Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia

Brady, Roscoe O.; Gonsalvez, Irene; Lee, Ivy; Öngür, Döst; Seidman, Larry J.; Schmahmann, Jeremy D.; Eack, Shaun M.; Keshavan, Matcheri S.; Pascual‐Leone, Álvaro; Halko, Mark A.

doi:10.1176/appi.ajp.2018.18040429

Cited by 282 publications

(228 citation statements)

References 44 publications

(42 reference statements)

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“…These findings are consistent with the observations that there are distinct and topographically precise CB contributions to cerebral intrinsic connectivity networks [24,25,39] and that rTMS applied to distinct CB regions can selectively modulate network functional connectivity in healthy individuals [145,216]. Further, dysfunctional connectivity between the CB and the dorsolateral prefrontal cortex is associated with negative symptom severity in schizophrenia, and improvement of the connectivity ameliorates the severity of the negative symptoms [217].…”

Section: Ccas In the Hereditary Ataxiassupporting

confidence: 88%

The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper

et al. 2019

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Sporadically advocated over the last two centuries, a cerebellar role in cognition and affect has been rigorously established in the past few decades. In the clinical domain, such progress is epitomized by the "cerebellar cognitive affective syndrome" ("CCAS") or "Schmahmann syndrome." Introduced in the late 1990s, CCAS reflects a constellation of cerebellar-induced sequelae, comprising deficits in executive function, visuospatial cognition, emotion-affect, and language, over and above speech. The CCAS thus offers excellent grounds to investigate the functional topography of the cerebellum, and, ultimately, illustrate the precise mechanisms by which the cerebellum modulates cognition and affect. The primary objective of this task force paper is thus to stimulate further research in this area. After providing an up-to-date overview of the fundamental findings on cerebellar neurocognition, the paper substantiates the concept of CCAS with recent evidence from different scientific angles, promotes awareness of the CCAS as a clinical entity, and examines our current insight into the therapeutic options available. The paper finally identifies topics of divergence and outstanding questions for further research.

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Section: Ccas In the Hereditary Ataxiassupporting

confidence: 88%

The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper

et al. 2019

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“…Compensatory reorganization changes are generally expected to correlate with improved behavioral function; although not necessarily, since it would also be reasonable to expect that compensatory mechanisms become more prominent as disease severity, and thus behavioral abnormalities, become more pronounced. Studies of neural stimulation might be able to provide causal evidence of cerebellar compensation in brain disorders, and indeed, recent studies in neuropsychiatry report behavioral improvement after cerebellar stimulation [129,130]. Technological advancements that allow targeting small and deep brain structures [131][132][133][134][135] underscore the potential for cerebellar stimulation to become a useful therapeutic modality in the clinical treatment of cognitive dysfunction.…”

Section: Cerebellar Cognitive Reserve (Guell X Schmahmann Jd)mentioning

confidence: 99%

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders

et al. 2019

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Cerebellar reserve refers to the capacity of the cerebellum to compensate for tissue damage or loss of function resulting from many different etiologies. When the inciting event produces acute focal damage (e.g., stroke, trauma), impaired cerebellar function may be compensated for by other cerebellar areas or by extracerebellar structures (i.e., structural cerebellar reserve). In contrast, when pathological changes compromise cerebellar neuronal integrity gradually leading to cell death (e.g., metabolic and immune-mediated cerebellar ataxias, neurodegenerative ataxias), it is possible that the affected area itself can compensate for the slowly evolving cerebellar lesion (i.e., functional cerebellar reserve). Here, we examine cerebellar reserve from the perspective of the three cornerstones of clinical ataxiology: control of ocular movements, coordination of voluntary axial and appendicular movements, and cognitive functions. Current evidence indicates that cerebellar reserve is potentiated by environmental enrichment through the mechanisms of autophagy and synaptogenesis, suggesting that cerebellar reserve is not rigid or fixed, but exhibits plasticity potentiated by experience. These conclusions have therapeutic implications. During the period when cerebellar reserve is preserved, treatments should be directed at stopping disease progression and/or limiting the pathological process. Simultaneously, cerebellar reserve may be potentiated using multiple approaches. Potentiation of cerebellar reserve may lead to compensation and restoration of function in the setting of cerebellar diseases, and also in disorders primarily of the cerebral hemispheres by enhancing cerebellar mechanisms of action. It therefore appears that cerebellar reserve, and the underlying plasticity of cerebellar microcircuitry that enables it, may be of critical neurobiological importance to a wide range of neurological/neuropsychiatric conditions.

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“…In the specific case of cerebellar cortex, damage to the cerebellar posterior lobe, which provides inputs to the DN, causes the cerebellar cognitive affective syndrome, characterized by deficits in executive, linguistic, visuospatial and affective processing (Guell et al 2015;Hoche et al 2016Hoche et al , 2018Schmahmann & Sherman 1998, Schmahmann et al 2009, Stoodley et al 2016). In addition, multiple studies have reported cerebellar cortical abnormalities in numerous disorders such as Alzheimer's disease (Guo et al 2016, Jacobs et al 2018, autism spectrum disorder (Arnold Anteraper et al 2018, D'Mello & Stoodley 2015, and schizophrenia (Moberget et al 2018), with preliminary evidence suggesting that cerebellar cortical stimulation might improve symptoms in these diseases (Brady et al 2019, Demirtas-Tatlidede et al 2010, Di Lorenzo et al 2013, Garg et al 2016, Stoodley et al 2017, Tikka et al 2015. The importance of our findings is thus underscored by the relevance of cerebellar cortex in neurology and psychiatry (Schmahmann et al 2019), as the majority of fibers exiting the cerebellar cortex synapse in DN before reaching extracerebellar structures such as cerebral cortex.…”

Section: Relevance For Cerebellar Neuroscience Neurology and Psychimentioning

confidence: 99%

Functional Territories of Human Dentate Nucleus

Guell

D’Mello

Hubbard

et al. 2019

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Anatomical connections link the cerebellar cortex with multiple distinct sensory, motor, association, and paralimbic areas of the cerebrum. These projections allow a topographically precise cerebellar modulation of multiple domains of neurological function, and underscore the relevance of the cerebellum for the pathophysiology of numerous disorders in neurology and psychiatry. The majority of fibers that exit the cerebellar cortex synapse in the dentate nuclei (DN) before reaching extracerebellar structures such as cerebral cortex. Although the DN have a central position in the anatomy of the cerebello-cerebral circuits, the functional neuroanatomy of human DN remains largely unmapped. Neuroimaging research has redefined broad categories of functional division in the human brain showing that primary processing, attentional (task positive) processing, and default-mode (task negative) processing are three central poles of neural macro-scale functional organization. This new macro-scale understanding of the range and poles of brain function has revealed that a broad spectrum of human neural processing categories (primary, task positive, task negative) is represented not only in the cerebral cortex, but also in the thalamus, striatum, and cerebellar cortex. Whether functional organization in DN obeys a similar set of macroscale divisions, and whether DN are yet another compartment of representation of a broad spectrum of human neural processing categories, remains unknown. Here we show for the first time that human DN is optimally divided into three functional territories as indexed by high spatio-temporal resolution resting-state MRI in 60 healthy adolescents, and that these three distinct territories contribute uniquely to default-mode, salience-motor, and visual brain networks. These conclusions are supported by novel analytical strategies in human studies of DN organization, including 64-channel MRI imaging, data-driven methods, and replication in an independent sample. Our findings provide a systems neuroscience substrate for cerebellar output to influence multiple broad categories of neural control -namely defaultmode, attentional, and multiple unimodal streams of information processing including motor and visual. They also provide a validated data-driven mapping of functions in human DN, crucial for the design of methodology and interpretation of results in future neuroimaging studies of brain function and dysfunction.

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Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia

Cited by 282 publications

References 44 publications

The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper

The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders

Functional Territories of Human Dentate Nucleus

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