- The mediotemporal lobe is critically involved in both initial learning of facts and events and their later consolidation.
- Dysfunction in the mediotemporal lobe is a major factor in age-related cognitive decline.
- The most significant component of the MTL is the hippocampus.
- The hippocampus contains specialized neurons that categorize incoming sensory information, and others that are involved in the forming of new associations.
- The hippocampus is crucial for episodic memory - the remembering of specific events and experiences. It is also particularly involved in spatial memory.
- The hippocampus appears to be involved in consolidation processes, but only in the initial stages and for the first few years. The part of the hippocampus called the dentate gyrus is crucial for encoding new information (and is thus implicated in working memory).
- The dentate gyrus is one of the few brain regions in which new nerve cells can be created in adult brains.
- The main processing part of the hippocampus, the cornu ammonis, is distinguished by a high number of neurons which loop back on themselves - enabling the output of the neuron to influence its input; this may be critical for associative power.
- Other components of the mediotemporal lobe include the rhinal cortex and the amygdala.
- The entorhinal cortex appears to be involved in long-term memory consolidation beyond the first few years. It is one of the first regions damaged in Alzheimer's.
- The perirhinal cortex is crucial for object recognition.
- The amygdala is primarily responsible for processing emotional responses. The connection between hippocampus and amygdala underlies the role of emotion in memory.
The mediotemporal lobe (MTL) is a concept rather than a defined brain structure. It includes the hippocampus, the amygdala, and the entorhinal and perirhinal cortices - all structures within the medial area of the temporal lobe.The temporal lobe is in general primarily concerned with sensory experience - specifically, with hearing, and with the integration of information from multiple senses. Part of the temporal lobe also plays a role in memory processing. It is situated below the frontal and parietal lobes, and above the hindbrain.
Originally conceived as an integrated memory system with a common function, this view of the MTL has recently been questioned. For one thing, the region didn’t evolve as one unit — the different regions arose at different times during primate evolution. Therefore, can it really be an integrated system with a common function? Work with rhesus monkeys suggests rather that these different parts may serve cooperative and even competitive functions.
This question, however, is really one for the specialist. As far as most of us are concerned, the concept of a "mediotemporal lobe" serves as a handy label for a group of connected brain structures that are all absolutely crucial for learning and memory (and reminds us of the location of these structures).
It should also be remembered that brain structures are notoriously "fuzzy" — different researchers will use different names, and group different structures. For example, one report has contrasted the functions of the MTL with that of the basal ganglia, although the amygdala is a member of both. Other studies talk of the hippocampus AND the dentate gyrus, although others put the dentate gyrus as a substructure of the hippocampus. I mention this only to warn you, if you find trawl through various reports and find such discrepancies. They can be confusing. I have tried to integrate such discrepancies into a consistent description that seems to make most sense. Just bear in mind that dividing the brain into separate structures is not an exact science.
Functions of the MTL
The MTL has been particularly implicated in the process of memory consolidation - the process by which new memories become progressively more stable (see my article on consolidation for more details). Lesions in the MTL typically produce amnesia characterized by the disproportionate loss of recently acquired memories. A recent imaging study confirms this view by showing temporally graded changes in MTL activity in healthy older adults.
Progressive atrophy in the mediotemporal lobe also appears to be the most significant predictor of cognitive decline in seniors. Elderly persons with a poor memory have less activity in the mediotemporal lobe when storing new information than elderly persons with a normally functioning memory.
The MTL also appears to be particularly important during initial learning. Research has found rapid modulation of activity in the MTL at the beginning of learning, with this activity rapidly declining with training.
All this indicates that the MTL is not only hugely important, but that it covers a quite extraordinary range of functions. The reason for this lies in the fact that the MTL is not a single brain structure.
Components of the MTL
It is probably fair to say that the original concept of the MTL was, at least in part, a reflection of the inability of early researchers to "see" the activity in the brain in very much detail. Now, of course, neurological techniques have progressed to the point of being able to pinpoint activity to a quite fantastic level. It is therefore now possible to some degree to disentangle the functions of the various components of the MTL.
The most significant of the individual components of the MTL is the hippocampus. The hippocampus, one of the oldest parts of the brain, is important for the forming, and perhaps long-term storage, of associative and episodic memories. It is thus absolutely critical for learning and memory, and a brain region much studied by researchers.
In recent years, the hippocampus has been specifically implicated in (among other things) the encoding of face-name associations, the retrieval of face-name associations, the encoding of events, the recall of personal memories in response to smells. It may also be involved in the processes by which memories are consolidated during sleep.
A variety of specialized neurons have been found in the hippocampus. For example,
- "categorizing cells", which streamline and simplify sensory information, markedly reducing the brain's workload, by categorizing stimuli into various classes (categories that have been acquired through experience).
- "changing cells", which appear to be involved in the initial formation of new associative memories, and may also, in some cases, be involved in the eventual storage of the associations in long-term memory.
- "place cells", which become active in response to specific spatial locations; some of these cells also seem to be sensitive to recent or impending events, thus enabling you to place location within a temporal context (e.g., is this somewhere I've just been, or somewhere I intended to go?).
The existence of place cells is supported by other evidence for the role of the hippocampus in spatial navigation and memory. For example, London taxi drivers (famous for their extensive knowledge of London - a spatial task) have been found to have, on average, significantly bigger hippocampuses than "ordinary motorists". In similar vein, the chickadee, a tiny songbird, gathers and stores seeds in the fall, and at this time its hippocampus expands in volume by some 30% by adding new nerve cells. It shrinks back in the spring.
The role of the hippocampus in episodic (event) memory is underscored by findings that deficiencies in the hippocampus play a key role in alcoholism-related Korsakoff's syndrome (a memory disorder), as well as Alzheimer's disease.
The hippocampus has also been implicated in memory consolidation processes, but evidence now suggests the hippocampus may participate only in consolidation processes lasting a few years. It is probably critical for the initial consolidation of memories that appears to take place during sleep. Rat studies have found that, during sleep (mostly the slow-wave phase), the thalamus at the base of their brains produced bursts of electrical activity, which were then detected in the somatosensory neocortex. Some 50 msec later, the hippocampus responded with a pulse of electricity. It’s suggested that this pulse is the hippocampus sending back compressed waves of the information learned during the day to the neocortex where they are filed away for future reference.
The evidence that some memories might be held in the hippocampus for several years, only to move on, as it were, to another region, is an interesting complication to our earlier simple view of memory dividing into "short-term memory" and "long-term memory". It seems that long-term memory, now better labeled as permanent memory, is far from being the straightforward storage system that we once envisaged. Not only do memories become reconstructed, but they become, it would seem, re-filed. The implications of this, still speculative, relocation, are as yet unknown. Perhaps memories in this "permastore" are more resistant to change.
Substructures of the hippocampus
There are several substructures within the hippocampus. It is only very recently that researchers have been able to go inside the hippocampus, as it were, and pinpoint hippocampal activity to particular substructures.
- the dentate gyrus: is the main entry point for nerve fibers into the hippocampal formation. Rat studies suggest that the dentate gyrus is crucial for the acquiring of new information, and the functioning of working memory. Most recently, it has been implicated with the cornu ammonis as being highly active during encoding offace-name pairs. The dentate gyrus is one of the very few regions in the adult brain that appears to allow neurogenesis (creation of new nerve cells). Neurogenesis in the dentate gyrus has been found to be significantly reduced in marmoset monkeys when exposed to stress. Dysfunction in the dentate gyrus appears to be linked to cognitive deficits in those suffering from Alzheimer's. The granule cells in the dentate gyrus project to the pyramidal cells in the cornu ammonis.
- the cornu ammonis: is thought to be the main site of memory processing in the hippocampal formation. Most recently, it has been implicated with the dentate gyrus as being highly active during encoding offace-name pairs. Part of the cornu ammonis (CA3) has been of special interest due to its high number of recursive neurons (nerve fibers which loop back on themselves - enabling the output of the neuron to influence its input). Most recently, the CA3 has been found to be crucial for recalling memories from partial representations of the original stimulus (for example, when memories are triggered by smells).
- the subiculum: can be thought of as the "last stage" of processing in the hippocampal formation. It is the primary target of the pyramidal cells in CA1. The subiculum is connected to the perirhinal, entorhinal and prefrontal cortices, and thus is in a position to integrate information from several sources and pass this information on. The subiculum however has been much less studied than the other substructures of the hippocampal formation. Recently, it has been found to be active during the retrieval of newly learned face-name associations.
The entorhinal cortex is a region upon which nerve fibers from many sensory systems converge. It is the main input to the hippocampus, and also the main output. This is why damage to this region is so serious. The entorhinal cortex is one of the first regions damaged in the early stages of Alzheimer's.
It has also been suggested that the entorhinal cortex handles “incremental learning” — learning that requires repeated experiences. “Episodic learning” — memories that are stored after only one occurrence — might be mainly stored in the hippocampus.
While the hippocampus appears to participate in memory consolidation processes only for the first few years, the entorhinal cortex seems to be associated with temporally graded changes extending up to 20 years - suggesting that it is the entorhinal cortex, rather than the hippocampus, that participates in memory consolidation over decades.
The perirhinal cortex has been a largely neglected region. It is adjacent to the visual processing area, as well as the entorhinal cortex, and recent research demonstrates that it is important for recognizing objects. In particular, it is crucial for recognizing the many features of an object, while still recognizing it as a single entity. The perirhinal cortex also appears to be involved in associating objects with other objects, and even with abstractions such as a goal. Unsurprisingly, in view of its involvement in recognition memory, it appears to play a critical role in establishing the familiarity of an item.
While the hippocampus is also involved in object recognition, the functions of the two regions appear quite different.
The amygdala is part of the basal ganglia, large "knots" of nerve cells deep in the cerebrum, thought to be involved in various aspects of motor behavior (Parkinson's disease, for example, is an affliction of the basal ganglia). The amygdala has many connections with other parts of the brain, and is critically involved in computing the emotional significance of events. Recent research indicates it is responsible for the influence of emotion on perception, through its connections with those brain regions that process sensory experiences. Rat studies also suggest that the amygdala, in tandem with the orbitofrontal cortex, is involved in the forming of new associations between cues and outcomes - in other words, it is the work of the amygdala to teach us what happens to us when we do something.
The connection between the amygdala and the hippocampus helps explain why emotion can have such powerful effect on learning and memory (to put it crudely, the amygdala remembers the feelings, and the hippocampus remembers what event elicited those feelings). (see article on emotion and memory)
The brain is a network
It must always be remembered that no structure within the brain acts on its own. This is reinforced by a recent study that found that, as subjects studied word lists, clusters of neurons in the rhinal cortex and the hippocampus fired synchronized electrical bursts, with this coordinated activity plummeting for a fraction of a second just after participants remembered a word from the list. This has led to speculation that memory relies more on the timing (coordination) than on the strength of neural activity.
We still know very little about the ways in which these structures interact; only as we gain more knowledge about this will we know whether we are justified in talking about a "mediotemporal lobe". Nevertheless, this region of the brain is undoubtedly vital for what we might term "stereotypical" memory - the memory domains we are most likely to be thinking of when we think of memory.
- Anderson, A.K. & Phelps, E.A. 2001. Lesions of the human amygdala impair enhanced perception of emotionally salient events. Nature, 411, 305-309.
- Ekstrom, A.D., Kahana, M.J., Caplan, J.B., Fields, T.A., Isham, E.A., Newman, E.L. & Fried, I. 2003. Cellular networks underlying human spatial navigation.Nature, 425 (6954), 184-7.
- Fell, J., Klaver, P., Lehnertz, K., Grunwald, T., Schaller, C., Elger, C.E. & Fernández, G. 2001. Human memory formation is accompanied by rhinal-hippocampal coupling and decoupling. Nature Neuroscience 4(12), 1259-1264.
- Haist, F., Gore, J.B. & Mao, H. 2001. Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature neuroscience, 4 (11), 1139-1145.
- Hampson, R.E., Pons, T.P., Stanford, T.R. & Deadwyler, S.A. 2004. Categorization in the monkey hippocampus: A possible mechanism for encoding information into memory. PNAS, 101, 3184-3189.
- McLeod, P., Plunkett, K. & Rolls, E.T. 1998. Introduction to Connectionist Modelling of Cognitive Processes. Oxford: Oxford University Press.
- Nakazawa, K., Quirk, M.C., Chitwood, R.A., Watanabe, M., Yeckel, M.F., Sun, L.D., Kato, A., Carr, C.A., Johnston, D., Wilson, M.A. & Tonegawa, S. 2002. Requirement for Hippocampal CA3 NMDA Receptors in Associative Memory Recall. Science 297, 211-218.
- Poldrack, R.A., Clark, J., Paré-blagoev, E.J., Shohamy, D., Moyano, J.C., Myers, C. & Gluck, M.A. 2001. Interactive memory systems in the human brain. Nature, 414, 546-550.
- Ribeiro, S., Gervasoni, D., Soares, E.S., Zhou, Y., Lin, S-C., Pantoja, J., Lavine, M. & Nicolelis, M.A.L. 2004. Long-Lasting Novelty-Induced Neuronal Reverberation during Slow-Wave Sleep in Multiple Forebrain Areas. PLoS Biol 2(1): e24 DOI:10.1371/journal.pbio.0020024.
- Rusinek, H., De Santi, S., Frid, D., Tsui, W-H., Tarshish, C.Y., Convit, A., & de Leon, M.J. 2003. Regional Brain Atrophy Rate Predicts Future Cognitive Decline: 6-year Longitudinal MR Imaging Study of Normal Aging. Radiology, 229, 691-696.
- Schoenbaum, G., Setlow, B., Saddoris, M.P. & Gallagher, M. 2003. Encoding Predicted Outcome and Acquired Value in Orbitofrontal Cortex during Cue Sampling Depends upon Input from Basolateral Amygdala. Neuron, 39, 855-867.
- Sirota, A., Csicsvari, J., Buhl, D. & Buzsáki, G. 2003. Communication between neocortex and hippocampus during sleep in rodents. Proc. Natl. Acad. Sci. USA, 100 (4), 2065-2069.
- Wirth, S., Yanike, M., Frank, L.M., Smith, A.C., Brown, E.N. & Suzuki, W.A. 2003. Single Neurons in the Monkey Hippocampus and Learning of New Associations. Science, 300, 1578-1581.
- Zeineh, M.M., Engel, S.A., Thompson, P.M. & Bookheimer, S.Y. 2003. Dynamics of the Hippocampus During Encoding and Retrieval of Face-Name Pairs, Science, 299, 577-580.