The medial forebrain bundle (MFB) is a

neural pathway In neuroanatomy, a neural pathway is the connection formed by axons that project from neurons to make synapses onto neurons in another location, to enable neurotransmission (the sending of a signal from one region of the nervous system to ano ...

containing

fibers Fiber (spelled fibre in British English; from ) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often inco ...

from the basal

olfactory The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste. In humans, it ...

regions, the periamygdaloid region and the septal nuclei, as well as fibers from

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...

regions, including the

ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is th ...

and

nigrostriatal pathway The nigrostriatal pathway is a bilateral dopaminergic pathway in the brain that connects the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum (i.e., the caudate nucleus and putamen) in the forebrain. It is one of th ...

Anatomy

The MFB passes through the lateral

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

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 The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The v ...

, which is a collection of dopaminergic neurons that projects from the

to the

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...

, 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 The reward system (the mesocorticolimbic circuit) is a group of neural structures responsible for incentive salience (i.e., "wanting"; desire or craving for a reward and motivation), associative learning (primarily positive reinforcement and c ...

, 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 Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

in the

. 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 Treatment-resistant depression (TRD) is often defined as major depressive disorder in which an affected person does not respond adequately to at least two different antidepressant medications at an adequate dose and for an adequate duration. Inad ...

. 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 stimulation Deep brain stimulation (DBS) is a type of neurostimulation therapy in which an implantable pulse generator is stereotactic surgery, surgically implanted subcutaneous tissue, below the skin of the chest and connected by Lead (electronics), leads ...

could be an effective form of treatment. However, the anatomical definition of the tract system targeted by deep brain stimulation in humans has been intensively discussed and may indeed form the anterior limb of the internal capsule (and not the medial forebrain bundle proper, as defined in rodents). This topic has been worked up by Suzanne Haber and other anatomists in detailed review articles. Subjects that receive the deep brain stimulation treatment in the medial forebrain bundle have been reported to have high remission rates with normative functioning and no adverse side effects. The medial forebrain bundle may also serve to study abuse-related drug effects through intracranial self-stimulation. ICSS targets the MFB at the level of the

lateral hypothalamus The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cogni ...

and elicits a range of responses from the subject through stimulation to acquire a baseline of responses. From this baseline the subject is then exposed to varying levels of stimuli in that are high/low in amplitude and frequency. These responses are then compared to the baseline of the subject to detect for sensitivity to the stimuli. Based on the sensitivity of the response from the subject, a level of inference on the drug abuse potential can be made.

Animal research

In animal studies studying the effects of Levodopa-induced dyskinesia, a major complication in the treatment of

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

, lesions in the medial forebrain bundle show a maximum level of severity and sensitivity to levodopa and provide insight into the mechanisms of Levodopa-induced dyskinesia. Other lesions in the mouse, particularly in the striatum 6-OHDA, show a variable sensitivity to levodopa and shows the difference in lesion severity based on location. In a study with rats, using intracranial self-stimulation implanted in the medial forebrain bundle, rats treated with

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

and

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

showed an increased speed at which they pressed a lever to induce self-stimulation. The study indicates that the medial forebrain bundle may be directly linked to motivational behavior that is induced by drugs. In a research on rats, the deep brain stimulation (DBS) on the MFB causes an increase in dopamine for 40 seconds which is above baseline but after 40 seconds, it wasn't increased above baseline.

References

External links

Overview at thebrain.mcgill.ca
{{Authority control Neuroanatomy Olfactory system