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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: Connectivity between prefrontal networks associated with self‐referential processing and regions sensitive to externally‐generated stimuli was modulated by participants’ ability to accurately assess the proportion of tones belonging to self versus other, shedding additional light on the neural mechanisms of agency.

3 citations


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

  • ...For example, the MPFC has previously been associated with the retrieval of autobiographical memory (Svoboda et al., 2006), remembering self- versus externally-generated words (Vinogradov et al., 2008), self-referential episodes (Zysset et al., 2002) and self-knowledge (reviewed in Van Overwalle, 2009)....

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  • ...Similarly, reduced task-related deactivation of the MPFC (Whitfield-Gabrieli et al., 2009; Pomarol-Clotet et al., 2008) and over-activation of this region during rest (Unschuld et al., 2014) has been associated with cognitive deficits related to schizophrenia....

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  • ...Imaging studies also suggest that the MPFC is a key substrate for social cognition (Gallagher et al., 2000; Goel, 1995), integrating self-other information across time (reviewed in Van Overwalle, 2009)....

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  • ...Similarly, reduced task-related deactivation of the MPFC (Whitfield-Gabrieli et al., 2009; Pomarol-Clotet et al., 2008) and over-activation of this region during rest (Unschuld et al....

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  • ...Given the findings implicating IC10 but not IC1, it may be that self-other action attribution is related to self-monitoring mediated by increased MPFC connectivity during rest rather than to processing the effects of other's actions....

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Book ChapterDOI
01 Jan 2019
TL;DR: Though a large number of studies have reported differences between patients with psychotic disorders and healthy controls in structural and functional neuroimaging measures, only few results are robust and consistent, and machine-learning algorithms might represent a good opportunity for the progress in this field.
Abstract: Different medical disciplines have adopted biomarkers in order to establish a diagnosis and predict clinical and functional outcome of a disease. In psychiatry, the search for biomarkers could lead to substantial improvement in mental disorder diagnosis and care. Different neuroimaging techniques have contributed to improve our understanding of brain structure and functioning in patients with psychotic disorders. However, though a large number of studies have reported differences between patients with psychotic disorders and healthy controls in structural and functional neuroimaging measures, only few results are robust and consistent. In addition, so far, even robust and consistent findings have differences at group level, which so far did not translate into applications at the individual level. The heterogeneity of psychotic disorders, the use of medications, and the infrequent replication of findings in independent patient cohorts from different centers have limited the identification of reliable neuroimaging biomarkers for diagnosis and outcome prediction of psychotic disorders. Machine-learning algorithms might represent a good opportunity for the progress in this field.

2 citations

Journal ArticleDOI
TL;DR: Increased gamma NP correlated with higher negative symptom scores in the schizophrenia group, but not with cognitive impairment in any of the groups of patients, and the correlation between gamma NP values and chronicity, symptoms, and cognition was not found.
Abstract: Background and Objectives “Noise power” (NP) is a measure that allows the assessment of the fast-firing synchronization of neural oscillations. We aimed to replicate higher gamma NP values in frontal and midline regions in patients with schizophrenia and re-evaluate its specificity to this disorder. We also aimed to assess the relationship of higher gamma NP values with drug treatment, chronicity, cognition and symptoms. Methods Gamma NP values were obtained from electroencephalograms recorded during an oddball paradigm from 29 patients with schizophrenia, 27 with bipolar disorder and 36 healthy controls. We compared these values between the groups to evaluate the specificity to diagnosis. Altered gamma NP values were compared between the patients who had and had not received different treatments to assess the relationship with drug treatment. We also analyse the correlation between gamma NP values and chronicity, symptoms, and cognition. Results Compared to controls, patients with schizophrenia presented increased gamma NP values in frontal and parietal midline regions, while bipolar patients showed increased gamma NP in the left frontal region. There was no significant relationship between drug treatment or chronicity with altered values. Increased gamma NP correlated with higher negative symptom scores in the schizophrenia group, but not with cognitive impairment in any of the groups of patients. Conclusions We replicated an increase in gamma NP in patients with schizophrenia and found that this alteration was also present in a milder form in bipolar patients. These alterations seem to be independent of pharmacological treatment and illness duration.

2 citations

Journal ArticleDOI
TL;DR: In this article, the benefits of NIRS for assessing the prefrontal pathophysiology during the resting state and some methodological issues to be noted while analyzing cerebral blood flow using near-infrared spectroscopy.
Abstract: Spontaneous brain activity occurs at rest, as represented by the default mode network. A resting paradigm is suitable for investigating brain function of patients with psychiatric diseases who may have difficulties adhering to goal-oriented tasks. Evidence accumulated in neuroimaging studies using functional magnetic resonance imaging has shown that the resting cerebral blood flow is impaired in psychiatric diseases. Near-infrared spectroscopy (NIRS), a simple neuroimaging modality, is an optimal tool for the resting paradigm, because it can offer a comfortable environment for measurement. Recent NIRS studies have demonstrated some promising data of altered resting activity in the prefrontal cortex of patients with schizophrenia, which may be exploited to develop further applications of NIRS in clinical psychiatry. Based on these findings, we emphasize the benefits of NIRS for assessing the prefrontal pathophysiology during the resting state and some methodological issues to be noted while analyzing cerebral blood flow using NIRS; moreover, we focus on interpreting these changes based on the complex nature of the spontaneous brain activity during resting state.

2 citations

Posted ContentDOI
03 Mar 2018-bioRxiv
TL;DR: The findings show that inter-individual differences in ANS activity are strongly linked to task-induced deactivation, and suggest that deactivation is a multifaceted construct potentially linked to ANS control, because distinct ANS measures correlate with deactivation in different regions.
Abstract: Neuroimaging research has shown that different cognitive tasks induce relatively specific activation patterns, as well as less task-specific deactivation patterns. Here we examined whether individual differences in Autonomic Nervous System (ANS) activity during task performance correlate with the magnitude of task-induced deactivation. In an fMRI study, participants performed a continuous mental arithmetic task in a task/rest block design, while undergoing combined fMRI and heart/respiration rate acquisitions using photoplethysmograph and respiration belt. As expected, task performance increased heart-rate and reduced the RMSSD, a cardiac index related to vagal tone. Across participants, higher heart rate during task was linked to increased activation in fronto-parietal regions, as well as to stronger deactivation in ventromedial prefrontal regions. Respiration frequency during task was associated with similar patterns, but in different regions than those identified for heart-rate. Finally, in a large set of regions, almost exclusively limited to the Default Mode Network, lower RMSSD was associated with greater deactivation, and furthermore, the vast majority of these regions were task-deactivated at the group level. Together, our findings show that inter-individual differences in ANS activity are strongly linked to task-induced deactivation. Importantly, our findings suggest that deactivation is a multifaceted construct potentially linked to ANS control, because distinct ANS measures correlate with deactivation in different regions. We discuss the implications for current theories of cortical control of the ANS and for accounts of deactivation, with particular reference to studies documenting a "failure to deactivate" in multiple clinical states.

2 citations


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

  • ...However, the interpretation of this finding has been unclear – deactivation in schizophrenia is not linked to task performance (Pomarol-Clotet et al., 2008) and for this reason, FTD in this population has been suggested to be generally related to the disease itself, perhaps indicating use of…...

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  • ...A good example is seen in research on schizophrenia, where several studies had reported a “failure to deactivate” (FTD) in schizophrenic populations (see Pomarol-Clotet et al., 2008)....

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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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How long can a schizophrenic go without sleep?

This represented a failure of deactivation in the schizophrenic patients.