scholarly journals Neural and Hemodynamic Responses to Optogenetic and Sensory Stimulation in the Rat Somatosensory Cortex

2015 ◽  
Vol 35 (6) ◽  
pp. 922-932 ◽  
Author(s):  
Bistra Iordanova ◽  
Alberto L Vazquez ◽  
Alexander J Poplawsky ◽  
Mitsuhiro Fukuda ◽  
Seong-Gi Kim

Introducing optogenetics into neurovascular research can provide novel insights into the cell-specific control of the hemodynamic response. To generalize findings from molecular approaches, it is crucial to determine whether light-activated circuits have the same effect on the vasculature as sensory-activated ones. For that purpose, rats expressing channelrhodopsin (ChR2) specific to excitatory glutamatergic neurons were used to measure neural activity, blood flow, hemoglobin-based optical intrinsic signal, and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during optogenetic and sensory stimulation. The magnitude of the evoked hemodynamic responses was monotonically correlated with optogenetic stimulus strength. The BOLD hemodynamic response function was consistent for optogenetic and sensory stimuli. The relationship between electrical activities and hemodynamic responses was comparable for optogenetic and sensory stimuli, and better explained by the local field potential (LFP) than the firing rate. The LFP was well correlated with cerebral blood flow, moderately with cerebral blood volume, and less with deoxyhemoglobin (dHb) level. The presynaptic firing rate had little impact on evoking vascular response. Contribution of the postsynaptic LFP to the blood flow response induced by optogenetic stimulus was further confirmed by the application of glutamate receptor antagonists. Overall, neurovascular coupling during optogenetic control of glutamatergic neurons largely conforms to that of a sensory stimulus.

2015 ◽  
Vol 35 (7) ◽  
pp. 1213-1219 ◽  
Author(s):  
Hye-Young Heo ◽  
John A Wemmie ◽  
Casey P Johnson ◽  
Daniel R Thedens ◽  
Vincent A Magnotta

Recent experiments suggest that T1 relaxation in the rotating frame ( T1ρ) is sensitive to metabolism and can detect localized activity-dependent changes in the human visual cortex. Current functional magnetic resonance imaging (fMRI) methods have poor temporal resolution due to delays in the hemodynamic response resulting from neurovascular coupling. Because T1ρ is sensitive to factors that can be derived from tissue metabolism, such as pH and glucose concentration via proton exchange, we hypothesized that activity-evoked T1ρ changes in visual cortex may occur before the hemodynamic response measured by blood oxygenation level-dependent (BOLD) and arterial spin labeling (ASL) contrast. To test this hypothesis, functional imaging was performed using BOLD, and ASL in human participants viewing an expanding ring stimulus. We calculated eccentricity phase maps across the occipital cortex for each functional signal and compared the temporal dynamics of T1ρ versus BOLD and ASL. The results suggest that T1ρ changes precede changes in the two blood flow-dependent measures. These observations indicate that T1ρ detects a signal distinct from traditional fMRI contrast methods. In addition, these findings support previous evidence that T1ρ is sensitive to factors other than blood flow, volume, or oxygenation. Furthermore, they suggest that tissue metabolism may be driving activity-evoked T1ρ changes.


2018 ◽  
Author(s):  
Ali Danish Zaidi ◽  
Niels Birbaumer ◽  
Eberhard Fetz ◽  
Nikos Logothetis ◽  
Ranganatha Sitaram

AbstractFunctional neuroimaging is a powerful non-invasive tool for studying brain function, using changes in blood-oxygenation as a proxy for underlying neuronal activity. The neuroimaging signal correlates with both spiking, and various bands of the local field potential (LFP), making the inability to discriminate between them a serious limitation for interpreting hemodynamic changes. Here, we record activity from the striate cortex in two anesthetized monkeys (Macaca mulatta), using simultaneous functional near-infrared spectroscopy (fNIRS) and intra-cortical electrophysiology. We find that low-frequency LFPs correlate with hemodynamic signal’s peak amplitude, whereas spiking correlates with its peak-time and initial-dip. We also find spiking to be more spatially localized than low-frequency LFPs. Our results suggest that differences in spread of spiking and low-frequency LFPs across cortical surface influence different parameters of the hemodynamic response. Together, these results demonstrate that the hemodynamic response-amplitude is a poor correlate of spiking activity. Instead, we demonstrate that the timing of the initial-dip and the hemodynamic response are much more reliable correlates of spiking, reflecting bursts in spike-rate and total spike-counts respectively.


2019 ◽  
Author(s):  
Aleksandra Bortel ◽  
Roland Pilgram ◽  
Ze Shan Yao ◽  
Amir Shmuel

ABSTRACTFunctional MRI (fMRI) utilizes changes in metabolic and hemodynamic signals to indirectly infer the underlying local changes in neuronal activity. To investigate the mechanisms of fMRI responses, spontaneous fluctuations, and functional connectivity in the resting-state, it is important to pursue fMRI in animal models. Animal studies commonly use dexmedetomidine sedation. It has been demonstrated that potent sensory stimuli administered under dexmedetomidine are prone to inducing seizures in Sprague-Dawley (SD) rats.Here we combined optical imaging of intrinsic signals and cerebral blood flow with neurophysiological recordings to measure responses in rat area S1FL to electrical forepaw stimulation administered at 8 Hz. We show that the increased susceptibility to seizures starts no later than 1 hour and ends no sooner than 3 hours after initiating a continuous administration of dexmedetomidine. By administering different combinations of anesthetic and sedative agents, we demonstrate that dexmedetomidine is the sole agent necessary for the increased susceptibility to seizures. The increased susceptibility to seizures prevails under a combination of 0.3%-0.5% isoflurane and dexmedetomidine anesthesia. The blood-oxygenation and cerebral blood flow responses to seizures induced by forepaw stimulation have a higher amplitude and a larger spatial extent relative to physiological responses to the same stimuli. The epileptic activity and the associated blood oxygenation and cerebral blood flow responses stretched beyond the stimulation period. We observed seizures in response to forepaw stimulation with 1-2 mA pulses administered at 8 Hz. In contrast, responses to stimuli administered at 4 Hz were seizure-free. We demonstrate that such seizures are generated not only in SD rats but also in Long-Evans rats, but not in C57BL6 mice stimulated with similar potent stimuli under dexmedetomidine sedation.We conclude that high-amplitude hemodynamic functional imaging responses evoked by peripheral stimulation in rats sedated with dexmedetomidine are possibly due to the induction of epileptic activity. Therefore, caution should be practiced in experiments that combine the administration of potent stimuli with dexmedetomidine sedation. We propose stimulation paradigms that elicit seizure-free, well detectable neurophysiological and hemodynamic responses in rats. We further conclude that the increased susceptibility to seizures under dexmedetomidine sedation is species dependent.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emily T. Wood ◽  
Kaitlin K. Cummings ◽  
Jiwon Jung ◽  
Genevieve Patterson ◽  
Nana Okada ◽  
...  

AbstractSensory over-responsivity (SOR), extreme sensitivity to or avoidance of sensory stimuli (e.g., scratchy fabrics, loud sounds), is a highly prevalent and impairing feature of neurodevelopmental disorders such as autism spectrum disorders (ASD), anxiety, and ADHD. Previous studies have found overactive brain responses and reduced modulation of thalamocortical connectivity in response to mildly aversive sensory stimulation in ASD. These findings suggest altered thalamic sensory gating which could be associated with an excitatory/inhibitory neurochemical imbalance, but such thalamic neurochemistry has never been examined in relation to SOR. Here we utilized magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to examine the relationship between thalamic and somatosensory cortex inhibitory (gamma-aminobutyric acid, GABA) and excitatory (glutamate) neurochemicals with the intrinsic functional connectivity of those regions in 35 ASD and 35 typically developing pediatric subjects. Although there were no diagnostic group differences in neurochemical concentrations in either region, within the ASD group, SOR severity correlated negatively with thalamic GABA (r = −0.48, p < 0.05) and positively with somatosensory glutamate (r = 0.68, p < 0.01). Further, in the ASD group, thalamic GABA concentration predicted altered connectivity with regions previously implicated in SOR. These variations in GABA and associated network connectivity in the ASD group highlight the potential role of GABA as a mechanism underlying individual differences in SOR, a major source of phenotypic heterogeneity in ASD. In ASD, abnormalities of the thalamic neurochemical balance could interfere with the thalamic role in integrating, relaying, and inhibiting attention to sensory information. These results have implications for future research and GABA-modulating pharmacologic interventions.


2013 ◽  
Vol 109 (11) ◽  
pp. 2732-2738 ◽  
Author(s):  
Elias B. Issa ◽  
Xiaoqin Wang

During sleep, changes in brain rhythms and neuromodulator levels in cortex modify the properties of individual neurons and the network as a whole. In principle, network-level interactions during sleep can be studied by observing covariation in spontaneous activity between neurons. Spontaneous activity, however, reflects only a portion of the effective functional connectivity that is activated by external and internal inputs (e.g., sensory stimulation, motor behavior, and mental activity), and it has been shown that neural responses are less correlated during external sensory stimulation than during spontaneous activity. Here, we took advantage of the unique property that the auditory cortex continues to respond to sounds during sleep and used external acoustic stimuli to activate cortical networks for studying neural interactions during sleep. We found that during slow-wave sleep (SWS), local (neuron-neuron) correlations are not reduced by acoustic stimulation remaining higher than in wakefulness and rapid eye movement sleep and remaining similar to spontaneous activity correlations. This high level of correlations during SWS complements previous work finding elevated global (local field potential-local field potential) correlations during sleep. Contrary to the prediction that slow oscillations in SWS would increase neural correlations during spontaneous activity, we found little change in neural correlations outside of periods of acoustic stimulation. Rather, these findings suggest that functional connections recruited in sound processing are modified during SWS and that slow rhythms, which in general are suppressed by sensory stimulation, are not the sole mechanism leading to elevated network correlations during sleep.


1997 ◽  
Vol 92 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Gervais Tougas ◽  
Markad Kamath ◽  
Geena Watteel ◽  
Debbie Fitzpatrick ◽  
Ernest L. Fallen ◽  
...  

1. The heart and the oesophagus have similar sensory pathways, and sensations originating from the oesophagus are often difficult to differentiate from those of cardiac origin. We hypothesized that oesophageal sensory stimuli could alter neurocardiac function through autonomic reflexes elicited by these oesophageal stimuli. In the present study, we examined the neurocardiac response to oesophageal stimulation and the effects of electrical and mechanical oesophageal stimulation on the power spectrum of beat-to-beat heart rate variability in male volunteers. 2. In 14 healthy volunteers, beat-to-beat heart rate variability was compared at rest and during oesophageal stimulation, using either electrical (200 μs, 16 mA, 0.2 Hz) or mechanical (0.5 s, 14 ml, 0.2 Hz) stimuli. The power spectrum of beat-to-beat heart rate variability was obtained and its low- and high-frequency components were determined. 3. Distal oesophageal stimulation decreased heart rate slightly (both electrical and mechanical) (P < 0.005), and markedly altered heart rate variability (P < 0.001). Both electrical and mechanical oesophageal stimulation increased the absolute and normalized area of the high-frequency band within the power spectrum (P < 0.001), while simultaneously decreasing the low-frequency power (P < 0.005). 4. In humans, oesophageal stimulation, whether electrical or mechanical, appears to amplify respiratory-driven cardiac vagoafferent modulation while decreasing sympathetic modulation. The technique provides access to vagoafferent fibres and thus may yield useful information on the autonomic effects of visceral or oesophageal sensory stimulation.


1996 ◽  
Vol 81 (3) ◽  
pp. 1174-1183 ◽  
Author(s):  
H. Obrig ◽  
C. Hirth ◽  
J. G. Junge-Hulsing ◽  
C. Doge ◽  
T. Wolf ◽  
...  

We studied cerebral hemodynamic response to a sequential motor task in 56 subjects to investigate the time course and distribution of blood oxygenation changes as monitored by near-infrared spectroscopy (NIRS). To address whether response is modulated by different performance velocities, a group of subjects (n = 12) was examined while performing the motor task at 1, 2, and 3 Hz. The results demonstrate that 1) the NIRS response reflects localized changes in cerebral hemodynamics, 2) the response, consisting of an increase in oxygenated hemoglobin concentration [oxy-Hb] and a decrease in deoxygenated hemoglobin concentration ([deoxy-Hb]), is lateralized and increases in amplitude with higher performance rates, and 3) changes in [oxy-Hb] and [deoxy-Hb] differ in time course. Changes in [oxy-Hb] are biphasic, with a fast initial increase and a pronounced poststimulus undershoot. The stimulus-associated decrease in [deoxy-Hb] is monophasic, and response latency is greater. We conclude that NIRS is able to detect even small changes in cerebral hemodynamic response to functional stimulation.


2017 ◽  
Vol 39 (2) ◽  
pp. 302-312 ◽  
Author(s):  
Li Zhao ◽  
David C Alsop ◽  
John A Detre ◽  
Weiying Dai

Global synchronization across specialized brain networks is a common feature of network models and in-vivo electrical measurements. Although the imaging of specialized brain networks with blood oxygenation sensitive resting state functional magnetic resonance imaging (rsfMRI) has enabled detailed study of regional networks, the study of globally correlated fluctuations with rsfMRI is confounded by spurious contributions to the global signal from systemic physiologic factors and other noise sources. Here we use an alternative rsfMRI method, arterial spin labeled perfusion MRI, to characterize global correlations and their relationship to correlations and anti-correlations between regional networks. Global fluctuations that cannot be explained by systemic factors dominate the fluctuations in cerebral blood flow. Power spectra of these fluctuations are band limited to below 0.05 Hz, similar to prior measurements of regional network fluctuations in the brain. Removal of these global fluctuations prior to measurement of regional networks reduces all regional network fluctuation amplitudes to below the global fluctuation amplitude and changes the strength and sign of inter network correlations. Our findings support large amplitude, globally synchronized activity across networks that require a reassessment of regional network amplitude and correlation measures.


Sign in / Sign up

Export Citation Format

Share Document