Encyclopedia of Clinical Neuropsychology

Living Edition
| Editors: Jeffrey Kreutzer, John DeLuca, Bruce Caplan

Medial Temporal Lobe

  • Jonathan A. OlerEmail author
  • Rothem Kovner
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-56782-2_1168-2



The medial temporal lobe is an anatomical construct composed of the cerebral cortices on the mesial surface temporal lobe, as well as the subcortical gray-matter structures that lie beneath the surface of the temporal cortex. It is also a functional construct and is a term typically associated with the parahippocampal region (perirhinal, entorhinal, and parahippocampal cortices) and the hippocampal formation (CA fields, dentate gyrus, and subicular complex), a set of highly interconnected brain areas critical for the formation of long-term episodic memory (the medial temporal lobe memory system; MTLMS). While the phrase “medial temporal lobe” is most often used in reference to the mnemonic function of the hippocampus, the amygdala, a grouping of nuclei situated just in front of the hippocampus (see Fig. 1), also technically constitutes part of the medial temporal lobe (see Fig. 2). The amygdala, however, is generally associated with the processing of emotional salience and memories (e.g., threat conditioning; see LeDoux 2015), which can also therefore be considered a function of the medial temporal lobe. Though often overlooked (Aralasmak et al. 2006), the medial temporal lobe contains important white matter tracts that connect it to regions outside of the medial temporal lobe. These include, for example, (a) the uncinate fasciculus, a pathway connecting the deep structures of the medial temporal lobe and the temporal cortex with the prefrontal cortex (Schmahmann et al. 2007), and (b) the ventral amygdalofugal pathway and the stria terminalis, which link the amygdala with the bed nucleus of the stria terminalis, the hypothalamus, and the brain stem.
Fig. 1

In this horizontal slice through an MRI of the human brain, the primary structures of medial temporal can be seen. The amygdala lies just in front of the hippocampal formation, which is surrounded by the cortex of the parahippocampal gyrus, forming the medial wall of the temporal lobe (Reprinted with permission from Mendoza and Foundas 2008)

Fig. 2

Photomicrographs depicting amygdala and hippocampal histology. (a) Acetylcholinesterase (AChE) and (b) Nissl-stained tissue (a and b are adjacent sections) revealing the CA1, CA3, and dentate gyrus (DG). (c) AChE and (d) Nissl-stained tissue (c and d are adjacent sections) revealing the nuclei of the amygdala. Abbreviations: Pu putamen, CeL lateral division of central nucleus, CeM medial division of central nucleus, M medial nucleus, Bmc magnocellular division of basal nucleus, Bi intermediate division of basal nucleus, Bpc parvocellular division of basal nucleus, ABmc magnocellular division of accessory basal nucleus, ABpc parvocellular division of accessory basal nucleus, La lateral nucleus; PL paralaminar nucleus

Historical Background

Classically, the structures of the medial temporal lobe are considered part of the limbic system, which in addition to the amygdala and hippocampus include the cingulate gyrus, anterior thalamic nuclei, septal nuclei, mammillary bodies, and associated white matter tracts (e.g., fornix, stria terminalis). These limbic structures together made up the famous circuit of Papez, which at the time was hypothesized to underlie the expression of emotion in animals. Work by Kluver and Bucy (Bucy and Kluver 1955) demonstrated that the MTLMS is important for emotion regulation and memory. The role of the medial temporal lobe in memory formation was not fully understood until 1953, when Dr. William Scoville, a surgeon at Hartford Hospital in Connecticut, performed an experimental brain surgery in hopes of relieving a patient of severe intractable epileptic seizures. The patient was 27-year-old Henry Molaison (1926–2008), who became one of (if not) the most studied cases in the history of clinical neuropsychology. H.M. (as the famous patient came to be known) became severely amnesic following the procedure, which had removed most of the medial temporal lobes from both hemispheres of his brain. H.M.’s amnesia was profound. Until his death, he suffered from severe anterograde amnesia (the inability to create new episodic memories), as well as retrograde amnesia (the inability to recall things that happened in the weeks prior to the lesion); however, he remained capable of recalling facts and remote memories from the years before the experimental surgery. The temporally graded nature of retrograde amnesia suggests that long-term memory is consolidated over time and that eventually the retrieval of that memory is no longer dependent on the medial temporal lobe.

H.M.’s memory impairment was highly selective. There was no significant change in personality or intelligence, and he remained able to acquire new motor skills (intact procedural learning) despite having no memory of ever learning them. Although he was unaware of his contribution to the understanding of human memory systems, H.M. opened a new era in the neuropsychology of memory, spawning decades of research into the function of the hippocampal system.

Current Knowledge

The MTLMS receives information about ongoing experience via projections from higher-order sensory association regions of parietal, temporal, and frontal cortex. These multisensory inputs ultimately coalesce in the entorhinal cortex, the region surrounding the rhinal sulcus on the bottom of the temporal lobe. The entorhinal cortex is thought of as the highest level of association cortex in the brain and gives rise to the main source of cortical information to the circuits of the hippocampus (see Fig. 3). This circuitry is believed to be responsible for the establishment and maintenance of long-term memory. The organization of this circuitry – funneling sensory information into the hippocampus and hippocampal projections back to the sensory regions giving rise to the initial input – is thought to allow for the consolidation of episodic/declarative memory. The term “consolidation” refers to the time-dependent process of long-term memory storage. The understanding of memory consolidation comes from observation of patients with retrograde amnesia (the inability to recall things that happened in the time prior to the medial temporal lobe damage). Patients with amnesia resulting from medial temporal lobe damage are typically still able to recall facts and remote memories from the years before the injury. The “temporally graded” nature of retrograde amnesia suggests that memory consolidation is a protracted process that can take years and that eventually the retrieval of that memory is no longer dependent on the medial temporal lobe. However, the long-standing hypothesis that long-term memory eventually becomes entirely independent of the medial temporal lobe has been challenged (Nadel and Moscovitch 2001).
Fig. 3

A schematic diagram of the medial temporal lobe structures and major connections important for episodic/declarative memory. SUB subicular complex, DG dentate gyrus, CA1, CA3 the CA fields of the hippocampus

Future Directions

There are many remaining questions with regard to medial temporal lobe function. For example, a recent finding suggests that certain forms of object perception may rely on the perirhinal cortex; however, this question is highly controversial, and the debate as to whether the medial temporal lobe is a dedicated memory system or also plays a role in perception remains a subject of debate (see Suzuki and Baxter 2009). Another highly debated question regarding medial temporal lobe function in rodents is whether the electrophysiological activity of neurons in the hippocampus represents spatial or relational information (see Nadel and Eichenbaum 1999). This question stems from the striking spatial activity coded by place cells in the hippocampus (see Fig. 4). Indeed, the discovery of cells that constitute a positioning system in the brain earned the 2014 Nobel Prize in Physiology or Medicine. Rats with damage to the hippocampus are impaired on behavioral tasks that test spatial memory; however, questions remain as to the underlying fundamental role of the hippocampus that leads to the disruption in spatial memory. One side of the debate posits that the hippocampus contains a representation of the environment, termed a cognitive map, that when damaged leaves the rat incapable of remembering its position in the environment. This hypothesis, however, does not completely account for the impairments in episodic/declarative memory seen in human patients with focal damage to the MTLMS. The alternate hypothesis suggests that place cell activity is but one example of the type conjunctive relationships among environmental stimuli that the networks of the medial temporal lobe can code for.
Fig. 4

An example of the spatially selective firing of a place cell recorded from the CA1 region of the hippocampus while a rat repeatedly traversed a Figure-8 maze to find food reinforcement at each corner. The gray lines represent the location of the animals as it ran around the maze. Each black dot indicates that the neuron fired an action potential when the animal was in that location, and the circumscribed region where the cell fires is termed a “place field”

More recent was the discovery of a functional dissociation within the hippocampus, such that the anterior portion hippocampus is more important for aspects of emotion (e.g., anxiety) processing, while the posterior hippocampus plays a role in spatial memory (Fanselow and Dong 2010). This evidence highlights the multiple complex functions of medial temporal lobe in integrating and processing environmental stimuli both spatially and emotionally. Though it was disputed for many years, the dentate gyrus of the hippocampus is a region that continues to add new neurons in adulthood (Gross 2000). This process, known as adult neurogenesis, may be critical for normal memory processing, which declines during normal aging, and possibly related to the efficacy of anti-depressant drugs, such as selective serotonin reuptake inhibitors (SSRIs; Castrén and Hen 2013). Notably, exercise increases adult neurogenesis in the short term, but only a subset of these neurons get integrated into the system. Therefore, it is still unclear whether exercise improves memory formation in the long term (Duzel et al. 2016).

Over the years, regions within the MTLMS have often been linked to emotion. This system is extremely elaborate and is not well understood. A wide variety of studies demonstrate that the amygdala and the hippocampus are important for different aspects of emotional responding and that communication between these regions is important in mediating social responding. Importantly, the regions within the MTLMS often receive information from other parts of the brain through long-range white matter tracts. The role of white matter in the MTLMS and disorders related to memory and emotion had been largely unexplored until the development diffusion tensor imaging (DTI) technology. One tract, the uncinate fasciculus, has been implicated in various neuropsychiatric disorders (e.g., Tromp et al. 2012), and current studies are underway to identify whether white matter integrity of the uncinate fasciculus may be used as a biomarker for certain disorders (Von Der Heide et al. 2013).


References and Readings

  1. Amaral, D. G. (1999). Introduction: What is where in the medial temporal lobe? Hippocampus, 9, 1–6.CrossRefPubMedGoogle Scholar
  2. Aralasmak, A., Ulmer, J. L., Kocak, M., et al. (2006). Association, commissural, and projection pathways and their functional deficit reported in literature. Journal of Computer Assisted Tomography, 30(5), 695–715.CrossRefPubMedGoogle Scholar
  3. Bucy, P. C., & Kluver, H. (1955). An anatomical investigation of the temporal lobe in the monkey (Macaca Mulatta). The Journal of Comparative Neurology, 103(2), 151–251.CrossRefPubMedGoogle Scholar
  4. Burwell, R. D. (2000). The parahippocampal region: Corticocortical connectivity. Annals of the New York Academy of Sciences, 911, 25–42.CrossRefPubMedGoogle Scholar
  5. Castrén, E., & Hen, R. (2013). Neuronal plasticity and antidepressant actions. Trends in Neurosciences, 36, 259–267.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Corkin, S. (2002). What’s new with the amnesic patient H.M.? Nature Reviews Neuroscience, 3, 153–160.CrossRefPubMedGoogle Scholar
  7. Duzel, E., van Praag, H., & Sendtner, M. (2016). Can physical exercise in old age improve memory and hippocampal function? Brain, 139(Pt 3), 662–673.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Fanselow, M. S., & Dong, H. W. (2010). Are the dorsal and ventral hippocampus functionally distinct structures? Neuron, 65, 7–19.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Gross, C. G. (2000). Neurogenesis in the adult brain: Death of a dogma. Nature Reviews. Neuroscience, 1, 67–73.CrossRefPubMedGoogle Scholar
  10. LeDoux, J. E. (2015). Anxious: Using the brain to understand and treat fear and anxiety. New York: Viking.Google Scholar
  11. Mendoza, J., & Foundas, A. (2008). Clinical neuroanatomy: A neurobehavioral approach. New York: Springer Science and Business.Google Scholar
  12. Nadel, L., & Eichenbaum, H. (1999). Introduction to the special issue on place cells. Hippocampus, 9, 341–345.CrossRefPubMedGoogle Scholar
  13. Nadel, L., & Moscovitch, M. (2001). The hippocampal complex and long-term memory revisited. Trends in Cognitive Sciences, 5, 228–230.CrossRefPubMedGoogle Scholar
  14. Scoville, W. B., & Milner, B. (1957). Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery and Psychiatry, 20, 11–21.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Schmahmann, J. D., Pandya, D. N., Wang, R., et al. (2007). Association fibre pathways of the brain: Parallel observations from diffusion spectrum imaging and autoradiography. Brain, 130(Pt 3), 630–653.CrossRefPubMedGoogle Scholar
  16. Squire, L. R., Stark, C. E., & Clark, R. E. (2004). The medial temporal lobe. Annual Review of Neuroscience, 27, 279–306.CrossRefPubMedGoogle Scholar
  17. Suzuki, W. A., & Baxter, M. G. (2009). Memory, perception, and the medial temporal lobe: A synthesis of opinions. Neuron, 61, 678–679.CrossRefPubMedGoogle Scholar
  18. Tromp, D. P., Grupe, D. W., Oathes, D. J., McFarlin, D. R., Hernandez, P. J., Kral, T. R., Lee, J. E., Adams, M., Alexander, A. L., & Nitschke, J. B. (2012). Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder. Archives of General Psychiatry, 69, 925–934.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Von Der Heide, R. J., Skipper, L. M., Klobusicky, E., & Olson, I. R. (2013). Dissecting the uncinate fasciculus: Disorders, controversies and a hypothesis. Brain, 136, 1692–1707.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of PsychiatryUniversity of Wisconsin-MadisonMadisonUSA