Unraveling the impenetrable nature of amnesia: A new beginning

Research into the neural mechanisms putatively mediating memory consolidation (how memories stabilize over time [Ebbinghaus 1885]), has exploded in the last 30 yr, resulting in one Nobel Prize (Kandel 2001). Subfields, such as long-term potentiaton (LTP), are now industries in and of themselves. The term “long-term potentiation” brings up over 7000 hits on PubMed alone. Across all levels of analyses, there has been impressive insights into the mechanisms stabilizing memories. In the typical memory “consolidation” experiment, animals would receive some manipulation such as an injection of a drug that inhibits one of the putative molecular candidates implicated in plasticity. If animals demonstrated intact short-term memory and impaired long-term memory, then this was taken as an operational demonstration that the behavioral impairment was due to an impairment in the consolidation of the memory (Dudai 2004; McGaugh 2004). In addition, the targeted molecular pathway would be added to the list of mechanisms mediating the consolidation/storage of memory. Because of the tremendous success of this field, it might come as a surprise to some scientists that there is any unanswered issue about the nature of amnesia.

However, the issue concerning the nature of amnesia was never unanimously resolved. Other interpretations of amnesia were historically put forth describing the impairment as an inability to access an existing memory (e.g., Lewis 1969; Millin et al. 2001). After decades of debate, no resolution to this issue was found. Those that believed amnesia to be an impairment in the ability to retrieve memories went on to propose behavioral theories of memories in which amnesia was the result of an inability to retrieve the memory (e.g., Spear 1973; Lewis 1979; Miller and Marlin 1984). On the other hand, those who proposed that amnesia was an impairment in the storage of the memory went on to lead the physiological field in its search for the molecular and cellar mechanisms mediating memory consolidation (McGaugh 2000).

One result of this breakup is that behavioral theories of memory and the physiological view of memory have been divorced for 30 yr. Of course, it is in the field’s best interest to resolve the current conceptual divide on this issue. Any scientific description of a phenomenon needs to explain it across multiple levels of analyses. However, in the area of memory consolidation there is a substantial disconnection between the physiological and the behavioral and cognitive levels of analyses. One hope of this special section is that it will bring as many of the perspectives concerning the nature of amnesia side by side for consideration. It has also brought in perspectives from different levels of analyses. The hope is that this will inspire readers to think of new ways to bridge the different positions and levels of analyses, and thus be instrumental in inserting new momentum into the fundamental question regarding the nature of amnesia.

Below are excerpts from the letter of invitation, which was sent to the scientists who contributed to this special section:

“Dear Colleagues,

I would like to invite you to write a review or empirical paper for publication in a special issue of the journal Learning & Memory, to be distributed at the 2006 Society for Neuroscience meeting. The special issue will discuss the current status of the old question whether experimental amnesia reflects memory loss or retrieval failure. As you all are aware, this question was never completely resolved. Even after decades of intense inquiry and debate, usually involving research that employed consolidation paradigms, today there are still two views of experimental amnesia that exhibit little conceptual overlap (e.g., cf. Miller and Matzel [2000] and McGaugh [2000]).

Recently, the controversy concerning the qualitative nature of amnesia has resurfaced, marked by the rediscovery of reconsolidation at the neurobiological level. Currently there is little appreciation for the inherent difficulty of interpreting the results of recovery from amnesia experiments. For example, many simply take response recovery as sufficient evidence that the original memory has overcome retrieval impairment. In addition, the field of memory currently appears to be falling into the same experimental pitfalls that contributed to a stalemate on this issue 30 yr ago. In my opinion, this special issue will therefore provide a much-needed focus on the relevant issues in this debate, in which currently recovery of performance is incorrectly likened to recovery of memory. To this end, the editors at Learning & Memory and I believe that addressing these issues in a special issue would be of considerable value for the field.

“If you choose to participate in this project, submission can be in the form of an empirical paper (either a Brief Communication or Research Article) or a review article. Should you choose to submit a review, the following is a list of potential issues that you may wish to consider:

1. What is the nature of amnesia, and what is the strongest evidenced for this view?

2. Why was there never unanimity on this issue?

3. What kind of studies can move this issue forward from the current historical stalemate? If your view of amnesia is compatible with retrieval impairment, then please address whether this explanation of amnesia can be falsified. If your view of amnesia is storage impairment, then please illustrate whether the absence of a memory can be proven empirically.”