Paul D Metzak

University of British Columbia - Vancouver, Vancouver, British Columbia, Canada

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Publications (16)73.8 Total impact

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    ABSTRACT: Background: Task-based functional neuroimaging studies of schizophrenia have not yet replicated the increased coordinated hyperactivity in speech-related brain regions that is reported with symptom-capture and resting-state studies of hallucinations. This may be due to suboptimal selection of cognitive tasks. Methods: In the current study, we used a task that allowed experimental manipulation of control over verbal material and compared brain activity between 23 schizophrenia patients (10 hallucinators, 13 nonhallucinators), 22 psychiatric (bipolar), and 27 healthy controls. Two conditions were presented, one involving inner verbal thought (in which control over verbal material was required) and another involving speech perception (SP; in which control verbal material was not required). Results: A functional connectivity analysis resulted in a left-dominant temporal-frontal network that included speech-related auditory and motor regions and showed hypercoupling in past-week hallucinating schizophrenia patients (relative to nonhallucinating patients) during SP only. Conclusions: These findings replicate our previous work showing generalized speech-related functional network hypercoupling in schizophrenia during inner verbal thought and SP, but extend them by suggesting that hypercoupling is related to past-week hallucination severity scores during SP only, when control over verbal material is not required. This result opens the possibility that practicing control over inner verbal thought processes may decrease the likelihood or severity of hallucinations.
    Schizophrenia Bulletin 02/2014; · 8.80 Impact Factor
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    ABSTRACT: Optimally interpreting our situations and experiences frequently requires comparing the evidence supporting conflicting hypotheses and deciding which to accept. This decision is comparable to an "Aha!" moment reached during insightful problem solving. We used a probabilistic reasoning task to investigate the neural activity underlying these processes. Participants rated the probability that a given focal hypothesis, rather than its alternative, was true. Decisions to accept the focal hypothesis elicited a stronger signal than decisions to reject it in a network involving the dorsal anterior cingulate cortex (dACC) and functionally connected frontal, parietal, and occipital regions. Follow-up analyses suggested that this was not simply a higher overall level of activation within the dACC or other individual regions of the network, but reflected a stronger signal for the network as a whole. This result is discussed in terms of functional connectivity between the dACC and other brain regions as a possible mechanism for coherence between components of a mental representation.
    Neuropsychologia 03/2013; · 3.48 Impact Factor
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    ABSTRACT: When switching tasks, if stimuli are presented that contain features that cue two of the tasks in the set (i.e., bivalent stimuli), performance slowing is observed on all tasks. This generalized slowing extends to tasks in the set which have no features in common with the bivalent stimulus and is referred to as the bivalency effect. In previous work, the bivalency effect was invoked by presenting occasionally occurring bivalent stimuli; therefore, the possibility that the generalized slowing is simply due to surprise (as opposed to bivalency) has not yet been discounted. This question was addressed in two task switching experiments where the occasionally occurring stimuli were either bivalent (bivalent version) or merely surprising (surprising version). The results confirmed that the generalized slowing was much greater in the bivalent version of both experiments, demonstrating that the magnitude of this effect is greater than can be accounted for by simple surprise. This set of results confirms that slowing task execution when encountering bivalent stimuli may be fundamental for efficient task switching, as adaptive tuning of response style may serve to prepare the cognitive system for possible future high conflict trials. When switching tasks, if the presented stimuli are univalent with respect to the current set of tasks (i.e., they carry features specific to only one task in the current set of tasks), under some conditions, these tasks can be performed equally quickly compared to when the same tasks are carried out in a repeated sequence (Allport & Wylie, 2000; Jersild, 1927; Rogers & Monsell, 1995; Wylie & Allport, 2000). However, when stimuli are pre-sented that are bivalent, that is, carry features shared by two tasks in a set of tasks, performance is substantially slowed (Rubin & Meiran, 2005). For a concrete example, if one task requires naming the colour of letters printed in colour, and the other requires making case decisions about the same letters, coloured letters are biva-lent stimuli with respect to the set of tasks, whereas coloured bars or uncoloured letters would be univalent stimuli with respect to the set of tasks. In previous task switching studies (Grundy et al.
    Journal of Cognitive Psychology 01/2013;
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    ABSTRACT: Working memory (WM) is not a unitary construct. There are distinct processes involved in encoding information, maintaining it on-line, and using it to guide responses. The anatomical configurations of these processes are more accurately analyzed as functionally connected networks than collections of individual regions. In the current study we analyzed event-related functional magnetic resonance imaging (fMRI) data from a Sternberg Item Recognition Paradigm WM task using a multivariate analysis method that allowed the linking of functional networks to temporally-separated WM epochs. The length of the delay epochs was varied to optimize isolation of the hemodynamic response (HDR) for each task epoch. All extracted functional networks displayed statistically significant sensitivity to delay length. Novel information extracted from these networks that was not apparent in the univariate analysis of these data included involvement of the hippocampus in encoding/probe, and decreases in BOLD signal in the superior temporal gyrus (STG), along with default-mode regions, during encoding/delay. The bilateral hippocampal activity during encoding/delay fits with theoretical models of WM in which memoranda held across the short term are activated long-term memory representations. The BOLD signal decreases in the STG were unexpected, and may reflect repetition suppression effects invoked by internal repetition of letter stimuli. Thus, analysis methods focusing on how network dynamics relate to experimental conditions allowed extraction of novel information not apparent in univariate analyses, and are particularly recommended for WM experiments for which task epochs cannot be randomized.
    NeuroImage 10/2012; · 6.25 Impact Factor
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    ABSTRACT: An important aspect of schizophrenia symptomatology is inner-outer confusion, or blurring of ego boundaries, which is linked to symptoms such as hallucinations and Schneiderian delusions. Dysfunction in the cognitive processes involved in the generation of private thoughts may contribute to blurring of the ego boundaries through increased activation in functional networks including speech- and voice-selective cortical regions. In the present study, the neural underpinnings of silent verbal thought generation and speech perception were investigated using functional magnetic resonance imaging (fMRI). Functional connectivity analysis was performed using constrained principal component analysis for fMRI (fMRI-CPCA). Group differences were observable on two functional networks: one reflecting hyperactivity in speech- and voice-selective cortical regions (e.g., bilateral superior temporal gyri (STG)) during both speech perception and silent verbal thought generation, and another involving hyperactivity in a multiple demands (i.e., task-positive) network that included Wernicke's area, during silent verbal thought generation. This set of preliminary results suggests that hyperintensity of functional networks involving voice-selective cortical regions may contribute to the blurring of ego boundaries characteristic of schizophrenia.
    Psychiatry Research 06/2012; 202(2):110-7. · 2.46 Impact Factor
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    ABSTRACT: During task switching, if we occasionally encounter stimuli that cue more than one task (i.e., bivalent stimuli), response slowing is observed on all univalent trials within that block, even when no features overlap with the bivalent stimuli. This observation is known as the bivalency effect. Previous fMRI work (Woodward et al., 2008) clearly suggests a role for the dorsal anterior cingulate cortex (dACC) in the bivalency effect, but the time course remains uncertain. Here, we present the first high-temporal resolution account for the bivalency effect using stimulus-locked event-related potentials. Participants alternated among three simple tasks in six experimental blocks, with bivalent stimuli appearing occasionally in bivalent blocks (blocks 2, 4, and 6). The increased reaction times for univalent stimuli in bivalent blocks demonstrate that these stimuli are being processed differently from univalent stimuli in purely univalent blocks. Frontal electrode sites captured significant amplitude differences associated with the bivalency effect within time windows 100-120 ms, 375-450 ms, and 500-550 ms, which may reflect additional extraction of visual features present in bivalent stimuli (100-120 ms) and suppression of processing carried over from irrelevant cues (375-450 ms and 500-550 ms). Our results support the fMRI findings and provide additional evidence for involvement of the dACC. Furthermore, the bivalency effect dissipated with extended practice both behaviorally and electrophysiologically. These findings are discussed in relation to the differential processing involved in a controlled response style. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.
    Human Brain Mapping 12/2011; · 6.88 Impact Factor
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    ABSTRACT: Constrained principal component analysis (CPCA) with a finite impulse response (FIR) basis set was used to reveal functionally connected networks and their temporal progression over a multistage verbal working memory trial in which memory load was varied. Four components were extracted, and all showed statistically significant sensitivity to the memory load manipulation. Additionally, two of the four components sustained this peak activity, both for approximately 3 s (Components 1 and 4). The functional networks that showed sustained activity were characterized by increased activations in the dorsal anterior cingulate cortex, right dorsolateral prefrontal cortex, and left supramarginal gyrus, and decreased activations in the primary auditory cortex and "default network" regions. The functional networks that did not show sustained activity were instead dominated by increased activation in occipital cortex, dorsal anterior cingulate cortex, sensori-motor cortical regions, and superior parietal cortex. The response shapes suggest that although all four components appear to be invoked at encoding, the two sustained-peak components are likely to be additionally involved in the delay period. Our investigation provides a unique view of the contributions made by a network of brain regions over the course of a multiple-stage working memory trial.
    Human Brain Mapping 06/2011; 32(6):856-71. · 6.88 Impact Factor
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    Liang Wang, Paul D Metzak, Todd S Woodward
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    ABSTRACT: Numerous investigations into schizophrenia have reported impairment in self-other source monitoring, and studies on healthy subjects have suggested that the medial prefrontal cortex (mPFC) is a critical region underlying self-monitoring abilities. In the current study, we examined the mPFC-related modulation of other brain regions in schizophrenia during self-other monitoring using a psychophysiological interaction approach. Twenty-three patients with schizophrenia and 33 healthy controls performed a self-other source monitoring task while undergoing functional magnetic resonance imaging (fMRI) scanning. Independent component analysis was used to identify the mPFC region of interest, and the averaged mPFC time course was extracted and entered into a general linear regression model for use with the psychophysiological interaction analysis, with Self vs. Other monitoring being the psychological condition of interest. Results suggested that connectivity between the mPFC and the left superior temporal gyrus (LSTG) was greater in the Other than the Self condition for the healthy subjects, but this was reversed for the schizophrenia patients, such that mPFC-LSTG connectivity was greater during Self than the Other condition. The modified functional connectivity associated with the performance of recollection of self-source information suggests that schizophrenia patients invoke circuits normally involved in retrieving other-generated information when processing self-generated information, thereby providing a possible biological basis for the self-other confusion characteristic of schizophrenia.
    Schizophrenia Research 02/2011; 125(2-3):136-42. · 4.59 Impact Factor
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    ABSTRACT: Working memory (WM) is one of the most impaired cognitive processes in schizophrenia. Functional magnetic resonance imaging (fMRI) studies in this area have typically found a reduction in information processing efficiency but have focused on the dorsolateral prefrontal cortex. In the current study using the Sternberg Item Recognition Test, we consider networks of regions supporting WM and measure the activation of functionally connected neural networks over different WM load conditions. We used constrained principal component analysis with a finite impulse response basis set to compare the estimated hemodynamic response associated with different WM load condition for 15 healthy control subjects and 15 schizophrenia patients. Three components emerged, reflecting activated (task-positive) and deactivated (task-negative or default-mode) neural networks. Two of the components (with both task-positive and task-negative aspects) were load dependent, were involved in encoding and delay phases (one exclusively encoding and the other both encoding and delay), and both showed evidence for decreased efficiency in patients. The results suggest that WM capacity is reached sooner for schizophrenia patients as the overt levels of WM load increase, to the point that further increases in overt memory load do not increase fMRI activation, and lead to performance impairments. These results are consistent with an account holding that patients show reduced efficiency in task-positive and task-negative networks during WM and also partially support the shifted inverted-U-shaped curve theory of the relationship between WM load and fMRI activation in schizophrenia.
    Schizophrenia Bulletin 01/2011; 38(4):803-13. · 8.80 Impact Factor
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    ABSTRACT: Memory for context and episodic memory have been identified as primary contributors to cognitive impairments in schizophrenia. This study examined neural networks involved in episodic memory-for-context in schizophrenia using a multimodal strategy including a graph theoretical approach, combined with an assessment of the contribution of structural impairments to disruption in the efficiency of functional brain networks. Twenty-three patients with schizophrenia and 33 healthy controls performed an episodic memory-for-context task while undergoing functional magnetic resonance imaging scanning. Graph theory was used to characterize the small-world properties of functional connections between activated regions, and a morphometric analysis was used to investigate schizophrenia-related structural deficits. Similar functional activations were identified in the two groups; however, although small-world properties were present in the topological organization of the functional networks in both groups, significant reductions in local, but not global, efficiency were observed in the schizophrenia group. Several key network "hub" regions related to recollection, such as the bilateral dorsal anterior cingulate gyrus, showed reduced gray matter volume in schizophrenia patients. These findings suggest that loss of gray matter volume may contribute to local inefficiencies in the architecture of the network underlying memory-for-context in schizophrenia.
    Journal of Neuroscience 09/2010; 30(39):13171-9. · 6.91 Impact Factor
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    ABSTRACT: In this study we used functional magnetic resonance imaging to investigate age-related changes in large-scale brain functional networks during memory encoding and recognition in 12 younger and 16 older adults. For each participant, functional brain networks were constructed by computing temporal correlation matrices of 90 brain regions and analyzed using graph theoretical approaches. We found the age-related changes mainly in the long-range connections with widespread reductions associated with aging in the fronto-temporal and temporo-parietal regions, and a few age-related increases in the posterior parietal regions. Graph theoretical analysis revealed that the older adults had longer path lengths linking different regions in the functional brain networks as compared to the younger adults. Further analysis indicated that the increases in shortest path length in the networks were combined with the loss of long-range connections. Finally, we showed that for older adults, frontal areas played reduced roles in the network (reduced regional centrality), whereas several default-mode regions played increased roles relative to younger subjects (increased regional centrality). Together, our results suggest that normal aging is associated with disruption of large-scale brain systems during the performance of memory tasks, which provides novel insights into the understanding of age-related decline in multiple cognitive functions.
    NeuroImage 04/2010; 50(3):862-72. · 6.25 Impact Factor
  • Schizophrenia Research - SCHIZOPHR RES. 01/2010; 117:467-467.
  • NeuroImage 01/2009; 47. · 6.25 Impact Factor
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    ABSTRACT: When switching tasks, if stimuli are presented that cue two of the tasks in the task set (i.e., bivalent stimuli), performance slowing is observed on all tasks, including those not cued by the bivalent stimulus. This slowing has been coined the bivalency effect, and may reflect adaptive tuning of the response style under conditions that appear to require adjustments in control over the course of action. Recent work on the function of the dorsal anterior cingulate (dACC) cortex has suggested that this neural region may be recruited under such conditions. In the current task switching study, we used tightly matched experimental and control conditions to isolate the bivalency effect. As predicted, dACC activation was associated with the bivalency effect, supporting an account stating that the role of the dACC is to signal a break in task inertia in order to adaptively tune the response style due to conditions that may require adjustments in control over the course of action. This result may extend the conflict monitoring account of dACC activation to situations where conflict occurred on past trials (i.e., conflict is not elicited by the current stimulus), and/or may support a more generalized account of dACC function involving monitoring internal states for conditions that may require adjustments in control over the course of action.
    NeuroImage 05/2008; 40(3):1311-8. · 6.25 Impact Factor
  • Schizophrenia Research - SCHIZOPHR RES. 01/2008; 102(1):96-96.
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    ABSTRACT: Dysfunction in the cognitive processes involved in generation of thoughts has been linked to schizophrenia, partly due to the presence of symptoms involving self-other or inner-outer confusion, such as hallucinations and Schneiderian delusions. In the present study, we investigated the neural underpinnings of verbal thought generation and verbal auditory perception using fMRI. Constrained principal component analysis (CPCA; Takane & Hunter, 1991; Hunter & Takane, 2002; Woodward et al., 2006) was used to identify networks of cerebral activation associated with generating thoughts and auditory perception in schizophrenia patients. Two experimental conditions were examined. In the first condition, participants were required to mentally generate a definition of a common word presented on the screen. In the second condition, they were required to listen to the definition of a common word presented on the screen. All definitions started with the phrase “Something you” (e.g., pen: something you use for writing). An overt generation practice session using a different set of words was performed to familiarize the participants with the task. Each condition consisted of 30 words. Five schizophrenia patients and ten healthy controls participated. All were right-handed and native speakers of English. An event-related fMRI protocol was used during two 9.25 minute scanning sessions in a 3T scanner for a total of 440 images. Preprocessing was performed using SPM5 and statistical analyses were carried out using constrained principal component analysis (CPCA) with a finite impulse response (FIR) model, and an orthogonal rotation applied on both conditions simultaneously.Four reliable components were extracted. The first component extracted (Figure 1) included the visual cortex and showed a higher intensity for the thought generation condition relative to the auditory perception condition, but did not differ between groups. The second component (Figure 2) mainly involved the superior temporal cortex (and primary auditory cortex), and showed a greater hemodynamic response for patients relative to controls regardless of condition. The third component (Figure 3) involved the task negative network (Fox et al., 2005) and did not differ between conditions or groups. The fourth component (Figure 4) represented the task positive network (Fox et al., 2005) and differed between conditions, whereby higher activity was found for the thought generation condition compared to the auditory perception condition. These results suggest that, regardless of groups and relative to the auditory perception condition, the thought generation involves more visual cortex activation as well as an overall intensified task positive network. With regards to the task negative network, both conditions and groups showed similar patterns of activation. One component, involving the bilateral superior temporal cortices (and primary auditory cortices) showed a greater hemodynamic response for patients relative to controls regardless of condition. This indicates that schizophrenia patients activate the auditory cortex more when mentally generating thoughts as well as in auditory perception. The finding suggests that overactivation of the primary auditory cortex is characteristic of schizophrenia (Frith et al., 1995), and may be a necessary (but not sufficient) state for the presence of hallucinations and/or Schneiderian delusions.
    OHBM conference.