Resting-state fMRI mapping of cerebellar functional dysconnections involving multiple large-scale networks in patients with schizophrenia

Chen, Yen-Ling; Tu, Pei-Chi; Lee, Ying-Chiao; Chen, Ying-Shiue; Li, Cheng Ta; Su, Tung‐Ping

doi:10.1016/j.schres.2013.05.029

Cited by 79 publications

(51 citation statements)

References 50 publications

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“…38,39 Functional dysconnectivity is known to be widespread in patients with schizophrenia, and our findings accordingly revealed alterations in the premotor cortex, basal ganglia 40,41 and cerebellum. 42,43 Deficient cerebellar function, for instance, has been associated with high-order cognitive deficits in patients with schizophrenia, as proposed in the "cognitive dysmetria" model of schizophrenia. 44,45 These interpretations, however, mainly consist of an exercise of reverse inference, as no direct association was found between functional dysconnectivity and the severity of either clinical symptoms or cognitive deficits in patients with schizophrenia.…”

Section: A B Cmentioning

confidence: 99%

Altered brain connectivity in patients with schizophrenia is consistent across cognitive contexts

Orban

Desseilles

Mendrek

et al. 2017

JPN

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IntroductionBeyond abnormal activity of focal brain areas, 1 aberrant functional interactions between brain regions are thought to be a core feature of schizophrenia. [2][3][4] Among the current issues related to this influential idea is whether abnormal functional connectivity in patients with schizophrenia is contextdependent. 5 Resting-state fMRI characterizes intrinsic functional brain connectivity, which is guided by endogenous processes and spontaneous thoughts in the absence of any explicit task. 6 Resting-state functional brain imaging in patients with schizophrenia has revealed a widespread functional dysconnectivity between brain regions that are also known to exhibit abnormal levels of activation in relation to impairments in task performance and/or symptomatology. 7-11However, a critical issue with the study of resting-state functional connectivity in patients with schizophrenia is the poor control over the cognitive state of these individuals, which may confound the interpretation of the results. Patients with schizophrenia experience pronounced disturbances of thoughts and differ from controls with regards to their internal mentations and cognitive states during rest. 12 The question of the context-independence of abnormal functional connectivity in patients with schizophrenia may thus be best adressed by characterizing such alterations using well-defined behavioural paradigms. To date, research has focused on determining whether alterations in brain connectivity were further modulated by task complexity in single cognitive domains. 13-15However, to our knowledge, there is no sufficiently powered study that specifically examined commonalities and differences in dysconnectivity across distinct cognitive tasks. 16In the present work, we sought to assess whether the degree of cognitive similarity would impact the results by looking at 2 cognitive domains that strongly differ from one another, emotional versus visuomotor processing. We further distinguished the emotional processing task based on an additional embedded component, either incidental learning or recognition memory. These 3 paradigms were studied with a connectome-wide general linear model analysis. We characterized context-independent effects through commonalities in the main effects of abnormal functional connectivity across the 3 tasks. We evaluated context-dependent effects of abnormal connectivity using interaction analyses that looked for changes in functional connectivity between tasks in patients Correspondence to: P. Orban, CRIUGM, Université de Montréal, 4545 Queen Mary, Montreal, QC H3W 1W5; pierre.orban@criugm.qc.ca Submitted July 13, 2015; Revised Nov. 19, 2015; Accepted Jan. 5, 2016; Early-released Apr. 19, 2016 DOI: 10.1503 Background: Schizophrenia has been defined as a dysconnection syndrome characterized by aberrant functional brain connectivity. Using task-based fMRI, we assessed to what extent the nature of the cognitive context may further modulate abnormal functional brain connectivity. Methods: We analyzed data matc...

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Section: A B Cmentioning

confidence: 99%

Altered brain connectivity in patients with schizophrenia is consistent across cognitive contexts

Orban

Desseilles

Mendrek

et al. 2017

JPN

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“…[28][29][30][31] In part this may reflect the fact that until recently, the involvement of the cerebellum in nonmotor functions was not well-appreciated, perhaps making it a potentially less attractive target for work trying to understand the neural basis of cognitive and affective, as well as motor deficits in schizophrenia. However, there is now strong evidence that the cerebellum plays important roles in nonmotor cognitive and affective functions 32-37 though the precise mechanistic contributions that the cerebellum makes to these functions remains to be elucidated.…”

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confidence: 99%

“…Further, several previous studies have found evidence of altered connectivity between the thalamus and the cerebellum. [28][29][30][31]59 However, much remains to be understood in terms of the nature of cerebellar and thalamic connectivity dysfunction in schizophrenia and related psychotic disorders. The 3 articles in this special section on thalamic and cerebellar functional and structure and connectivity in psychosis are contributions that attempt to address some of the critical unanswered questions in this domain.…”

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confidence: 99%

Cerebellar-Thalamic Connectivity in Schizophrenia

Deanna

2014

Schizophrenia Bulletin

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The literature on alterations in brain structure and function in schizophrenia, particularly in relationship to impairments in cognitive, motor, and affective functions, has made it increasingly clear that changes in the function of a single brain region cannot explain the range of impairments seen in this illness. [1][2][3][4] This realization has led to a surgence of interest in studies examining neurobiological changes in schizophrenia from the perspective of brain networks and connections among brain regions and networks, with a particular focus on neural circuits known to work together to support sensory, cognitive, and emotional processes. 5 This shift in focus is consistent with long-standing hypotheses about schizophrenia as a "dysconnection" syndrome, where impairments in cognition and behavior occur because of a failure of coordinated action across multiple brain regions. As many researchers have noted, 6 versions of this hypothesis were put forth as early as the work of Wernicke 7 and Bleuler. 8 Further, theories about abnormalities in connections among brain regions have also played a central role in more recent theories of the pathophysiology of schizophrenia. For example, one such prominent theory, put forth by Andreasen and colleagues, 9 suggested that schizophrenia involves a disruption in the integration of cortical-subcortical-cerebellar circuits, a hypothesis termed "cognitive dysmetria." Although the cognitive dysmetria hypothesis suggested the critical involvement of cerebellar, striatal, and thalamic circuits as well as cortical circuits, the majority of the work on structural and functional connectivity deficits in schizophrenia has focused on cortical and striatal dysfunction and disconnection, 10-14 with the need for additional work on the thalamus. Alterations in the structure [15][16][17] and function of the thalamus are prominent in the schizophrenia literature. 2,[18][19][20][21] As shown in anatomical studies of primates, the thalamus is topographically organized into parallel pathways connecting specific thalamic nuclei to different regions of cortex brain regions, 22 helping to form parallel loops for various types of information processing between subcortical and cortical regions. A growing number of studies have examined deficits in thalamic connectivity in schizophrenia, with several studies finding alterations in the functional connectivity between the thalamus and regions in the prefrontal in individuals with schizophrenia, 23-27 consistent with the known anatomical connectivity of the thalamus.Surprisingly few studies have examined cerebellar dysconnectivity in schizophrenia, or abnormalities in cerebellar-thalamic connections. [28][29][30][31] In part this may reflect the fact that until recently, the involvement of the cerebellum in nonmotor functions was not well-appreciated, perhaps making it a potentially less attractive target for work trying to understand the neural basis of cognitive and affective, as well as motor deficits in schizophrenia. However, there is now str...

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“…The bilateral cerebellum showed reduced functional connectivity to some regions, such as bilateral middle cingulate cortex and right paracentral lobule including left middle temporal gyrus, right thalamus, and bilateral cerebellum in schizophrenia patients in an fMRI and DTI study [78]. Another fMRI study showed that cerebellar-thalamic disconnections were the most prominent and were common to all cognitive-related networks, whereas cortico-cerebellar connectivity involved both an increase and decrease in functional connectivity, and depended more on the nature of the specific network [80]. These reports suggested that the functional disconnection and damaged anatomical connectivity between the cerebellum and other regions was related to dysfunction in schizophrenia.…”

Section: Cerebellummentioning

confidence: 99%

Females with schizophrenia have abnormal functional cortical connectivity in the gamma frequency during an auditory oddball task using magnetoencephalography

Fujimoto¹,

Okumura²,

Takeuchi³

et al. 2014

OJPsych

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We studied differences in imaginary coherence (IC) of the gamma band between brain regions of female schizophrenia patients during the auditory oddball task using magnetoencephalography (MEG). Subjects were 12 right-handed female schizophrenia patients, who were evaluated by the Positive and Negative Syndrome Scales (PANSS). Functional connectivity during an auditory oddball task was reconstructed in low gamma (30 -50 Hz) and high gamma (50 -100 Hz and 100 -150 Hz) bands, and represented by IC using seeds determined by the significant oscillatory power changes obtained by event-related synchronization (ERS) and event-related desynchronization (ERD) power measurements. Gamma ERS (30 -50 Hz) power was decreased in the left precuneus at 500 -750 ms and in the right precuneus at 750 -1000 ms. IC in the gamma band (50 -100 Hz) was decreased between the right precuneus (seed) and right paracentral lobule (target) and between the right precuneus and right hypothalamus at 0 -250 ms. IC in the gamma band (100 -150 Hz) was increased between the left precuneus and right cuneus (Brodmann area 7) at 250 -500 ms, between the left precuneus and right culmen at 500 -750 ms, and between the left precuneus and right cuneus (Brodmann area 17), between the left precuneus and right posterior cingulate cortex, and between the left precuneus and right caudate nucleus at 750 -1000 ms. In the high gamma band (50 -100 Hz) at 0 -250 ms, significant positive correlations were shown between IC and conceptual disorganization in PANSS scores, between IC and unusual thought content score, and between IC and positive scale score. IC within the high gamma band in female schizophrenia patients showed two types of functional disconnection, intrahemispheric and interhemispheric. IC between the right or left precuneus and other specific cortical areas showed dysfunction, suggesting that the parietal lobe plays an important role in dysfunction in connectivity in the gamma band during the oddball task.

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Resting-state fMRI mapping of cerebellar functional dysconnections involving multiple large-scale networks in patients with schizophrenia

Cited by 79 publications

References 50 publications

Altered brain connectivity in patients with schizophrenia is consistent across cognitive contexts

Altered brain connectivity in patients with schizophrenia is consistent across cognitive contexts

Cerebellar-Thalamic Connectivity in Schizophrenia

Females with schizophrenia have abnormal functional cortical connectivity in the gamma frequency during an auditory oddball task using magnetoencephalography

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