Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, R. Ross; Lukas, Scott E.

doi:10.1016/j.pnpbp.2011.05.015

Cited by 18 publications

(13 citation statements)

References 61 publications

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“…Instead the connectivity may reflect some aberrant state that occurs at the expense of task-related function. Our data support this notion since here we show that visual RSNs exhibited increased connectivity, while previously we reported that in these same participants zolpidem reduced BOLD activation during visual stimulation (Licata et al, 2011a). Similarly, acute challenge with alcohol increased resting state correlations in a visual RSN (Esposito et al, 2010) while prior to that it had been shown to reduce BOLD signal activation in visual cortical areas during presentation of a stimulus (Levin et al, 1998; Calhoun et al, 2004).…”

Section: Discussionsupporting

confidence: 91%

“…All scanning sessions began at 10:30 am. The resting state scan preceded a passive visual stimulation scan as well as a key press task scan, both of which were reported on previously (Licata et al, 2011a). …”

Section: Methodsmentioning

confidence: 99%

“…One prominent reason for this is the relative ease with which this imaging paradigm can be implemented. Evaluating the brain at rest not only requires little from study participants, but assessments are not confounded by drug effects on activity or task performance (e.g., attention; see discussion in Licata et al, 2011a). Moreover, as the understanding grows regarding how RSNs represent functional neuronal systems (Smith et al, 2009), examining drug effects on functional connectivity may reveal important mechanistic information about drug action.…”

Section: Introductionmentioning

confidence: 99%

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The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm

et al. 2013

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Networks of brain regions having synchronized fluctuations of the blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) time-series at rest, or “resting state networks” (RSNs), are emerging as a basis for understanding intrinsic brain activity. RSNs are topographically consistent with activity-related networks subserving sensory, motor, and cognitive processes, and studying their spontaneous fluctuations following acute drug challenge may provide a way to understand better the neuroanatomical substrates of drug action. The present within-subject double-blind study used BOLD fMRI at 3T to investigate the functional networks influenced by the non-benzodiazepine hypnotic zolpidem (Ambien®). Zolpidem is a positive modulator of γ-aminobutyric acidA (GABAA) receptors, and engenders sedative effects that may be explained in part by how it modulates intrinsic brain activity. Healthy participants (n= 12) underwent fMRI scanning 45 min after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured while participants gazed at a static fixation point (i.e., at rest). Data were analyzed using group independent component analysis (ICA) with dual regression and results indicated that compared to placebo, the highest dose of zolpidem increased functional connectivity within a number of sensory, motor, and limbic networks. These results are consistent with previous studies showing an increase in functional connectivity at rest following administration of the positive GABAA receptor modulators midazolam and alcohol, and suggest that investigating how zolpidem modulates intrinsic brain activity may have implications for understanding the etiology of its powerful sedative effects.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm

et al. 2013

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“…A study investigating the relation of baseline GABA concentration as measured by MRS and the fMRI response in visual cortex [27] found that the signal variations of the BOLD contrast are linked to baseline GABA levels in a significant negative correlation, associating higher BOLD signal changes with lower GABA levels and vice versa. Results from a study investigating the effects of Zolpidem, a drug enhancing GABAergic inhibition, on visual response to a checkerboard pattern [28] point into the same direction, linking GABA-mediated inhibition and reduced BOLD responses. GABA receptors as the major inhibitory neurotransmitter receptors are found abundantly in the cortex.…”

Section: Discussionmentioning

confidence: 91%

Brain Activation in Motor Sequence Learning Is Related to the Level of Native Cortical Excitability

et al. 2013

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Cortical excitability may be subject to changes through training and learning. Motor training can increase cortical excitability in motor cortex, and facilitation of motor cortical excitability has been shown to be positively correlated with improvements in performance in simple motor tasks. Thus cortical excitability may tentatively be considered as a marker of learning and use-dependent plasticity. Previous studies focused on changes in cortical excitability brought about by learning processes, however, the relation between native levels of cortical excitability on the one hand and brain activation and behavioral parameters on the other is as yet unknown. In the present study we investigated the role of differential native motor cortical excitability for learning a motor sequencing task with regard to post-training changes in excitability, behavioral performance and involvement of brain regions. Our motor task required our participants to reproduce and improvise over a pre-learned motor sequence. Over both task conditions, participants with low cortical excitability (CElo) showed significantly higher BOLD activation in task-relevant brain regions than participants with high cortical excitability (CEhi). In contrast, CElo and CEhi groups did not exhibit differences in percentage of correct responses and improvisation level. Moreover, cortical excitability did not change significantly after learning and training in either group, with the exception of a significant decrease in facilitatory excitability in the CEhi group. The present data suggest that the native, unmanipulated level of cortical excitability is related to brain activation intensity, but not to performance quality. The higher BOLD mean signal intensity during the motor task might reflect a compensatory mechanism in CElo participants.

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“…Most hypnotics are benzodiazepine receptor agonists known to impair various aspects of cognition (Barker et al, ; Vermeeren, ). Benzodiazepine receptors are widely distributed throughout the brain (McCabe & Wamsley, ; Zezula, Cortes, Probst, & Palacios, ), and previous fMRI and PET studies have demonstrated that benzodiazepine receptor agonists inhibit neuronal activities involved in separate cognitive tasks (Licata et al, ; Mintzer et al, ). The results of an electroencephalogram study demonstrated that low doses of triazolam, similar to those used in the present study, can cause cortical dysfunction (Urata et al, ).…”

Section: Discussionmentioning

confidence: 99%

Effects of hypnotics on prefrontal cortex activity during a verbal fluency task in healthy male subjects: A near‐infrared spectroscopy study

Tsuruta

Iwamoto

Banno

et al. 2018

Human Psychopharmacology

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Objective To assess the effects of hypnotics on prefrontal cortex activity in healthy subjects using near‐infrared spectroscopy (NIRS) in a double‐blind, placebo‐controlled crossover trial. Methods Eighteen healthy males received acute doses of ramelteon (8 mg), triazolam (0.125 mg), or placebo in a predetermined randomization schedule, with a washout period of more than 1 week. All subjects performed a verbal fluency task during NIRS assessments at baseline and at 1 and 4 hr post‐dose. The number of words correctly generated during the task (behavioral performance) and scores on the Stanford Sleepiness Scale (SSS) were also recorded at each test time. Results Compared with the placebo, triazolam (0.125 mg) significantly decreased oxyhemoglobin (oxy‐Hb) concentration change in NIRS during the posttask period and significantly increased behavioral performance, whereas triazolam (0.125 mg) and ramelteon (8 mg) significantly increased SSS scores. Conclusions The differential effects of two types of hypnotics on oxy‐Hb change measured by NIRS were observed in acute dosing, suggesting that when assessing brain activity of patients with psychiatric disorders, researchers should consider how certain types of hypnotics can influence brain function. This would also provide useful information to clinicians when prescribing hypnotics suitable for their patients' conditions.

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Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

Cited by 18 publications

References 61 publications

The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm

The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm

Brain Activation in Motor Sequence Learning Is Related to the Level of Native Cortical Excitability

Effects of hypnotics on prefrontal cortex activity during a verbal fluency task in healthy male subjects: A near‐infrared spectroscopy study

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