Abstract
BackgroundThe “dysconnection hypothesis” proposes that schizophrenia is best understood in terms of aberrant brain functional integration and synaptic neuromodulation, which may underlie illness psychopathology and cognitive decline. Impairments in the P300 potential are well documented in schizophrenia and progressive over the years with the illness. We used Dynamic Causal Modeling (DCM) to investigate intrinsic (self-) connectivity in a frontoparietal cortical hierarchy during a P300 task; that is, how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors.MethodsThirty-one patients with schizophrenia (16 first episode and 15 chronic patients) and 31 healthy controls underwent EEG recordings during an auditory oddball paradigm to elicit the P300 response. We studied 16 frontoparietal models (primary auditory, superior parietal, and superior frontal sources) and identified an optimal model of neural coupling, explaining illness ‘diagnosis’ and ‘chronicity’ effects, as well as their interactions with ‘task condition’.ResultsThe winning model included changes in connectivity in all 3 hierarchical levels. Compared to healthy controls, all patients (chronic and first episode) showed decreased self-inhibition – i.e., increased cortical excitability – in right superior parietal gyrus across task conditions. On the other hand, first episode patients – but not chronic – showed in the left frontal and parietal source a reversal of the normal synaptic gain changes in response to targets, relative to standard tones.DiscussionWe confirmed that both subjects with chronic and first episode schizophrenia show a context-independent loss of parietal synaptic gain control. Importantly, in the highest levels of the hierarchy, first episode patients showed a specific abnormal gain modulation pattern in response to task-relevant stimuli not present in those chronically treated. Abnormal synaptic gain is plausibly caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells, and may be independent of illness advance and chronic pharmacological treatment.
Highlights
Transcranial Direct Current Stimulation is a non-invasive neuromodulation technique which uses a weak electric current from electrodes across the scalp to modulate targeted brain areas
Ten schizophrenia patients with auditory hallucination were recruited from the outpatient clinic of Seoul National University Hospital (SNUH)
The anode was placed over the left dorsolateral prefrontal cortex (DLPFC), and the cathode was placed over the left temporo-parietal area (TPA)
Summary
We found no significant differences in vertex-wise gyrification between CHR and HC at either corrected or uncorrected levels (p>0.05). Discussion: Our preliminary findings suggest that CHR subjects do not show whole-brain gyrification abnormalities when compared with healthy subjects. These negative results agree with literature suggesting that cortical convolution might be more affected by neurodevelopmental or genetic factors, and deviations from normal patterns might not be detectable in heterogeneous samples of at-risk subjects wherein the etiology and ultimate prognosis is unknown. In order to better investigate differences in cortical folding and address the role of gyrification as neuroanatomical biomarker for psychosis, future investigations should focus on subgroups within CHR populations (e.g. patients groups defined by basic symptoms, ultra-high risk, or familial risk) in addition to specific analyses of individuals with higher neurodevelopmental (e.g., obstetric complications) or genetic (e.g., polygenic risk) loadings. Junhee Lee*,1, Youngwoo Yoon, Andrea Wijtenburg, Laura Rowland, In Chan Song, Kang Ik Cho, Minah Kim, Tae Young Lee, Jun Soo Kwon4 1Seoul National University Hospital; 2Institute of Human Behavioral Medicine, SNU-MRC; 3Maryland Psychiatric Research Center; 4Seoul National University College of Medicine
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