Human ability to switch from one cognitive task to another involves both endogenous preparation without an external stimulus and exogenous adjustment in response to the external stimulus. In an event-related functional MRI study, participants performed pairs of two tasks that are either the same (task repetition) or different (task switch) from each other. On half of the trials, foreknowledge about task repetition or task switch was available. On the other half, it was not. Endogenous preparation seems to involve lateral prefrontal cortex (BA 46/45) and posterior parietal cortex (BA 40). During preparation, higher activation increases in inferior lateral prefrontal cortex and superior posterior parietal cortex were associated with foreknowledge than with no foreknowledge. Exogenous adjustment seems to involve superior prefrontal cortex (BA 8) and posterior parietal cortex (BA 39/40) in general. During a task switch with no foreknowledge, activations in these areas were relatively higher than during a task repetition with no foreknowledge. These results suggest that endogenous preparation and exogenous adjustment for a task switch may be independent processes involving different brain areas.

Objective-Although deficits in cognitive control are thought to contribute to the diverse cognitive and behavioral abnormalities in individuals with schizophrenia, the neural mechanisms underlying these deficits remain unclear. In this event-related functional magnetic resonance imaging (fMRI) study, the authors tested the hypothesis that during cognitive control tasks, impaired activation of the dorsolateral prefrontal cortex in schizophrenia patients is associated with disrupted coordinated activity between this prefrontal region and a distributed brain network that supports cognitive control.Method-Through the use of an event-related design, 25 patients with first-episode schizophrenia and 24 healthy comparison subjects, matched on demographic characteristics, were assessed while performing a version of the AX continuous performance task. Functional neuroimaging data were analyzed using 1) univariate (region-of-interest blood-oxygen-leveldependent [BOLD] time series and whole brain voxel-wise regression) analysis to confirm the presence of dorsolateral prefrontal cortex dysfunction and 2) multivariate analysis to examine dorsolateral prefrontal cortex functional connectivity. In addition, correlations between dorsolateral prefrontal cortex functional connectivity and the following variables were investigated: clinical symptoms, task performance, and coordinated brain activity associated with cognitive control.Results-Schizophrenia patients exhibited a specific deficit in cognitive control, with significantly reduced accuracy in the BX condition relative to any other condition. Univariate fMRI revealed dorsolateral prefrontal cortex dysfunction during the high cognitive control condition. Multivariate analysis revealed significant impairment in functional connectivity between the dorsolateral prefrontal cortex and task-relevant brain regions. were also found between dorsolateral prefrontal cortex functional connectivity and cognitive performance, behavioral disorganization, and global functioning.Conclusions-These findings suggest that there is an association between decreased dorsolateral prefrontal cortex activity and connectivity and a task-related neural network. This deficit in coordinated brain activity may result in the disabling disorganization symptoms related to impaired cognition in individuals with schizophrenia. Kraepelin (1) described the behavioral disorganization and cognitive deficits in schizophrenia as "an orchestra without a conductor," which presciently suggests that cognitive control-the coordination of thoughts and actions that facilitates goal-oriented behavior-is one of the key higher-order cognitive processes impaired in individuals with schizophrenia. The findings of basic studies in cognitive neuroscience suggest that the neural correlate of cognitive control is the coordinated activity of task-relevant brain regions, and the dorsolateral prefrontal cortex plays a key role in this process (2-4).Although dorsolateral prefrontal cortex dysfunction has been one of the most rep...

Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control -the ability to maintain task context online to support adaptive functioning in the face of response competition-in 22 adolescents aged 12-18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7, 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms.

Models of cognitive control posit a key modulatory role for the pontine locus coeruleus-norepinephrine (LC-NE) system. In nonhuman primates, phasic LC-NE activity confers adaptive adjustments in cortical gain in task-relevant brain networks, and in performance, on a trial-by-trial basis. This model has remained untested in humans. We used the pharmacological agent modafinil to promote low-tonic/high-phasic LC-NE activity in healthy humans performing a cognitive control task during event-related functional magnetic resonance imaging (fMRI). Modafanil administration was associated with decreased task-independent, tonic LC activity, increased task-related LC and prefrontal cortex (PFC) activity, and enhanced LC-PFC functional connectivity. These results confirm in humans the role of the LC-NE system in PFC function and cognitive control and suggest a mechanism for therapeutic action of procognitive noradrenergic agents.

Visual perception of a stimulus is a function of the visual context in which it is displayed. Surround suppression is a specific form of contextual modulation whereby the perceived contrast of a center stimulus is decreased by a high-contrast surround. Recent studies have demonstrated that individuals with schizophrenia are less prone to visual contextual effects, suggesting impairments in cortical lateral connectivity. We tested whether altered contextual modulation in schizophrenia is stimulus orientation selective. Participants viewed an annulus consisting of contrast-reversing sinusoidal gratings and determined if any one segment of the annulus had lower contrast relative to the other segments. Three stimulus configurations were tested: no surround (NS), parallel surround (PS), and orthogonal surround (OS). In the PS condition, the annulus was embedded in a 100% contrast grating parallel to the annulus gratings. In the OS condition, the surround grating was rotated 90 degrees relative to the orientation of the annulus gratings. The main dependent measure was the suppression index-the change in contrast threshold in the OS and PS conditions relative to the NS condition. There was a group x condition interaction such that patients had significantly lower PS suppression index than controls, but there were no group differences in the OS suppression index. We conclude that individuals with schizophrenia possess an abnormality in surround suppression that is specific for stimulus orientation. In conjunction with physiological and anatomical evidence from basic and postmortem studies, our results suggest a deficit of inhibition in primary visual cortex in schizophrenia.

Background-Methamphetamine (MA) abuse is associated with neurotoxicity to frontostriatal brain regions with concomitant deleterious effects on cognitive processes. Deficits in behavioral control are thought to be one contributing factor to the sustainment of addictive behaviors in chronic MA abuse.

Objective Despite schizophrenia patients’ reports of diminished experience of emotion in interviews and self-report measures, their emotional experience in the presence of emotional stimuli and in daily life (“in the moment”) appears largely intact. To examine emotion-cognition interactions, the authors tested the hypothesis that schizophrenia patients have unimpaired in-the-moment emotional reactivity but have a deficit in prefrontal cortical mechanisms needed to maintain and report on experience following exposure to emotional stimuli. Method Using a slow event-related functional MRI paradigm, the authors examined the brain activity of 23 schizophrenia patients and 24 healthy comparison subjects during trials in which they viewed an affective picture and, after a delay, reported their emotional experience while viewing it. Results The patients’ self-reports of emotional experience differed from those of the healthy subjects when they rated their experience on dimensions inconsistent with the stimulus valence but not when the dimension was consistent with it. In the presence of emotional stimuli, brain activity in the patients was similar to that of the comparison subjects. During the delay, however, patients showed decreased activation in a network of brain structures, including the dorsolateral prefrontal cortex and other prefrontal, limbic, and paralimbic areas. In patients, the delay-related response of the dorsolateral prefrontal cortex to pleasant stimuli correlated negatively with an anhedonia measure. Conclusions These results suggest that schizophrenia is characterized by a failure of prefrontal circuitry supporting the link between emotion and goal-directed behavior and that the failure of this mechanism may contribute to deficits in processes related to emotion-cognition interaction.

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