Functional imaging of olfaction by CBV fMRI in monkeys: Insight into the role of olfactory bulb in habituation

Zhao, Fuqiang; Holahan, Marie A.; Houghton, Andrea K.; Hargreaves, Richard; Evelhoch, Jeffrey L.; Winkelmann, Christopher T.; Williams, Donald S.

doi:10.1016/j.neuroimage.2014.12.001

Cited by 25 publications

(26 citation statements)

References 50 publications

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“…Hence, the isoflurane dose used in our study can be considered reasonably low, however, sufficient for the maintenance and prevention of any motion from painful thermal stimulus. Various other anesthesia paradigms have been used in animal fMRI studies, e.g., combined anesthesia consisting of 0.3% - 0.5% isoflurane and various opioids [ 69 ], neuromuscular blocking agents [ 98 ], sedatives [ 99 ] and hypnotic agents [ 100 ]. However, many of these anesthetics also have analgesic effect, which may impart undesired pharmacological actions for applying this animal model to develop novel pain treatments.…”

Section: Discussionmentioning

confidence: 99%

Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates

Asad¹,

Seah²,

Baumgartner³

et al. 2016

PLoS ONE

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BackgroundApproximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored.MethodologyHere we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm) application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail).Principal FindingsGroup comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the ‘pain matrix’, including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8), while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures.ConclusionsThese findings provide insights into the specific brain regions involved with aversive, ‘pain-like’, responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate the preclinical efficacy of novel analgesics.

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Section: Discussionmentioning

confidence: 99%

Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates

Asad¹,

Seah²,

Baumgartner³

et al. 2016

PLoS ONE

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“…The gas flow was split into two pathways, one of which received odorized gas through a bubbling bottle containing the odor solution. The two pathways join together prior to entering the nostrils [ 17 ]. During the odor stimulation period, the odor was introduced by opening two valves at the inlet and outlet of the bubbling bottle through a control signal from MRI sequence.…”

Section: Methodsmentioning

confidence: 99%

“…Techniques which can measure the olfactory response in the olfactory system of NHPs are limited. An fMRI technique which can measure the olfactory response in NHPs has been successfully developed recently, and the odorant-induced olfactory fMRI activations can be robustly observed in the OB of NHPs [ 17 ]. This fMRI technique can be used to study the mechanism of olfactory processing in NHPs by testing the effects of pharmacological agents on the odorant-induced olfactory fMRI signals.…”

Section: Introductionmentioning

confidence: 99%

“…Cerebral blood volume (CBV) fMRI, which uses an intravascular contrast agent consisting of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO), has been used to study odorant-evoked olfaction in rats [ 22 , 23 ], and NHPs [ 17 ]. CBV fMRI is sensitive to neural activation-induced vascular responses, and has a higher sensitivity compared to BOLD fMRI [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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fMRI study of the role of glutamate NMDA receptor in the olfactory processing in monkeys

et al. 2018

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Studies in rodents show that olfactory processing in the principal neurons of olfactory bulb (OB) and piriform cortex (PC) is controlled by local inhibitory interneurons, and glutamate NMDA receptor plays a role in this inhibitory control. It is not clear if findings from studies in rodents translate to olfactory processing in nonhuman primates (NHPs). In this study, the effect of the glutamate NMDA receptor antagonist MK801 on odorant-induced olfactory responses in the OB and PC of anesthetized NHPs (rhesus monkeys) was investigated by cerebral blood volume (CBV) fMRI. Isoamyl-acetate was used as the odor stimulant. For each NHP, sixty fMRI measurements were made during a 4-h period, with each 4-min measurement consisting of a 1-min baseline period, a 1-min odor stimulation period, and a 2-min recovery period. MK801 (0.3 mg/kg) was intravenously delivered 1 hour after starting fMRI. Before MK801 injection, olfactory fMRI activations were observed only in the OB, not in the PC. After MK801 injection, olfactory fMRI activations in the OB increased, and robust olfactory fMRI activations were observed in the PC. The data indicate that MK801 enhances the olfactory responses in both the OB and PC. The enhancement effects of MK801 are most likely from its blockage of NMDA receptors on local inhibitory interneurons and the attenuation of the inhibition onto principal neurons. This study suggests that the mechanism of local inhibitory control of principal neurons in the OB and PC derived from studies in rodents translates to NHPs.

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“…Anesthetized animals are generally applied in MRI studies to minimize the animal motion even though MRI of awake NHPs can eliminate the adverse anesthesia effects in the brain but it requires extensive animal training and special experimental settings (67-69) which are not available in most research labs. Even though anesthetics like isoflurane substantially suppress the neural activation in the NHP brain, the brain functionality can still be evaluated with fMRI techniques (70,71). Also, the handling of anesthetized NHPs requires comprehensive physiological monitoring and professional veterinarian support to maintain animals in proper conditions and comply with the NIH guidelines of animal care and usage.…”

Section: Technical Challenges and Limitations Of Asl Perfusion Mri Inmentioning

confidence: 99%

Arterial spin labeling perfusion magnetic resonance imaging of non-human primates

Zhang¹,

Li²

2016

Quant. Imaging Med. Surg.

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Non-human primates (NHPs) resemble most aspects of humans in brain physiology and anatomy and are excellent animal models for translational research in neuroscience, biomedical research and pharmaceutical development. Cerebral blood flow (CBF) offers essential physiological information of the brain to examine the abnormal functionality in NHP models with cerebral vascular diseases and neurological disorders or dementia. Arterial spin labeling (ASL) perfusion MRI techniques allow for high temporal and spatial CBF measurement and are intensively used in studies of animals and humans. In this article, current high-resolution ASL perfusion MRI techniques for quantitative evaluation of brain physiology and function in NHPs are described and their applications and limitation are discussed as well.

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Functional imaging of olfaction by CBV fMRI in monkeys: Insight into the role of olfactory bulb in habituation

Cited by 25 publications

References 50 publications

Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates

Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates

fMRI study of the role of glutamate NMDA receptor in the olfactory processing in monkeys

Arterial spin labeling perfusion magnetic resonance imaging of non-human primates

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