Date Published: June 7, 2018
Publisher: Public Library of Science
Author(s): Jing Fang, Selver Demic, Sen Cheng, Judith Homberg.
Major depressive disorder (MDD) is associated with an impairment of episodic memory, but the mechanisms underlying this deficit remain unclear. Animal models of MDD find impaired adult neurogenesis (AN) in the dentate gyrus (DG), and AN in DG has been suggested to play a critical role in reducing the interference between overlapping memories through pattern separation. Here, we study the effect of reduced AN in MDD on the accuracy of episodic memory using computational modeling. We focus on how memory is affected when periods with a normal rate of AN (asymptomatic states) alternate with periods with a low rate (depressive episodes), which has never been studied before. Also, unlike previous models of adult neurogenesis, which consider memories as static patterns, we model episodic memory as sequences of neural activity patterns. In our model, AN adds additional random components to the memory patterns, which results in the decorrelation of similar patterns. Consistent with previous studies, higher rates of AN lead to higher memory accuracy in our model, which implies that memories stored in the depressive state are impaired. Intriguingly, our model makes the novel prediction that memories stored in an earlier asymptomatic state are also impaired by a later depressive episode. This retrograde effect exacerbates with increased duration of the depressive episode. Finally, pattern separation at the sensory processing stage does not improve, but rather worsens, the accuracy of episodic memory retrieval, suggesting an explanation for why AN is found in brain areas serving memory rather than sensory function. In conclusion, while cognitive retrieval biases might contribute to episodic memory deficits in MDD, our model suggests a mechanistic explanation that affects all episodic memories, regardless of emotional relevance.
Major depressive disorder (MDD) is the most common mood disorder, estimated to affect 20% of the population at some point of a person’s lifetime [1–3]. MDD is characterized by a constellation of behavioural, emotional and cognitive symptoms, especially in the domain of memory . Numerous studies have reported a selective impairment of episodic memory during depressive episodes [5–8]. Some studies even find an almost linear relationship between scores on a depression rating scale and episodic memory performance [9, 10]. Unlike episodic memory, however, semantic memory, the other type of declarative memory, is relatively intact in MDD patients [11, 12].
We have developed a computational model to study episodic memory deficits in MDD. We assumed that MDD is associated with a reduction of AN in the DG, and that this reduction in AN impairs pattern separation. We hypothesized that the impairment of pattern separation in turn reduces the accuracy of episodic memory retrieval. In our model, episodic memories are encoded based on a semantic representation of the sensory inputs . We investigated episodic memory deficit in MDD with an intact semantic system, which is consistent with observations that semantic memory is not affected in MDD [11, 12]. Our model of episodic memory is built around the idea that episodic memories are best represented by sequences of neural activity patterns [28, 29, 56, 63]. This aspect distinguishes our model from other models of neurogenesis, which only consider the storage and retrieval of static patterns.