7Background: Previous schizophrenia research involving the "beads task" has suggested an association between delusions and 2 reasoning biases: (1) "jumping to conclusions" (JTC), whereby early, resolute decisions are formed on the basis of little evidence and (2) overadjustment of probability estimates following a single instance of disconfirmatory evidence. In the current study, we used a novel JTC-style paradigm to provide new information about a cognitive operation common to these 2 reasoning biases. Methods: Using a task that required participants to rate the likelihood that a fisherman was catching a series of black or white fish from Lake A and not Lake B, and vice versa, we compared the responses of 4 groups (healthy, bipolar, nondelusional schizophrenia and delusional schizophrenia) when we manipulated 2 elements of the Bayesian formula: incoming data and prior odds. Results: Regardless of our manipulations of the Bayesian formula, the delusional schizophrenia group gave significantly higher likelihood ratings for the lake that best matched the colour of the presented fish, but the ratings for the nonmatching lake did not differ from the other groups. Limitations: The limitations of this study include a small sample size for the group of severely delusional patients and a preponderance of men in the schizophrenia sample. Conclusion: Delusions in schizophrenia are associated with hypersalience of evidence-hypothesis matches but normal salience of nonmatches. When the colour of the incoming data is uniform (fish of only one colour), this manifests as JTC early in a series, and when the colour of incoming data varies (both black and white fish), this manifests as an overadjustment midseries. This account can provide a unifying explanation for delusion-associated performance patterns previously observed in the beads task in schizophrenia.

A bias against disconfirmatory evidence (BADE) appears to be related to delusions in schizophrenia. However, preliminary studies have either not used the most comprehensive version of the BADE task, not included a psychiatric control group, and/or have used difference score methodology instead of analyzing all available measures. In the current study a comprehensive version of the BADE task was administered to people with schizophrenia, bipolar disorder and a healthy control group. The BADE task required rating four interpretations of delusion-neutral scenarios three times (in sequence) as increasingly disambiguating information was presented. A principal component analysis (PCA) carried out on all measures determined that two independent cognitive processes appear to combine to determine all responses on the BADE task: Integration of Evidence and Conservatism, with only the former discriminating between the severely delusional schizophrenia group and all other groups. Thus, integration of evidence appears to be functioning sub-optimally in severely delusional schizophrenia patients, resulting in a bias against disconfirmatory evidence (BADE). The cognitive process theorized to be underlying this effect is hypersalience of evidence-hypothesis matches.

Acetylcholine (ACh) plays a permissive role in developmental plasticity of fibers from the lateral geniculate nucleus (LGN) to the primary visual cortex (V1). These fibers remain plastic and express long-term potentiation (LTP) in adult rodents, but it is not known if ACh modulates this form of plasticity in the mature V1. We show that, in anesthetized rats, theta burst stimulation (TBS) of the LGN using 5 or 40 theta cycles produced moderate (approximately 20%) and stronger (approximately 40%) potentiation, respectively, of field postsynaptic potentials recorded in the ipsilateral V1. Basal forebrain stimulation (100 Hz) 5 min after TBS enhanced LTP induced by both weak (5 theta cycles) and strong (40 theta cycles) induction protocols. Both effects were reduced by systemic administration of the muscarinic receptor antagonist scopolamine. Basal forebrain stimulation did not enhance LTP when applied 30 min after or 5 min prior to TBS, suggesting that ACh affects early LTP induction mechanisms. Application of the cholinergic agonist carbachol in V1 by means of reverse microdialysis mimicked the effect of basal forebrain stimulation. We conclude that heterosynaptic facilitation of V1 plasticity by ACh extends beyond early postnatal maturation periods and acts to convert weak potentiation into pronounced, long-lasting increases in synaptic strength.

Long-term potentiation (LTP) and long-term depression are thought to mediate activity-dependent brain plasticity but their role in the development of the thalamocortical auditory system in vivo has not been investigated. In adult urethane-anaesthetized rats, theta-burst stimulation of the medial geniculate nucleus produced robust LTP (40% amplitude enhancement) of field post-synaptic evoked potentials recorded in the superficial layers of the primary auditory cortex. Low-frequency (1-Hz) stimulation resulted in transient depression ( approximately 40%) of field post-synaptic evoked potential amplitude. Both LTP and synaptic depression were found to be dependent on cortical N-methyl-d-aspartate receptors. Thalamocortical plasticity was also assessed after continuous white noise exposure, thought to arrest auditory cortex maturation when applied during the critical period of post-natal primary auditory cortex development. Rats housed in continuous white noise for the first 50 days of post-natal life exhibited greater LTP ( approximately 80%) than controls reared in unaltered acoustic environments. The protocol used to elicit depression also resulted in substantial LTP ( approximately 50%) in white noise-reared animals. Adults housed in white noise for the same length of time exhibited normal LTP but displayed greater and persistent levels of synaptic depression ( approximately 70%). Thus, the absence of patterned auditory stimulation during early post-natal life appears to retard sensory-dependent thalamocortical synaptic strengthening, as indicated by the preferential readiness for synaptic potentiation over depression. The fact that the same auditory manipulation in adults results in synapses favouring depression demonstrates the critical role of developmental stage in determining the direction of synaptic modification in the thalamocortical auditory system.