Left-Dominant Temporal-Frontal Hypercoupling in Schizophrenia Patients With Hallucinations During Speech Perception

Lavigne, Katie M.; Rapin, Lucile; Metzak, Paul D.; Whitman, Jennifer C.; Jung, Kwanghee; Dohen, Marion; Lœvenbruck, Hélène; Woodward, Todd S.

doi:10.1093/schbul/sbu004

Cited by 39 publications

(43 citation statements)

References 47 publications

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“…Our results are in line with functional imaging studies reporting a hypercoupling between frontal and temporal regions in non-psychotic individuals with hallucinations (Diederen et al, 2013) and in AVH + patients with schizophrenia (Lavigne et al, 2015). The WM alterations observed in patients with predominantly negative symptoms could be linked to a high susceptibility of WM tracts to inflammatory mediators in this population (Alba-Ferrara and de Erausquin, 2013).…”

Section: Discussionsupporting

confidence: 92%

Integrity of the arcuate fasciculus in patients with schizophrenia with auditory verbal hallucinations: A DTI-tractography study

Psomiades

Fonteneau

Mondino

et al. 2016

NeuroImage: Clinical

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Auditory verbal hallucinations (AVH) of schizophrenia are associated with a disrupted connectivity between frontal and temporoparietal language areas. We hypothesized that this dysconnectivity is underpinned by white matter abnormalities in the left arcuate fasciculus, the main fiber bundle connecting speech production and perception areas. We therefore investigated the relationship between AVH severity and the integrity of the arcuate fasciculus measured by diffusion tensor imaging (DTI) tractography in patients with schizophrenia.Thirty-eight patients with treatment-resistant schizophrenia were included: 26 presented with daily severe treatment-resistant AVH, 12 reported prominent negative symptoms and no AVH. Fractional anisotropy (FA) was measured along the length of the left and right anterior arcuate fasciculi and severity of AVH was assessed using P3 PANSS item.FA values were significantly higher in the left arcuate fasciculus in patients with AVH than in no AVH patients (F(1,35) = 3.86; p = 0.05). No difference was observed in the right arcuate fasciculus. There was a significant positive correlation between FA value in the left arcuate fasciculus and the severity of AVH (r = 0.36; p = 0.02). No correlation was observed between FA values and PANSS total score suggesting a specific relationship between AVH severity and the left arcuate fasciculus integrity.These results support the hypothesis of a relationship between left frontotemporal connectivity and AVH in patients with schizophrenia and suggest that whilst a disruption of frontotemporal connectivity might be present to ensure the emergence of AVH, more severe anatomical alterations may prevent the occurrence of AVH in patients with schizophrenia.

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Section: Discussionsupporting

confidence: 92%

Integrity of the arcuate fasciculus in patients with schizophrenia with auditory verbal hallucinations: A DTI-tractography study

Psomiades

Fonteneau

Mondino

et al. 2016

NeuroImage: Clinical

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“…shown to be favored at the cell and tissue level by FH interaction with polyanions such as glycosaminoglycans on mammalian cell surfaces (39,43). Thus, to study the effect of FH on C3 proconvertase and C3 convertase formation in conditions mimicking FH interaction with cell surfaces, we performed C3bB(Ni 2ϩ ) and C3bBb(Ni 2ϩ ) formation assays using wells coated with mixtures of C3b and HS (3 or 30 g/ml, Fig.…”

Section: Effect Of Fh On C3bb(ni 2ϩ ) C3 Proconvertase and C3bbb(ni 2mentioning

confidence: 99%

Insights into the Effects of Complement Factor H on the Assembly and Decay of the Alternative Pathway C3 Proconvertase and C3 Convertase

Bettoni

Bresin

Noris

et al. 2016

Journal of Biological Chemistry

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The activated fragment of C3 (C3b) and factor B form the C3 proconvertase (C3bB), which is cleaved by factor D to C3 convertase ( Immunol. 122, 75-81) indicated that the complement alternative pathway regulator factor H (FH) competes with factor B for C3b binding; however, the capability of FH to prevent C3bB assembly has not been formally investigated. Moreover, in the few published studies FH did not favor C3bB dissociation. Whether FH may affect C3bBb formation from C3bB is unknown. We set up user-friendly assays based on combined microplate/Western blotting techniques that specifically detect either C3bB or C3bBb, with the aim of investigating the effect of FH on C3bB assembly and decay and C3bBb formation and decay. We document that FH does not affect C3bB assembly, indicating that FH does not efficiently compete with factor B for C3b binding. We also found that FH does not dissociate C3bB. FH showed a strong C3bBb decay-accelerating activity, as reported previously, and also exerted an apparent inhibitory effect on C3bBb formation. The latter effect was not fully attributable to a rapid FH-mediated dissociation of C3bBb complexes, because blocking decay with properdin and C3 nephritic factor did not restore C3bBb formation. FH almost completely prevented release of the smaller cleavage subunit of FB (Ba), without modifying the amount of C3bB complexes, suggesting that FH inhibits the conversion of C3bB to C3bBb. Thus, the inhibitory effect of FH on C3bBb formation is likely the sum of inhibition of C3bB conversion to C3bBb and of C3bBb decay acceleration. Further studies are required to confirm these findings in physiological cell-based settings.The complement system is a complex network of plasma proteins that cooperate in the defense against foreign microorganisms and in the maintenance of tissue homeostasis (1-3). Interest in the complement system was rekindled in the past decade by accumulating evidence that genetically determined complement dysregulation is involved in two rare devastating disorders of the kidney, atypical hemolytic uremic syndrome (aHUS) 3 and C3 glomerulopathy (C3G) (4 -8), as well as in age-related macular degeneration, the leading cause of blindness for older people (9). Finding that treatment with eculizumab (10), a monoclonal antibody that blocks the formation of terminal complement complex C5b-9, efficiently cured aHUS (11, 12) and C3G (13-15) further corroborated the role of complement in human disease (16).Complement can be triggered by three activation pathways, the classical, the lectin, and the alternative (AP) pathways, all leading to the formation of unstable protease complexes, named C3 convertases, that cleave the inactive central component C3 into C3a and C3b fragments. C3b molecules deposited on pathogens or damaged self-cells provide a molecular platform for the formation of an active AP C3 convertase, C3bBb, which enzymatically generates many more C3b molecules, resulting in a positive feedback loop. Notably, the AP C3 convertase is crucial within the complement ca...

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“…Thus, a clear pattern of increased interaction among the auditory-language and striatal brain regions occurs while patients hallucinate. This finding could explain why AVH are such realistic experiences of speech: increased coordinated activity in this circuitry has been observed during speech perception relative to inner verbal thought (Lavigne et al, 2015). However, the number of symptom capture studies is still low, and more data are needed in this regard.…”

Section: Discussionmentioning

confidence: 88%

“…However, using speech perception, and comparing AVH and NoAVHs patients, another study found increased coordinated activity in the STG and dACC/SMA (Lavigne et al, 2015). The importance of the co-activation of the STG and the dACC/SMA parallels the RS work, and observation of a disconnection is apparently more frequent in the task-based than in the resting-state studies.…”

Section: Functional Connectivity Studiesmentioning

confidence: 99%

Interaction of language, auditory and memory brain networks in auditory verbal hallucinations

Ćurčić‐Blake

Ford

Hubl

et al. 2017

Progress in Neurobiology

181

155

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HighlightsThe language, auditory and memory/limbic networks are of particular relevance for auditory verbal hallucinations.An increased interaction among the auditory-language and striatal brain regions occurs while patients hallucinate.Fronto-temporal connections are often altered in AVH individuals, but there is no consensus regarding increase or decrease.Connections of the interhemispheric auditory pathway are stronger for first episode patients, but they are weaker in chronic patients.The majority of studies support hybrid AVH hypotheses in which all three networks and the striatal network are involved.

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Left-Dominant Temporal-Frontal Hypercoupling in Schizophrenia Patients With Hallucinations During Speech Perception

Cited by 39 publications

References 47 publications

Integrity of the arcuate fasciculus in patients with schizophrenia with auditory verbal hallucinations: A DTI-tractography study

Integrity of the arcuate fasciculus in patients with schizophrenia with auditory verbal hallucinations: A DTI-tractography study

Insights into the Effects of Complement Factor H on the Assembly and Decay of the Alternative Pathway C3 Proconvertase and C3 Convertase

Interaction of language, auditory and memory brain networks in auditory verbal hallucinations

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