Functional connectivity between parietal and temporal lobes mediates internal forward models during speech production.

Internal forward models hypothesize functional links between motor and sensory systems for predicting the consequences of actions. Recently, the cascaded theory proposes that somatosensory estimation in the inferior parietal lobe (IPL) can be a relay computational structure, converting motor signals into predictions of auditory consequences in a serial processing manner during speech production. The study used fMRI with functional connectivity (FC) analyses to investigate the proposed cascaded processes using three speech tasks: overt articulation (OA), silent articulation (SA) and imagined articulation (IA). The FC results showed that connectivity between aIPL and STG was increased in OA compared with SA, suggesting that the relationship between somatosensory and auditory estimations can be modulated by speech tasks. Moreover, stronger connectivity between IFGoper and pIPL, and between pIPL and STG were observed in SA and IA compared with OA. These results are consistent with a cascaded process in the internal forward models.

Comparison of brain network between schizophrenia and bipolar disorder: A multimodal MRI analysis of comparative studies.

OBJECTIVE: Cognitive impairment is a shared symptom of Schizophrenia (SCZ) and bipolar disorder (BP), but the underlying neural mechanisms for both remain unclear. We aimed to identify abnormalities in the structural and functional brain network of patients with SCZ and BP. METHODS: The study included 69 patients with SCZ, 40 with BP, and 63 healthy controls (HC). After neurocognitive function assessment, resting-state functional magnetic resonance imaging and diffusion tensor imaging were acquired respectively. We compared the network of structural connectivity (SC) and functional connectivity (FC) among the three groups and performed graph theoretical analyses. The SC-FC coupling was calculated, and the correlations between the cognitive function scores and network properties were ascertained. RESULTS: The BP group showed significantly higher indicators in subnetworks and graph theory analysis than SCZ and HC. Several brain regions, such as the inferior parietal lobe, exhibited differences among all pairwise comparisons and showed significant correlations with cognitive scores in both SCZ and BP. SC-FC coupling did not significantly differ between the three groups but showed close associations with clinical performance. Interestingly, the direction of correlations between the network properties and cognition tends to present the opposite between SCZ and BP, especially regarding the working memory, attention, and language sections. CONCLUSIONS: The FC and SC network of the SCZ group appeared more inefficient and disconnected than BP. The network demonstrated to be closely but differently associated with cognitive function at both local and global levels, indicating the potentially separated pathologies of cognition deficits in SCZ and BP.

Altered brain activity in the bilateral frontal cortices and neural correlation with cognitive impairment in schizophrenia.

Cognitive impairments are core aspects of schizophrenia and are highly related to poor outcomes. However, the effect of therapy on cognitive impairments remains unsatisfactory as its biological mechanisms are not fully understood. The purpose of this study was to investigate the disrupted intrinsic neural activity of the frontal areas and to further examine the functional connectivity of frontal areas related to cognitive impairments in schizophrenia. We collected brain imaging data using a 3T Siemens Prisma MRI system in 32 patients with schizophrenia and 34 age- and sex-matched healthy controls. The mean fractional amplitude of low-frequency fluctuation (mfALFF) in the frontal regions was calculated and analyzed to evaluate regional neural activity alterations in schizophrenia. Seed regions were generated from clusters showing significant changes in mfALFF in schizophrenia, and its resting-state functional connectivity (rs-FC) with other brain regions were estimated to detect possible aberrant rs-FC indicating cognitive impairments in schizophrenia. We found that mfALFF in the bilateral frontal cortices was increased in schizophrenia. mfALFF-based rs-FC revealed that decreased rs-FC between left middle frontal gyrus (MFG) and left medial superior frontal gyrus (MFSG) was associated with poor delayed memory (r = 0.566, Bonferroni-corrected p = 0.012). These findings demonstrate increased neural activity in the frontal cortices in schizophrenia. FC analysis revealed a diminished rs-FC pattern between the left MFG and left MSFG that was associated with cognitive impairments. These findings have provided deeper insight into the alterations in brain function related to specific domains of cognitive impairment and may provide evidence for precise interventions for cognitive deficits in schizophrenia.

Deficits in multi-scale top-down processes distorting auditory perception in schizophrenia.

Cognitive models postulate that impaired source monitoring incorrectly weights the top-down prediction and bottom-up sensory processes and causes hallucinations. However, the underlying mechanisms of the interaction, such as whether the incorrectly weighting is ubiquitously on all levels of sensory features and whether different top-down processes have distinct effects in subgroups of schizophrenia are still unclear. This study investigates how multi-scale predictions influence perception of basic tonal features in schizophrenia. Sixty-three schizophrenia patients with and without symptoms of auditory verbal hallucinations (AVHs), and thirty healthy controls identified target tones in noise at the end of tone sequences. Predictions of different timescales were manipulated by either an alternating pattern in the preceding tone sequences (long-term regularity) or a repetition between the target tone and the tone immediately before (short-term repetition). The sensitivity index, d prime (d'), was obtained to assess the modulation of predictions on tone identification. Patients with AVHs showed higher d' when the target tones conformed to the long-term regularity of alternating pattern in the preceding tone sequence than when the target tones were inconsistent with the pattern. Whereas, the short-term repetition modulated the tone identification in patients without AVHs. Predictions did not influence tone identification in healthy controls. Our results suggest that impaired source monitoring in schizophrenia patients with AVHs heavily weights top-down predictions over bottom-up perceptual processes to form incorrect perception. The weighting function in source monitoring can extend to the processes of basic tonal features, and predictions at multiple timescales could differentially modulate perception in different clinical populations. The impaired interaction between top-down and bottom-up processes might underlie the development of hallucination symptoms in schizophrenia.

Effects and potential mechanisms of transcranial direct current stimulation (tDCS) on auditory hallucinations: A meta-analysis.

Auditory hallucinations are the most common psychiatric symptoms of schizophrenia with high recurrence and refractoriness. Transcranial direct current stimulation (tDCS), a novel, non-invasion and affordable brain stimulation technique, has been recently applying on the schizophrenia patients to treat the auditory hallucinations. To analyze the efficacy of tDCS treatment on such symptoms and to reveal its potential working mechanisms, we carried out a structured literature search in PubMed, Embase and Cochrane Library database up to May 12, 2018. Five studies that met inclusion criteria with a total of 137 patients were included in this meta-analysis. After pooling all the data, we found that there was no significant effect between active group and sham group of tDCS (p = 0.18). When we removed one study that did not collaboratively stimulate the frontal-temporal sites, the active tDCS group marks a significant improvement of therapeutic effect compared with sham group (p = 0.007). Our findings suggested that tDCS could be a promising tool to alleviate auditory hallucinations, provided that the simulation sites and protocols are targeting at the sensorimotor frontal-parietal network.

Effects of omega-3 fatty acids on metabolic syndrome in patients with schizophrenia: a 12-week randomized placebo-controlled trial.

RATIONALE: Individuals with schizophrenia are at increased risk of developing metabolic syndrome (MetS) due to their lifestyle and antipsychotic treatment. Our previous study showed that patients with both schizophrenia and MetS present an increased expression and production of tumor necrosis factor-alpha (TNF-alpha). Omega-3 fatty acids have a documented role in suppressing TNF-alpha; therefore, we hypothesized that they may be of value in relieving inflammation and improving metabolic disturbance in patients with both schizophrenia and MetS. OBJECTIVES: This study employed a randomized placebo-controlled trial to investigate the effects of omega-3 fatty acids on MetS in patients with schizophrenia. METHODS: We recruited 80 patients with both schizophrenia and MetS who received long-term olanzapine monotherapy. The patients were randomly assigned to the OMG-3 group (n = 40) or the placebo group (n = 40). RESULTS: Patients with both schizophrenia and MetS had significantly higher levels of TNF-alpha than the control subjects (Z = - 4.37, P < 0.01). There was a significant correlation between omega-3 fatty acid treatment and reduced triglyceride (TG) levels (Fgroup × time = 13.42; df = 1, 66; P < 0.01) when the patients completed this study. Along with metabolic improvement, omega-3 fatty acids decreased TNF-alpha levels after 12 weeks of treatment (Fgroup × time = 6.71; df = 1, 66; P = 0.012). We also found that the extent of TNF-alpha decrease was significantly correlated with that of TG decrease (r = 0.38, P = 0.001). CONCLUSIONS: Our findings provide suggestive evidence that omega-3 fatty acids have beneficial effects on TG metabolism in patients with both schizophrenia and MetS that parallel decreased inflammation levels.

A Comprehensive Analysis of the CaMK2A Gene and Susceptibility to Alzheimer's Disease in the Han Chinese Population.

There is ample evidence suggesting that calcium/calmodulin-dependent protein kinase II alpha (CaMK2A) may play an important role in the pathophysiology of Alzheimer's disease (AD). This genetic study aimed to investigate whether CaMK2A confers susceptibility to the development of AD in the Han Chinese population. A total of seven single nucleotide polymorphisms (SNPs) within CaMK2A were screened in two independent cohorts from southwestern China (333 AD patients and 334 controls) and eastern China (382 AD patients and 426 controls) to discern the potential association between this gene and AD. In addition, a cross-platform normalized expression resource was used to investigate whether CaMK2A is differentially expressed in the brain between individuals with AD and the controls. In addition, expression quantitative trait loci (eQTL) analysis was used to explore the differences in CaMK2A expression in the brain among different genotypes. The cross-platform normalized data showed significant differences in CaMK2A expression in the hippocampus, entorhinal cortex and temporal cortex between the AD patients and the control subjects (|log FC| > 0.1, P < 0.05); however, only the differences in the hippocampus and temporal cortex remained after the multiple comparisons correction [false discovery rate (FDR)-corrected, P < 0.05]. The frequency of the rs4958445 genotype was significantly different between the AD subjects and the controls from southwestern China (P = 0.013, P = 0.034 after FDR correction). When the two samples were combined, rs4958445 still showed a significant association with AD (P = 0.044). Haplotype analysis indicated that the T-A-C-A-T-C-C and T-G-C-A-T-C-C haplotypes in the southwestern cohort and the T-G-C-G-C-T-C haplotype in the eastern cohort, consisting of rs10051644, rs6869634, rs3797617, rs3756577, rs4958445, rs10515639 and rs6881743, showed a significant association with AD (P = 0.037, P = 0.026 and P = 0.045, respectively). Furthermore, the brain eQTL analysis revealed a significant association between the rs4958445 polymorphism and CaMK2A expression in the inferior olivary nucleus (P = 0.029). Our results suggest an important role for CaMK2A in the pathophysiology of AD in the Han Chinese population, especially the southwestern population.

Influence of olanzapine on serum prolactin levels and BMI in female patients with schizophrenia.

OBJECTIVES: It has been well documented that elevation of serum prolactin (PRL) level and weight gain are common in patients receiving treatment with atypical antipsychotics. The existing evidences show that serum PRL is elevated in schizophrenic patients treated with olanzapine. However, little is known about the long-term effects of olanzapine on PRL levels and weight gain in female patients with schizophrenia. MATERIALS AND METHODS: This study addressed this issue by investigating the relationship between serum PRL level and body mass index (BMI). Seventy-nine female patients with first-episode schizophrenia were recruited and received olanzapine monotherapy for 12 weeks. Serum PRL level and BMI were measured at baseline and at 4, 8, 12 weeks. Thirty-five age-matched healthy female individuals were recruited as controls. The severity of psychiatric symptoms was evaluated using the Positive and Negative Syndrome Scale. RESULTS: The olanzapine treatment for 12 weeks significantly increased serum PRL (P<0.01) level and BMI (P<0.01). A positive correlation between the pre- and posttreatment changes in serum PRL level and BMI was observed (r=0.247, P=0.028). CONCLUSION: Our findings suggest that PRL might conceivably modulate weight gain in female patients with schizophrenia receiving olanzapine treatment; however, the exact mechanism remains unclear.