Dissociable auditory mismatch response and connectivity patterns in adolescents with schizophrenia and adolescents with bipolar disorder with psychosis: A magnetoencephalography study

BACKGROUND: There is overlap between schizophrenia and bipolar disorder regarding genetic risk as well as neuropsychological and structural brain deficits. Finding common and distinct event-response potential (ERP) responses and connectivity patterns may offer potential biomarkers to distinguish the disorders. OBJECTIVE: To examine the neuronal auditory response elicited by a roving mismatch negativity (MMN) paradigm using magnetoencephalography (MEG). PARTICIPANTS: 15 Adolescents with schizophrenia (ASZ), 16 adolescents with bipolar disorder with psychosis (ABP), and 14 typically developing individuals (TD) METHODS: The data were analysed using time-series techniques and dynamic causal modelling (DCM). OUTCOME MEASURES: MEG difference wave (deviant - standard) at primary auditory (~90ms), MMN (~180ms) and long latency (~300ms). RESULTS: The amplitude of difference wave showed specific patterns at all latencies. Most notably, it was significantly reduced ABP compared to both controls and ASZ at early latencies. In contrast, the amplitude was significantly reduced in ASZ compared to both controls and ABP. The DCM analysis showed differential connectivity patterns in all three groups. Most notably, inter-hemispheric connections were strongly dominated by the right side in ASZ only. CONCLUSIONS: Dissociable patterns of the primary auditory response and MMN response indicate possible developmentally sensitive, but separate biomarkers for schizophrenia and bipolar disorder

Abnormal intrinsic and extrinsic connectivity within the magnetic mismatch negativity brain network in schizophrenia: a preliminary study

Altered neuroplasticity is increasingly invoked as a mechanism underpinning dysconnectivity in schizophrenia. We used Dynamic Causal Modelling to compare connectivity during the magnetic auditory Mismatch Negativity (MMN), an index of error prediction, between schizophrenia patients and controls. Patients showed reduced intrinsic connectivity within the primary auditory cortex suggestive of impaired local neuronal adaptation and disrupted forward and backward extrinsic connectivity throughout the MMN network indicative of reduced higher order input in disambiguating activity in lower network nodes. Our study provides the first empirical description of the dysplastic changes underpinning dysconnectivity between primary sensory and higher order cortical areas in schizophrenia

Who Said Large Banks Don't Experience Scale Economies? Evidence from a Risk-Return-Driven Cost Function

Earlier studies found little evidence of scale economies at large banks; later studies using data from the 1990s uncovered such evidence, providing a rationale for very large banks seen worldwide. Using more recent data, we estimate scale economies using two production models. The standard risk-neutral model finds little evidence of scale economies. The model using more general risk preferences and endogenous risk-taking finds large scale economies. We show that these economies are not driven by too-big-to-fail considerations. We evaluate the cost implications of breaking up the largest banks into banks of smaller size

Neuromarketing and consumer neuroscience:contributions to neurology

Background: 'Neuromarketing' is a term that has often been used in the media in recent years. These public discussions have generally centered around potential ethical aspects and the public fear of negative consequences for society in general, and consumers in particular. However, positive contributions to the scientific discourse from developing a biological model that tries to explain context-situated human behavior such as consumption have often been neglected. We argue for a differentiated terminology, naming commercial applications of neuroscientific methods 'neuromarketing' and scientific ones 'consumer neuroscience'. While marketing scholars have eagerly integrated neuroscientific evidence into their theoretical framework, neurology has only recently started to draw its attention to the results of consumer neuroscience.Discussion: In this paper we address key research topics of consumer neuroscience that we think are of interest for neurologists; namely the reward system, trust and ethical issues. We argue that there are overlapping research topics in neurology and consumer neuroscience where both sides can profit from collaboration. Further, neurologists joining the public discussion of ethical issues surrounding neuromarketing and consumer neuroscience could contribute standards and experience gained in clinical research.Summary: We identify the following areas where consumer neuroscience could contribute to the field of neurology:. First, studies using game paradigms could help to gain further insights into the underlying pathophysiology of pathological gambling in Parkinson's disease, frontotemporal dementia, epilepsy, and Huntington's disease.Second, we identify compulsive buying as a common interest in neurology and consumer neuroscience. Paradigms commonly used in consumer neuroscience could be applied to patients suffering from Parkinson's disease and frontotemporal dementia to advance knowledge of this important behavioral symptom.Third, trust research in the medical context lacks empirical behavioral and neuroscientific evidence. Neurologists entering this field of research could profit from the extensive knowledge of the biological foundation of trust that scientists in economically-orientated neurosciences have gained.Fourth, neurologists could contribute significantly to the ethical debate about invasive methods in neuromarketing and consumer neuroscience. Further, neurologists should investigate biological and behavioral reactions of neurological patients to marketing and advertising measures, as they could show special consumer vulnerability and be subject to target marketing

Downregulation of Chloroplast RPS1 Negatively Modulates Nuclear Heat-Responsive Expression of HsfA2 and Its Target Genes in Arabidopsis

Heat stress commonly leads to inhibition of photosynthesis in higher plants. The transcriptional induction of heat stress-responsive genes represents the first line of inducible defense against imbalances in cellular homeostasis. Although heat stress transcription factor HsfA2 and its downstream target genes are well studied, the regulatory mechanisms by which HsfA2 is activated in response to heat stress remain elusive. Here, we show that chloroplast ribosomal protein S1 (RPS1) is a heat-responsive protein and functions in protein biosynthesis in chloroplast. Knockdown of RPS1 expression in the rps1 mutant nearly eliminates the heat stress-activated expression of HsfA2 and its target genes, leading to a considerable loss of heat tolerance. We further confirm the relationship existed between the downregulation of RPS1 expression and the loss of heat tolerance by generating RNA interference-transgenic lines of RPS1. Consistent with the notion that the inhibited activation of HsfA2 in response to heat stress in the rps1 mutant causes heat-susceptibility, we further demonstrate that overexpression of HsfA2 with a viral promoter leads to constitutive expressions of its target genes in the rps1 mutant, which is sufficient to reestablish lost heat tolerance and recovers heat-susceptible thylakoid stability to wild-type levels. Our findings reveal a heat-responsive retrograde pathway in which chloroplast translation capacity is a critical factor in heat-responsive activation of HsfA2 and its target genes required for cellular homeostasis under heat stress. Thus, RPS1 is an essential yet previously unknown determinant involved in retrograde activation of heat stress responses in higher plants

Early Category-Specific Cortical Activation Revealed by Visual Stimulus Inversion

Visual categorization may already start within the first 100-ms after stimulus onset, in contrast with the long-held view that during this early stage all complex stimuli are processed equally and that category-specific cortical activation occurs only at later stages. The neural basis of this proposed early stage of high-level analysis is however poorly understood. To address this question we used magnetoencephalography and anatomically-constrained distributed source modeling to monitor brain activity with millisecond-resolution while subjects performed an orientation task on the upright and upside-down presented images of three different stimulus categories: faces, houses and bodies. Significant inversion effects were found for all three stimulus categories between 70–100-ms after picture onset with a highly category-specific cortical distribution. Differential responses between upright and inverted faces were found in well-established face-selective areas of the inferior occipital cortex and right fusiform gyrus. In addition, early category-specific inversion effects were found well beyond visual areas. Our results provide the first direct evidence that category-specific processing in high-level category-sensitive cortical areas already takes place within the first 100-ms of visual processing, significantly earlier than previously thought, and suggests the existence of fast category-specific neocortical routes in the human brain