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BACKGROUND AND HYPOTHESIS: Despite accounting for significant disease morbidity in schizophrenia, the neuropathological basis of negative symptoms remains poorly understood and options for treatment limited. Our recent study identified robust associations between diminished auditory cortex (AC) dynamic range and social functioning impairments and negative symptoms in first episode psychosis (FESz). The current investigation examined the progression of these relationships 4-8 months from baseline testing. STUDY DESIGN: Twenty-six FESz and 38 healthy controls (HC) were tested at baseline and follow-up. Magnetoencephalography (MEG) was recorded during binaural presentation of tones (75, 80, and 85 dB). Assessments included the MATRICS cognitive consensus battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS) and the Positive and Negative Syndrome Scale. STUDY RESULTS: Overall, FESz exhibited a blunted response to increasing tone intensity relative to HC. While this deficit did not change over time at the group level, recovery of right hemisphere AC dynamic range (85-75 dB response) among FESz individuals was associated with reductions in negative symptoms (ρ = -0.50). Diminished dynamic range was also associated with impaired GFS (ρ = 0.65), GFR (ρ = 0.51), and MCCB (ρ = 0.49) at baseline and increased negative symptoms at baseline (ρ = -0.53) and follow-up (ρ = -0.51). CONCLUSION: Despite persistent dynamic range impairment in FESz as a group, individual recovery of this AC response property was associated with significant reduction in negative symptoms. Identification of a functional neural deficit that tracts progression of negative symptoms during a critical period for disease modification is essential to the management of these devastating and historically treatment refractory symptoms.
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Transtornos Psicóticos , Esquizofrenia , Humanos , Transtornos Psicóticos/complicações , Ajustamento SocialRESUMO
BACKGROUND: Pitch and duration mismatch negativity (pMMN/dMMN) are related to left Heschl's gyrus gray matter volumes in first-episode schizophrenia (FESz). Previous methods were unable to delineate functional subregions within and outside Heschl's gyrus. The Human Connectome Project multimodal parcellation (HCP-MMP) atlas overcomes this limitation by parcellating these functional subregions. Further, MMN has generators in inferior frontal cortex, and therefore, may be associated with inferior frontal cortex pathology. With the novel use of the HCP-MMP to precisely parcellate auditory and inferior frontal cortex, we investigated relationships between gray matter and pMMN and dMMN in FESz. METHODS: pMMN and dMMN were measured at Fz from 27 FESz and 27 matched healthy controls. T1-weighted MRI scans were acquired. The HCP-MMP atlas was applied to individuals, and gray matter volumes were calculated for bilateral auditory and inferior frontal cortex parcels and correlated with MMN. FDR correction was used for multiple comparisons. RESULTS: In FESz only, pMMN was negatively correlated with left medial belt in auditory cortex and area 47L in inferior frontal cortex. Duration MMN negatively correlated with the following auditory parcels: left medial belt, lateral belt, parabelt, TA2, and right A5. Further, dMMN was associated with left area 47L, right area 44, and right area 47L in inferior frontal cortex. CONCLUSIONS: The novel approach revealed overlapping and distinct gray matter associations for pMMN and dMMN in auditory and inferior frontal cortex in FESz. Thus, pMMN and dMMN may serve as biomarkers of underlying pathological deficits in both similar and slightly different cortical areas.
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BACKGROUND: Functional connectivity abnormalities between Broca's and Wernicke's areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca's and Wernicke's areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca's-Wernicke's-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP. METHODS: White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI). RESULTS: FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different. CONCLUSIONS: Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca's and Wernicke's areas. Other bilateral tracts' gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers.
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Transtornos Psicóticos Afetivos/patologia , Percepção Auditiva , Área de Broca/patologia , Corpo Caloso/patologia , Alucinações/patologia , Transtornos Psicóticos/patologia , Putamen/patologia , Esquizofrenia/patologia , Área de Wernicke/patologia , Substância Branca/patologia , Adolescente , Adulto , Transtornos Psicóticos Afetivos/diagnóstico por imagem , Área de Broca/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Alucinações/diagnóstico por imagem , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Transtornos Psicóticos/diagnóstico por imagem , Putamen/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Área de Wernicke/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
Impairments in early-stage visual processing are observed in chronic psychosis. However, their presence, localization within the brain, and contribution to cognitive symptoms remain less well established early in disease course. The present study utilized magnetoencephalography (MEG) to examine sensory responses within primary visual cortex (V1). MEG was recorded from 38 individuals diagnosed with a schizophrenia spectrum illness at first psychotic episode (FESz) and 38 matched healthy controls (HC) during visual search tasks. The inverse solution for cortical activity contributing to the M100 visual evoked field was derived. Task performance and V1 activation were compared between groups. FESz exhibited a reduced V1 response relative to HC. This group deficit, however, was selective for the left hemisphere (LH). A similar interaction was observed for response time with FESz exhibiting slower responses to right visual field targets, a difference not observed among HC. Among FESz, larger LH V1 activity was associated with larger hallucination subscale scores on the Scale for the Assessment of Positive Symptoms. Early-stage visual processing deficits localized to V1 are present at disease onset in the schizophrenia spectrum. This impairment appears to be restricted to the LH, consistent with previous reports detailing a predominantly LH disease process in early psychosis, and activity within this region was associated with an increased experience of hallucinations. These findings detail the cortical responses contributing to visual processing impairments and their relationship with symptoms at disease onset, advancing our understanding of their developmental trajectory over the course of psychotic illness.