Effects of tDCS Combined With Retrieval Practice on Semantic Memory in Patients With Schizophrenia

The semantic processing deficit stands as a central feature of cognitive abnormalities in schizophrenia. Both transcranial direct current stimulation (tDCS) and retrieval practice have been demonstrated as external techniques capable of ameliorating the semantic processing deficit in individuals with schizophrenia. The inquiry examines whether the combined effect of tDCS and retrieval practice, following tDCS intervention targeting the left dorsolateral prefrontal cortex (L-DLPFC) in patients with schizophrenia, contributes to the preservation of semantic memory in these individuals.

Investigators recruited 52 patients diagnosed with schizophrenia from hospitals. After five consecutive days of tDCS intervention (2 mA × 20 mins, twice per day), Investigators administered a word list memorization task comparing retrieval practice and restudy strategies. Subsequently, Investigators observed their immediate and delayed memory performance through tests.

Treatment was administered by two examiners, and after a total of 10 sessions over 5 consecutive days, a final group of 52 patients participated in the learning and testing phase. Among them, 27 received anodal stimulation, while 25 received sham stimulation. Each participant of each stimulation type was involved in both learning conditions, meaning that all participants completed both retrieval and restudy learning and testing.

1. Stimulation phase:

   In the anodal group, the anode was placed over the left DLPFC (F3), and the cathode was placed over the contralateral supraorbital area (FP2). A direct current of 2mA was applied for 20 minutes during each stimulation session. Stimulation was conducted twice a day, at 9 a.m. and 2 p.m., for 5 consecutive days, totaling 10 sessions. In the sham group, the stimulation parameters, including the stimulation site and duration, were identical to those of the anodal group. However, during the 10-second ramp-up and ramp-down periods before and after stimulation, patients were unaware that the current was turned off.
2. Learning phase:

   The experimental procedure followed the classic retrieval practice paradigm, which included a learning phase and a final test phase.

   During the experiment, participants were informed that they would learn two lists of words. Subsequently, they might either learn the words again or complete a list recall test, and will be given a final test shortly thereafter. The learning of the retrieval practice list and the restudy list was conducted in a randomly balanced manner. Each word was presented for 5 seconds, with a 500-millisecond interval between words. To avoid providing secondary retrieval cues between examples, all words were shuffled pseudo-randomly within categories. Each list contained 17 words, consisting of 5 examples from each of the 3 experimental categories (15 experimental examples, 2 filler examples). The first and last words presented in each list were filler words, thus controlling for the primacy and recency effects on memory.

   For the retrieval practice list, participants underwent two learning sessions and two retrieval sessions (S-T-S-T). During retrieval, participants were instructed to write down all the words they had just remembered within 5 minutes. For the restudy list, participants underwent four study sessions (S-S-S-S). Between each learning cycle, participants completed a 3-minute simple arithmetic task (dispersed attention task).
3. Testing phase:

Immediate Test: Participants were instructed to recall as many words as possible from the learned lists within 10 minutes after completing all learning tasks.

Delayed Test: Participants were informed to recall as many words as possible from the learned lists within 10 minutes 24 hours later.

Eligibility Criteria:
Inclusion Criteria:

1. Meeting the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5);
2. Aged 18 years or older, regardless of gender, with an educational level of elementary school or above;
3. All patients received stable-level antipsychotic medication treatment, were in a stable phase of disease treatment, able to understand the testing requirements, and cooperated to complete all research tasks;
4. No history of neurological disorders or other serious physical illnesses, and no history of intellectual disability;
5. No color blindness, color weakness, or other color vision impairments, with normal vision or corrected vision.

Exclusion Criteria:

1. Clear cognitive impairment caused by somatic or cerebral organic lesions, such as cerebrovascular diseases, traumatic brain injury, etc;
2. Individuals with mental disorders caused by substance dependence or abuse, or the use of psychoactive substances;
3. History of brain injury or other central nervous system-related organic diseases;
4. Individuals at significant risk of suicide or harming others;
5. Participation in similar experiments in the past 30 days prior to baseline.