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Biomedical subjects

Jonathan D Cohen

Publications and source records attributed to Jonathan D Cohen.

11 recordsLinked to original sources

Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia.

BACKGROUND: Schizophrenic patients show deficits in working memory (WM) and inhibition of prepotent responses. We examined brain activity while subjects performed tasks that placed demands on WM and overriding prepotent response tendencies, testing predictions that both processes engage overlapping prefrontal cortical (PFC) regions and that schizophrenic patients show reduced PFC activity and performance deficits reflecting both processes. METHODS: Functional magnetic resonance imaging data were acquired while 16 schizophrenic and 15 healthy subjects performed the N-Back task that varied WM load and a version of the AX-CPT that required overriding a prepotent response tendency. RESULTS: Both tasks engaged overlapping cortical networks (e.g., bilateral dorsolateral PFC, Broca's area, parietal cortex). Increased WM load monotonically increased activity; preparation to override a prepotent response produced greater and more enduring activity. Group differences on each task emerged in a right dorsolateral PFC region: schizophrenic subjects showed lesser magnitude increases under conditions of high WM and prepotent response override demands, with concomitant performance impairments. CONCLUSIONS: Schizophrenic patients exhibit PFC-mediated deficits in WM and preparation to override prepotent responses. Findings are consistent with the operation of a single underlying PFC-mediated cognitive control mechanism and with physiologic dysfunction of the dorsolateral PFC in schizophrenic patients reflecting impairments in this mechanism.

Adult↗

Context-processing deficits in schizophrenia: diagnostic specificity, 4-week course, and relationships to clinical symptoms.

Previous research on schizophrenia suggests that context-processing disturbances are one of the core cognitive deficits present in schizophia. However, it is not clear whether such deficits are specific to schizophrenia as compared with other psychotic disorders. To address this question, the authors administered a version of the AX Continuous Performance Test designed to assess context processing in a sample of healthy controls, patients with schizophrenia, and patients with other psychotic disorders. Participants were tested at index (when medication naive and experiencing their first contact with psychiatric services) and 4 weeks later, following medication treatment. At index, patients with schizophrenia and the psychotic comparison group demonstrated similar impairments in context processing. However, context-processing deficits improved in the psychotic comparison group at 4 weeks but did not improve in patients with schizophrenia.

Adult↗

Neural and behavioral substrates of mood and mood regulation.

A review of behavioral and neurobiological data on mood and mood regulation as they pertain to an understanding of mood disorders is presented. Four approaches are considered: 1) behavioral and cognitive; 2) neurobiological; 3) computational; and 4) developmental. Within each of these four sections, we summarize the current status of the field and present our vision for the future, including particular challenges and opportunities. We conclude with a series of specific recommendations for National Institute of Mental Health priorities. Recommendations are presented for the behavioral domain, the neural domain, the domain of behavioral-neural interaction, for training, and for dissemination. It is in the domain of behavioral-neural interaction, in particular, that new research is required that brings together traditions that have developed relatively independently. Training interdisciplinary clinical scientists who meaningfully draw upon both behavioral and neuroscientific literatures and methods is critically required for the realization of these goals.

Affect↗

Hyperscanning: simultaneous fMRI during linked social interactions.

"Plain question and plain answer make the shortest road out of most perplexities." Mark Twain-Life on the Mississippi. A new methodology for the measurement of the neural substrates of human social interaction is described. This technology, termed "Hyperscan," embodies both the hardware and the software necessary to link magnetic resonance scanners through the internet. Hyperscanning allows for the performance of human behavioral experiments in which participants can interact with each other while functional MRI is acquired in synchrony with the behavioral interactions. Data are presented from a simple game of deception between pairs of subjects. Because people may interact both asymmetrically and asynchronously, both the design and the analysis must accommodate this added complexity. Several potential approaches are described.

Brain↗

Computational perspectives on dopamine function in prefrontal cortex.

Dopamine and the prefrontal cortex are critical for thought and behaviour. Recently, computational models have tried to elucidate the specific and intricate roles of dopamine in the prefrontal cortex, at the neurophysiological, system and behavioral levels, with varying degrees of success.

Animals↗

Prefrontal cortex and dynamic categorization tasks: representational organization and neuromodulatory control.

We present a computational model of the intradimensional/ extradimensional (ID/ED) task (a variant of the Wisconsin card sorting task) that simulates the performance of intact and frontally lesioned monkeys on three different kinds of rule changes (Dias et al., 1997, J Neurosci 17:9285-9297). Although Dias et al. interpret the lesion data as supporting a model in which prefrontal cortex is organized into different processing functions, our model suggests an alternative account based on representational content. A key aspect of the model is that prefrontal cortex representations are organized according to different levels of abstraction, with orbital areas encoding more specific featural information and dorsolateral areas encoding more abstract dimensional information. This representational scheme of the model is integrated with two additional key elements: (i) activation-based working memory representations controlled by a dynamic gating mechanism that simulates the hypothesized phasic actions of dopaminergic neuromodulation in prefrontal cortex, which acts to stabilize or destabilize frontal representations based on success in the task; and (ii) a weight-based associative learning system simulating posterior cortex and other subcortical areas, where the stimulus-response mappings are encoded. Frontal cortex contributes to the task via top-down activation-based biasing of task-appropriate features and dimensions in this posterior cortex system - this top-down biasing is specifically important for overcoming prepotent associations after a sorting rule reverses. The ability of the model to capture the double-dissociation observed by Dias et al. with orbital versus dorsolateral lesions supports the validity of these principles, many of which have also been useful in accounting for other frontal phenomena.

Animals↗

Automatic tube compensation-assisted respiratory rate to tidal volume ratio improves the prediction of weaning outcome.

OBJECTIVE: To assess whether the respiratory rate to tidal volume ratio (RVR) measured while receiving automatic tube compensation (ATC) [RVRATC] would have a better predictive value as a weaning measure than unassisted RVR. DESIGN: Prospective cohort study. SETTING: General ICU of a tertiary-care university hospital. PATIENTS: Forty-three patients who received mechanical ventilation for > 24 h and were considered ready for weaning. INTERVENTIONS: All patients underwent a 60-min spontaneous breathing trial (SBT) [positive end-expiratory pressure of 5 cm H(2)O; ATC, 100%]. Patients tolerating the trial (n = 35) were extubated immediately. The following parameters were measured at the onset and end of the SBT: RVR, RVRATC, peak airway pressure (Paw), airway occlusion pressure, and minute ventilation. The outcome measure was successful extubation (ability to maintain spontaneous breathing for > 48 h). MEASUREMENTS AND RESULTS: Median age was 55 years (range, 25 to 88 years), median APACHE (acute physiology and chronic health evaluation) II score was 15.5 (range, 3 to 29), and median duration of mechanical ventilation prior to the SBT was 7 days (range, 1 to 40 days). Extubation was successful in 25 patients (72%). There were no significant differences in baseline characteristics between patients successfully extubated (group 1) and those requiring reintubation. On multivariate analysis, RVRATC measured at 60 min (RVR(60)ATC) was most predictive of successful extubation (p = 0.03). The area under the receiver operator characteristic curve was also highest for RVR(60)ATC (0.81 +/- 0.03) as compared to RVR (0.77 +/- 0.03), RVRATC (0.75 +/- 0.04), and RVR measured at 60 min (0.69 +/- 0.05). The ratio of RVR(60)ATC to Paw was the best predictor (0.84 +/- 0.02). CONCLUSIONS: RVRATC measured at the end of the SBT was the best predictor of successful extubation. A new ratio (ratio of RVRATC to Paw) was most predictive and deserves further study.

Adult↗

Mechanisms underlying dependencies of performance on stimulus history in a two-alternative forced-choice task.

In choice reaction time tasks, response times and error rates demonstrate differential dependencies on the identities of up to four stimuli preceding the current one. Although the general profile of reaction times and error rates, when plotted against the stimulus histories, may seem idiosyncratic, we show that it can result from simple underlying mechanisms that take account of the occurrence of stimulus repetitions and alternations. Employing a simple connectionist model of a two-alternative forced-choice task, we explored various combinations of repetition and alternation detection schemes in an attempt to account for empirical results from the literature and from our own studies. We found that certain combinations of the repetition and the alternation schemes provided good fits to the data, suggesting that simple mechanisms may serve to explain the complicated but highly reproducible higher order dependencies of task performance on stimulus history.

Adolescent↗

A computational model of anterior cingulate function in speeded response tasks: effects of frequency, sequence, and conflict.

A growing body of evidence from functional neuroimaging and computational modeling studies indicates that the anterior cingulate cortex (ACC) detects the presence of response conflict and conveys this information to other brain regions, enabling subsequent adjustments in cognitive control. The present study examined previous empirical findings of increased ACC for low-frequency stimuli across three distinct speeded response tasks (two-alternative forced choice, go/no-go, and oddball). Simulations conducted in a neural network model incorporating sequential priming mechanisms (developed in Cho et al., 2002) confirmed that a computational measure of response conflict was higher on low-frequency trials across all three tasks. In addition, the model captured detailed aspects of behavioral reaction time and accuracy data, predicted the dynamics of ACC activity related to trial sequence effects, and provided evidence for the functional role of conflict information in performance monitoring and optimization. The results indicate that the conflict-monitoring hypothesis, augmented by mechanisms for encoding stimulus history, can explain key phenomena associated with performance in sequential speeded response tasks.

Adolescent↗

Simplified dynamics in a model of noradrenergic modulation of cognitive performance.

Neurophysiological work in monkeys has shown that changes in tonic and stimulus-induced activity in the noradrenergic brainstem nucleus locus coeruleus (LC) are tightly correlated with fluctuations in behavioral performance in a visual discrimination task. Simulation work suggests transitions between observed modes of LC activity may be mediated by changes in the level of coherent firing among individual LC neurons. We have simplified this simulation by abstracting the LC to a simple, excitable system in two variables modeled after the FitzHugh-Nagumo relaxation oscillator. This abstracted LC simulates population-level dynamics of the nucleus relevant to its influence on behavior. Coherence within the nucleus was simulated as a single parameter which amplified external input to the abstracted LC while attenuating tonic, uncorrelated activity. Simulated results captured LC dynamics and their relationship with behavior observed in monkeys. Behavior was further simulated over a range of potential LC states not, as yet, directly observed. These results suggest a reverse sigmoidal relationship between false alarm rate and coherence, and a more complex, non-monotonic relationship between response time and coherence.

Animals↗