A computational neuroimaging study of reinforcement learning and goal-directed exploration in schizophrenia spectrum disorders.

BACKGROUND: Prior evidence indicates that negative symptom severity and cognitive deficits, in people with schizophrenia (PSZ), relate to measures of reward-seeking and loss-avoidance behavior (implicating the ventral striatum/VS), as well as uncertainty-driven exploration (reliant on rostrolateral prefrontal cortex/rlPFC). While neural correlates of reward-seeking and loss-avoidance have been examined in PSZ, neural correlates of uncertainty-driven exploration have not. Understanding neural correlates of uncertainty-driven exploration is an important next step that could reveal insights to how this mechanism of cognitive and negative symptoms manifest at a neural level. METHODS: We acquired fMRI data from 29 PSZ and 36 controls performing the Temporal Utility Integration decision-making task. Computational analyses estimated parameters corresponding to learning rates for both positive and negative reward prediction errors (RPEs) and the degree to which participates relied on representations of relative uncertainty. Trial-wise estimates of expected value, certainty, and RPEs were generated to model fMRI data. RESULTS: Behaviorally, PSZ demonstrated reduced reward-seeking behavior compared to controls, and negative symptoms were positively correlated with loss-avoidance behavior. This finding of a bias toward loss avoidance learning in PSZ is consistent with previous work. Surprisingly, neither behavioral measures of exploration nor neural correlates of uncertainty in the rlPFC differed significantly between groups. However, we showed that trial-wise estimates of relative uncertainty in the rlPFC distinguished participants who engaged in exploratory behavior from those who did not. rlPFC activation was positively associated with intellectual function. CONCLUSIONS: These results further elucidate the nature of reinforcement learning and decision-making in PSZ and healthy volunteers.

Motivational deficits in schizophrenia relate to abnormalities in cortical learning rate signals.

Individuals from across the psychosis spectrum display impairments in reinforcement learning. In some individuals, these deficits may result from aberrations in reward prediction error (RPE) signaling, conveyed by dopaminergic projections to the ventral striatum (VS). However, there is mounting evidence that VS RPE signals are relatively intact in medicated people with schizophrenia (PSZ). We hypothesized that, in PSZ, reinforcement learning deficits often are not related to RPE signaling per se but rather their impact on learning and behavior (i.e., learning rate modulation), due to dysfunction in anterior cingulate and dorsomedial prefrontal cortex (dmPFC). Twenty-six PSZ and 23 healthy volunteers completed a probabilistic reinforcement learning paradigm with occasional, sudden, shifts in contingencies. Using computational modeling, we found evidence of an impairment in trial-wise learning rate modulation (α) in PSZ before and after a reinforcement contingency shift, expressed most in PSZ with more severe motivational deficits. In a subsample of 22 PSZ and 22 healthy volunteers, we found little evidence for between-group differences in VS RPE and dmPFC learning rate signals, as measured with fMRI. However, a follow-up psychophysiological interaction analysis revealed decreased dmPFC-VS connectivity concurrent with learning rate modulation, most prominently in individuals with the most severe motivational deficits. These findings point to an impairment in learning rate modulation in PSZ, leading to a reduced ability to adjust task behavior in response to unexpected outcomes. At the level of the brain, learning rate modulation deficits may be associated with decreased involvement of the dmPFC within a greater RL network.

The role of working memory in analogical mapping.

The impact of a working-memory load on analogical mapping was examined in two experiments, using a dual-task paradigm. In Experiment 1, we used a phonological working-memory load; in Experiment 2, we used a phonological working-memory load and an executive working-memory load. The subjects were required to identify correspondences between visual scenes, either for single objects or for three objects simultaneously. The results indicated that the imposition of either a phonological or an executive working-memory load decreased the frequency with which the subjects identified correspondences between scenes based on relations and increased the frequency with which they identified correspondences based on object attributes. The frequency with which subjects made relational mappings was increased by the instruction to find correspondences for multiple objects in a scene simultaneously, rather than for just one. These results indicate that mapping on the basis of relations places greater demands on both modality-specific buffers and executive components of working memory than does mapping on the basis of object attributes.

Testing a typology of batterers.

A. Holtzworth-Munroe and G. L. Stuart (1994) proposed a tripartite typology of men who batter their female partners based on the severity of violence, extent of violence, and personality disorder characteristics. The current study attempts to empirically validate this typology using data from 75 domestically violent (DV) men and their partners, and 32 maritally distressed, nonviolent (DNV) comparison couples. Mixture analysis results generally supported the model, although 2 types were not distinguishable on personality disorder characteristics as predicted. Generally violent batterers were significantly more violent within and outside the relationship. The pathological group was moderately violent within and outside the relationship and endorsed numerous psychological symptoms. Family-only batterers endorsed fewer symptoms and were less violent. Violence in the family of origin, attachment, and communication skills also differentiated the 3 types and DNV men.

Spinal cord stimulation: a quarter century of development and investigation. A review of its development and effectiveness in 1,336 cases.

The past two and a half decades have seen the development of a spinal cord stimulator from the early 2-electrode fixed system to the present multielectrode computerized systems. During these 25 years, spinal cord stimulation has been studied in the treatment of motor disorders. The effectiveness was studied in 1,336 cases, including cerebral palsy (456), dystonia (173), torticollis (90), multiple sclerosis (130), spinocerebellar degeneration (71), spinal cord injury (303) and posttraumatic brain injury (113). It has become increasingly evident that the maximum therapeutic effect is achieved by virtue of the applied field variables of the spinal cord level stimulated, the field configuration, its polarity, and the frequency of the stimulation. These observations have led to investigational corollaries of the therapeutic specificity of the applied field, the neurophysiologic mechanisms of these fields and the underlying abnormal neurophysiologic substrate, which may indeed be secondary to abnormalities in the nerve impulse itself.

Affect, verbal content, and psychophysiology in the arguments of couples with a violent husband.

The purpose of this investigation was to study the affect, psychophysiology, and violent content of arguments in couples with a violent husband. On the basis of self-reports of violent arguments, there were no wife behaviors that successfully suppressed husband violence once it began; moreover, husband violence escalated in response to nonviolent as well as violent wife behaviors, whereas wife violence escalated only in reaction to husband violence or emotional abuse. Only wives were fearful during violent and nonviolent arguments. The observational coding of nonviolent arguments in the laboratory revealed that both battering husbands and their wives (DV) were angrier than their maritally distressed but nonviolent (DNV) counterparts. As predicted, on the more provocative anger codes, only DV men differed from their DNV counterparts. However, DV wives were as verbally aggressive toward their husbands as DV husbands were toward their wives.

Differences in sodium and D-glucose transport between hamster and rat lungs.

The purpose of this study was to characterize phloridzin- and amiloride-sensitive transport across blood-gas barrier of hamster and rat lungs. Air spaces of isolated perfused lungs were instilled with a solution containing 22Na or L-[3H]glucose, D-[14C]glucose, and fluorescein isothiocyanate-labeled dextran. Apparent permeability-surface area products (PS) were calculated. Phloridzin (Na(+)-dependent D-glucose transport inhibitor) had no effect on D-glucose or sodium transport out of air spaces in hamster lungs. In contrast, in rat lungs, phloridzin decreased PS for D-glucose by 89% and that for Na by 28%. Trapping of 14CO2 in vascular samples was measured to estimate metabolism. Unlabeled air space D-glucose increased appearance of perfused D-[14C]glucose in air spaces of rat lungs. We conclude that Na(+)-dependent D-glucose transport is important for D-glucose uptake in rat lungs but not in hamster lungs. In hamster lungs, amiloride (Na+ transport inhibitor) also decreased PS for sodium, but drugs known to stimulate sodium transport in rat lungs had no effect. Thus, species differences in active transport processes exist in the distal air spaces of mammalian lungs.

Testing the integrity of a psychotherapy protocol: assessment of adherence and competence.

Manipulation checks should be used in psychotherapy trials to confirm that therapists followed the treatment manuals and performed the therapy competently. This article is a review of some strategies that have been used to document treatment integrity; also, their limitations are discussed here. Recommendations for improving these checks are presented. Specific guidelines are offered regarding when and how to assess both therapist adherence to treatment protocols and competence.

Power and violence: the relation between communication patterns, power discrepancies, and domestic violence.

This study hypothesized that power discrepancies in the marital relationship, where the husband is subordinate, serve as risk factors for husband-to-wife violence. The construct of marital power was assessed from 3 power domains operationalized by discrepancies in economic status, decision-making power, communication patterns, and communication skill. Three groups of married couples (N = 95) were compared: domestically violent (DV), maritally distressed/nonviolent (DNV), and maritally happy/nonviolent (HNV). DV couples were more likely than the 2 nonviolent groups to engage in husband demand/wife withdraw interactions. Within the DV group, husbands who had less power were more physically abusive toward their wives. Thus, violence may be compensatory behavior to make up for husbands' lack of power in other arenas of marriage. Difficulties in assessing marital power and future direction for the study of power and violence are discussed.

Recruiting nonviolent men as control subjects for research on marital violence: how easily can it be done?

Data regarding the prevalence of violence among subjects recruited for nonviolent control groups in five studies are presented. These studies examined subjects recruited using a variety of methods, including couples seeking marital therapy and couples recruited from newspaper advertisements. Across the studies, it appears that up to one-third of maritally nondistressed couples and one-half of maritally distressed couples report that husband violence has occurred in their relationship. The implications of these data for the recruitment of control groups in future studies of marital violence are discussed, and questions regarding the ease of recruiting nonviolent couples for control groups are raised.

The systematic collection of patient data in a centre for child and adolescent psychiatry.

Computerisation of case records has been slow to take place in child psychiatry, partly because of the amount of detailed and sometimes complex information required. A program for storing case records has been developed and it has proved of great value in epidemiological work, for example, regarding patient age structures and family compositions.

Lung cancer in Florida. Risks associated with residence in the central Florida phosphate mining region.

A case-control study that included 25,398 cases of lung cancer among Florida residents, first diagnosed in 1981-1983, was conducted to determine if residence in the central Florida phosphate mining region was associated with an increased risk of lung cancer. A twofold increase in lung cancer risk was observed among male nonsmokers who lived in the study area. Risks were elevated for all major lung cancer cell types, with the highest risks observed for small cell carcinoma of the lung. Among cigarette smokers, a slight, but not statistically significant, additional increase in risk was associated with residence in the study area. Among women, no significant elevations in risk were observed for persons who lived in the study area. The greatest increase in risk among women was for small cell carcinomas, but the elevations were not statistically significant.

Spinal cord stimulation and motor disorders.

Spinal cord stimulation has been investigated by us during the past 10 years in the treatment of various disorders of the motor system. The effectiveness was studied in 735 cases, including cerebral palsy (212), dystonia (129), torticollis (66), spinal cord injury (169), and degenerative diseases (159). Our results indicate that in properly selected patients, stimulating the spinal neural axis is therapeutically effective in the majority of the cases treated. Our data demonstrate that the level stimulated, the pattern and the polarity of the applied field, and the frequency of the stimulation are critical to achieve a satisfactory therapeutic result and must be individualized in each patient.

Spinal cord stimulation revisited: psychological effects.

97 patients undergoing spinal cord stimulation (SCS) were studied for a median of 24 days after initiation of treatment. SCS was associated with significant improvement in memory, visuo-spatial integration, activation, cognitive efficiency, attention and overall psychological status. Significant emotional improvement in self-image, anxiety and depression was also confirmed following SCS. Diagnosis did not differentially affect psychological outcome except for relief of anxiety, which was less pronounced in the case of torticollis and multiple sclerosis. The role of spinal cord modulation of behavioral activation and physiological arousal was discussed.

Ventricular fluid somatostatin concentration decreases in childhood-onset dystonia.

Somatostatin was measured in CSF from individuals with a variety of neurologic diseases. In ventricular CSF, somatostatin concentration was significantly lower in individuals with childhood-onset dystonia than in individuals with other forms of dystonia or with other disorders. Severity of childhood dystonia correlated with somatostatin concentration, suggesting a progressive dysfunction of somatostatin-containing neurons with increasing disease severity. There were no significant differences in somatostatin concentration in lumbar CSF. Multiple forms of immunoreactive somatostatin were found in a pool of lumbar CSF from normal individuals. Labeled somatostatin administered intra-arterially to rats failed to cross the blood-brain barrier.

Spinal cord stimulation in the treatment of spasmodic torticollis.

This report presents our observations in 63 patients undergoing chronic spinal cord stimulation for treatment of spasmodic torticollis. In this series there were 23 patients (36.5%) who demonstrated marked improvement, characterized by no evidence of torticollis, full range of motility of the head and neck and no pain. Moderate improvement was found in 20 patients (31.8%) who showed minimal residual torticollis, but had full motility and no pain. There were 5 patients (7.9%) considered mildly improved who demonstrated decrease in their torticollic position, spasms and pain, but retained some element of torticollis and/or some limitation of motility. Correlations were made demonstrating the effect on the results of age, sex, electrode array, the configuration of the applied field and the parameters of stimulation.

Vasoactive intestinal peptide in cerebrospinal fluid.

Immunoreactive vasoactive intestinal peptide (VIP) was measured in lumbar and ventricular cerebrospinal fluid (CSF) from patients with various neurological disorders and in 2 hour aliquots of cisternal fluid removed continuously from rhesus monkeys. Although most of the VIP in concentrated pools of human ventricular fluid and of monkey cisternal fluid co-eluted with synthetic porcine VIP28 on a column of Sephadex G-25 superfine, there was evidence that smaller immunoreactive fragments were also present. A circadian pattern of CSF VIP concentration was observed in 2 of the 3 monkeys studied, with highest levels occurring at night and lowest during the day. Ventricular fluid VIP levels were highest in hydrocephalic children and lowest in patients with multiple sclerosis or epilepsy, while VIP was not detectable in ventricular fluid from patients in coma following a severe head injury. There were no significant differences in VIP concentrations in CSF from patients with dystonia. Parkinson's disease, or Alzheimer's disease, suggesting that VIP containing neurons are not affected in these disorders. Lumbar fluid VIP levels were low in patients undergoing aneurysm surgery. Since VIP is a potent vasodilator, these findings may have important implications in relation to the development of vasospasm following subarachnoid hemorrhage.