Psychotherapy and Neuroscience

Consolidation Deficits & Retrograde Amnesia

Damage to the hippocampus and surrounding structures (medial temporal lobe-MTL) results in temporal graded retrograde amnesia. Middle age patients incurring damage to the MTL have intact early childhood autobiographical and episodic memories, and semantic memories for facts and situations. They incur retrograde (past) amnesia for autobiographical, episodic, and semantic memory from the date of insult to 11-40 years, duration contingent on the extent of extra-MTL damage (Buchanan, Tranel, & Adolphs, 2005; Reed & Squire, 1998; Stefanacci, Buffalo, Schmolck, & Squire, 2000). This suggests a time-limited role for the hippocampus in processing long term memory. Patients with MTL damage also lose their capacity for making future new long-term memory for respective explicit/declarative learning, termed anterograde (future) amnesia, from the date of insult onward (Manns, Hopkins, & Squire, 2003). Therefore patients who lose hippocampal function lose their ability for making new declarative memories and lose their ability for remembering declarative and explicit memory for as little as 11 years and as much of 40 years post-insult. Earlier memories from childhood and early adulthood without a viable hippocampus are intact, suggesting a time-limited role for the hippocampus in processing long term memory. Moreover in intact subjects neuroimaging findings support the need for a viable hippocampus, as it is needed for successful autobiographical memory retrieval within five years after a memory’s and an event’s occurrence (Piefke, Weiss, Zilles, Markowitsch, & Fink, 2003).

The findings of MTL damaged patients suggest that an intact hippocampal region is needed for learning new facts, identifying new people, having new knowledge of one’s surroundings since date of insult and for “declaring one’s memory” that define(s) that experience” (Eichenbaum & Cohen, 2001, p. 168) even if that declaration is linked with inner state words and thoughts. They demonstrate that the MTL, in particular the hippocampal proper, is needed for the initial creation, storage and retrieval of long-term declarative memory (Reed & Squire, 1998). They also suggest that there is a window for intermediate term memory (Eichenbaum, 1994) when memory is still fragile and dependent on the extra-hippocampal regions extending as little as 10 years and as much as 40 years (Kapur & Brooks, 1999). Finally they also illustrate that when the oldest memories are intact and retrievable, prior to the amnesia window, they are not dependent on hippocampal processes (Squire & Alvarez, 1995). This is also supported by neuroimaging findings. Remote memories are apparently stored in other brain regions like the sensory and prefrontal cortices (Maguire, Henson, Mummery, & Frith, 2001). Figure 3 summarizes processes noted above.

Consolidation & Coactivation of Long Term Memory

view a larger depiction of this diagram

These findings in total suggest that the hippocampus-extra-hippocampal-cortical regions have a time dependent role in processing experience for later retrieval and memory. This process is called memory consolidation. The hippocampus during consolidation repeatedly co-activates and replays neural information in its adjacent structures that in turn co-activate neurons in sensory-prefrontal cortical regions. (Frankland & Bontempi, 2005) Post-experience neural reactivation patterns during rest not only match to neural activity reminiscent of the actual experience, but also preserve temporal order (Fries, Fernandez, & Jensen, 2003). This reactivation process produces long-lasting changes in the medial temporal lobe connections with cortex (Nadel & Bohbot, 2001). With continual reactivation cortical connections eventually become strong and stable enough to support independent cortical recreation of the original representation with retrieval (Kali & Dayan, 2004; Squire & Alvarez, 1995; Wiltgen, Brown, Talton, & Silva, 2004). An intact hippocampus is important for the development of long-term memory on or around the learning event; the surrounding structures remain important for longer periods thereafter (Squire, Clark, & Knowlton, 2001).

Different memory systems are thus linked with characteristic types of learning. Corticostriatal response learning is characteristic of implicit-nondeclarative learning. Corticohippocampal place learning is characteristic of explicit-declarative learning. Loss of one region and learning system allows expression of another region and learning system. Any compensatory response by expressed regions will be limited by their regional functional specialization as noted earlier.

As the hippocampus performs its function in explicit, declarative memory processing, thought process is deliberate and purposeful. As the hippocampal region, in conjunction with its adjacent structures and more extended sensory and prefrontal cortical structures, consolidates memory in a time-dependent manner, it makes long term memory retrievable. It not only processes intentional explicit/declarative learning and memory but also memory that is unintentional implicit/nondeclarative when learning conditions present challenges. Again this distinction is important as the hippocampus has an intermediate role during implicit fear conditioning. Fear conditioning is an example of implicit learning. It deserves greater elaboration due to its relevance to PTSD.


Buchanan, T.W., Tranel, D., & Adolphs, R. (2005). Emotional autobiographical memories in amnesic patients with medial temporal lobe damage. Journal of Neuroscience, 25(12), 3151-3160.

Eichenbaum, H. (1999). Conscious awareness, memory, and the hippocampus. Nature Neuroscience, 2(9), 775-776.

Eichenbaum, H., & Cohen, N.J. (2001). From conditioning to conscious recollection. New York: Oxford University Press.

Frankland, P.W., & Bontempi, B. (2005). The organization of recent and remote memories. Nature Reviews in Neuroscience, 6(2), 119-130.

Fries, P., Fernandez, G., & Jensen, O. (2003). When neurons form memories. Trends in Neurosciences, 26(3), 123-124.

Kali, S., & Dayan, P. (2004). Off-line replay maintains declarative memories in a model of hippocampal-neocortical interactions. Nature Neuroscience, 7(3), 286-294.

Kapur, N., & Brooks, D.J. (1999). Temporally-specific retrograde amnesia in two cases of discrete bilateral hippocampal pathology. Hippocampus, 9(3), 247-254.

Maguire, E.A., Henson, R.N., Mummery, C.J., & Frith, C.D. (2001). Activity in prefrontal cortex, not hippocampus varies parametrically with increasing remoteness of memories. Neuroreport, 12(3), 441-444.

Manns, J.R., Hopkins, R.O., & Squire, L.R. (2003). Semantic memory and the human hippocampus. Neuron, 38(1), 127-133.

Nadel L., & Bohbot V. (2001). Consolidation of memory. Hippocampus, 11(1), 56-60.

Piefke, M., Weiss, P.H., Zilles, K., Markowitsch, H.J., & Fink, G.R. (2003). Differential remoteness and emotional tone modulate the neural correlates of autobiographical memory. Brain, 126(Pt 3), 650-68.

Reed, J.M., & Squire, L.R. (1998). Retrograde amnesia for facts and events: findings from four new cases. Journal of Neuroscience, 18(10), 3943-3954.

Squire, L.R., & Alvarez, P. (1995). Retrograde amnesia and memory consolidation: a neurobiological perspective. Current Opinion in Neurobiology, 5(2), 169-177.

Squire, L.R., Clark, R.E., & Knowlton, B.J. (2001). Retrograde amnesia. Hippocampus, 11(1), 50-55.

Stefanacci, L., Buffalo, E.A., Schmolck, H., & Squire, L.R. (2000) Profound amnesia after damage to the medial temporal lobe: a neuroanatomical and neuropsychological profile of patient E.P. Journal of Neuroscience, 20(18), 7024-36.

Wiltgen, B.J., Brown, R.A., Talton, L.E., & Silva, A.J. (2004). New circuits for old memories: the role of the neocortex in consolidation. Neuron, 44(1), 101-108.