The Michael J. Fox Foundation has a good, basic introduction to the neurobiology of Parkinson’s disease. The brief animate video provides an overview of affected parts of the brain as well as the role that dopamine, a neurotransmitter – a chemical in the brain that allows brain cells to communicate with each other – plays in Parkinson’s disease. Click on the link below and then click on the video link titled PARKINSON’S AND THE BRAIN to learn more about how Parkinson’s disease affects the brain.
Can We Cure Parkinson’s Disease?
The National Parkinson’s Foundation produced a series of brief videos providing overviews of Parkinson’s disease related topics by prominent clinicians and researchers in the field of Parkinson’s disease. In one video, we are provided with an overview of the questions of whether or not we can cure Parkinson’s disease and how do we treat Parkinson’s disease.
The short answer is: no, we cannot right now cure Parkinson’s disease. We have hopes that stem cell therapies will work but there are a number of issues related to stem cells that make them potentially problematic (e.g., how do we make sure they don’t turn into cancers).
We can, however, treat symptoms of Parkinson’s disease with drug, physical, and cognitive therapies. L-dopa is effective at reducing tremors in most people and well as increasing rate and speed of movement. In some cases, deep brain stimulation is warranted. It has shown to be quite effective for many people. But for now we cannot cure Parkinson’s disease.
Writing Memories In the Brains of Flies
Source for the following post: BBC NEWS | Science & Environment | Bad memories written with lasers
The brains of flies are far simpler than the brains of humans. Previously, researchers had discovered that only 12 neurons were involved in the formation of associative memories in flies. This most recent study builds on this knowledge. If these 12 neurons are involved in forming memories, could researchers trigger these neurons and create memories?
According to a recently published paper in Cell, the answer is “Yes.” Using genetically-modified flies with adenosine-5′-triphosphate (ATP) activated neurons (the ATP is triggered by lasers), the researchers were able to affect the flies such that “the flies associated the smell with a bad experience, so the laser flash gave the fly a memory of a bad experience that it never actually had.”
Here’s a link to the journal article (requires a subscription).
Here’s the abstract:
“Dopaminergic neurons are thought to drive learning by signaling changes in the expectations of salient events, such as rewards or punishments. Olfactory conditioning in Drosophila requires direct dopamine action on intrinsic mushroom body neurons, the likely storage sites of olfactory memories. Neither the cellular sources of the conditioning dopamine nor its precise postsynaptic targets are known. By optically controlling genetically circumscribed subsets of dopaminergic neurons in the behaving fly, we have mapped the origin of aversive reinforcement signals to the PPL1 cluster of 12 dopaminergic cells. PPL1 projections target restricted domains in the vertical lobes and heel of the mushroom body. Artificially evoked activity in a small number of identifiable cells thus suffices for programming behaviorally meaningful memories. The delineation of core reinforcement circuitry is an essential first step in dissecting the neural mechanisms that compute and represent valuations, store associations, and guide actions.”
You can also listen to an interview with one of the researchers on this episode of NPR’s Science Friday.
As we learn more about how memories are created we might be able to understand and fix problems when memories fail.
The Relationship Between Executive Function and Processing Speed
Understanding the relationship between brain (specifically subcortical structures) and cognitive processes is a field still in its infancy. The rise of structural and functional neuroimaging that started in the 1970s and really began to mature in the 1990s (with even greater changes and advancements being made today), led to the ability to measure the structure and function of various brain regions in vivo. This was and is important for neuropsychologists because it allowed them to more accurately assess the relationship between the brain and cognitive and behavioral functions.
Processing speed is a basic cognitive or brain processes that subserves many other higher-order cognitive domains. Among those higher domains is executive functioning, a somewhat broad construct that involves the organization of behaviors and behavior responses, selective attention of pertinent information and suppression of unnecessary information, and maintenance and shifting of cognitive sets. Thus, executive functioning is dependent on processing speed but processing speed is not dependent on executive functioning. If executive functioning is a car, processing speed is the engine. Having a faster or more powerful engine means that the car can go faster. More efficient engines allow the car to function at a higher level of efficiency. Thus, while processing speed and executive functions are distinct, they are related with processing speed as one of the basic cognitive processes driving executive functions.
As an example of the interaction between executive functions and processing speed in clinical applications we can look at the Stroop Color-Word task. A person who is not only able to read the words or name the colors quickly but also able to inhibit the undesired but automatic process (namely, word reading on the incongruent color-word task) will receive a higher score on the Stroop task. This would, in combination with other executive function tests, be evidence for intact or even good executive functioning.
Even on non-speeded executive tasks those with fast processing speed can benefit because they can sort through information more quickly and hopefully, efficiently – speed and efficiency are related but not exactly the same. However, not all tests of executive function rely on processing speed. A person, for example, could be slow on the Wisconsin Card Sort Test, yet not exhibit any “executive dysfunction” in that they could complete all the categories and not have an abnormal number of perseverative errors. This simply demonstrates that “executive functions” are diverse and varied.
As a basic process that is dependent on basic neuronal function and glial support, any sort of focal or diffuse injury to the brain can affect processing speed. An example of this is traumatic brain injury, which frequently results in diffuse axonal injury; this diffuse injury negatively affects cognitive processing speed. Any time the white matter is focally or grossly disrupted, processing speed is in danger of disruption itself. This disruption of white matter could be anything from axonal damage, loss of oligodendroglia (which form the myelin), or even low levels of neurotransmitters.
White matter disruption also occurs in multiple sclerosis where diffuse lesions are apparent in the white matter. This disruption also occurs more often in people with heightened vascular risk factors, such as hypertension, diabetes, and cardiovascular disease. People who have these vascular risk factors and subsequent damage to their white matter (this damage or disruption is frequently termed leukoaraiosis) have reduced processing speed and attention (Viana-Baptista et al., 2008). Lesions to subcortical structures, such as the caudate, also result in reduced processing speed (Benke et al., 2003) in addition to executive dysfunction.
In subcortical disease processes such as Huntington’s disease, which usually starts with atrophy of the caudate nuclei, or Parkinson’s disease, which starts with a loss of the majority of dopaminergic cells in the substantia nigra, processing speed is consistently affected. Some common symptoms of Parkinson’s disease are freezing and a shuffling gait; even though these symptoms are motoric, they can be indicative of the global cognitive slowing that also occurs. However, it seems that processing speed is heavily dependent on the integrity of white matter.
Because of the diffusivity of processing speed, I am not aware of any areas of the brain shown to be necessary for processing speed, outside of global white matter. As I mentioned above, damage to the caudate has been shown to affect processing speed but damage to almost any area of the brain, especially if the white matter is disrupted results in slowed processing speed. Neuropsychologists often talk about a patient who has executive dysfunction, slowed speed of processing, as well as some other cognitive deficits as exhibiting signs of a frontal-subcortical disruption – a frontal-subcortical profile. So far, no one has localized processing speed to a single area – many brain structures or areas affect it.
At this point, processing speed and executive functions cannot be “mapped” to separate basal ganglia structures or loops. Of the three classically recognized cortico-striato-thalamo-cortical loops involved in cognitive and emotional processes rather than basic motor processes, which were first introduced by Alexander, Delong, and Strick (1986), the dorsolateral prefrontal cortex circuit appears to be most correlated with processing speed (Mega & Cummings, 1994). This is also the circuit most strongly linked with executive functioning. It appears that rather than utilizing different circuits processing speed and executive functions utilize the same circuits; however, processing speed is much more globalized.
References
Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357-381.
Benke, T., Delazer, M., Bartha, L., Auer, A. (2003). Basal ganglia lesions and the theory of fronto-subcortical loops: Neuropsychological findings in two patients with left caudate lesions. Neurocase, 9, 70-85.
Mega, M. S., & Cummings, J. L. (1994). Frontal-subcortical circuits and neuropsychiatric disorders. The Journal of Neuropsychiatry and Clinical Neurosciences, 6, 358-370.
Viana-Baptista M, Bugalho P, Jordão C, Ferreira N, Ferreira A, Forjaz Secca M, Esperança-Pina JA, Ferro JM. (2008). Cognitive function correlates with frontal white matter apparent diffusion coefficients in patients with leukoaraiosis. Journal of Neurology, 255, 360-366.
What is Executive Function?
Executive function is a term that describes a wide range of cognitive behaviors and processes. It is broad enough of a term that some people simply describe it as, “what the frontal lobes do.” When asked what exactly the frontal lobes do do, some revert to the circular definition of “executive functions.” However, executive functions are distinct from – but related to – what the frontal lobes do. The frontal lobes are involved in motor functions (e.g., pre-motor and primary motor areas), eye movement (e.g., frontal eye fields), memory (e.g., acetylcholine-producing portions of the basal forebrain), and language (BA 44,45 or Broca’s area). In addition, some executive functions incorporate areas of the brain outside the frontal lobes – the parietal lobes or basal ganglia, for example. Like many cognitive domains, executive functions are part of a distributed network of brain structures and regions.
Most neuropsychologists however, would define (or at least accept the following definition of) executive function similar to this: Executive function is the ability to selectively attend to, work with, and plan for specific information. This means that executive function is deciding what information, cognitions, or stimuli are relevant, holding and working with that information, and then planning what to do with it. As such, executive function is largely the roles of planning and organization. It is also the ability to recognize and learn patterns (i.e., cognitive sets) but also have the cognitive flexibility to respond to set changes and make a shift in set. Executive function also involves being able to select the appropriate response or behavior while at the same time inhibiting inappropriate responses or behaviors.
Executive functions have been compared to the conductor of an orchestra who, in order to make sense of the disparate instruments, sounds, and parts, must coordinate the members and lead the efforts of all the components of the orchestra. Executive functions also have been compared to chief executive officers of companies. These comparisons demonstrate that executive functions are arguably the most complex and highest of all cognitive functions. However, just like most other cognitive functions, executive functions are comprised of relatively simple processes (e.g., attention and processing speed) – it is just the unique combination of these more basic processes that makes executive functions so powerful.
One potential problem with executive function as a cognitive domain is that it is large and loose. Many tests have been developed, or at least used, to assess executive function (e.g., Wisconsin Cart Sort Test, Stroop Color-Word Task, clock drawing, and so forth). Even though all such tests are used as measures of executive functioning, scores on them do not always correlate highly with each other. They do not always cluster together when subjected to principal components analysis or even structural equations modeling. This means that even though neuropsychologists have many purported tests of executive function, they all seem to measure different aspects of executive function. This might partially result from executive functioning tests being differentially affected by basic cognitive processes such as processing speed.
Even though, as previously mentioned, I do not believe executive functions and frontal lobe functions are synonymous terms, are we able to localize executive functions to the frontal lobes? Largely we can. The most evidence from neuroimaging studies and neurological injuries demonstrate that the prefrontal cortex – the area of the brain that is phylogenetically youngest and most advanced and as such, proportionately larger in humans than any animal – is necessary (but not necessarily sufficient) for executive functioning. When this area is disrupted in humans, they exhibit poor decision-making skills, including poor planning and poor maintenance or self-regulation of behavior. One area of the prefrontal cortex particularly involved in executive functions is the dorsolateral prefrontal cortex (area 46) – although both the orbitofrontal and anterior cingulate are involved in aspects of executive functions.
In 1986 Alexander, Delong, and Strick published their seminal work on five parallel and closed cortico-striato-thalamo-cortical loops. These frontal-subcortical circuits were hypothesized to be involved in a range of behaviors and cognitions based on the varying cortical connections of the loops. Previously, many researchers did not well-understand the role that the basal ganglia played in any sort of “higher” function; in fact, most viewed the basal ganglia as involved mainly in motor behaviors. Alexander, Delong, and Strick’s article set off a flurry of research into the functions of these frontal-subcortical circuits, which have been verified as existent in humans (Middleton & Strick, 2000). Over time different theories have modified these circuits, including that they are composed of direct, indirect, and hyperdirect pathways, which all function at different speeds or timings to allow the basal ganglia to regulate behavior. Mink (1996) proposed that actions (e.g., producing a specific word) are regulated by the direct and indirect pathways, which serve as large components of our ability to select and inhibit correct and incorrect responses, respectively. It is as if each individual fronto-cortical loop allows us to properly attend to the correct behavior or response and inhibit all other behaviors or responses, much like the DLPFC and orbitofrontal cortex and their associated loops are involved in the selection and inhibition of behavior, both major aspects of executive function.
Just as damage to the dorsolateral prefrontal cortex (DLPFC) produces deficits in executive function, damage to any part of the DLPFC loop also results in executive dysfunction. Benke, Delazer, Bartha, and Auer (2003) presented two clinical cases of patients with left caudate lesions (the lesions also affected part of the anterior limb of the internal capsule as well as portions of the putamen and pallidum; however, the infarcts affected the caudate the most). Among other deficits, both patients had executive function impairments, including problem-solving deficits, many perseverative errors, and set-shifting problems. Even though the patients had no direct DLPFC damage, they exhibited similar deficits to patients with DLPFC lesions. These executive deficits persisted over time.
As a cognitive domain, and even as broad as it might be, executive functioning has ecological validity. Price and colleagues (2008) found that executive dysfunction was related to greater difficulty performing IADLs. Specifically, patients with executive dysfunction had more difficulty performing IADLs than patients with memory deficits did. Thus, how quickly, flexibly, and accurately people can organize, solve, plan, or attend to specific neuropsychological tasks seems to correlate with their accomplishment of everyday tasks of life, such as finances, driving, and shopping.
References
Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357-381.
Benke, T., Delazer, M., Bartha, L., Auer, A. (2003). Basal ganglia lesions and the theory of fronto-subcortical loops: Neuropsychological findings in two patients with left caudate lesions. Neurocase, 9, 70-85.
Middleton FA, & Strick PL. (2001). Basal ganglia output and cognition: evidence from anatomical, behavioral, and clinical studies. Brain Cogn., 42, 183-200.
Mink, J. W. (1996). The basal ganglia: Focused selection and inhibition of competing motor programs. Prog Neurobiol, 50, 381-425.
Price, C.C., Garvan, C., and Monk, T. (2008). Type and severity of cognitive impairment in older adults after non-cardiac surgery. Anesthesiology, 108, 8-17.
Mad Cow And Alzheimer’s Have Surprising Link : NPR
Mad Cow And Alzheimer’s Have Surprising Link : NPR. If this research showing a link between prion proteins and the deleterious effects of beta-amyloid plaques in rat brains holds true in humans, it has huge implications for finding a cure for Alzheimer’s disease. That would be as big as the polio vaccine or eradicating small pox. This is some research that is worth watching closely.
At INS
I’m at INS (the annual conference of the International Neuropsychological Society) in Atlanta so I won’t be updating the blog until next week.
Psychobiology and Social Psychology
There are at least two big trends in social psychology, or at least ones that may great affect social psychology. Currently, at least according to Berntson and Cacioppo (2000), one of the fastest growing trends in psychology as a whole is psychobiology. This trend is also seen in social psychology. Another movement is that of the internet (McKenna & Bargh, 2000). As the legitimacy of the internet grew, there was more research interest in it and more interest in using it for research purposes. I will first discuss psychobiology and then the internet. I will finish with my prediction of where social psychology is going.
I think psychobiology is a growing area in part because of the many technological advances that are being applied to psychology (namely, brain imaging and computer modeling). Psychology is becoming a technology-driven science. I think that social psychology will all move this way because of the new ways to study the concepts of social psychology. In part, it provides new ways to research “old” topics, not that anything in social psychology is that old.
Researchers can now look at biological foundations of social behavior and perception. For example, maybe there is a certain area of the brain that is activated when people name racial stereotypes. Also, there could be a different area activated when people are asked what stereotypes they believe, if any. Maybe people who say they do not believe the stereotypes still have the same area of the brain activated as those who do believe them, but in addition they could have additional brain activity associated with suppressing those stereotypes. Knowing this would help us understand that stereotypes really are prevalent, but some people are just really good at suppressing them and don’t even know that they are doing it. I know this was a slightly vague hypothesis, but my point is that psychobiology has a lot to add the social psychology.
Continue reading “Psychobiology and Social Psychology”
Oldest Human Brain Remains Found
Archeologists discovered what may be the oldest human brain. The brain matter is within a skull and is fossilized, or in a similar state. Researchers estimate that the brain dates to around 300 BC. Here’s the link to the BBC story.
Patient HM’s Passing
On Tuesday, December 2, 2008, Henry M., the most famous patient in modern neuroscience research and literature, passed away. He was 82. In 1953, H.M. had an experimental brain operation to try to stop his frequent seizures; his medial temporal lobes were resected bilaterally, with significant portions of his amygdalas and hippocampi in both cerebral hemispheres removed (parts of the brain are still resected in intractable epilepsy cases, however neurosurgeons do not perform that exact surgery any more because of the negative effects). His seizures stopped but immediately after the operation he had a severe anterograde amnesia. This means that from when he received the operation at age 27, he was unable to establish new memories for world events and for general information.
His amnesia became the focus of much scientific study from after his operation until the present. No one patient has been studied more in the 20th and 21st centuries than H.M. His memory impairment was also interesting because his overall intellectual abilities were still intact as was his personality. Neuropsychologists and neuroscientists will forever be grateful for the things they learned from H.M.
The New York Times has a very nice article about H.M.