Brainy Behavior

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).

*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.

The brain is an interesting organ. Its complexity is far beyond any other part of the body, which is what makes studying it so difficult. Individual differences affect how the brain functions – to an extent – and how it reacts to stressors, damage, or decay. When the brain is injured or dysfunctions, we can learn about its normal functioning. There have been some widely publicized cases of brain damage and the effect that damage has on cognition and life. One such case was the Terry Schiavo case that caught widespread national attention two years ago. The lessons we learned from Terry were mostly political, legal, and moral ones. What about cases where there is more than minimal higher-order brain functioning as in Terry’s case?

A number of years ago some researchers reported the case of a man who had damage to his thalamus, a structure in the middle of the brain that is viewed as a “relay center” for the brain, among other functions. In this man’s case he had an anomia (i.e., lack of ability to name) for medical instruments and terms. He was not a doctor or other health care professional, he just had great difficulty naming medically-related terms. There have been other similar cases where people have had random category naming difficulties following brain injury. It is cases like this that make the study of the brain so interesting.

Over the years there have been a number of famous brain injury patients. Gage was a railroad foreman in the 1800s whose personality and emotionality changed after a tamping rod was blasted through his frontal lobes in a horrific accident. H.M. is a man whose medial temporal lobes were removed in surgery. Following the surgery he had severe anterograde amnesia (that roughly means he doesn’t remember anything that happened after his surgery) and mild retrograde amnesia (he doesn’t remember the few days prior to his surgery either). From HM researchers learned a lot about the memory system and how the medial temporal lobes are involved in memory processes (although the theories are still under development and some ideas about how information is processed into long-term memory are controversial). Then there have been cases of people with temporal lobe damage who have lost the ability to recognize objects or people. The study of brain dysfunction is fascinating and informative. Sometimes one doesn’t know what to expect.