Biomedical subjects

Clayton E Curtis

Publications and source records attributed to Clayton E Curtis.

13 recordsLinked to original sources

PubMed2006

Sustained activity in topographic areas of human posterior parietal cortex during memory-guided saccades.

In a previous study, we identified three cortical areas in human posterior parietal cortex that exhibited topographic responses during memory-guided saccades [visual area 7 (V7), intraparietal sulcus 1 (IPS1), and IPS2], which are candidate homologs of macaque parietal areas such as the lateral intraparietal area and parietal reach region. Here, we show that these areas exhibit sustained delay-period activity, a critical physiological signature of areas in macaque parietal cortex. By varying delay duration, we disambiguated delay-period activity from sensory and motor responses. Mean time courses in the parietal areas were well fit by a linear model comprising three components representing responses to (1) the visual target, (2) the delay period, and (3) the eye movement interval. We estimated the contributions of each component: the response amplitude during the delay period was substantially smaller (<30%) than that elicited by the transient visual target. All three parietal regions showed comparable delay-period response amplitudes, with a trend toward larger responses from V7 to IPS1 and IPS2. Responses to the cue and during the delay period showed clear lateralization with larger responses to trials in which the target was placed in the contralateral visual field, suggesting that both of these components contributed to the topography we measured.

Biological Clocks↗

PubMed2006

Selection and maintenance of saccade goals in the human frontal eye fields.

In a delayed-response task, response selection marks an important transition from sensory to motor processing. Using event-related functional magnetic resonance imaging, we imaged the human brain during performance of a novel delayed-saccade task that isolated response selection from visual encoding and motor execution. The frontal eye fields (FEFs) and intraparietal sulcus (IPS) both showed robust contra-lateralized activity time-locked to response selection. Moreover, response selection affected delay-period activity differently in these regions; it persisted throughout the memory delay period following response selection in the FEF but not IPS. Our results indicate that the FEF and IPS both make important but distinct contributions to spatial working memory. The mechanism that the FEF uses to support spatial working memory is tied to the selection and prospective coding of saccade goals, whereas the role of the IPS may be more tied to retrospective coding of sensory representations.

Adult↗

PubMed2005

Differential effects of distraction during working memory on delay-period activity in the prefrontal cortex and the visual association cortex.

Maintaining relevant information for later use is a critical aspect of working memory (WM). The lateral prefrontal cortex (PFC) and posterior sensory cortical areas appear to be important in supporting maintenance. However, the relative and unique contributions of these areas remain unclear. We have designed a WM paradigm with distraction to probe the contents of maintenance representations in these regions. During delayed recognition trials of faces, selective interference was evident behaviorally with face distraction leading to significantly worse performance than with scene distraction. Event-related fMRI of the human brain showed that maintenance activity in the lateral PFC, but not in visual association cortex (VAC), was selectively disrupted by face distraction. Additionally, the functional connectivity between the lateral PFC and the VAC was perturbed during these trials. We propose a hierarchical and distributed model of active maintenance in which the lateral PFC codes for abstracted mnemonic information, while sensory areas represent specific features of the memoranda. Furthermore, persistent coactivation between the PFC and sensory areas may be a mechanism by which information is actively maintained.

Adult↗

PubMed2005

Coherence between fMRI time-series distinguishes two spatial working memory networks.

Widespread and distributed brain regions are thought to form networks that together support working memory. We recently demonstrated that different cortical areas maintain relatively different codes across a memory delay (Curtis et. al., J Neurosci, 2004; 24:3944-3952). The frontal eye fields (FEF), for example, were more active during the delay when the direction of the memory-guided saccade was known compared to when it was not known throughout the delay. Other areas showed the opposite pattern. Despite these task-dependent differences in regional activity, we could only assume but not address the functional interactions between the identified nodes of the putative network. Here, we use a bivariate technique, coherence, to formally characterize functional interactions between a seed region and other brain areas. We find that the type of representational codes that are being maintained in working memory biases frontal-parietal interactions. For example, coherence between FEF and other oculomotor areas was greater when a motor representation was an efficient strategy to bridge the delay period. However, coherence between the FEF and higher-order heteromodal areas, e.g., dorsolateral prefrontal cortex, was greater when a sensory representation must be maintained in working memory.

Adolescent↗

PubMed2005

Functional interactions between oculomotor regions during prosaccades and antisaccades.

Human behavior reflects a continual negotiation of automatic and directed actions. The oculomotor network is a well-characterized neural system in which to study this balance of behavioral control. For instance, saccades made toward and away from a flashed visual stimulus (prosaccades and antisaccades, respectively) are known to engage different cognitive processes. Brain regions important for such controlled execution include the presupplementary motor area (pre-SMA), frontal eye fields (FEF), and intraparietal sulcus (IPS). Recent work has emphasized various elements of this network but has not explored the functional interactions among regions. We used event-related fMRI to image human brain activity during performance of an interleaved pro/antisaccade task. Since traditional univariate statistics cannot address issues of functional connectivity, a multivariate technique is necessary. Coherence between fMRI time series of the pre-SMA with the FEF and IPS was used to measure functional interactions. The FEF, but not IPS, showed significant differential coherence between pro- and antisaccade trials with pre-SMA. These results suggest that the pre-SMA coordinates with FEF to maintain a controlled, preparatory set for task-appropriate oculomotor execution.

Adult↗

PubMed2005

Working memory functioning in schizophrenia patients and their first-degree relatives: cognitive functioning shedding light on etiology.

There is accumulating evidence for involvement of the prefrontal cortex (PFC) in the pathophysiology of schizophrenia. A primary function supported by the PFC is working memory (WM). Findings from WM studies in schizophrenia can provide insight into the nature of clinical symptoms and cognitive deficits associated with this disorder, as well as begin to suggest areas of underlying neuropathology. To date, studies have not adequately investigated different WM domains (e.g., verbal, spatial, or object) or processing requirements (e.g., maintenance, monitoring, or manipulation), shown to be associated with distinct patterns of neural activation, in schizophrenia patients and their well relatives. Accordingly, this study evaluated the performance of schizophrenia patients, their first-degree biological relatives, and nonpsychiatric controls on a comprehensive battery of WM tasks and investigated the association among WM deficits and schizophrenia-spectrum psychopathology. The findings indicate that schizophrenia patients are consistently impaired on WM tasks, irrespective of WM domain or processing requirements. In contrast, their unaffected relatives are only impaired on WM tasks with higher central executive processing requirements. This pattern of WM performance may further implicate DLPFC dysfunction in the liability for schizophrenia and has implications for future cognitive, genetic, and neurodevelopmental research.

Adult↗

PubMed2004

Canceling planned action: an FMRI study of countermanding saccades.

We investigated the voluntary control of motor behavior by studying the process of deciding whether or not to execute a movement. We imaged the human dorsal cortex while subjects performed a countermanding task that allowed us to manipulate the probability that subjects would be able to cancel a planned saccade in response to an imperative stop signal. We modeled the behavioral data as a race between gaze-shifting mechanisms and gaze-holding mechanisms towards a finish line where a saccade is generated or canceled, and estimated that saccade cancelation took approximately 160 ms. The frontal eye fields showed greater activation on stop signal trials regardless of successful cancelation, suggesting coactivation of saccade and fixation mechanisms. The supplementary eye fields, however, distinguished between successful and unsuccessful cancelation, suggesting a role in monitoring performance. These oculomotor regions play distinct roles in the decision processes mediating saccadic choice.

Adolescent↗

PubMed2004

Antisaccade performance is impaired in medically and psychiatrically healthy biological relatives of schizophrenia patients.

Schizophrenia patients and their relatives have been found to exhibit increased reflexive errors on the antisaccade task, suggesting the deficit reflects genetic susceptibility for schizophrenia. To evaluate the degree to which antisaccade error is elevated in schizophrenia relatives, we carried out a meta-analysis of the existing literature and a primary study examining whether the magnitude of reported differences between relative and nonpsychiatric comparison groups could be due to differences in participant inclusion criteria. Meta-analysis yielded a moderate to large effect size across studies comparing relatives and controls (Cohen's d=0.61; Glass' d(g)=0.87). Antisaccade performance in medically and psychiatrically healthy relatives (n=45), who were selected from a larger sample of relatives based on criteria applied to healthy controls, was significantly more impaired than in healthy control participants (d=0.81, d(g)=0.93). Moreover, excluded (n=71) and included relatives did not differ (d=0.14, d(g)=0.13). The results indicate that the antisaccade deficit is a robust phenomenon in unaffected schizophrenia relatives that is not due to differences in inclusion criteria between relatives and controls, and thus are consistent with a growing literature indicating that the antisaccade deficit will be a valuable endophenotype of schizophrenia.

Adolescent↗

PubMed2004

Maintenance of spatial and motor codes during oculomotor delayed response tasks.

The most compelling neural evidence for working memory is persistent neuronal activity bridging past sensory cues and their contingent future motor acts. This observation, however, does not answer what is actually being remembered or coded for by this activity. To address this fundamental issue, we imaged the human brain during maintenance of spatial locations and varied whether the memory-guided saccade was selected before or after the delay. An oculomotor delayed matching-to-sample task (match) was used to measure maintained motor intention because the direction of the forthcoming saccade was known throughout the delay. We used a nonmatching-to-sample task (nonmatch) in which the saccade was unpredictable to measure maintained spatial attention. Oculomotor areas were more active during match delays, and posterior parietal cortex and inferior frontal cortex were more active during nonmatch delays. Additionally, the fidelity of the memory was predicted by the delay-period activity of the frontal eye fields; the magnitude of delay-period activity correlated with the accuracy of the memory-guided saccade. Experimentally controlling response selection allowed us to functionally separate nodes of a network of frontal and parietal areas that usually coactivate in studies of working memory. We propose that different nodes in this network maintain different representational codes, motor and spatial. Which code is being represented by sustained neural activity is biased by when in the transformation from perception to action the response can be selected.

Adolescent↗

PubMed2004

Multiple dimensions of schizotypy in first degree biological relatives of schizophrenia patients.

Considerable research has been devoted to identifying individuals predisposed to schizophrenia, with much of the effort devoted to identifying the personality characteristics of the biological relatives of schizophrenia patients. Although resource-consuming interviews have yielded promising results, investigators have long sought self-report measures that index genetic risk for schizophrenia. The Schizotypal Personality Questionnaire (SPQ) is a self-report measure that assesses the nine features of DSM-defined schizotypy. The SPQ, modified to include validity scales, was administered to 135 nonpsychotic first degree relatives of schizophrenia patients and 112 healthy controls. Principal components analysis (PCA) yielded three factors that correlated highly with previously reported factors (social-interpersonal, cognitive-perceptual, and disorganization). Social-interpersonal deficits were found to best differentiate relatives from controls. Contrary to the hypothesis that schizophrenia relatives are more defensive in responding to schizotypy questionnaires, relatives were significantly less defensive than controls. The results demonstrate that a multidimensional paper-and-pencil measure can characterize schizotypal features in schizophrenia relatives, which will be useful for the further delineation of the heritable schizophrenia spectrum phenotype.

Child↗

PubMed2004

The effects of prefrontal lesions on working memory performance and theory.

The effects of experimental lesions of the monkey prefrontal cortex have played a predominant role in current conceptualizations of the functional organization of the lateral prefrontal cortex, especially with regard to working memory. The loss or sparing of certain performance abilities has been shown to be attributable to differences in the specific requirements of behavioral testing (e.g., spatial vs. non-spatial memoranda) along with differences in the specific locations of applied ablations (e.g., dorsal vs. ventral prefrontal cortex). Such findings, which have accumulated now for over a century, have led to widespread acceptance that the dorsolateral and ventrolateral aspects of the prefrontal cortex may perform different, specialized roles in higher order cognition. Nonetheless, it remains unclear and controversial how the lateral prefrontal cortex is functionally organized. Two main views propose different types of functional specialization of the dorsal and ventral prefrontal cortex. The first contends that the lateral prefrontal cortex is segregated according to the processing of spatial and nonspatial domains of information. The second contends that domain specialization is not the key to the organization of the prefrontal cortex, but that instead, the dorsal and ventral prefrontal cortices perform qualitatively different operations. This report critically reviews all relevant monkey lesion studies that have served as the foundation for current theories regarding the functional organization of the prefrontal cortex. Our goals are to evaluate how well the existing lesion data support each theory and to enumerate caveats that must be considered when interpreting the relevant literature.

Animals↗

PubMed2003

Success and failure suppressing reflexive behavior.

The dynamic interplay between reflexive and controlled determinants of behavior is one of the most general organizing principles of brain function. A powerful analogue of this interplay is seen in the antisaccade task, which pits reflexive and willed saccadic mechanisms against one another. Event-related functional magnetic resonance imaging of the human brain showed greater prestimulus preparatory activity in the pre-supplementary motor area before voluntary antisaccades (saccades away from a target) compared with reflexive prosaccades (saccades to a target). Moreover, this preparatory activity was critically associated with reflex suppression; it predicted whether the reflex was later successfully inhibited in the trial. These dataillustrate a mechanism for top-down control over reflexive behavior.

Adult↗

PubMed2003

Smooth pursuit and antisaccade performance evidence trait stability in schizophrenia patients and their relatives.

Several forms of eye movement dysfunction (EMD) have been widely regarded as candidate endophenotypes of schizophrenia, ultimately capable of identifying individuals carrying schizophrenia susceptibility genes and elucidating the pathophysiology of schizophrenia. As an indication of their trait-like status, candidate endophenotypes optimally evidence stability over time. However, there have been few published reports of test-retest reliability of several forms of EMD in schizophrenia patients and their relatives. In the current investigation, schizophrenia patients and the first-degree biological relatives of schizophrenia patients (n=15) were administered by an eye movement battery including smooth pursuit, antisaccade and prosaccade tasks, and re-tested after an average of 1.82 years (range=14-24 months). Adequate test-retest reliabilities of smooth pursuit closed-loop gain (Pearson r=0.72), antisaccade error rate (r=0.73), saccade reaction time to correct antisaccade responses (r=0.73), and prosaccade hypometria (r=0.72) were observed. Lower reliabilities were obtained for smooth pursuit open-loop gain (r=0.52) and prosaccade reaction time (r=0.43). The results are supportive of the trait-like characteristics of particular forms of EMD in schizophrenia families and of the candidacy of EMD as an endophenotypic marker of schizophrenia.

Adult↗