Perusing Psychology

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.

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.

Click here to continue reading.

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.

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. Come back for more about his case in the coming days.

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.

I have to apologize for the paucity of posts on this blog. The grind of my semester got to me. After a few week break it’s time for a neuroanatomy post.

WIthin the temporal lobe of the brain is an elongated structure called the hippocampus. Some people have compared its shape to that of a seahorse (the word hippocampus comes from the Greek {hippos + campos}, which roughly means “seahorse”). This structure is special for a number of reasons. One is its role in memory encoding and consolidation.

From cytoarchitectonic standpoint, the hippocampus is special because unlike the surrounding cortex, it consists of only three layers instead of six. The hippocampus is phylogenetically an old part of the cortex, which means that it is an older branch on the evolutionary tree, whereas the rest of the cortex (more accurately called the neocortex), especially cortex of the frontal lobes, is a much newer development.

The hippocampus (to be more accurate, there are two hippocampi – one in each cerebral hemisphere) resides within the medial portion of the temporal lobe. It is continuous with the parahippocampal cortex, entorhinal cortex (the hippocampus receives its main input from this cortex), and perirhinal cortex. I’ll not write about the internal structure of the hippocampus, which becomes fairly complex, due to the brief nature of this post.

The hippocampus sends white matter tracts off its dorsal and posterior portions (the hippocampus also communicates through other tracts and pathways – this circuit is not the only output of the hippocampus). These white matter tracts are the fimbria of the hippocampus (technically, the fimbria are the “offshoots” of the alveus of the hippocampus). The fimbria proceeds upwards from the posterior portion of the hippocampus, at which point it ceases to be the fimbria and is called the fornix.

The fornices (plural of fornix) are prominent white matter tracts passing above the thalamus and medially in the brain. The fibers travel forward, then turn downward just posterior to the anterior commissure (a white matter tract that connects both hemispheres) to terminate in the mammillary bodies, two bumps on the ventral side of the brain. They are part of the hypothalamus of the brain. From there, the pathway courses upward through the mammilothalamic tract (MTT) to the anterior nucleus of the thalamus. From there axons course to the cingulate gyrus, then to the underlying cingulum (large white matter tract), and back to the hippocampus (via the parahippocampal and entorhinal cortices). This circuit is part of the limbic system and is called the Papez (pronounced “papes” – rhymes with capes) circuit. This circuit is important for emotion (and memory).

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.

The New York Times has a very nice article about Frontotemporal demetia (FTD). This type of dementia is interesting, affecting personality, inhibition, attention, and language. It is similar to Alzheimer’s Disease but has a different progression and manifestation. Anyway, the article provides a nice picture of the disease.

I’m continuing my recent trend of basic cognitive psychology posts. The following post is about the Modal Model of memory, which has been highly influential for a number of decades but it is slowly being modified over time. I won’t get into the more modern modifications of the modal model, rather, in my post I present the very traditional view of memory, even if it is somewhat controversial today. For example, a number of psychologists do not believe that short term memory really exists (working memory fills in the gap). In any case, my post serves as a brief introduction to a classic view of memory and of the primacy and recency effects.

The modal model of memory has three main components. They are: sensory register, short-term memory (STM), and long-term memory (LTM). This Atkinson and Shiffrin model of memory assumes that the processes of moving information from the sensory store to short-term and then long-term memory takes place in discrete stages. At any of these stages information can be lost through interference or decay. Another assumption of this model is that information processing has to start in the sensory register and be attended to, then move to STM, and then to LTM with rehearsal.

The serial position effect (split into the primacy and recency effects) is that the first few and last few items in a word list, for example, are the easiest to remember. A graph of this effect would be roughly parabolic (i.e., U-shaped). The primacy effect occurs because people have time to rehearse the first few items until the STM capacity is reached. The recency effect occurs because the last items are still in STM and have not decayed yet so they are easy to remember. The items in the middle of lists are easy to forget because STM capacity is too full for much rehearsal by then and as more items are presented, older items in STM are “pushed out.”

There are ways to hinder the primacy or recency effects though. If items are presented rapidly then there is not time to rehearse the items and the primacy effect fades away. If there is a distracting task given at the end of the main task (similar to Peterson and Peterson’s 1959 study testing the decay rate of STM), then the recency effect disappears due to STM capacity being taken up by the distracters, which leads to decay of the information in STM. These findings indicate that the systems governing primacy and recency effects are separate. The findings also gave support to the modal model because researchers identified the primacy effect with the transfer of STM into LTM. The recency effect is just an example of information being in STM.

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.