"Cognitive Dysmetria" as an Integrative Theory of Schizophrenia: A Dysfunction in Cortical-Subcortical-Cerebellar Circuitry?

Andreasen, Nancy C.; Paradiso, Sergio; O'Leary, Daniel S.

doi:10.1093/oxfordjournals.schbul.a033321

Cited by 1,081 publications

(704 citation statements)

References 161 publications

(145 reference statements)

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“…Providing a semantic organizational strategy during word encoding normalizes subsequent recognition accuracy in patients with schizophrenia (Ragland et al, 2003). This suggests that deficits in verbal memory may result in part from aberrant fronto-temporal interactions, a hypothesis that fits well with the prevailing view of schizophrenia as a disorder of disturbed neural and psychological integration Andreasen et al, 1998).…”

Section: Introductionsupporting

confidence: 56%

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Wolf

Gur

Valdez

et al. 2007

Psychiatry Research: Neuroimaging

107

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Cognitive deficits, including impaired verbal memory, are prominent in schizophrenia and lead to increased disability. Functional neuroimaging of patients with schizophrenia performing memory tasks has revealed abnormal activation patterns in prefrontal cortex and temporo-limbic regions. Aberrant fronto-temporal interactions thus represent a potential pathophysiological mechanism underlying verbal memory deficits, yet this hypothesis of disturbed connectivity is not tested directly with standard activation studies. We performed within-subject correlations of frontal and temporal timeseries to measure functional connectivity during verbal encoding. Our results confirm earlier findings of aberrant fronto-temporal connectivity in schizophrenia, and extend them by identifying distinct alterations within dorsal and ventral prefrontal cortex. Relative to healthy controls, patients with schizophrenia had reduced connectivity between the dorsolateral prefrontal cortex (DLPFC) and temporal lobe areas including parahippocampus and superior temporal gyrus. In contrast, patients showed increased connectivity between a region of ventrolateral prefrontal cortex (VLPFC) and these same temporal lobe regions. Higher temporal-DLPFC connectivity during encoding was associated with better subsequent recognition accuracy in controls, but not patients. Temporal-VLPFC connectivity was uncorrelated with recognition accuracy in either group. The results suggest that reduced temporal-DLPFC connectivity in schizophrenia could underlie encoding deficits, and increased temporal-VLPFC connectivity may represent an ineffective compensatory effort.

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Section: Introductionsupporting

confidence: 56%

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Wolf

Gur

Valdez

et al. 2007

Psychiatry Research: Neuroimaging

107

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“…The cerebellum is well known from structural and functional studies to be affected in schizophrenia patients. As well, it plays a major role in the cortico-cerebellarthalamus-cortical circuit (CCTCC), hypothesized (Andreasen et al, 1998;Martin and Albers, 1995) to play an important role in schizophrenia. The consistency of these three families across both approaches implies that their relationship is not indicative of noise/artifact signals and could represent a significant between group difference.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown the vermis to be implicated in schizophrenia from structural and functional MRI analyses, where it was found to be significantly reduced in patients (Okugawa et al, 2003). Functional studies have also implicated the cerebellum as a dysfunctional area in schizophrenia (Andreasen et al, 1998;Ende et al, 2005;Kim et al, 2007), though the vermis is not often discussed due to the frequent use by researchers of the Talairach atlas, which does not distinguish the vermis as a distinct brain region (Talairach and Tournoux, 1988).…”

Section: Discussionmentioning

confidence: 99%

Hybrid ICA–Bayesian network approach reveals distinct effective connectivity differences in schizophrenia

et al. 2008

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We utilized a discrete dynamic Bayesian network (dDBN) approach (Burge et al., 2007) to determine differences in brain regions between patients with schizophrenia and healthy controls on a measure of effective connectivity, termed the approximate conditional likelihood score (ACL) (Burge and Lane, 2005). The ACL score represents a class-discriminative measure of effective connectivity by measuring the relative likelihood of the correlation between brain regions in one group versus another. The algorithm is capable of finding non-linear relationships between brain regions because it uses discrete rather than continuous values and attempts to model temporal relationships with a first-order Markov and stationary assumption constraint (Papoulis, 1991). Since Bayesian networks are overly sensitive to noisy data, we introduced an independent component analysis (ICA) filtering approach that attempted to reduce the noise found in fMRI data by unmixing the raw datasets into a set of independent spatial component maps. Components that represented noise were removed and the remaining components reconstructed into the dimensions of the original fMRI datasets. We applied the dDBN algorithm to a group of 35 patients with schizophrenia and 35 matched healthy controls using an ICA filtered and unfiltered approach. We determined that filtering the data significantly improved the magnitude of the ACL score. Patients showed the greatest ACL scores in several regions, most markedly the cerebellar vermis and hemispheres. Our findings suggest that schizophrenia patients exhibit weaker connectivity than healthy controls in multiple regions, including bilateral temporal and frontal cortices, plus cerebellum during an auditory paradigm.

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“…The cerebellum also has been implicated in psychiatric disorders including schizophrenia (Andreasen, Paradiso and O'Leary, 1998;Andreasen, 1999), bipolar disorder (Lauterbach, 1996), and autism (Carper and Courchesne, 2000). In schizophrenia abnormalities in the cerebellar node of the cortico-cerebellar-thalamic-cortical (CCTC) circuit are indicated by both structural and functional findings (e.g., Stephan et al, 2001;Ho et al, 2003;Keller et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Theoretically, the "cognitive dysmetria" model (Andreasen et al, 1998;Andreasen, 1999) posits that disturbances in a cortico-cerebellar-thalamic-cortical circuit underlie important features of the disorder and its course. As a node in the this circuit, the influence of the cerebellum is underscored by feedback and feedforward loops connecting it with areas of the brain implicated in schizophrenia such as the thalamus and limbic system (Kalil, 1981;Orioli and Strick, 1989), and prefrontal cortex (Schmahmann and Pandya, 1995).…”

Section: Introductionmentioning

confidence: 99%

Cerebellum volume and eyeblink conditioning in schizophrenia

Edwards

Newman

Bismark

et al. 2008

Psychiatry Research: Neuroimaging

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Although accumulating evidence suggests that cerebellar abnormalities may be linked to the symptoms and course of schizophrenia, few studies have related structural and functional indices of cerebellar integrity. The present study examined the relationship between the volume of specific subregions of the cerebellum and cerebellar function, as measured by eyeblink conditioning. Nine individuals with schizophrenia and six healthy comparison participants completed structural magnetic resonance imaging of the brain and a delay eyeblink conditioning procedure. Volumetric measurements were taken for the whole brain, whole cerebellum, cerebellar anterior lobules I-V and posterior lobules VI-VII. The schizophrenia group had smaller cerebellar anterior lobes and exhibited impaired eyeblink conditioning compared to the comparison group. In the comparison group, larger anterior volume correlated with earlier conditioned response onset latencies and increased amplitudes of the unconditioned blink response during paired trials (i.e., when the conditioned and unconditioned stimuli co-occurred). The findings that smaller anterior cerebellar volumes and EBC impairments were associated with schizophrenia are consistent with non-human studies showing that anterior cerebellar abnormalities are associated with associative deficits in delay eyeblink conditioning. The lack of a significant correlation between indices of eyeblink conditioning and cerebellar volume within the schizophrenic group suggests an aberrant relationship between cerebellar structure and function.

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"Cognitive Dysmetria" as an Integrative Theory of Schizophrenia: A Dysfunction in Cortical-Subcortical-Cerebellar Circuitry?

Cited by 1,081 publications

References 161 publications

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Hybrid ICA–Bayesian network approach reveals distinct effective connectivity differences in schizophrenia

Cerebellum volume and eyeblink conditioning in schizophrenia

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