ascending and descending fibers. The mesolimbic pathway, which is a collection of dopaminergic neurons that projects from the ventral tegmental area to the nucleus accumbens, is a component pathway of the MFB. The MFB is one of the two major pathways connecting the limbic forebrain, midbrain, and hindbrain. The other one is the dorsal diencephalic conduction (DDC) system. The two pathways seem to have parallel neural circuits, and share similar physiology and function. Function It is commonly accepted that the MFB is a part of the reward system, involved in the integration of reward and pleasure. Electrical stimulation of the medial forebrain bundle is believed to cause sensations of pleasure. This hypothesis is based upon intracranial self-stimulation (ICSS) studies. Animals will work for MFB ICSS, and humans report that MFB ICSS is intensely pleasurable. Another research technique that was used in determining the function of the MFB was microdialysis. Reinforcing electrical stimulation of the MFB using this method has shown to cause a release in dopamine in the nucleus accumbens. Other microdialysis studies have shown that the presence of natural reinforcers such as food, water, and a sex partner cause a release in dopamine in the nucleus accumbens. This shows that the electrical stimulation of the MFB causes a similar effect compared to natural reinforcers. The medial forebrain bundle has been shown to be linked to an individual's grief/sadness system through regulation of the individual's seeking/pleasure system. Potential role in diagnosis/treatment The medial forebrain bundle may serve as a target in treating treatment-resistant depression. Since the MFB connects areas of the brain which are involved with motivated behavior, mood regulation, and antidepressant response the stimulation of the MFB through deep brain