Differential involvement of brainstem noradrenergic and midbrain dopaminergic nuclei in cognitive control

Köhler, Stefanie; Bär, Karl‐Jürgen; Wagner, Gerd

doi:10.1002/hbm.23173

Cited by 42 publications

(58 citation statements)

References 73 publications

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“…Executive control is necessary for resolution of conflict among responses to sensory stimuli (Posner, ) and the alerting effect could be interpreted as an enhancement of sensory signal perception after a warning stimulus (Fan et al, ). Using the Stroop task, LC was shown to be significantly correlated with the Stroop interference with changing functional connectivity pattern to the dorsal ACC and PFC (Köhler, Bär, & Wagner, ), indicating its role in executive control.…”

Section: Discussionmentioning

confidence: 99%

In vivo anatomical mapping of human locus coeruleus functional connectivity at 3 T MRI

Liebe

Kaufmann

et al. 2020

Human Brain Mapping

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The locus coeruleus (LC) is involved in numerous crucial brain functions and several disorders like depression and Alzheimer's disease. Recently, the LC resting-state functional connectivity (rs-fc) has been investigated in functional MRI by calculating the blood oxygen level-dependent (BOLD) response extracted using Montreal Neurological Institute (MNI) space masks. To corroborate these results, we aimed to investigate the LC rs-fc at native space by improving the identification of the LC location using a neuromelanin sensitive sequence. Twenty-five healthy male participants (mean age 24.8 ± 4.2) were examined in a Siemens MAGNETOM Prisma 3 T MRT applying a neuromelanin sensitive T1TSE sequence and functional MRI. We compared the rs-fc of LC calculated by a MNIbased approach with extraction of the BOLD signal at the exact individual location of the LC after applying CompCor and field map correction. As a measure of advance, a marked increase of regional homogeneity (ReHo) of time series within LC could be achieved with the subject-specific approach. Furthermore, the methods differed in the rs-fc to the right temporoparietal junction, which showed stronger connectivity to the LC in the MNIbased method. Nevertheless, both methods comparably revealed LC rs-fc to multiple brain regions including ACC, bilateral thalamus, and cerebellum. Our results are relevant for further research assessing and interpreting LC function, especially in patient populations examined at 3 T MRI. K E Y W O R D S locus coeruleus, neuromelanin sensitive MRI, resting-state functional connectivity

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Section: Discussionmentioning

confidence: 99%

In vivo anatomical mapping of human locus coeruleus functional connectivity at 3 T MRI

Liebe

Kaufmann

et al. 2020

Human Brain Mapping

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“…Tonic activity represents a kind of baseline arousal and is low during certain automatic behavior and drowsiness (Rajkowski et al, 1994;Aston-Jones et al, 1999). LC neurons become phasically activated by salient external or internal stimuli (Corbetta et al, 2008;Köhler et al, 2016). Analogously, skin conductance was divided into a tonic and phasic constituent and is most probably also influenced by the LC-noradrenergic system (Yamamoto et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Sympathetic and Parasympathetic Modulation of Pupillary Unrest

et al. 2020

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Pupillary unrest is an established indicator of drowsiness or sleepiness. How sympathetic and parasympathetic activity contribute to pupillary unrest is not entirely unclear. In this study, we investigated 83 young healthy volunteers to assess the relationship of pupillary unrest to other markers of the autonomic nervous system. Sample entropy (SE) and the established pupillary unrest index (PUI) were calculated to characterize pupil size variability. Autonomic indices were derived from heart rate, blood pressure, respiration, and skin conductance. Additionally, we assessed individual levels of calmness, vigilance, and mood. In an independent sample of 26 healthy participants, we stimulated the cardiovagal system by a deep breathing test. PUI was related to parasympathetic cardiac indices and sleepiness. A linear combination of vagal heart rate variability [root mean square of heart beat interval differences (RMSSD)] and skin conductance fluctuations (SCFs) was suited best to explain interindividual variance of PUI. Complexity of pupil diameter (PD) variations correlated to indices of sympathetic skin conductance. Furthermore, we found that spontaneous fluctuations of skin conductance are accompanied by increases of pupil size. In an independent sample, we were able to corroborate the relation of PUI with RMSSD and skin conductance. A slow breathing test enhanced RMSSD and PUI proportionally to each other, while complexity of PD dynamics decreased. Our data suggest that the slow PD oscillations (f < 0.15 Hz) quantified by PUI are related to the parasympathetic modulation. Sympathetic arousal as detected by SCFs is associated to transient pupil size increases that increase non-linear pupillary dynamics.

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“…Prefrontal and anterior cingulate inputs were assumed to enable the transition between different activity levels of LC (Corbetta et al, ). Recently, we demonstrated increased LC activation in the Stroop interference condition in healthy subjects and detected stronger functional connectivity of the LC with the dorsal fronto‐cingulo‐parietal network (Köhler, Bär, & Wagner, ).…”

Section: Discussionmentioning

confidence: 93%

“…We hypothesized an abnormal activation pattern of the dopaminergic VTA and the SN in patients with schizophrenia relative to healthy controls. Furthermore, given the important role of the LC‐NA system in cognitive functioning (Arnsten & Rubia, ; Aston‐Jones & Waterhouse, ) and the pronounced cognitive deficits in schizophrenia (Barch & Sheffield, ) as well as based on the findings of our recent study (Köhler, Bär, & Wagner, ), we additionally expected to find an abnormal activation pattern in the LC in patients with schizophrenia relative to healthy controls.…”

Section: Introductionmentioning

confidence: 97%

“…In a recent study of our group (Köhler, Bär, & Wagner, ), we explicitly investigated functional activation patterns of the VTA and LC in healthy volunteers during the Stroop task, measuring cognitive control. We observed significant BOLD activation of both the VTA/SN and LC during the Stroop interference condition and a significant functional connectivity between VTA/SN and the nigrostriatal/mesolimbic dopaminergic system as well as between LC and the dorsolateral/ventrolateral PFC.…”

Section: Introductionmentioning

confidence: 99%

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Activation of brainstem and midbrain nuclei during cognitive control in medicated patients with schizophrenia

Köhler

Wagner

Bär

2018

Human Brain Mapping

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Evidence suggests that cognitive control functions as well as the underlying brain network, anchored by the prefrontal cortex (PFC) and the dorsal anterior cingulate cortex (dACC), are dysfunctional in schizophrenia. Catecholamine producing midbrain and brainstem nuclei are densely connected with the PFC and dACC and exert profound contributions to cognitive control processes. Dysfunctions within the underlying neurotransmitter systems are considered to play a central role in the occurrence of various symptoms of schizophrenia. We sought to investigate the putatively abnormal activation pattern of the dopaminergic midbrain nuclei, that is, ventral tegmental area (VTA) and substantia nigra as well as that of the noradrenergic locus coeruleus (LC) in patients with schizophrenia during cognitive control. A total of 28 medicated patients and 27 healthy controls were investigated with the manual version of the Stroop task using event-related fMRI. The main finding was a reduced BOLD activation in the VTA during both Stroop task conditions in patients in comparison to controls, which correlated significantly with the degree of negative symptoms. We further detected a comparable LC activation in in patients and healthy controls. However, in controls LC activation was significantly correlated with the Stroop interference time, which was not observed in patients. The finding of reduced VTA activation in schizophrenia patients lends further support to the assumed dysfunction of the DA system in schizophrenia. In addition, despite comparable LC activation, the nonsignificant correlation with the Stroop interference time might indicate altered LC functioning in schizophrenia and, thus, needs further investigations.

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Differential involvement of brainstem noradrenergic and midbrain dopaminergic nuclei in cognitive control

Cited by 42 publications

References 73 publications

In vivo anatomical mapping of human locus coeruleus functional connectivity at 3 T MRI

In vivo anatomical mapping of human locus coeruleus functional connectivity at 3 T MRI

Sympathetic and Parasympathetic Modulation of Pupillary Unrest

Activation of brainstem and midbrain nuclei during cognitive control in medicated patients with schizophrenia

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