Decreased fMRI activity in the hippocampus of patients with schizophrenia compared to healthy control participants, tested on a wayfinding task in a virtual town

Ledoux, Andrée-Anne; Phillips, Jennifer L.; Labelle, Alain; Smith, Andra; Bohbot, Véronique D.; Boyer, Patrice

doi:10.1016/j.pscychresns.2012.10.005

Cited by 34 publications

(38 citation statements)

References 48 publications

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“…To the best of our knowledge, all the virtual navigation studies in schizophrenia have used a necessarily constrained paradigm of place learning using rodent models such as the Morris water maze (Morris et al, 1982; Astur et al, 2004; Hanlon et al, 2006, 2012; Folley et al, 2010) and radial arm maze (Olton and Samuelson, 1976; Spieker et al, 2012) or circumscribed environments such as a virtual park (Weniger and Irle, 2008) and virtual town (Ledoux et al, 2013). These were designed to test specific neural structures, principally the hippocampus, and/or specific cognitive domains, such as allocentric memory (Weniger and Irle, 2008; Folley et al, 2010), working and reference memory (Spieker et al, 2012), working and relational memory (Hanlon et al, 2012), and episodic memory (Ledoux et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…These were designed to test specific neural structures, principally the hippocampus, and/or specific cognitive domains, such as allocentric memory (Weniger and Irle, 2008; Folley et al, 2010), working and reference memory (Spieker et al, 2012), working and relational memory (Hanlon et al, 2012), and episodic memory (Ledoux et al, 2013). These studies were typically based on a multiple-trial learning paradigm where performance is measured across repetitive trial and error attempts to find one or more game-like rewards, or required extensive exploratory navigation prior to testing to ensure familiarity with all the landmarks subsequently used as targets.…”

Section: Discussionmentioning

confidence: 99%

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Simulating real world functioning in schizophrenia using a naturalistic city environment and single-trial, goal-directed navigation

Zawadzki

Girard

Foussias

et al. 2013

Front. Behav. Neurosci.

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Objective: To develop a virtual reality platform that would serve as a functionally meaningful measure of cognition in schizophrenia and that would also complement standard batteries of cognitive tests during clinical trials for cognitive treatments in schizophrenia, be amenable to human neuroimaging research, yet lend itself to neurobiological comparison with rodent analogs.Method: Thirty-three patients with schizophrenia and 33 healthy controls matched for age, sex, video gaming experience, and education completed eight rapid, single-trial virtual navigation tasks within a naturalistic virtual city. Four trials tested their ability to find different targets seen during the passive viewing of a closed path that led them around different city blocks. Four subsequent trials tested their ability to return to four different starting points after viewing a path that took them several blocks away from the starting position.Results: Individuals with schizophrenia had difficulties in way-finding, measured as distance travelled to find targets previously encountered within the virtual city. They were also more likely not to notice the target during passive viewing, less likely to find novel shortcuts to targets, and more likely to become lost and fail completely in finding the target. Total travel distances across all eight trials strongly correlated (negatively) with neurocognitive measures and, for 49 participants who completed the Quality of Life Scale, psychosocial functioning.Conclusion: Single-trial, goal-directed navigation in a naturalistic virtual environment is a functionally meaningful measure of cognitive functioning in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Simulating real world functioning in schizophrenia using a naturalistic city environment and single-trial, goal-directed navigation

Zawadzki

Girard

Foussias

et al. 2013

Front. Behav. Neurosci.

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“…The hippocampus is dysfunctional in schizophrenia (Weiss, 2003; Ongür, 2006; Ragland, 2001; Ledoux, 2013; Heckers, and Konradi, 2010). Meta-analyses have concluded that schizophrenia is associated with memory impairment (Heinrichs, and Zakzanis, 1998; Aleman, 1999) and that hippocampal recruitment is impaired during the performance of memory tasks (Weiss, 2003; Heckers, 1998).…”

Section: Introductionmentioning

confidence: 99%

Increased hippocampal CA1 cerebral blood volume in schizophrenia

Talati

Rane

Köse

et al. 2014

NeuroImage: Clinical

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Hippocampal hyperactivity has been proposed as a biomarker in schizophrenia. However, there is a debate whether the CA1 or the CA2/3 subfield is selectively affected. We studied 15 schizophrenia patients and 15 matched healthy control subjects with 3T steady state, gadolinium-enhanced, absolute cerebral blood volume (CBV) maps, perpendicular to the long axis of the hippocampus. The subfields of the hippocampal formation (subiculum, CA1, CA2/3, and hilus/dentate gyrus) were manually segmented to establish CBV values. Comparing anterior CA1 and CA2/3 CBV between patients and controls revealed a significant subfield-by-diagnosis interaction. This interaction was due to the combined effect of a trend of increased CA1 CBV (p = .06) and non-significantly decreased CA2/3 CBV (p = 0.14) in patients relative to healthy controls. These results support the emerging hypothesis of increased hippocampal activity as a biomarker of schizophrenia and highlight the importance of subfield-level investigations.

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“…Impairment of this cognitive coordination could be responsible for cognitive disorganization in psychosis including inappropriate associations, deficits in contextual binding, and impaired discrimination between relevant and irrelevant information (Ellenbroek and Cools, 1990; Silverstein et al, 2000; Phillips and Silverstein, 2003; Uhlhaas et al, 2004; Hemsley, 2005). Spatial, contextual, and episodic-like memory critically depends on the hippocampus (Moscovitch et al, 2006) and hippocampal pathology (Harrison, 2004; Tamminga et al, 2012; Ledoux et al, 2013) and episodic memory deficits are common in schizophrenia (Weiss et al, 2003; Barch, 2005; Boyer et al, 2007; Ranganath et al, 2008). However, most laboratory tests of hippocampal function occur in static environments or involve only one-off changes or between-session alternations.…”

Section: Introductionmentioning

confidence: 99%

MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis

Kubík¹,

Buchtová

Valeš

et al. 2014

Front. Behav. Neurosci.

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Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena – Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated neurons.

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Decreased fMRI activity in the hippocampus of patients with schizophrenia compared to healthy control participants, tested on a wayfinding task in a virtual town

Cited by 34 publications

References 48 publications

Simulating real world functioning in schizophrenia using a naturalistic city environment and single-trial, goal-directed navigation

Simulating real world functioning in schizophrenia using a naturalistic city environment and single-trial, goal-directed navigation

Increased hippocampal CA1 cerebral blood volume in schizophrenia

MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis

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