Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations.
Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital-cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH.
Centre of Excellence in Biomedical Image (CEIB), Regional Ministry of Health in the Valencia Region (CS), C./Micer Masco nº 31-33, Valencia 46010, Spain ; Brain Connectivity Lab, Prince Felipe Research Centre (CIPF), C./Eduardo Primo Yúfera (Científic), nº 3, Valencia 46012, Spain ; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISC III. Avda. Blasco Ibáñez 15, Valencia 46010, Spain ; GIBI230 (Grupo de Investigación Biomédica en Imagen, CIBER-BBN), Instituto de Investigación Sanitaria (IIS), Spain.
Maria
M
de la Iglesia-Vaya
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISC III. Avda. Blasco Ibáñez 15, Valencia 46010, Spain ; Department of Psychiatry, Clinic Hospital, Avda. Blasco Ibáñez, 17, Valencia 46010, Spain.
Maria José
MJ
Escartí
Centre for Biomaterials and Tissue Engineering, Universidad Politécnica de Valencia, Valencia, Spain.
Jose
J
Molina-Mateo
Department of Radiology, Faculty of Medicine of Valencia, Avda. Blasco Ibáñez, 15, Valencia 46010, Spain ; GIBI230 (Grupo de Investigación Biomédica en Imagen, CIBER-BBN), Instituto de Investigación Sanitaria (IIS), Spain.
Luis
L
Martí-Bonmatí
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISC III. Avda. Blasco Ibáñez 15, Valencia 46010, Spain ; Department of Psychobiology, Faculty of Psychology. University of Valencia, Avda. Blasco Ibáñez, 21, Valencia 46010, Spain.
Marien
M
Gadea
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA ; NYU Langone Medical Center, New York, NY, USA.
Francisco Xavier
FX
Castellanos
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISC III. Avda. Blasco Ibáñez 15, Valencia 46010, Spain ; Department of Psychiatry, Clinic Hospital, Avda. Blasco Ibáñez, 17, Valencia 46010, Spain.
Eduardo J
EJ
Aguilar García-Iturrospe
Instituto de Aplicaciones de las Tecnologías de la Información y de las Comunicaciones Avanzadas (ITACA), Universidad Politécnica de Valencia, Camino de Vera, s/n 46022, Valencia, Spain.
Montserrat
M
Robles
Department of Radiology, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
Bharat B
BB
Biswal
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISC III. Avda. Blasco Ibáñez 15, Valencia 46010, Spain ; Department of Psychiatry, Clinic Hospital, Avda. Blasco Ibáñez, 17, Valencia 46010, Spain.
Julio
J
Sanjuan
D000161:Acoustic Stimulation / Q000379:methods; D000328:Adult; D001303:Auditory Cortex / Q000503:physiopathology; D002531:Cerebellum / Q000503:physiopathology; D006212:Hallucinations / Q000175:diagnosis* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D012559:Schizophrenia / Q000175:diagnosis* / Q000503:physiopathology*; D013702:Temporal Lobe / Q000503:physiopathology; D055815:Young Adult
AH, auditory hallucinations; Auditory hallucinations; BOLD, blood oxygenation level dependent; BPRS, Brief Psychiatric Rating Scale; CCTC, cortico-cerebellar–thalamic–cortical; Cerebellum; CoI, component of interest; Effective connectivity; Functional connectivity; GCCA, Granger causal connectivity analysis; ICA, independent component analysis; ICA-TC, ICA-time course; MRI, functional magnetic resonance imaging; MVAR, multivariate autoregression; PANSS, Positive and Negative Syndrome Scale; PSYRATS, Psychotic Symptom Rating Scale; SPM, statistical parametric maps; Schizophrenia; Synchrony