关键词: 抑郁症, 经颅磁刺激, 背外侧前额叶, 主动遗忘, 社会反馈, 负性记忆, 定向遗忘

Abstract:

Depression is a common mental disorder characterized by persistent low mood and anhedonia. While healthy people can voluntarily forget unpleasant events, depressed patients cannot or have difficulty in forgetting negative stimuli. Studies focused on healthy population have found that memory suppression is not only associated with decreased neural activation in the hippocampus, but also significantly activates a wide network in the prefrontal cortex, especially the right dorsolateral prefrontal cortex (DLPFC). Meanwhile, studies have demonstrated that depressed participants could not effectively recruit their frontal brain network responsible for inhibition control of negative materials. Thus, the key question of this study is to examine whether an enhancement of the neural activation in DLPFC using transcranial magnetic stimulation (TMS) could improve the ability of voluntary forgetting of negative information in depressed patients.
We recruited a total of 123 participants. Among them, 31 healthy participants were stimulated by TMS at the right DLPFC (right DLPFC-activated controls), 32 patients and 30 patients were stimulated by TMS at the left and right DLPFC respectively (left and right DLPFC-activated patients). The other 30 patients were assigned into a sham TMS group. This study contained three independent variables. The two within-subject variables were TMS (baseline or TMS condition) and directed forgetting instruction (remember or forget), and the between-subject variable was group (left or right DLPFC-activated patient, or right DLPFC-activated control). We focused on the memory suppression of social feedbacks in this study, since social feedback processing plays a vital role in everyday interpersonal activities. Previous studies have found that depressed patients cannot perceive and evaluate social feedbacks accurately and adaptively, which makes negative social experiences being an important inducing factor of depression. Meanwhile, evidence indicates that depressed patients have more deficits in processing social relative to nonsocial information.
Results of the explicit memory test showed that the recall accuracy of social rejection was higher in patients than healthy controls in baseline condition, suggesting that patients had difficulty in voluntarily forgetting negative social feedback. After we used the TMS to activate the left or right DLPFC of participants, we found no significant difference in the recall accuracy of social rejection between the three groups. This result suggested that the ability of memory suppression for negative social feedback was improved by TMS in patients. Moreover, it was also found that patients rated the feedback senders as being more attractive after they had forgotten negative social feedback provided by these feedback senders.
The main contribution of this study is that we first attempt to improve the ability of memory suppression of negative information in depressed patients using the TMS technique. Still now, there have been only two neuroscience studies focusing on the deficits of directed forgetting in depression ( Xie, Jiang, & Zhang, 2018; Yang et al., 2016). Beyond these two studies, we demonstrated a causal relationship between the DLPFC and memory suppression impairment in depressed patients by employing TMS to facilitate the function of DLPFC. Thus, we provide a potential neural target for the clinical treatment of depressed patients with voluntary forgetting deficits. In addition to depression, difficulties in voluntary forgetting is a common problem found in patients diagnosed with post-traumatic stress disorder, anxiety disorder (including obsessive compulsive disorder), schizophrenia and many other mental disorders. Meanwhile, difficulties in forgetting the euphoria or enjoyment coming from drugs or high-calorie foods might be an important reason for the persistence and aggravation of drug addiction and bulimia. Our finding suggests that the right DLPFC may be a potential brain target for the treatment of memory suppression deficits in these disorders. Facilitating the cognitive control of this brain region using the TMS is expected to restore the inhibitory control function of patients and thus significantly improve their voluntary forgetting ability, helping them to relieve symptoms and recover from disorders.

Key words: depression, transcranial magnetic stimulation, dorsolateral prefrontal cortex, voluntary forget, social feedback, negative memory, directed forgetting