Faculty Bibliography

We conducted an event-related potential (ERP) study to investigate the electrocortical dynamics of attentional feature-based processing in the Stroop matching task. Participants in the study (n = 37) compared the ink color of a colored word with the meaning of a color-word in white ink. The two task stimuli were presented simultaneously or with SOAs (Stimulus Onset Asynchrony) of 400 and 1,200 ms. The Stroop matching effect was maximal during SOA-0, was reduced at SOA-400, and was inverted at SOA-1200. We focused the ERP analysis on the N1 component. Paralleling the behavioral results, the N1 amplitude was greater for congruent stimuli than incongruent stimuli during SOA-0. This difference was attenuated at SOA-400, and at SOA-1200, an inverse pattern was observed. The results provide evidence that early selection processing participated in the Stroop matching task phenomenon and also suggest that the temporal modulation of early attention is a function of task characteristics such as SOA

CONTEXT: Perceptual closure is the ability to identify objects based on partial information and depends on the function of a distributed network of brain regions that include the dorsal and the ventral visual streams, prefrontal cortex (PFC), and hippocampus. OBJECTIVE: To evaluate network-level interactions during perceptual closure in schizophrenia using parallel event-related potential (ERP), functional magnetic resonance imaging (fMRI), and neuropsychological assessment. DESIGN: Case-control study. SETTING: Inpatient and outpatient facilities associated with the Nathan Kline Institute for Psychiatric Research. Patients Twenty-seven patients with schizophrenia or schizoaffective disorder and 23 healthy controls. Intervention Event-related potentials were obtained from 24 patients and 20 healthy volunteers in response to fragmented (closeable) and control-scrambled (noncloseable) line drawings. Functional MRI was performed in 11 patients and 12 controls. Main Outcome Measure Patterns of between-group differences for predefined ERP components and fMRI regions of interest were determined using both analysis of variance and structural equation modeling. Global neuropsychological performance was assessed using standard neuropsychological batteries. RESULTS: Patients showed impaired generation of event-related components reflecting early sensory and later closure-related activity. In fMRI, patients showed impaired activation of the dorsal and ventral visual regions, PFC, and hippocampus. Impaired activation of dorsal stream visual regions contributed significantly to impaired PFC activation, which contributed significantly to impaired activation of the hippocampus and ventral visual stream. Impaired ventral stream and hippocampal activation contributed significantly to deficits on neuropsychological measures of perceptual organization. CONCLUSIONS: Schizophrenia is associated with severe activation deficits across a distributed network of sensory and higher order cognitive regions. Deficit in early visual processing within the dorsal visual stream contributes significantly to impaired frontal activation, which, in turn, leads to dysregulation of the hippocampus and ventral visual stream. Dysfunction within this network underlies deficits in more traditional neurocognitive measures, supporting distributed models of brain dysfunction in schizophrenia

Sensory processing deficits in schizophrenia have been documented for several decades, but their underlying neurophysiological substrates are still poorly understood. In the visual system, the pattern of pathophysiology reported in several studies is suggestive of dysfunction within the magnocellular visual pathway beginning in early sensory cortex or even subcortically. The present study used functional magnetic resonance imaging to investigate further the neurophysiological bases of visual processing deficits in schizophrenia and in particular the potential role of magnocellular stream dysfunction. Sinusoidal gratings systematically varying in spatial frequency content were presented to subjects at low and high levels of contrast to differentially bias activity in magnocellular and parvocellular pathways based on well established differences in neuronal response profiles. Hemodynamic responses elicited by different spatial frequencies were mapped over the occipital lobe and then over the entire brain. Retinotopic mapping was used to localize the occipital activations with respect to the boundaries of visual areas V1 and V2, which were demarcated in each subject. Relative to control subjects, schizophrenia patients showed markedly reduced activations to low, but not high, spatial frequencies in multiple regions of the occipital, parietal, and temporal lobes. These findings support the hypothesis that schizophrenia is associated with impaired functioning of the magnocellular visual pathway and further suggest that these sensory processing deficits may contribute to higher-order cognitive deficits in working memory, executive functioning, and attention

BACKGROUND: Deficits in working memory performance are among the most widely replicated findings in schizophrenia. Roles of encoding vs. memory retention in working memory remain unresolved. The present study evaluated working memory performance in schizophrenia using an AX-type continuous performance test (AX-CPT) paradigm. METHODS: Participants included 48 subjects with schizophrenia and 27 comparison subjects. Behavior was obtained in 3 versions of the task, which differed based upon ease of cue interoperability. In a simple cue version of the task, cue letters were replaced with red or green circles. In the complex cue version, letter/color conjunctions served as cues. RESULTS: In the base version of the task, patients showed increased rates of false alarms to invalidly cued targets, similar to prior reports. However, when the cue stimuli were replaced with green or red circles to ease interpretation, patients showed similar false alarm rates to controls. When feature conjunction cues were used, patients were also disproportionately affected relative to controls. No significant group by interstimulus interval interaction effects were observed in either the simple or complex cue conditions, suggesting normal retention of information even in the presence of overall performance decrements. CONCLUSIONS: These findings suggest first, that cue manipulation disproportionately affects AX-CPT performance in schizophrenia and, second, that substantial behavioral deficits may be observed on working memory tasks even in the absence of disturbances in mnemonic retention.

Changing plans depends on executive control, the orchestration of behavior based on knowledge of both goal and context. Dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) cortices are clearly involved in these processes. Intracranial recordings in these regions were obtained from a monkey performing an executive control-challenging task that is widely used in clinic and laboratory to assess the integrity of cognitive function, the AX version of the continuous performance task (AX-CPT), and directly compared to scalp-recorded evoked potentials in humans. In this task the subject presses a button when detecting a frequent cue-target probe sequence in a stream of letters presented on a computer screen, and withholds response following incorrect sequences. Thus correct performance requires correct encoding of cue and probe instruction and inhibitory control. Intracranial recordings showed that DLPFC in the monkey was primarily activated by conditions that required inhibition of imminent action, as had been shown in human event-related potential (ERP) recordings. Different subregions of monkey ACC were activated primarily by either initiating or inhibiting action, whereas human ERP had shown ACC activation in both situations. We suggest that simultaneous activation of both types of subregions in conflict conditions may account the ubiquitous ACC activation observed with fMRI and ERP in those conditions

In primates, the frontal eye field (FEF) contains separate representations of saccadic and smooth-pursuit eye movements. The smooth-pursuit region (FEFsem) in macaque monkeys lies principally in the fundus and deep posterior wall of the arcuate sulcus, between the FEF saccade region (FEFsac) in the anterior wall and somatomotor areas on the posterior wall and convexity. In this study, cortical afferents to FEFsem were mapped by injecting retrograde tracers (WGA-HRP and fast blue) into electrophysiologically identified FEFsem sites in two monkeys. In the frontal lobe, labeled neurons were found mostly on the ipsilateral side in the (1) supplementary eye field region and lateral area F7; (2) area F2 along the superior limb of the arcuate sulcus; and (3) in the buried cortex of the arcuate sulcus extending along the superior and inferior limbs and including FEFsac and adjacent areas 8, 45, and PMv. Labeled cells were also found in the caudal periprincipal cortex (area 46) in one monkey. Labeled cells were found bilaterally in the frontal lobe in the deep posterior walls of the arcuate sulcus and postarcuate spurs and in cingulate motor areas 24 and 24c. In postcentral cortical areas all labeling was ipsilateral and there were two major foci of labeled cells: (1) the depths of the intraparietal sulcus including areas VIP, LIP, and PEa, and (2) the anterior wall and fundus of the superior temporal sulcus including areas PP and MST. Smaller numbers of labeled cells were found in superior temporal sulcal areas FST, MT, and STP, posterior cingulate area 23b, area 3a within the central sulcus, areas SII, RI, Tpt in the lateral sulcus, and parietal areas 7a, 7b, PEc, MIP, DP, and V3A. Many of these posterior afferent cortical areas code visual-motion (MT, MST, and FST) or visual-motion and vestibular (PP, VIP) signals, consistent with the responses of neurons in FEFsem and with the overall physiology and anatomy of the smooth-pursuit eye movement system