Sub-millimeter variation in human locus coeruleus is associated with dimensional measures of psychopathology: An in vivo ultra-high field 7-Tesla MRI study

Morris, Laurel S.; Tan, Aaron; Smith, D.; Grehl, Mora; Han-Huang, Kuang; Naidich, Thomas P.; Charney, Dennis S.; Balchandani, Priti; Kundu, Prantik; Murrough, James W.

doi:10.1016/j.nicl.2019.102148

Cited by 31 publications

(31 citation statements)

References 62 publications

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“…Similarly, current functional MRI of LC involves image acquisition at standard voxel sizes of ~3 mm to attain good functional sensitivity. Recent work using high-field MRI and computational segmentation algorithms has been used to measure LC structure and volume with sub-millimeter resolution ( Morris et al, 2020 ). This was successfully performed in human subjects with and without pathological anxiety, demonstrating enlarged LC in patients, associated with poorer attentional control and higher anxious arousal ( Morris et al, 2020 ).…”

Section: Future Directions In Approaches To Studying the Lc In Humansmentioning

confidence: 99%

“…Recent work using high-field MRI and computational segmentation algorithms has been used to measure LC structure and volume with sub-millimeter resolution ( Morris et al, 2020 ). This was successfully performed in human subjects with and without pathological anxiety, demonstrating enlarged LC in patients, associated with poorer attentional control and higher anxious arousal ( Morris et al, 2020 ). Further applications of this work in larger sample sizes and using fMRI will be critical for the translation of the wealth of pre-clinical work described, to clinical settings.…”

Section: Future Directions In Approaches To Studying the Lc In Humansmentioning

confidence: 99%

“…Other biological measures such as pupil dilation and 3-methoxy-4-hydroxyphenylglycol (MHPG) – a major metabolite of NE – can be measured in both humans ( Murphy et al, 2014 ; Raskind et al, 1984 ; Southwick et al, 1993 ) and pre-clinical models ( Aston-Jones and Cohen, 2005 ; Gilzenrat et al, 2010 ; Joshi et al, 2016 ; Korf et al, 1973a , 1973b ). To date, there is predominantly indirect evidence of LC’s role in human pathological anxiety, however more recent work with ultra-high field 7-T magnetic resonance imaging (MRI) is enabling direct examination of the human LC in vivo ( Morris et al, 2020 ; Priovoulos et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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The role of the locus coeruleus in the generation of pathological anxiety

Morris

McCall

Charney

et al. 2020

Brain and Neuroscience Advances

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139

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This review aims to synthesise a large pre-clinical and clinical literature related to a hypothesised role of the locus coeruleus norepinephrine system in responses to acute and chronic threat, as well as the emergence of pathological anxiety. The locus coeruleus has widespread norepinephrine projections throughout the central nervous system, which act to globally modulate arousal states and adaptive behavior, crucially positioned to play a significant role in modulating both ascending visceral and descending cortical neurocognitive information. In response to threat or a stressor, the locus coeruleus–norepinephrine system globally modulates arousal, alerting and orienting functions and can have a powerful effect on the regulation of multiple memory systems. Chronic stress leads to amplification of locus coeruleus reactivity to subsequent stressors, which is coupled with the emergence of pathological anxiety-like behaviors in rodents. While direct in vivo evidence for locus coeruleus dysfunction in humans with pathological anxiety remains limited, recent advances in high-resolution 7-T magnetic resonance imaging and computational modeling approaches are starting to provide new insights into locus coeruleus characteristics.

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Section: Future Directions In Approaches To Studying the Lc In Humansmentioning

confidence: 99%

Section: Future Directions In Approaches To Studying the Lc In Humansmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of the locus coeruleus in the generation of pathological anxiety

Morris

McCall

Charney

et al. 2020

Brain and Neuroscience Advances

Self Cite

139

View full text Add to dashboard Cite

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“…Additionally, early histological evidence suggested that LC degeneration occurs during the course of normal aging ( Vijayashankar and Brody, 1979 ; Manaye et al, 1995 ), but these findings have also been refuted ( Mouton et al, 1994 ; Theofilas et al, 2017 ). Thus, whether patterns of LC contrast over the course of normal aging represents cessation of neuromelanin production, changes in neuron morphology, and/or are indicative of cell or dendrite loss is a hotly contested subject ( Clewett et al, 2016 ; Liu et al, 2019 ; Morris et al, 2020 ). While volumetric analysis of the LC also suffers from issues in segmentation ( Liu K. Y. et al, 2017 ; Betts et al, 2019b ), utilizing isotropic acquisition parameters and combining it with postmortem stereological counts may help disentangle the changes to LC structure over the course of disease.…”

Section: Human Studiesmentioning

confidence: 99%

What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease

Kelberman

Keilholz

2020

Front. Neurosci.

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The locus coeruleus (LC) has long been underappreciated for its role in the pathophysiology of Alzheimer’s disease (AD), Parkinson’s disease (PD), and other neurodegenerative disorders. While AD and PD are distinct in clinical presentation, both are characterized by prodromal protein aggregation in the LC, late-stage degeneration of the LC, and comorbid conditions indicative of LC dysfunction. Many of these early studies were limited to post-mortem histological techniques due to the LC’s small size and location deep in the brainstem. Thus, there is a growing interest in utilizing in vivo imaging of the LC as a predictor of preclinical neurodegenerative processes and biomarker of disease progression. Simultaneously, neuroimaging in animal models of neurodegenerative disease holds promise for identifying early alterations to LC circuits, but has thus far been underutilized. While still in its infancy, a handful of studies have reported effects of single gene mutations and pathology on LC function in disease using various neuroimaging techniques. Furthermore, combining imaging and optogenetics or chemogenetics allows for interrogation of network connectivity in response to changes in LC activity. The purpose of this article is twofold: (1) to review what magnetic resonance imaging (MRI) and positron emission tomography (PET) have revealed about LC dysfunction in neurodegenerative disease and its potential as a biomarker in humans, and (2) to explore how animal models can be used to test hypotheses derived from clinical data and establish a mechanistic framework to inform LC-focused therapeutic interventions to alleviate symptoms and impede disease progression.

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“…While no studies on LC-MRI have been yet performed in epileptic patients, in 2020, Gollion and colleagues performed an LC-MRI assessment in patients suffering from migraine with aura and they did not find any difference between patients and controls [90]. Concerning psychiatric disorders, LC intensity was found to be reduced in depression [50,51], while LC volume was increased in subjects suffering from post-traumatic stress disorders (PTSD) and anxiety disorders [91].…”

Section: Lc-mri In Other Neurological Diseases and Psychiatric Disordersmentioning

confidence: 99%

Locus Coeruleus Magnetic Resonance Imaging in Neurological Diseases

Galgani¹,

Lombardo

Latta

et al. 2020

Curr Neurol Neurosci Rep

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Purpose of Review Locus coeruleus (LC) is the main noradrenergic nucleus of the brain, and its degeneration is considered to be key in the pathogenesis of neurodegenerative diseases. In the last 15 years,MRI has been used to assess LC in vivo, both in healthy subjects and in patients suffering from neurological disorders. In this review, we summarize the main findings of LC-MRI studies, interpreting them in light of preclinical and histopathological data, and discussing its potential role as diagnostic and experimental tool. Recent findings LC-MRI findings were largely in agreement with neuropathological evidences; LC signal showed to be not significantly affected during normal aging and to correlate with cognitive performances. On the contrary, a marked reduction of LC signal was observed in patients suffering from neurodegenerative disorders, with specific features. Summary LC-MRI is a promising tool, which may be used in the future to explore LC pathophysiology as well as an early biomarker for degenerative diseases.

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Sub-millimeter variation in human locus coeruleus is associated with dimensional measures of psychopathology: An in vivo ultra-high field 7-Tesla MRI study

Cited by 31 publications

References 62 publications

The role of the locus coeruleus in the generation of pathological anxiety

The role of the locus coeruleus in the generation of pathological anxiety

What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease

Locus Coeruleus Magnetic Resonance Imaging in Neurological Diseases

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