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In order to analyze functional connectivity in untreated and treated patients with schizophrenia, resting-state fMRI data were obtained for whole-brain functional connectivity analysis from 22 first-episode neuroleptic-naïve schizophrenia (NNS), 61 first-episode neuroleptic-treated schizophrenia (NTS) patients, and 60 healthy controls (HC). Reductions were found in untreated and treated patients in the functional connectivity between the posterior cingulate gyrus and precuneus, and this was correlated with the reduction in volition from the Positive and Negative Symptoms Scale (PANSS), that is in the willful initiation, sustenance, and control of thoughts, behavior, movements, and speech, and with the general and negative symptoms. In addition in both patient groups interhemispheric functional connectivity was weaker between the orbitofrontal cortex, amygdala and temporal pole. These functional connectivity changes and the related symptoms were not treated by the neuroleptics. Differences between the patient groups were that there were more strong functional connectivity links in the NNS patients (including in hippocampal, frontal, and striatal circuits) than in the NTS patients. These findings with a whole brain analysis in untreated and treated patients with schizophrenia provide evidence on some of the brain regions implicated in the volitional, other general, and negative symptoms, of schizophrenia that are not treated by neuroleptics so have implications for the development of other treatments; and provide evidence on some brain systems in which neuroleptics do alter the functional connectivity.

Conditional execution and suppression of gaze shift are important in everyday life. To examine the possible involvement of the lateral prefrontal cortex (LPFC) in this process, we induced a local and reversible inactivation by injecting muscimol into 66 sites within the LPFC of monkeys and examined muscimol's effect on their performance in an oculomotor Go/No-Go task. This task required a subject to execute (Go) or suppress (No-Go) its gaze toward a target location in response to an instructional visual cue. Local injection of muscimol into 22 regions of the LPFC resulted in significant increases in the number of error saccades toward a few specific target locations during No-Go trials, whereas there were no error saccades in the Go trials. The onset latency of error saccades in No-Go trials was significantly longer than that of correct saccades in Go trials, but their velocity and amplitude were similar to those of correct saccades in Go trials. Go correct saccades appeared intact after the injections. These findings provide evidence that different regions of the LPFC are involved in the conditional suppression of gaze shift toward a few specific target locations, which may occur through a top-down suppressive mechanism.

Prior research showed that attentional deficits are observed in Alzheimer's disease (AD). These deficits can further impair other cognitive processes. The present experiment was designed to study the shifts in attention induced by a noradrenergic drug (S 12024-2) through their electrophysiological correlates in 12 outpatients with mild AD, using an auditory oddball paradigm. The P3a component, known to be related to automatic attentional processing, was increased by the drug, whereas no changes occurred either in PN or in P3b, which are considered to reflect conscious processing. These results point to an involvement of the noradrenergic system in the modulation of automatic attentional processing, and provide evidence for weakening of the orienting reflex in AD, due to a possible noradrenergic deficit in patients with mild AD.

Background: The aim of the present study was to further investigate a previously reported attention-related impairment in dependent amphetamine users using event-related potential (ERP) indices of selective attention., Methods: ERPs were recorded during an auditory selective attention task (SAT) that involved detecting infrequent long-duration target tones presented among short-duration tones that varied in location (left vs. right ear) and pitch (low vs. high). Amphetamine users (n = 19) were divided into two groups, high dependence (n = 10) and low dependence (n = 10), based on amphetamine Severity of Dependence Scale scores, and compared to an age-matched control group (n = 9)., Results: The high-dependence group showed slowed reaction time and reduced early processing negativity and peak N1 amplitude to location-relevant nontarget stimuli. Poor performance on the SAT was highly correlated with deficits in early processing, which were also related to poor performance on the Wechsler Memory Scale Attention/Concentration index., Conclusions: It is suggested that severely dependent users suffer an inability to selectively enhance the sensory processing of relevant auditory information. This may produce poor automatic preferential processing of relevant information and increase load on limited attentional resources.

Background: Substantial evidence now shows that the genetic vulnerability to schizophrenia can be manifested clinically in first-degree relatives of people with schizophrenia, even without the full manifestations of the disorder. One pattern of problems observed involves the combination of negative symptoms and neuropsychological deficits. We have investigated whether a low dose of a novel antipsychotic medication, risperidone, could attenuate these clinical problems in non-psychotic, first-degree relatives, and report here findings from our first 4 cases., Methods: Twelve adults who were first-degree relatives of patients with schizophrenia were evaluated for the presence of negative symptoms and neuropsychological deficits (in attention and working memory, long-term verbal memory and executive functions). Four subjects who met our predetermined criteria, and who did not demonstrate medical contraindications, were enrolled in a 6-week trial of risperidone. Clinical and medical measures were assessed before, during and after treatment. Doses of risperidone started at 0.25 mg and were increased to 1.0-2.0 mg/day., Results: These subjects showed substantial reductions in negative symptoms, and one subject showed modest reductions. All four subjects showed substantial improvements on some tests of attention and working memory. Side effects of risperidone were temporary and mainly mild., Conclusions: These initial findings support two conclusions. First, clinical deficits in non-psychotic first-degree relatives of people with schizophrenia are identifiable, and to a significant extent, reversible. Second, risperidone may eventually serve as an effective treatment for people whose lives are impaired by similar or related problems.

Objective: Caffeine is widely consumed by children around the world. The purpose of this study was to determine whether children manifest withdrawal effects after cessation of caffeine intake., Method: Thirty normal children completed the single-blind, within-subjects, repeated-measures study with weekly sessions. Subjects were tested four times: (1) baseline (on regular caffeine diet); (2) on caffeine (approximately 120 to 145 mg/day); (3) during withdrawal (24 hours after discontinuation of caffeine taken for 13 consecutive days); and (4) at return to baseline. Subjects were evaluated with self-report measures of symptoms and objective measures of attention, motor performance, processing speed, and memory., Results: During caffeine withdrawal, there was a significant deterioration on response time of a visual continuous performance test of attention. This finding is consistent with caffeine withdrawal. The deterioration in response time appeared to persist for 1 week., Conclusions: Twenty-four hours after children discontinued caffeine, there was a decrease in performance on reaction time of a task requiring sustained attention. Further work is indicated to determine whether children manifest caffeine withdrawal effects after cessation of caffeine intake.