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Journal ArticleDOI

Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network?

TL;DR: Patients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task, including an area in the anterior prefrontal/anterior cingulate cortex that corresponds to one of the two midline components of the ‘default mode network’ implicated in functions related to maintaining one's sense of self.
Abstract: BackgroundFunctional imaging studies using working memory tasks have documented both prefrontal cortex (PFC) hypo- and hyperactivation in schizophrenia. However, these studies have often failed to consider the potential role of task-related deactivation.MethodThirty-two patients with chronic schizophrenia and 32 age- and sex-matched normal controls underwent functional magnetic resonance imaging (fMRI) scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups.ResultsThe controls showed activation in the expected frontal regions. There were also clusters of deactivation, particularly in the anterior cingulate/ventromedial PFC and the posterior cingulate cortex/precuneus. Compared to the controls, the schizophrenic patients showed reduced activation in the right dorsolateral prefrontal cortex (DLPFC) and other frontal areas. There was also an area in the anterior cingulate/ventromedial PFC where the patients showed apparently greater activation than the controls. This represented a failure of deactivation in the schizophrenic patients. Failure to activate was a function of the patients' impaired performance on the n-back task, whereas the failure to deactivate was less performance dependent.ConclusionsPatients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task. The area of failure of deactivation is in the anterior prefrontal/anterior cingulate cortex and corresponds to one of the two midline components of the ‘default mode network’ implicated in functions related to maintaining one's sense of self.
Citations
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Journal ArticleDOI
TL;DR: These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.
Abstract: Increased activation of the dorsolateral prefrontal cortex region during working memory manipulation is a compensatory mechanism in at-risk individuals.

29 citations

Journal ArticleDOI
TL;DR: Volumetric deficits in the default network and in the DLPFC may be related to familial diathesis in schizophrenia and to functional connectivity abnormalities in those at familial risk.

29 citations

Journal ArticleDOI
TL;DR: There is an elevated gamma activity unrelated to task processing over regions coherent with the DMN topography in patients with schizophrenia, and the same type of gamma activity over frontal regions is inversely related to performance in tasks with high involvement in these frontal areas.
Abstract: BackgroundBrain activity is less organized in patients with schizophrenia than in healthy controls (HC). Noise power (scalp-recorded electroencephalographic activity unlocked to stimuli) may be of use for studying this disorganization.MethodFifty-four patients with schizophrenia (29 minimally treated and 25 stable treated), 23 first-degree relatives and 27 HC underwent clinical and cognitive assessments and an electroencephalographic recording during an oddball P300 paradigm to calculate noise power magnitude in the gamma band. We used a principal component analysis (PCA) to determine the factor structure of gamma noise power values across electrodes and the clinical and cognitive correlates of the resulting factors.ResultsThe PCA revealed three noise power factors, roughly corresponding to the default mode network (DMN), frontal and occipital regions respectively. Patients showed higher gamma noise power loadings in the first factor when compared to HC and first-degree relatives. In the patients, frontal gamma noise factor scores related significantly and inversely to working memory and problem-solving performance. There were no associations with symptoms.ConclusionsThere is an elevated gamma activity unrelated to task processing over regions coherent with the DMN topography in patients with schizophrenia. The same type of gamma activity over frontal regions is inversely related to performance in tasks with high involvement in these frontal areas. The idea of gamma noise as a possible biological marker for schizophrenia seems promising. Gamma noise might be of use in the study of underlying neurophysiological mechanisms involved in this disease.

29 citations


Cites background from "Failure to deactivate in the prefro..."

  • ...…such as the default mode network (DMN), including, for example, medial frontal, posterior cingulate, lateral parietal and hippocampal areas (Spreng et al. 2009), do not decrease their amount of activity as expected during the performance of a cognitive task (Pomarol-Clotet et al. 2008)....

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  • ...In addition, the regions that should increase their activity with the task do not activate properly (Pomarol-Clotet et al. 2008; Whitfield-Gabrieli et al. 2009; Ongur et al. 2010)....

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  • ...2009), do not decrease their amount of activity as expected during the performance of a cognitive task (Pomarol-Clotet et al. 2008)....

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Journal ArticleDOI
TL;DR: An increased connectivity in patients within major nodes of the default mode network (DMN)—a network known to be involved in the evaluation of internal mental states—is demonstrated, indicating an increased activity of internal, self-related processing at the expense of a normal responsiveness toward external rewards and incentives.
Abstract: Objective: Obsessive-compulsive disorder (OCD) is characterized by anxiety-provoking, obsessive thoughts (i.e., obsessions) which patients react to with compulsive behaviors (i.e., compulsions). Due to the transient feeling of relief following the reduction of obsession-induced anxiety, compulsions are often described as relieving or even rewarding. Several studies investigated functional activation during reward processing in OCD, but findings are heterogeneous up to now and little is known about potential alterations in functional connectivity. Method: Against this background we studied OCD patients (n = 44) and healthy controls (n = 37) during the receipt of monetary reward by assessing both activation and functional connectivity. Results: Patients showed a decreased activation in several frontal regions and the posterior cingulate (PCC, BA31) together with a stronger connectivity between the PCC and the vmPFC (BA10). Conclusion: Present findings demonstrate an increased connectivity in patients within major nodes of the default mode network (DMN)-a network known to be involved in the evaluation of internal mental states. These results may indicate an increased activity of internal, self-related processing at the expense of a normal responsiveness toward external rewards and incentives. This, in turn, may explain the constant urge for additional reinforcement and patients' inability to inhibit their compulsive behaviors.

29 citations


Cites background from "Failure to deactivate in the prefro..."

  • ...Studies also reported that although the DMN is active during rest, certain parts of it such as vmPFC, ACC, precuneus and PCC are deactivated during performing various cognitive tasks (47, 48)....

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Journal ArticleDOI
TL;DR: Gamma noise power may represent a useful and non-invasive tool for studying brain dysfunction in psychotic illness and an inefficient activation pattern in schizophrenia is suggested.
Abstract: Background There is an increasing consideration for a disorganized cerebral activity in schizophrenia, perhaps relating to a synaptic inhibitory deficit in the illness. Noise power (scalp-recorded electroencephalographic activity unlocked to stimuli) may offer a non-invasive window to assess this possibility. Methods 29 minimally-treated patients with schizophrenia (of which 17 were first episodes) and 27 healthy controls underwent clinical and cognitive assessments and an electroencephalographic recording during a P300 paradigm to calculate signal-to-noise ratio and noise power magnitudes in the theta and gamma bands. Results In comparison to controls, a significantly higher gamma noise power was common to minimally-treated and first episode patients over P3, P4, T5 and Fz electrode sites. Those high values were directly correlated to negative symptom severity and inversely correlated to verbal memory scores in the patients. There were no differences in signal-to-noise ratio magnitudes among the groups. Gamma noise power at Fz discriminated significantly between patients and controls. No significant differences were found in theta noise power or in gamma noise power over the other electrode sites between the groups of patients and controls. Limitations We have not assessed phase-locked and non-phase locked power changes, a complementary approach that may yield useful information. Conclusions Gamma noise power may represent a useful and non-invasive tool for studying brain dysfunction in psychotic illness. These results suggest an inefficient activation pattern in schizophrenia.

28 citations


Cites background from "Failure to deactivate in the prefro..."

  • ..., 2011), the impaired taskrelated deactivation of DMN in schizophrenia (Pomarol-Clotet et al., 2008) could be accompanied by higher gamma activity during a cognitive task on the correspondingDMN regions....

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  • ...…oscillations and modulation of cerebral blood flow (Niessing et al., 2005; Scheeringa et al., 2011), the impaired taskrelated deactivation of DMN in schizophrenia (Pomarol-Clotet et al., 2008) could be accompanied by higher gamma activity during a cognitive task on the correspondingDMN regions....

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References
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Journal ArticleDOI
TL;DR: A review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB) on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data.

12,097 citations

Book
01 Jan 1966
TL;DR: This book discusses statistical decision theory and sensory processes in signal detection theory and psychophysics and describes how these processes affect decision-making.
Abstract: Book on statistical decision theory and sensory processes in signal detection theory and psychophysics

11,820 citations


"Failure to deactivate in the prefro..." refers methods in this paper

  • ...The behavioural measure used was the signal detection theory index of sensitivity, dk (Green & Swets, 1966)....

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Journal ArticleDOI
TL;DR: A baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF is identified, suggesting the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
Abstract: A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

10,708 citations


"Failure to deactivate in the prefro..." refers background or result in this paper

  • ...This interpretation is supported by (a) the spatial correspondence between this area and that identified in studies of the default mode network (e.g. Gusnard et al. 2001 ; Raichle et al. 2001), and (b) the fact that the controls in our study showed deactivation in the same area while performing the n-back task....

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  • ...the inferior parietal cortex and parts of the temporal lobe including the hippocampus), these are thought to constitute a ‘default mode network’ that is active at rest or when engaging in ‘stimulus-independent’ thought, but which undergoes a reduction in activity when attentiondemanding goal-directed cognition needs to be undertaken (Gusnard et al. 2001 ; Raichle et al. 2001 ; Greicius et al. 2003 ; Gusnard, 2005)....

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  • ...…is supported by (a) the spatial correspondence between this area and that identified in studies of the default mode network (e.g. Gusnard et al. 2001 ; Raichle et al. 2001), and (b) the fact that the controls in our study showed deactivation in the same area while performing the n-back task....

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  • ...…a ‘default mode network’ that is active at rest or when engaging in ‘stimulus-independent’ thought, but which undergoes a reduction in activity when attentiondemanding goal-directed cognition needs to be undertaken (Gusnard et al. 2001 ; Raichle et al. 2001 ; Greicius et al. 2003 ; Gusnard, 2005)....

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Journal ArticleDOI
TL;DR: This study constitutes, to the knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network.
Abstract: Functional imaging studies have shown that certain brain regions, including posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently show greater activity during resting states than during cognitive tasks. This finding led to the hypothesis that these regions constitute a network supporting a default mode of brain function. In this study, we investigate three questions pertaining to this hypothesis: Does such a resting-state network exist in the human brain? Is it modulated during simple sensory processing? How is it modulated during cognitive processing? To address these questions, we defined PCC and vACC regions that showed decreased activity during a cognitive (working memory) task, then examined their functional connectivity during rest. PCC was strongly coupled with vACC and several other brain regions implicated in the default mode network. Next, we examined the functional connectivity of PCC and vACC during a visual processing task and show that the resultant connectivity maps are virtually identical to those obtained during rest. Last, we defined three lateral prefrontal regions showing increased activity during the cognitive task and examined their resting-state connectivity. We report significant inverse correlations among all three lateral prefrontal regions and PCC, suggesting a mechanism for attenuation of default mode network activity during cognitive processing. This study constitutes, to our knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network. Our findings also provide insight into how this network is modulated by task demands and what functions it might subserve.

6,025 citations


"Failure to deactivate in the prefro..." refers background in this paper

  • ...the inferior parietal cortex and parts of the temporal lobe including the hippocampus), these are thought to constitute a ‘default mode network’ that is active at rest or when engaging in ‘stimulus-independent’ thought, but which undergoes a reduction in activity when attentiondemanding goal-directed cognition needs to be undertaken (Gusnard et al. 2001 ; Raichle et al. 2001 ; Greicius et al. 2003 ; Gusnard, 2005)....

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  • ...…a ‘default mode network’ that is active at rest or when engaging in ‘stimulus-independent’ thought, but which undergoes a reduction in activity when attentiondemanding goal-directed cognition needs to be undertaken (Gusnard et al. 2001 ; Raichle et al. 2001 ; Greicius et al. 2003 ; Gusnard, 2005)....

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Journal ArticleDOI
TL;DR: This work explores the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations, including the manner in which a baseline is defined and the implications of such a baseline for the understanding ofbrain function.
Abstract: Functional brain imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.

3,285 citations


"Failure to deactivate in the prefro..." refers background or result in this paper

  • ...Two studies, however, had opposite results to ours : Harrison et al. (2007) found that 12 schizophrenic patients showed greater deactivation of both the anterior and posterior cingulate midline loci than in 14 controls during a task requiring response suppression. Using an auditory oddball task, Garrity et al. (2007) found that 21 patients with schizophrenia showed a complex pattern of abnormality compared to 22 normal controls, but deactivation was increased in the anterior cingulate/ superior medial frontal gyri. The remaining two studies (Bluhm et al. 2007 ; Zhou et al. 2007) focused exclusively on connectivity, and cannot be directly compared with our findings. Of note, Kennedy et al. (2006) have also documented default mode network dysfunction in adult high-functioning autisticspectrum patients, although they found that the failure of deactivation affected both the anterior and posterior midline loci of the network....

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  • ...Gusnard et al. 2001 ; Raichle et al. 2001), and (b) the fact that the controls in our study showed deactivation in the same area while performing the n-back task. Menzies et al. (2007) also interpreted the failure to deactivate they found in schizophrenia in terms of default mode network dysfunction. However, as neither we nor Menzies et al. (2007) set out specifically to examine default mode network function in schizophrenia, such an interpretation should be regarded as provisional....

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  • ...Two studies, however, had opposite results to ours : Harrison et al. (2007) found that 12 schizophrenic patients showed greater deactivation of both the anterior and posterior cingulate midline loci than in 14 controls during a task requiring response suppression. Using an auditory oddball task, Garrity et al. (2007) found that 21 patients with schizophrenia showed a complex pattern of abnormality compared to 22 normal controls, but deactivation was increased in the anterior cingulate/ superior medial frontal gyri....

    [...]

  • ...the inferior parietal cortex and parts of the temporal lobe including the hippocampus), these are thought to constitute a ‘default mode network’ that is active at rest or when engaging in ‘stimulus-independent’ thought, but which undergoes a reduction in activity when attentiondemanding goal-directed cognition needs to be undertaken (Gusnard et al. 2001 ; Raichle et al. 2001 ; Greicius et al. 2003 ; Gusnard, 2005)....

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  • ...Gusnard et al. (2001) have also reviewed various lines of evidence that suggest that different parts of the default mode network are involved in gathering information about the world, orienting oneself to salient environmental stimuli, theory of mind and self-representation....

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This represented a failure of deactivation in the schizophrenic patients.