PBS Frontline Explores Parkinson’s Disease

Here is the video PBS recently made about Parkinson’s disease called My Father, My Brother, and Me. From what I’ve watched so far, it’s done a good job putting a face to Parkinson’s disease while also focusing on the research and clinical aspects of it.

The charitable accumbens

CharityCNN posted an interesting article about how when people choose to be charitable (i.e., give money away) that the nucleus accumbens, which is termed the “pleasure center” of the brain, and the caudate nucleus showed heightened activity. It’s turning out that the nucleus accumbens is involved in far more activities than we’ve ever realized. It’s an area of the brain that is heavily tied to the dopaminergic system and is directly tied to drug use, eating, sex, and pretty much anything else that people can enjoy. In addition, assumed dysfunction or dysregulation of the nucleus accumbens is tied to addictive behaviors. It’s not surprising then that a behavior that is enjoyable to so many – being charitable – is related to activity in the nucleus accumbens. Maybe some people are just Scrooges because they have too little dopamine in their brains [pure speculation and meant to be slightly humorous but it is a hypothesis that could be worth testing].

Image courtesy of benevolink

Dopamine, the Basal Ganglia, and Learning

A significant proportion of dopamine (DA) is produced in the substantia nigra pars compacta (SNpc) and is carried to the striatum via the nigrostriatal pathway. While this pathway has been traditionally linked with motor functioning, recent research has implicated striatal DA involvement in language (Crosson, 2003) and learning (Seger, 2006). One disease in which there is considerable DA disruption is Huntington’s Disease (HD). In HD the head of the caudate is typically the first brain structure affected by neuronal cell loss. This cell loss not only affects connections with the SNpc but also affects the connections between the striatum and the prefrontal cortex. In HD the disruption of these dopaminergic pathways leads to disruptions in motor and cognitive functioning.

How DA disruptions affect cognition has been explained by theories that are modifications of Mink’s model (1996) of center and surround (i.e., direct and indirect) basal ganglia regulation. Within the caudate there are two main families of DA receptors – D1 and D2. These receptors have been shown to have different functioning within the basal ganglia (Seger, 2006) – the D1 receptor is involved with the direct pathway and the D2 receptor is involved in the indirect pathway. The D1, or direct pathway, can be viewed as increasing the strength of the signal of the desired response while the D2, or indirect pathway, serves to reduce the noise of the competing undesired responses. Dopaminergic systemic disruption in HD should thus decrease the signal-to-noise ratio, which results in the person having a greater difficulty selecting the desired response (see model below).

Center-surround model of basal ganglia-based learning and memory

*Model based on Mink (1996) and Frank, Seeberger, and O’Reilly (2004)

There is evidence that in early stages of Huntington’s disease, D2 receptors are the first to be affected, with less binding occurring at D2 receptors presumably due to receptor loss. As the disease progresses, the D1 receptors also start to become depleted, with the end result of widespread DA dysfunction (Glass, Dragunow, & Faull, 2000). This DA dysfunction possibly affects verbal learning and recall by impacting the indirect pathway in the early stages of HD and indiscriminately the whole direct and indirect system in later stages of the disease process.

References

Crosson (2003). Left and right basal ganglia and frontal activity during language generation: Contributions to lexical, semantic, and phonological processes. Journal of the International Neuropsychological Society, 9, 1061-1077.

Frank, M. J., Seeberger, L. C., & O’Reilly, R. C. (2004). By carrot or by stick: Cognitive reinforcement learning in Parkinsonism. Science, 306, 1940-1943.

Glass, M., Dragunow, M., & Faull, R. L. M. (2000). The pattern of neurodegeneration in Huntington’s disease: A comparative study of cannabinoid, dopamine, adenosine and GABAA receptor alterations in the human basal ganglia in Huntington’s disease. Neuroscience, 97(3), 505-19.

Seger, C. A. (2006). The basal ganglia in human learning. Neuroscientist, 12(4), 285-290.