Resting-State Functional Connectivity of the Locus Coeruleus in Humans: In Comparison with the Ventral Tegmental Area/Substantia Nigra Pars Compacta and the Effects of Age

Zhang, Sheng; Hu, Sien; Chao, Herta H.; Li, Chiang‐Shan R.

doi:10.1093/cercor/bhv172

Cited by 96 publications

(99 citation statements)

References 153 publications

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“…We also noted that LC—a major source of noradrenergic projections—was the only region showing more negative than positive cortical/subcortical connections. Another fMRI study comparing LC and VTA functional connectivity found more widespread negative connections involving LC compared with VTA,20 with LC showing positive connectivity to thalamus and limbic areas and negative connectivity to rolandic and association neocortex, resembling our observations. Concordance between our findings in control subjects and prior studies may help validate the reliability of our results.…”

Section: Discussionsupporting

confidence: 88%

Functional connectivity disturbances of the ascending reticular activating system in temporal lobe epilepsy

Englot

D’Haese

Konrad

et al. 2017

J Neurol Neurosurg Psychiatry

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Objective Seizures in temporal lobe epilepsy (TLE) disturb brain networks and lead to connectivity disturbances. We previously hypothesised that recurrent seizures in TLE may lead to abnormal connections involving subcortical activating structures including the ascending reticular activating system (ARAS), contributing to neocortical dysfunction and neurocognitive impairments. However, no studies of ARAS connectivity have been previously reported in patients with epilepsy. Methods We used resting-state functional MRI recordings in 27 patients with TLE (67% right sided) and 27 matched controls to examine functional connectivity (partial correlation) between eight brainstem ARAS structures and 105 cortical/subcortical regions. ARAS nuclei included: cuneiform/subcuneiform, dorsal raphe, locus coeruleus, median raphe, parabrachial complex, pontine oralis, pedunculopontine and ventral tegmental area. Connectivity patterns were related to disease and neuropsychological parameters. Results In control subjects, regions showing highest connectivity to ARAS structures included limbic structures, thalamus and certain neocortical areas, which is consistent with prior studies of ARAS projections. Overall, ARAS connectivity was significantly lower in patients with TLE than controls (p<0.05, paired t-test), particularly to neocortical regions including insular, lateral frontal, posterior temporal and opercular cortex. Diminished ARAS connectivity to these regions was related to increased frequency of consciousness-impairing seizures (p<0.01, Pearson’s correlation) and was associated with impairments in verbal IQ, attention, executive function, language and visuospatial memory on neuropsychological evaluation (p<0.05, Spearman’s rho or Kendell’s tau-b). Conclusions Recurrent seizures in TLE are associated with disturbances in ARAS connectivity, which are part of the widespread network dysfunction that may be related to neurocognitive problems in this devastating disorder.

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Section: Discussionsupporting

confidence: 88%

Functional connectivity disturbances of the ascending reticular activating system in temporal lobe epilepsy

Englot

D’Haese

Konrad

et al. 2017

J Neurol Neurosurg Psychiatry

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“…The so-called resting state fMRI provides data to query brain connectivity, which numerous investigations over the last decade have shown to mirror anatomic connections [22, 23]. In fact, by examining how individual voxels of the brain are connected to one another, researchers have also employed various analytical tools to identify or refine the networks of brain regions that function in a concerted manner [24-26].…”

Section: Techniques To Study the Cns In Clinical Researchmentioning

confidence: 99%

Central nervous system regulation of eating: Insights from human brain imaging

2016

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Appetite and body weight regulation are controlled by the central nervous system (CNS) in a rather complicated manner. The human brain plays a central role in integrating internal and external inputs to modulate energy homeostasis. Although homeostatic control by the hypothalamus is currently considered to be primarily responsible for controlling appetite, most of the available evidence derives from experiments in rodents, and the role of this system in regulating appetite in states of hunger/starvation and in the pathogenesis of overeating/obesity remains to be fully elucidated in humans. Further, cognitive and affective processes have been implicated in the dysregulation of eating behavior in humans, but their exact relative contributions as well as the respective underlying mechanisms remain unclear. We briefly review each of these systems here and present the current state of research in an attempt to update clinicians and clinical researchers alike on the status and future directions of obesity research.

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“…Recent studies have demonstrated the feasibility of LC functional connectivity studies (Bär et al, 2016;Köhler et al, 2016;Zhang et al, 2016). However, the extent to which the adrenergic arousal circuitry is modulated during altered arousal states has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Modulation of Noradrenergic Arousal Circuitry Disrupts Functional Connectivity of the Locus Ceruleus in Humans

et al. 2017

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State-dependent activity of locus ceruleus (LC) neurons has long suggested a role for noradrenergic modulation of arousal. However, in vivo insights into noradrenergic arousal circuitry have been constrained by the fundamental inaccessibility of the human brain for invasive studies. Functional magnetic resonance imaging (fMRI) studies performed during site-specific pharmacological manipulations of arousal levels may be used to study brain arousal circuitry. Dexmedetomidine is an anesthetic that alters the level of arousal by selectively targeting ␣2 adrenergic receptors on LC neurons, resulting in reduced firing rate and norepinephrine release. Thus, we hypothesized that dexmedetomidine-induced altered arousal would manifest with reduced functional connectivity between the LC and key brain regions involved in the regulation of arousal. To test this hypothesis, we acquired resting-state fMRI data in right-handed healthy volunteers 18 -36 years of age (n ϭ 15, 6 males) at baseline, during dexmedetomidine-induced altered arousal, and recovery states. As previously reported, seed-based resting-state fMRI analyses revealed that the LC was functionally connected to a broad network of regions including the reticular formation, basal ganglia, thalamus, posterior cingulate cortex (PCC), precuneus, and cerebellum. Functional connectivity of the LC to only a subset of these regions (PCC, thalamus, and caudate nucleus) covaried with the level of arousal. Functional connectivity of the PCC to the ventral tegmental area/pontine reticular formation and thalamus, in addition to the LC, also covaried with the level of arousal. We propose a framework in which the LC, PCC, thalamus, and basal ganglia comprise a functional arousal circuitry.

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Resting-State Functional Connectivity of the Locus Coeruleus in Humans: In Comparison with the Ventral Tegmental Area/Substantia Nigra Pars Compacta and the Effects of Age

Cited by 96 publications

References 153 publications

Functional connectivity disturbances of the ascending reticular activating system in temporal lobe epilepsy

Functional connectivity disturbances of the ascending reticular activating system in temporal lobe epilepsy

Central nervous system regulation of eating: Insights from human brain imaging

Pharmacological Modulation of Noradrenergic Arousal Circuitry Disrupts Functional Connectivity of the Locus Ceruleus in Humans

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