Failure to deactivate medial prefrontal cortex in people at high risk for psychosis

2015 ◽  
Vol 30 (5) ◽  
pp. 633-640 ◽  
Author(s):  
I. Falkenberg ◽  
C. Chaddock ◽  
R.M. Murray ◽  
C. McDonald ◽  
G. Modinos ◽  
...  

AbstractImpaired working memory is a core feature of schizophrenia and is linked with altered engagement the lateral prefrontal cortex. Although altered PFC activation has been reported in people with increased risk of psychosis, at present it is not clear if this neurofunctional alteration differs between familial and clinical risk states and/or increases in line with the level of psychosis risk. We addressed this issue by using functional MRI and a working memory paradigm to study familial and clinical high-risk groups. We recruited 17 subjects at ultra-high-risk (UHR) for psychosis, 10 non-affected siblings of patients with schizophrenia (familial high risk [FHR]) and 15 healthy controls. Subjects were scanned while performing the N-back working memory task. There was a relationship between the level of task-related deactivation in the medial PFC and precuneus and the level of psychosis risk, with deactivation weakest in the UHR group, greatest in healthy controls, and at an intermediate level in the FHR group. In the high-risk groups, activation in the precuneus was associated with the level of negative symptoms. These data suggest that increased vulnerability to psychosis is associated with a failure to deactivate in the medial PFC and precuneus during a working memory task, and appears to be most evident in subjects at clinical, as opposed to familial high risk.

2021 ◽  
Author(s):  
Wei Zhang ◽  
Lei Guo ◽  
Dongzhao Liu ◽  
Guizhi Xu

Abstract Spatial working memory (SWM) refers to a short-term system for temporary manipulation of spatial information and requires the cooperation of multiple brain regions. Despite evidence that hippocampus (HPC) and prefrontal cortex (PFC) are involved in SWM, how PFC and HPC coordinate the neural information during SWM remains puzzling. In this study, local field potentials (LFPs) were recorded simultaneously from rat ventral HPC and medial PFC during SWM tasks. Then cross-frequency coupling algorithm was used as functional connectivity for construction of undirected networks; Grange causality algorithm was used as effective connectivity for construction of directed networks. Finally, information interactions across two brain regions were analyzed based on undirected and directed networks. Experimental results show that LFPs power in PFC and HPC both decreased over learning days and peaked before the reference point during SWM, moreover, LFPs mainly distributed in theta and gamma. From the undirected aspect, undirected PFC subnetwork and HPC subnetwork have the same effect on information transmission for SWM; the PAC between PFC-gamma and HPC-theta in undirected PFC-HPC network is related to SWM formation and contributes to information interactions between PFC and HPC. From the directed aspect, the effect of information transmission in directed HPC subnetwork is greater than PFC subnetwork; the enhancement of coordination between directed PFC and HPC subnetworks contributes to correct execution of SWM tasks; directed HPC→PFC network plays a predominant role in information interaction; with the increasing of learning days, PFC and HPC tend to be the causal sink and causal source of information flow.


2012 ◽  
Vol 26 (3) ◽  
pp. 288-303 ◽  
Author(s):  
Larry J. Seidman ◽  
Eric C. Meyer ◽  
Anthony J. Giuliano ◽  
Hans C. Breiter ◽  
Jill M. Goldstein ◽  
...  

2020 ◽  
pp. 1-11
Author(s):  
Yang Jiang ◽  
Juan Li ◽  
Frederick A. Schmitt ◽  
Gregory A. Jicha ◽  
Nancy B. Munro ◽  
...  

Background: Early prognosis of high-risk older adults for amnestic mild cognitive impairment (aMCI), using noninvasive and sensitive neuromarkers, is key for early prevention of Alzheimer’s disease. We have developed individualized measures in electrophysiological brain signals during working memory that distinguish patients with aMCI from age-matched cognitively intact older individuals. Objective: Here we test longitudinally the prognosis of the baseline neuromarkers for aMCI risk. We hypothesized that the older individuals diagnosed with incident aMCI already have aMCI-like brain signatures years before diagnosis. Methods: Electroencephalogram (EEG) and memory performance were recorded during a working memory task at baseline. The individualized baseline neuromarkers, annual cognitive status, and longitudinal changes in memory recall scores up to 10 years were analyzed. Results: Seven of the 19 cognitively normal older adults were diagnosed with incident aMCI for a median 5.2 years later. The seven converters’ frontal brainwaves were statistically identical to those patients with diagnosed aMCI (n = 14) at baseline. Importantly, the converters’ baseline memory-related brainwaves (reduced mean frontal responses to memory targets) were significantly different from those who remained normal. Furthermore, differentiation pattern of left frontal memory-related responses (targets versus nontargets) was associated with an increased risk hazard of aMCI (HR = 1.47, 95% CI 1.03, 2.08). Conclusion: The memory-related neuromarkers detect MCI-like brain signatures about five years before diagnosis. The individualized frontal neuromarkers index increased MCI risk at baseline. These noninvasive neuromarkers during our Bluegrass memory task have great potential to be used repeatedly for individualized prognosis of MCI risk and progression before clinical diagnosis.


2020 ◽  
Author(s):  
Sihai Li ◽  
Christos Constantinidis ◽  
Xue-Lian Qi

ABSTRACTThe dorsolateral prefrontal cortex plays a critical role in spatial working memory and its activity predicts behavioral responses in delayed response tasks. Here we addressed whether this predictive ability extends to categorical judgments based on information retained in working memory, and is present in other brain areas. We trained monkeys in a novel, Match-Stay, Nonmatch-Go task, which required them to observe two stimuli presented in sequence with an intervening delay period between them. If the two stimuli were different, the monkeys had to saccade to the location of the second stimulus; if they were the same, they held fixation. Neurophysiological recordings were performed in areas 8a and 46 of the dlPFC and 7a and lateral intraparietal cortex (LIP) of the PPC. We hypothesized that random drifts causing the peak activity of the network to move away from the first stimulus location and towards the location of the second stimulus would result in categorical errors. Indeed, for both areas, when the first stimulus appeared in a neuron’s preferred location, the neuron showed significantly higher firing rates in correct than in error trials. When the first stimulus appeared at a nonpreferred location and the second stimulus at a preferred, activity in error trials was higher than in correct. The results indicate that the activity of both dlPFC and PPC neurons is predictive of categorical judgments of information maintained in working memory, and the magnitude of neuronal firing rate deviations is revealing of the contents of working memory as it determines performance.SIGNIFICANCE STATEMENTThe neural basis of working memory and the areas mediating this function is a topic of controversy. Persistent activity in the prefrontal cortex has traditionally been thought to be the neural correlate of working memory, however recent studies have proposed alternative mechanisms and brain areas. Here we show that persistent activity in both the dorsolateral prefrontal cortex and posterior parietal cortex predicts behavior in a working memory task that requires a categorical judgement. Our results offer support to the idea that a network of neurons in both areas act as an attractor network that maintains information in working memory, which informs behavior.


2013 ◽  
Vol 535 ◽  
pp. 35-39 ◽  
Author(s):  
Kyungun Jhung ◽  
Sung-Hwan Cho ◽  
Ji-Hyun Jang ◽  
Jin Young Park ◽  
Dongkwan Shin ◽  
...  

1994 ◽  
Vol 1 (4) ◽  
pp. 293-304 ◽  
Author(s):  
Jonathan D. Cohen ◽  
Steven D. Forman ◽  
Todd S. Braver ◽  
B. J. Casey ◽  
David Servan-Schreiber ◽  
...  

2011 ◽  
Vol 467-469 ◽  
pp. 1291-1296
Author(s):  
Wen Wen Bai ◽  
Xin Tian

Working memory is one of important cognitive functions and recent studies demonstrate that prefrontal cortex plays an important role in working memory. But the issue that how neural activity encodes during working memory task is still a question that lies at the heart of cognitive neuroscience. The aim of this study is to investigate neural ensemble coding mechanism via average firing rate during working memory task. Neural population activity was measured simultaneously from multiple electrodes placed in prefrontal cortex while rats were performing a working memory task in Y-maze. Then the original data was filtered by a high-pass filtering, spike detection and spike sorting, spatio-temporal trains of neural population were ultimately obtained. Then, the average firing rates were computed in a selected window (500ms) with a moving step (125ms). The results showed that the average firing rate were higher during workinig memory task, along with obvious ensemble activity. Conclusion: The results indicate that the working memory information is encoded with neural ensemble activity.


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