Related Experiment Video
Updated: Jul 12, 2025
10:38
A Cognitive Paradigm to Investigate Interference in Working Memory by Distractions and Interruptions
Published on: July 16, 2015
13.7K
Medial Prefrontal Cortex Dysfunction Mediates Working Memory Deficits in Patients With Schizophrenia
John C Williams1,2, Zu Jie Zheng1, Philip N Tubiolo1,2
1Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.
Biological Psychiatry Global Open Science
|October 26, 2023
Summary
Working memory deficits in schizophrenia are linked to reduced medial prefrontal cortex (mPFC) deactivation during tasks. This mPFC deactivation mediates performance and is inversely associated with dopamine release.
Area of Science:
- Neuroscience
- Psychiatry
- Cognitive Science
Background:
- Schizophrenia (SCZ) is characterized by working memory (WM) deficits, impacting functional outcomes.
- While dorsolateral prefrontal cortex (PFC) is often studied, the medial PFC (mPFC) may also play a crucial role in SCZ.
- Understanding mPFC function in SCZ is vital for developing targeted interventions.
Purpose of the Study:
- To investigate the association between task-evoked mPFC deactivation and WM performance in SCZ.
- To determine if mPFC deactivation mediates WM deficits in SCZ.
- To explore the relationship between mPFC deactivation and cortical dopamine release in SCZ.
Main Methods:
- Functional magnetic resonance imaging (fMRI) was used to assess task-evoked brain activity during a visual object n-back task in patients with SCZ (n=41) and healthy controls (HCs) (n=40).
- Dopamine release capacity in the mPFC was measured using [11C]FLB457 and an amphetamine challenge in a subset of participants.
- Correlations between mPFC deactivation, WM performance, diagnosis, and dopamine release were analyzed.
Main Results:
- mPFC deactivation, but not dorsolateral PFC activation, correlated with WM task performance.
- Patients with SCZ exhibited reduced mPFC deactivation compared to HCs, and this reduction mediated the link between diagnosis and WM performance.
- A significant inverse association was found between mPFC deactivation and dopamine release capacity in HCs and across all participants, but not in patients with SCZ.
Conclusions:
- Reduced task-evoked mPFC deactivation is a key mediator of WM impairment in schizophrenia.
- These findings suggest mPFC deactivation may be a potential substrate for WM deficits in SCZ.
- Preliminary evidence indicates an inverse relationship between WM task-evoked mPFC deactivation and dopamine release capacity.
Related Concept Videos
01:24Working Memory
181
Working memory refers to a combination of components, including short-term memory and attention, that allow an individual to hold information temporarily as we perform cognitive tasks. It is an essential cognitive function that enables the execution of complex tasks such as problem-solving, comprehension, and reasoning. Unlike short-term memory, which simply involves the storage of information for a brief period, working memory involves the active manipulation and processing of this...
181
01:14Role of Cerebellum and Prefrontal Cortex in Memory
449
The cerebellum, while traditionally associated with motor control, also plays a crucial role in memory, particularly in procedural memory, which involves learning motor tasks that become automatic through repetition. For example, studies have shown that when the cerebellum is damaged, individuals or animals lose the ability to learn conditioned motor responses, such as the conditioned eye-blink response in classical conditioning experiments with rabbits. This study demonstrates the...
449
01:30Negative and Cognitive Symptoms of Schizophrenia
50
Negative symptoms of schizophrenia indicate a reduction or absence of typical behaviors and emotional responses found in healthy individuals, while positive symptoms reflect an excess or distortion of normal functioning.
Negative Symptoms
Negative symptoms of schizophrenia manifest as deficits in normal emotional and behavioral functioning, profoundly impacting daily life. Individuals with schizophrenia often display a flat affect, characterized by a near-total absence of emotional expression,...
Negative Symptoms
Negative symptoms of schizophrenia manifest as deficits in normal emotional and behavioral functioning, profoundly impacting daily life. Individuals with schizophrenia often display a flat affect, characterized by a near-total absence of emotional expression,...
50
01:30Attention-Deficit/Hyperactivity Disorder
73
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and impulsivity. It affects approximately 5-8% of children globally, with around 60-70% of cases persisting into adulthood. ADHD has significant implications for educational attainment, social interactions, and occupational success.
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
73
01:19Role of Hippocampus in Memory
276
The hippocampus, a critical brain structure, plays an essential role in memory processing, particularly in the formation and retrieval of memory. This small, seahorse-shaped region is located within the medial temporal lobe, with one hippocampus in each brain hemisphere. Experimental studies involving lesions in the hippocampi of rats have demonstrated significant impairments in tasks such as object recognition and maze navigation, indicating the hippocampus involvement in both recognition and...
276
01:29Biological Causes of Schizophrenia
61
Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
61