In Memory of H.M. – Live Video

The Brain Observatory – In Memory of H.M..

Click on the above link to watch H.M.’s brain being sliced into histological sections at the University of California – San Diego. The cutting resumes today (Thursday, December 3, 2009) at 11 AM EST. The researchers expect to cover the medial temporal lobes (including what is left of H.M.’s hippocampi). This is a historical event involving the brain of the most studied person in psychology and neuroscience. Who is H.M.? Click here to read my short post about him.

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.

Revisiting Clive

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

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.

Hippocampus Anatomy Video

To follow up my previous post on the hippocampus, here’s a video posted by drbobrd on YouTube. He uses a model of a brain to explain some brain anatomy, including the hippocampus and fornix.

The Hippocampus in 400 Words

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 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.

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 circuit. This circuit is important for emotion and memory.

Learning and Recall – Hippocampal Firing

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.

Hippocampal Volume Loss and Major Depression

Mood disorders range from major depressive disorders to major manic episodes. These disorders are both unipolar and bipolar. One main area of mood disorder research is that of unipolar major depression. Major depression can last just one episode or it can be a disorder, which can last for years with multiple depressive episodes over this extended period. The psychological aspects of depression are well understood but the biological foundations are less understood. As some evidence of this, the DSM-IV manual does not include any neurological information concerning major depression. In this handbook, depression is treated purely as a mental condition without an explanation of the biological aspects of the disorder. On the other hand, there are many psychopharmaceuticals prescribed to people with depression, which suggests that there is more than a cursory acknowledgment of the biological basis of this mental illness. However, this biological focus is mainly a focus on neurotransmitters and not anatomy. Recently, there have been numerous studies conducted to investigate the relationship between brain structure and depression (see Videbech & Ravnkilde, 2004). One of the structures most often studied in connection with depression is the hippocampus, which is a key structure for memory. The purpose of this paper is to investigate whether the hippocampus specifically is negatively impacted in depressed patients.

Frodl et al. (2002) investigated hippocampal changes in patients with first episode major depression. The authors had 30 adult depressed subjects (mean age = 40.3) and 30 matched controls (mean age = 40.6). The mean time of the depressive episode for the depression group was 0.71 years. The researchers collected MR images for all subjects. They compared the hippocampal volumes of the depressed group with the control group with ANCOVAs. Depressed men had significantly smaller left hippocampal volume than did healthy male subjects but right hippocampal volume was not significantly different. Female depressed subjects had significantly larger right hippocampal volume than did their matched controls and left volume did not differ, which implicates differing effects of depression on men and women. There was a significant left-right hippocampal volume disparity in the depressed patients but there was not one in the healthy subjects. Overall, the difference in hippocampal volume was not significant between the depressed and control groups though. There was also no significant correlation between age and hippocampal volume for either group but this finding goes against that of other research (Frodl et al.). On the other hand, between groups there was a significant reduction of hippocampal white matter volume. In other words, both male and female depressed patients had on average a reduction in the hippocampal white matter compared to the control subjects.

The authors concluded that there are likely physiologic gender differences in how males and females react to stress, which would explain why depressed males had smaller hippocampal volume and females did not. They believe this may be an example of the protective effects of estrogen against stress seen in other studies. In any case, there was a tendency for both depressed males and females to have significant left-right hippocampal asymmetry and reduced white matter. They concluded that this represents the beginning of left hippocampus volume loss and disrupted axonal transmission, respectively. The researchers could not conclude, however, that depression caused the volume loss. It may be that the loss came in response to stress or some other factor, which in turn predisposed the depressed subjects to major depression. Alternatively, the depression could have been the catalyst for the reduction (Frodl et al., 2002). Further longitudinal research is needed to uncover the causal relationship between depression and hippocampal volume.

Continue reading “Hippocampal Volume Loss and Major Depression”