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Post-operative Cognitive Dysfunction

September 29th, 2009 18 comments

Visit this link to my article on Brain Blogger to read a brief description of post-operative cognitive dysfunction (POCD). Here is a selection of what I wrote.

In the mid 1950s, Dr. Bedford reported on a number of older adults who exhibited cognitive problems (memory or planning or being able to sustain attention) following surgery where anesthesia was used. This effect is now called postoperative cognitive dysfunction (or decline; POCD). POCD typically lasts for a few months to a year with a small minority of patients exhibiting permanent decline. Studies about it were few at first, with most focusing on cognition following cardiac surgery. Over time and especially more recently, there has been an increase in research of POCD following non-cardiac surgeries (e.g., abdominal or orthopedic) as well as continued interest in POCD following cardiac surgery.

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Categories: cognition, memory Tags: , , ,

The Relationship Between Executive Function and Processing Speed

July 15th, 2009 1 comment

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?

July 10th, 2009 5 comments

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.

Revisiting Clive

November 20th, 2008 No comments

Yesterday I posted a video clip about Clive Wearing. Here is the first part of a different documentary about Clive. This video goes more in-depth about his condition. Clive is sometimes referred to as the man with the shortest memory. Not only were his two hippocampi destroyed, but also surrounding areas of the his temporal lobes as well as portions of his left frontal lobe. He also remembers very little from before his illness, which is quite rare; this condition is called retrograde amnesia. Clive lives in an ever-present now, without connection to past or future. Other parts to this video can be found on YouTube.

The Unusual Case of Clive Wearing

November 19th, 2008 No comments

Clive Wearing is a 70 year old British man who contracted herpes simplex encephalitis in 1985. The virus destroyed his hippocampi bilaterally (as well as surrounding areas). He has complete anterograde amnesia and can only remember up to about 20 seconds. He retained the ability to play the piano and conduct a choir (which he did previously to his illness); this is because this procedural memory involves different areas of the brain, including the basal ganglia and the cerebellum. I’ll revisit this case over the coming days. Meanwhile, here is a clip from a BBC production that presents part of Clive’s story.

Learning and Recall – Hippocampal Firing

September 5th, 2008 1 comment

Today in Science a team of scientists (Hagar Gelbard-Sagiv, Roy Mukamel, Michal Harel, Rafael Malach, and  Itzhak Fried) at the Weizmann Institute of Science in Israel, UCLA, and Tel Aviv University published their research where they directly recorded via implanted electrodes the firing of hippocampus neurons during learning and free recall. This represents the first time in humans this has been done. Here’s the abstract from Science:

The emergence of memory, a trace of things past, into human consciousness is one of the greatest mysteries of the human mind. Whereas the neuronal basis of recognition memory can be probed experimentally in human and nonhuman primates, the study of free recall requires that the mind declare the occurrence of a recalled memory (an event intrinsic to the organism and invisible to an observer). Here, we report the activity of single neurons in the human hippocampus and surrounding areas when subjects first view television episodes consisting of audiovisual sequences and again later when they freely recall these episodes. A subset of these neurons exhibited selective firing, which often persisted throughout and following specific episodes for as long as 12 seconds. Verbal reports of memories of these specific episodes at the time of free recall were preceded by selective reactivation of the same hippocampal and entorhinal cortex neurons. We suggest that this reactivation is an internally generated neuronal correlate of the subjective experience of spontaneous emergence of human recollection. (Published Online September 4, 2008; Science DOI: 10.1126/science.1164685)

The New York Times also has an article about the research.

Leukoaraiosis and Lacunes – A Very Brief Overview

March 12th, 2008 No comments

As people age, it is common for their brain white matter to change. These changes often appear as bright white spots on T2-weighted MR scans. These areas or spots of hyperintensity (i.e., white matter hyperintensities {WMH}) are also called leukoaraiosis (LA). Researchers are still investigating the exact nature and pathology of these abnormalities but our understanding of them is increasing. They most often seem to start around the lateral ventricles and spread from there, although it is possible to have punctate WMH throughout the brain white matter (i.e., WMH that are not connected to other regions). WMH on brain MRIs represent rarefaction of the white matter, including swelling, demyelination, and damage, although the exact nature and combination of the white matter changes is not known. These WMH can interfere with normal cognitive functioning, including processing speed, attention, inhibition, as well as global executive functioning (although these claims are still being investigated).

Other damage to white matter includes lacunes, which are little holes in the brain, much like the holes in Swiss cheese. They are caused by mini infarcts, or strokes, or other processes. Most of the time they are due to “silent strokes”, or strokes that are small enough that the person does not have any noticeable stroke symptoms. These lacunes can have similar impact on cognition as WMH. Both WMH and lacunes are related to vascular risk factors, such as hyper- or hypo-tension, diabetes, etc.

Optical Illusions That Make You Fatter and Your Wallet Lighter

October 30th, 2007 No comments

“Eat from small plates, drink from taller glasses.” Optical illusions lead us to eat and drink more, as illustrated by the examples in this article. There’s an old saying in cuisine…”the first bite is with the eye.”

Interesting article. I’m not sure if there is empirical data to support it but it does show that our perception of our food can affect how much we eat. Our actions are affected by so many different things, many of which we might not be aware.

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Word Superiority Effect and Parallel Processing

July 6th, 2007 2 comments

WordsOne experiment about cognitive brain functioning is the word superiority effect findings of Dr. Reicher in 1969. In this experiment either a word or a non-word (string of letters) is flashed on a screen. The subject is asked if the stimulus contained one of two letters, say a “C” or an “E”. When the stimulus did not resemble a word (e.g., XXCX) subjects were correct in identifying the target letter about 80% of the time. When the string of letters was similar to a word but not one (e.g., FELV) the subjects also correctly identified the target letter 80% of the time. However, the interesting finding was that when the stimulus was a word (e.g., TEND), subjects were correct in identification 90% of the time. So the word superiority effect is that subjects are most accurate in identifying a target letter when it is contained in a word as opposed to a string of letters.

This lends support to the theory that there are things that we can process in parallel and that that parallel processing (or parallel activation of word and letter) can be beneficial at times (such as helping subjects correctly identify individual letters more often when the letter is contained within a word rather than in a random string of letters). In other words, the whole word is recognized before all the letters individually are recognized. This then speeds up or aids processing because there are now a couple routes, per se, to that letter; there is the visual stimulus (seeing the letter) and the linguistic information (knowing that the letter is in the word) that both are activated and help people recognize letters better.

Image by uncommonmuse.

Dynamically filtering the brain

June 20th, 2007 No comments

Researchers believe that the prefrontal cortex acts as a dynamic filter for the brain. Dynamic filtering is selecting needed information for a current task from all the information streaming through the frontal cortex. This is why the prefrontal cortex acts as a dynamic filter, it must sort through the information and pick only that which is currently relevant.Filters

Thompson-Schill et al. (1997) wanted to study the dynamic filtering hypothesis so they had subjects generate verbs associated with presented nouns. In other words, if the person saw a “cat” they might say “meow” or “nap” or something else. Thompson-Schill et al. assigned subjects to a high or low noun-verb selection condition. In the high condition, subjects were shown nouns with many associated verbs (e.g., a ball is shown and subject could produce “bounce,” “hit,” “kick,” or “throw”) whereas in the low condition subjects are shown a noun with only one (in most cases) related verb (e.g., a chair is shown and subject says “sit”).

They conducted this experiment to see if the inferior frontal cortex is associated with just semantic memory (basically long-term-memory-type information) or if it an area that supports working memory processes (retrieving information from semantic memory and working with it—in this case filtering through it for relevant associations). The experimenters found that the inferior frontal cortex (IFC) was more activated in the high-selection conditions than in the low-selection condition. If it had not been more activated then it would merely have been a semantic, long term, memory-related area. Because of the higher activation it was concluded that the IFC was associated with working memory, specifically pulling relevant information from semantic memory. It acts as a filtering mechanism, a dynamic filter.

To confirm this finding Thompson-Schill et al. (1998) conducted another study with brain-damaged patients. They selected subjects with lesions of the IFC. They found that in the high-selection condition these patients failed to produce any verbs 15% of the time. But in the low-selection condition these lesioned subjects performed the same as control subjects. The researchers concluded that because those with IFC lesions could not generate verbs to go along with displayed nouns when there were possibly many to choose between, the lesion caused a deficit in selection. It was not a semantic deficit, but a working memory one. They could not decide what verb to use and so they said nothing. This provided neuropsychological evidence for the IFC acting as a dynamic filter for the frontal cortex, at least as far as semantic information is concerned.

Thompson-Schill et al. (1999) also conducted another study where they looked at the temporal lobe in addition to the IFC. They replicated their previous experiment with one key difference. They had the subjects complete two generative trials (one of naming an action verb like in previous experiments and the other was naming an associated color) with the same list of nouns shown the second time for the subjects. Some repeated the first association task and others did the color one the second time. They found that IFC activation increased when the association task changed but temporal lobe activation decreased the second trial for both association conditions. Gazzaniga, Ivry, and Mangun (2002) sum it up best, “The fact that the decrease was observed is consistent with the idea that semantic attributes, be they relevant or irrelevant to the task at hand, were automatically activated upon presentation of the nouns” (p. 522). This is further evidence that the IFC acts as a dynamic filter for the frontal lobes.

[Note: Contact me if you would like the references cited in my post].

Categories: brain, cognition, psychology Tags: