Author: Kimberly Johnston, Class of 2026

Schizophrenia (SCZ) is a mental disorder characterized by severe impairments in working memory (WM), a type of short-term memory responsible for temporarily storing and manipulating information needed to perform tasks, solve problems, and make decisions. A key region of the brain involved in this process is the medial prefrontal cortex (mPFC), which is active during internal thinking and deactivated during goal-directed tasks. Individuals with SCZ demonstrate reduced deactivation of the mPFC during WM tasks compared to healthy control participants (HCs), suggesting that an inability to shift from inward-focused thinking to task-oriented thinking may contribute to their impairments in WM. Researchers at Stony Brook University hypothesized that activation in the lateral prefrontal cortex (lPFC) and deactivation in the mPFC would be impaired in patients with SCZ. Additionally, the researchers predicted that dopamine release in the prefrontal cortex would be associated with greater activation and deactivation within respective regions of the lPFC and the mPFC.

Participants in the study were presented with a series of stimuli and had to indicate whether the current stimulus matched the one presented n steps earlier in the sequence. Accuracy and reaction time of HCs was significantly faster than of patients with SCZ. Deactivation in the mPFC was reduced in patients with SCZ compared to HCs and influenced the relationship between diagnosis and WM performance. This indicates that failure to deactivate the mPFC while performing a WM task is a relevant mechanism of cognitive impairment in patients with SCZ. Additionally, mPFC deactivation was associated with reduced dopamine release capacity in HCs but not in unmedicated patients with SCZ. This suggests that improper regulation of dopamine in the prefrontal cortex may contribute to WM deficits associated with SCZ. High dopamine is linked to poor control of impulses, which is related to excessive energy and hallucinations. 

Impairments in WM makes it harder to perform everyday tasks such as remembering a phone number while dialing it or following a recipe while cooking. The results of this study demonstrate that the mPFC should be considered as a potential target for novel therapeutics. Future studies must include a larger sample size in order to verify these findings. Advancements in SCZ treatments would improve the quality of life of patients and their loved ones taking care of them.

Figure 1: Dopamine, a neurotransmitter.

Works Cited:

[1] Williams, J., Zheng, Z., Tubiolo, P., et al. “Medial Prefrontal Cortex Dysfunction Mediates Working Memory Deficits in Patients with Schizophrenia.” Science Direct. (2023) https://doi.org/10.1016/j.bpsgos.2022.10.003   

[2] Image retrieved from: https://commons.wikimedia.org/wiki/File:Dopamin_-_Dopamine.svg