Visual event-related potentials in schizotypal personality disorder and schizophrenia

Schizophrenia (SZ) occurs among a spectrum of disorders with similar characteristics, including schizotypal personality disorder (SPD). Visual processing disturbances have been reported in both disorders, but it is not yet clear which processes are disturbed in both SZ and SPD, suggestive of a common endophenotype, and which appear only in SZ. In order to address this question, the authors evaluated visual event-related potentials (ERPs) elicited during a line-orientation discrimination task in control, SPD, and SZ participants. Visual ERPs allow specification of both the time course and physiological correlates of visual perception and cognition. SZ patients had smaller P100 and P300a amplitudes and prolonged P300b latency compared to the control group. SZ patients also had smaller N160, N200, P300a, and P300b amplitudes compared to the SPD group. SPD participants did not differ from control participants on any ERP measure. These data documented pervasive abnormalities in visual perception and attention in SZ but not in SPD, suggesting that these visual ERP disturbances may not represent a common endophenotype.     

A multimethod investigation of the behavioral activation system in bipolar disorder

Dysregulation in behavioral activation system (BAS) activity has been implicated in the pathogenesis of bipolar disorder (BPD). To characterize BAS activity and related facets in this disorder, the authors compared 59 participants with BPD to 44 controls on multiple measures of BAS activity, including a standardized behavioral task, self-reports, and electroencephalographic indexes of regional cortical activity. Levels of putative BAS activity differed depending on assessment strategy. When a behavioral task indexing reward sensitivity was used, euthymic BPD patients showed evidence of higher BAS activity than either control participants or patients who were in a mood episode. Following a mood induction procedure designed to elicit BAS activity, currently episodic patients showed relatively greater left anterior cortical activity than either euthymic or control participants. Implications of the findings for future research on BPD vulnerability are described.     

Timing dysfunctions in schizophrenia as measured by a repetitive finger tapping task

Schizophrenia may be associated with a fundamental disturbance in the temporal coordination of information processing in the brain, leading to classic symptoms of schizophrenia such as thought disorder and disorganized and contextually inappropriate behavior. Although a variety of behavioral studies have provided strong evidence for perceptual timing deficits in schizophrenia, no study to date has directly examined overt temporal performance in schizophrenia using a task that differentially engages perceptual and motor-based timing processes. The present study aimed to isolate perceptual and motor-based temporal performance in individuals diagnosed with schizophrenia using a repetitive finger-tapping task that has previously been shown to differentially engage brain regions associated with perceptual and motor-related timing behavior. Thirty-two individuals with schizophrenia and 31 non-psychiatric control participants completed the repetitive finger-tapping task, which required participants to first tap in time with computer-generated tones separated by a fixed intertone interval (tone-paced tapping), after which the tones were discontinued and participants were required to continue tapping at the established pace (self-paced tapping). Participants with schizophrenia displayed significantly faster tapping rates for both tone- and self-paced portions of the task compared to the non-psychiatric group. Individuals diagnosed with schizophrenia also displayed greater tapping variability during both tone- and self-paced portions of the task. The application of a mathematical timing model further indicated that group differences were primarily attributable to increased timing – as opposed to task implementation – difficulties in the schizophrenia group, which is noteworthy given the broad range of impairments typically associated with the disorder. These findings support the contention that schizophrenia is associated with a broad range of timing difficulties, including those associated with time perception as well as time production.     

Modulation of anxiety circuits by serotonergic systems

Anxiety is a complex emotional state associated with sustained heightened autonomic and behavioral arousal and an increase in avoidance behavior. Anxiety-related behavior is a form of risk assessment behavior that is associated with a level of uncertainty or unpredictability regarding the outcome of emotionally salient events, often when both rewarding and aversive outcomes are possible. In this review, we highlight recent advances in our understanding of the neural circuits regulating anxiety states and anxiety-related behavior with an emphasis on the role of brainstem serotonergic systems in modulating anxiety-related circuits. In particular, we explore the possibility that the regulation of anxiety states and anxiety-related behavior by serotonergic systems is dependent on a specific, topographically organized mesolimbocortical serotonergic system that originates in the mid-rostrocaudal and caudal parts of the dorsal raphe nucleus.     

Temporal processing dysfunction in schizophrenia

Schizophrenia may be associated with a fundamental disturbance in the temporal coordination of information processing in the brain, leading to classic symptoms of schizophrenia such as thought disorder and disorganized and contextually inappropriate behavior. Despite the growing interest and centrality of time-dependent conceptualizations of the pathophysiology of schizophrenia, there remains a paucity of research directly examining overt timing performance in the disorder. Accordingly, the present study investigated timing in schizophrenia using a well-established task of time perception. Twenty-three individuals with schizophrenia and 22 non-psychiatric control participants completed a temporal bisection task, which required participants to make temporal judgments about auditory and visually presented durations ranging from 300 to 600 ms. Both schizophrenia and control groups displayed greater visual compared to auditory timing variability, with no difference between groups in the visual modality. However, individuals with schizophrenia exhibited less temporal precision than controls in the perception of auditory durations. These findings correlated with parameter estimates obtained from a quantitative model of time estimation, and provide evidence of a fundamental deficit in temporal auditory precision in schizophrenia.     

Perceptual anomalies in schizophrenia co-occur with selective impairments in the gamma frequency component of midlatency auditory ERPs

This study aimed to establish concordance between phenomenological and psychophysiological indices of sensory gating disturbance in schizophrenia. Perceptually normal and deviant subgroups of schizophrenia (SZ) and healthy comparison (HC) participants were empirically determined on the basis of self-rated Sensory Gating Inventory scores. Contrasts by diagnosis and subgroup classification were conducted on event-related brain potential (ERP) response attenuation to paired auditory stimuli, measured in time (P50 ERP) and frequency (low frequency, 1-20 Hz; gamma band, 20-50 Hz) domains. The SZ sample evidenced significantly less low-frequency response attenuation than did HC but comparable P50 and gamma responses. The low-frequency response, however, appeared insensitive to variation in perceptual experience between SZ subgroups. Conversely, smaller P50 amplitude and weaker gamma response attenuation distinguished deviant SZ (n=17) from normal SZ (n=9) and normal HC (n=29) subgroups. Perceptually normal SZ and normal HC subgroups were statistically equivalent across all comparisons. These findings support hypotheses relating perceptual disturbance in schizophrenia to an early sensory input dysfunction, which is thought to involve gamma-mediated thalamocortical integration of sensory stimuli.     

The Monodic Fragment of Propositional Term Modal Logic

We study term modal logics, where modalities can be indexed by variables that can be quantified over. We suggest that these logics are appropriate for reasoning about systems of unboundedly many reasoners and define a notion of bisimulation which preserves propositional fragment of term modal logics. Also we show that the propositional fragment is already undecidable but that its monodic fragment (formulas using only one free variable in the scope of a modality) is decidable, and expressive enough to include interesting assertions.

     

Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety

Stress initiates a series of neuronal responses that prepare an organism to adapt to new environmental challenges. However, chronic stress may lead to maladaptive responses that can result in psychiatric syndromes such as anxiety and depressive disorders. Corticotropin-releasing factor (CRF) has been identified as a key neuropeptide responsible for initiating many of the endocrine, autonomic and behavioral responses to stress. The amygdala expresses high concentrations of CRF receptors and is itself a major extrahypothalamic source of CRF containing neurons. Within the amygdala, the basolateral nucleus (BLA) has an important role in regulating anxiety and affective responses. During periods of stress, CRF is released into the amygdala and local CRF receptor activation has been postulated as a substrate for stress-induced alterations in affective behavior. Previous studies have suggested that synaptic plasticity in the BLA contributes to mechanisms underlying long-term changes in the regulation of affective behaviors. Several studies have shown that acute glutamate receptor-mediated activation, by either GABA-mediated disinhibition or CRF-mediated excitation, induces long-term synaptic plasticity and increases the excitability of BLA neurons. This review summarizes some of the data supporting the hypotheses that stress induced plasticity within the amygdala may be a critical step in the pathophysiology of the development of chronic anxiety states. It is further proposed that such a change in the limbic neural circuitry is involved in the transition from normal vigilance responses to pathological anxiety, leading to syndromes such as panic and post-traumatic stress disorders.     

The role of neuropeptide Y in the amygdala on corticotropin-releasing factor receptor-mediated behavioral stress responses in the rat

Neuropeptide Y (NPY) is one of the most abundant peptides in the brain and has been shown to be a critical regulator of emotionality, most notably for its effect in decreasing anxiety-like behaviors. The stress response in both humans and animals has been shown to involve a cascade of biological events initiated by corticotropin releasing factor (CRF), another centrally acting peptide. Interestingly, NPY and CRF are present in similar brain regions mediating stress responses and may act in an opposing fashion. The basolateral nucleus of the amygdala (BLA) is a distinct division of the amygdala and contains CRF receptors and the highest concentration of NPY neurons. The current study investigates the behavioral effects in rodents when NPY is injected directly into the BLA prior to the pharmacological stressor, urocortin I (Ucn; a CRF receptor agonist) or the emotional stressor, restraint. The animals that underwent restraint were evaluated in the social interaction (SI) test, while those injected with Ucn into the BLA were assessed in the two floor choice test, a modified version of the conditioned-place avoidance paradigm. The results showed that injections of NPY into the BLA prior to Ucn significantly blocked the development of the avoidance behavior in the two floor choice test and the decrease in SI time that is usually seen following restraint stress. These results provide further support that an interaction between NPY and CRF within the BLA may be critical for maintaining a normal homeostatic emotional state.