Medial Temporal Lobe
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.
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
- LeDoux, J. E. (2015). Anxious: Using the brain to understand and treat fear and anxiety. New York: Viking.Google Scholar
- Mendoza, J., & Foundas, A. (2008). Clinical neuroanatomy: A neurobehavioral approach. New York: Springer Science and Business.Google Scholar
- 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