J. Waltz | University of Maryland Baltimore (original) (raw)

Papers by J. Waltz

Psychological Medicine

Background Prior evidence indicates that negative symptom severity and cognitive deficits, in peo... more 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 represen...

Cognitive, Affective, & Behavioral Neuroscience, 2018

Individuals from across the psychosis spectrum display impairments in reinforcement learning. In ... more 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.

Schizophrenia Bulletin, 2014

The current study examined the efficacy and safety of rasagiline, a selective MAO-B inhibitor, fo... more The current study examined the efficacy and safety of rasagiline, a selective MAO-B inhibitor, for the treatment of persistent negative symptoms. Methods: Sixty people with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder, who met a priori criteria for persistent negative symptoms, were randomized to receive rasagiline, 1 mg/d (n = 31) or placebo (n = 29) in a 12-week, double-blind, placebo-controlled clinical trial. The Scale for the Assessment of Negative Symptoms (SANS) total score was used to assess change in negative symptoms. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), N-Back test, a probabilistic learning task, and a delayed discounting task were used to assess cognition. Results: In a mixed model analysis of covariance (MM-ANCOVA), with time as a continuous variable, there was a significant treatment × time effect for SANS total score (F = 5.61(df = 1,40.3), P = .023). The treatment × time interaction effect was also significant for the SANS avolition subscale score (F(1,40.2) = 10.41, P = .002). In a post hoc MM-ANCOVA analyses, with time as a categorical variable, group differences were significant at week 12 for SANS total score (t(37.3) = 2.15; P = .04; d = −0.41) and SANS avolition subscale score (t(49.0) = 3.06; P = .004; d = −0.46). There was a significant difference in number of participants with a ≥20% reduction in SANS avolition score (χ 2 (1) = 10.94; P = .0009), but not in SANS total score (χ 2 (1) = 1.11; P = .29). There were no significant group differences on the RBANS, N-Back, probabilistic learning, or delayed discounting tasks. Conclusions: Study results support future studies of the utility of rasagiline for the treatment of negative symptoms, including avolition (clinicaltrials.gov trial number: NCT00492336).

Schizophrenia Research, 2014

Background: Many previous studies have established that individuals with schizophrenia (SZ) exper... more Background: Many previous studies have established that individuals with schizophrenia (SZ) experienced deficits in social cognition including Theory of Mind (ToM) disorders (Brüne 2005, Green et al. 2008). Very few studies have investigated these impairments in schizophrenia during natural communication situations (McCabe et al. 2004, Champagne-Lavau et al. 2009). However, to fully characterize ToM ability in schizophrenia, we need to understand several components of this ability that specifically appear during social interactions. In the present study, we were interesting in focus marking as a linguistic marker of ToM. We know that speakers use prosody to encode the difference between the given/contrastive statuses (i.e. focus marking) of discourse referents in accordance with their beliefs about the hearers' knowledge state. Specifically, in French, the contrastive information shows a tendency to be produced in a separate prosodic phrase from the rest of the utterance. In this study we tested whether the prosodic encoding of contrast is altered in SZ speech during social interaction and whether this alteration reflects ToM impairment. Methods: Ten individuals with a DSM-IV diagnosis of schizophrenia (SZ) and ten healthy control (HC) participants matched for age and educational level were recruited. They were all native French speakers. They were assessed on their ToM ability with the hinting task (Corcoran et al. 1995). Then, they were asked to play a collaborative game with an experimenter. During this game, the aim of the participant was to transfer a given route from his/her map to his/her interlocutor. To do so, he/she had to indicate to the interlocutor 32 pairs of noun-adjective fragments (e.g. You have to go between {the purple CANDLES} 1st fragment {and the purple CANDIES} 2nd fragment). For each pair, the noun of the second fragment could be either identical relative to the first one (e.g. candies vs. candies) or could contrast with it (e.g. candles vs. candies). This interactive task enabled us to measure acoustic correlates of prosodic phrasing to determine whether the same target noun was parsed separately from the adjective in the two focused conditions (unfocused: given vs. focused: contrastive). Results: A mixed effects logistic regression modelling including the 323 observations obtained from the participants' speech was performed to test the effect of focus condition (unfocused: given vs. focused: contrastive) on the prosodic phrasing produced by participants. The main results showed that SZ participants did not produce more separate nouns when the target noun was contrastive than when it was given (z=1.543, p=0.123). By contrast, HC participants produced more separate nouns when the target noun was contrastive than when it was given (z=3.830, p<0.0001). Such pattern of performance in the SZ group was significantly correlated with their ToM abilities. Discussion: These findings showed that SZ participants were unable to use prosody to indicate to their interlocutor which information is part of a contrastive focus, in relation with their difficulties to attribute knowledge to the person with whom they interact. Their production of prosodic phrasing reflecting attribution of knowledge during conversation is impaired. Thus, the interactive task we used appears to be an original option for studying ToM ability in schizophrenia since it is close to what happens in real-life interactions. Linguistic prosody seems to be a good target for cognitive remediation aiming to increase social cognition ability.

Schizophrenia Bulletin, 2013

This article reviews and synthesizes research on reward processing in schizophrenia, which has be... more This article reviews and synthesizes research on reward processing in schizophrenia, which has begun to provide important insights into the cognitive and neural mechanisms associated with motivational impairments. Aberrant cortical-striatal interactions may be involved with multiple reward processing abnormalities, including: (1) dopaminemediated basal ganglia systems that support reinforcement learning and the ability to predict cues that lead to rewarding outcomes; (2) orbitofrontal cortex-driven deficits in generating, updating, and maintaining value representations; (3) aberrant effort-value computations, which may be mediated by disrupted anterior cingulate cortex and midbrain dopamine functioning; and (4) altered activation of the prefrontal cortex, which is important for generating exploratory behaviors in environments where reward outcomes are uncertain. It will be important for psychosocial interventions targeting negative symptoms to account for abnormalities in each of these reward processes, which may also have important interactions; suggestions for novel behavioral intervention strategies that make use of external cues, reinforcers, and mobile technology are discussed.

Schizophrenia Bulletin, 2010

Proceedings of the National Academy of Sciences, 2007

Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI) signal have rece... more Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI) signal have recently been applied to investigate large-scale neuronal networks of the brain in the absence of specific task instructions. However, the underlying neural mechanisms of these fluctuations remain largely unknown. To this end, electrophysiological recordings and resting-state fMRI measurements were conducted in α-chloralose-anesthetized rats. Using a seed-voxel analysis strategy, region-specific, anesthetic dose-dependent fMRI resting-state functional connectivity was detected in bilateral primary somatosensory cortex (S1FL) of the resting brain. Cortical electroencephalographic signals were also recorded from bilateral S1FL; a visual cortex locus served as a control site. Results demonstrate that, unlike the evoked fMRI response that correlates with power changes in the γ bands, the resting-state fMRI signal correlates with the power coherence in low-frequency bands, particularly the δ band...

Neuropsychopharmacology, 2008

One prevalent theory of learning states that dopamine neurons signal mismatches between expected ... more One prevalent theory of learning states that dopamine neurons signal mismatches between expected and actual outcomes, called temporal difference errors (TDEs). Evidence indicates that dopamine system dysfunction is involved in negative symptoms of schizophrenia (SZ), including avolition and anhedonia. As such, we predicted that brain responses to TDEs in dopamine midbrain nuclei and target areas would be abnormal in SZ. A total of 18 clinically stable patients with chronic SZ and 18 controls participated in an fMRI study, which used a passive conditioning task. In the task, the delivery of a small amount of juice followed a light stimulus by exactly 6 s on approximately 75% of 78 total trials, and was further delayed by 4-7 s on the remaining trials. The delayed juice delivery was designed to elicit the two types of TDE signals, associated with the recognition that a reward was omitted at the expected time, and delivered at an unexpected time. Main effects of TDE valence and group differences in the positive-negative TDE contrast (unexpected juice deliveriesjuice omissions) were assessed through whole-brain and regions of interest (ROI) analyses. Main effects of TDE valence were observed for the entire sample in the midbrain, left putamen, left cerebellum, and primary gustatory cortex, bilaterally. Whole-brain analyses revealed group differences in the positive-negative TDE contrast in the right putamen and left precentral gyrus, whereas ROI analyses revealed additional group differences in the midbrain, insula, and parietal operculum, on the right, the putamen and cerebellum, on the left, and the frontal operculum, bilaterally. Further, these group differences were generally driven by attenuated responses in patients to positive TDEs (unexpected juice deliveries), whereas responses to negative TDEs (unexpected juice omissions) were largely intact. Patients also showed reductions in responses to juice deliveries on standard trials, and more blunted reinforcer responses in the left putamen corresponded to higher ratings of avolition. These results provide evidence that SZ patients show abnormal brain responses associated with the processing of a primary reinforcer, which may be a source of motivational deficits.

Memory & Cognition, 2000

This research was supported by NSF Grant SBR-9729023. We thank Art Markman for generously providi... more This research was supported by NSF Grant SBR-9729023. We thank Art Markman for generously providing us with electronic versions of the pictures used by Markman and Gentner (1993). Dedre Gentner, Steve Sloman, and an anonymous reviewer provided helpful comments on an earlier draft.

Psychological Science, 1999

The integration of multiple relations between mental representations is critical for higher level... more The integration of multiple relations between mental representations is critical for higher level cognition. For both deductive- and inductive-reasoning tasks, patients with prefrontal damage exhibited a selective and catastrophic deficit in the integration of relations, whereas patients with anterior temporal lobe damage, matched for overall IQ but with intact prefrontal cortex, exhibited normal relational integration. In contrast, prefrontal patients performed more accurately than temporal patients on tests of both episodic memory and semantic knowledge. These double dissociations suggest that integration of relations is a specific source of cognitive complexity for which intact prefrontal cortex is essential. The integration of relations may be the fundamental common factor linking the diverse abilities that depend on prefrontal function, such as planning, problem solving, and fluid intelligence.

Schizophrenia Bulletin, 2008

Schizophrenia Bulletin, 2012

Neuroimage, 2003

Working memory (WM) capacity limitations and their neurophysiological correlates are of special r... more Working memory (WM) capacity limitations and their neurophysiological correlates are of special relevance for the understanding of higher cognitive functions. Evidence from behavioral studies suggests that restricted attentional resources contribute to these capacity limitations. In an event-related functional magnetic resonance imaging (fMRI) study, we probed the capacity of the human visual WM system for up to four complex nonnatural objects using a delayed discrimination task. A number of prefrontal and parietal areas bilaterally showed increased blood oxygen level-dependent activity, relative to baseline, throughout the task when more than one object had to be held in memory. Monotonic increases in response to memory load were observed bilaterally in the dorsolateral prefrontal cortex (DLPFC) and the presupplementary motor area (pre-SMA). Conversely, activity in the frontal eye fields (FEFs) and in areas along the intraparietal sulcus (IPS) peaked when subjects had to maintain only two or three objects and decreased in the highest load condition. This dissociation of memory load effects on cortical activity suggests that the cognitive operations subserved by the IPS and FEF, which are most likely related to attention, fail to support visual WM when the capacity limit is approached. The correlation of brain activity with performance implies that only the operations performed by the DLPFC and pre-SMA, which support an integrated representation of visual information, helped subjects to maintain a reasonable level of performance in the highest load condition. These results indicate that at least two distinct cortical subsystems are recruited for visual WM, and that their interplay changes when the capacity limit is reached.

Background: The Iowa Gambling Task (IGT; Bechara et al., 1994) has frequently been used to assess... more Background: The Iowa Gambling Task (IGT; Bechara et al., 1994) has frequently been used to assess risky decision making in clinical populations, including patients with schizophrenia (SZ). Poor performance on the IGT is often attributed to reduced sensitivity to punishment, which contrasts with recent findings from reinforcement learning studies in schizophrenia.
Methods: In order to investigate possible sources of IGT performance deficits in SZ patients, we combined data from the IGT from 59 SZ patients and 43 demographically-matched controls with data from the Balloon Analog Risk Task (BART) in the same participants. Our analyses sought to specifically uncover the role of punishment sensitivity and delineate the capacity to integrate frequency and magnitude information in decision-making under risk.
Results: Although SZ patients, on average, made more choices from disadvantageous decks than controls did on the IGT, they avoided decks with frequent punishments at a rate similar to controls. Patients also exhibited excessive loss-avoidance behavior on the BART.
Conclusions: We argue that, rather than stemming from reduced sensitivity to negative consequences, performance deficits on the IGT in SZ patients are more likely the result of a reinforcement learning deficit, specifically involving the integration of frequencies and magnitudes of rewards and punishments in the trial-by-trial estimation of expected value.

Archives of general psychiatry, 2012

Negative symptoms are a core feature of schizophrenia, but their pathogenesis remains unclear. Ne... more Negative symptoms are a core feature of schizophrenia, but their pathogenesis remains unclear. Negative symptoms are defined by the absence of normal function. However, there must be a productive mechanism that leads to this absence. To test a reinforcement learning account suggesting that negative symptoms result from a failure in the representation of the expected value of rewards coupled with preserved loss-avoidance learning. Participants performed a probabilistic reinforcement learning paradigm involving stimulus pairs in which choices resulted in reward or in loss avoidance. Following training, participants indicated their valuation of the stimuli in a transfer test phase. Computational modeling was used to distinguish between alternative accounts of the data. A tertiary care research outpatient clinic. In total, 47 clinically stable patients with a diagnosis of schizophrenia or schizoaffective disorder and 28 healthy volunteers participated in the study. Patients were divided...

Schizophrenia bulletin, Jan 2, 2014

Objective: The current study examined the efficacy and safety of rasagiline, a selective MAO-B in... more Objective: The current study examined the efficacy and safety of rasagiline, a selective MAO-B inhibitor, for the treatment of persistent negative symptoms. Methods: Sixty people with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder, who met a priori criteria for persistent negative symptoms, were randomized to receive rasagiline, 1mg/d (n = 31) or placebo (n = 29) in a 12-week, double-blind, placebo-controlled clinical trial. The Scale for the Assessment of Negative Symptoms (SANS) total score was used to assess change in negative symptoms. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), N-Back test, a probabilistic learning task, and a delayed discounting task were used to assess cognition. Results: In a mixed model analysis of covariance (MM-ANCOVA), with time as a continuous variable, there was a significant treatment × time effect for SANS total score (F = 5.61(df = 1,40.3), P = .023...