Size of the spatial correlation between ECoG and fMRI activity

Functional magnetic resonance imaging (fMRI) is a unique window to the brain, enabling scientists to follow changes in brain activity in response to hormones, ageing, environment, drugs of abuse and other stimuli. There are two features that make fMRI unique when compared with other imaging modalities used in behavioural neuroscience. First, it can be entirely noninvasive: each animal can serve as its own control over the natural course of its life, vital for following neuroadaptation and other developmental processes critical to understanding behaviour. Second, fMRI has the spatial and temporal resolution to observe patterns of neuronal activity across the entire brain in less than a minute. Although fMRI does not have the cellular spatial resolution of immunostaining, nor the millisecond temporal resolution of electrophysiology, synchronised changes in neuronal activity across multiple brain areas seen with functional MRI can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviours. Thus, fMRI affords a systems approach to the study of the brain, complementing and building from other neurobiological techniques to understand how behaviour is organised across multiple brain regions. In this review, we present a general background to fMRI and the different imaging modalities that can be used in fMRI studies. Included are examples of the application of fMRI in behavioural neuroscience research, along with discussion of the advantages and disadvantages of this technology.

Background:Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine.Methods:Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03–0.6mg/kg) on the BOLD signal was investigated for 10min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated.Results:A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal.Conclusions:These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function.

We present a new method for the calculation of a blood oxygen level dependent (BOLD) signal which is meaningful for a quantitative comparison with near infrared spectroscopy (NIRS) data. Since optical tomography of the human brain still poses several difficulties, in this study we propose a way to project the BOLD signal on a two-dimensional (2D) map for comparison with NIRS data. The underlying assumption is that fMRI and NIRS are sensitive to similar aspects of the hemodynamic changes occurring during a functional task, and therefore they should have similar spatial and temporal features. We present a case study of functional activation during a finger-tapping test where we used the new method for the calculation of BOLD signal. For every optical source-detector pair we calculated a weighted BOLD signal by using a photon hitting-density weight function, and by using a simple back-projection algorithm we were able to generate BOLD 2D maps. We found that the weighted BOLD signals calculated from different source-detector pairs scale in a similar way to the corresponding oxy and deoxy-hemeoglobin concentration changes calculated from NIRS data, for most of the time range of the task. Therefore the BOLD 2D maps were quantitatively similar to the optical maps calculated at different times during the protocol.

Comment on “The physiology of developmental changes in BOLD functional imaging signals” by Harris, Reynell, and Attwell

The aim of this study was to investigate the delayed neuronal effects of acupuncture manipulations by observing blood oxygen level-dependent (BOLD) signal intensities. Fifteen (15) healthy, acupuncture-naive, right-handed subjects (all males; mean age, 23 years; range, 21-24 years) participated in this study. Each subject was scanned in eight sessions that consisted of two repeated baseline scans (Period 1), two repeated scans with acupuncture stimulation at right LR2 (Period 2), two repeated scans with retention (Period 3), and two repeated scans after removal of the needle (Period 4). Sixteen (16) regions of interest (ROI) were defined. The BOLD signals for each session were obtained for each ROI. A mixed-effects analysis of variance (ANOVA) test was performed in order to investigate the BOLD signal differences of the Periods in the 16 ROIs. The BOLD signal intensities increased in Periods 2 and 3, and then started to decrease in Period 4 in the right amygdala, supramarginal gyrus, temporal pole, and superior temporal gyrus. However, the BOLD signal intensity in Period 4 was significantly higher than that of Period 1. Especially, BOLD signal intensity was elevated promptly in the insula and the parahippocampal gyrus, whereas it was persistently elevated (delayed effect) in the amygdala. BOLD signals were persistently elevated for at least 8 minutes after removal of the acupuncture needle or for at least 19 minutes after rotation of an acupuncture needle in some specific brain areas previously linked with LR2. In those specific brain ROIs, neuronal activation accompanying and following acupuncture showed both prompt and delayed effects.

Decoding neural events from fMRI BOLD signal: A comparison of existing approaches and development of a new algorithm

We investigated the effects of resting state type on blood oxygen level-dependent (BOLD) signal and functional connectivity in two paradigms: participants either alternated between fixation and eyes closed or maintained fixation or eyes closed throughout each scan. The BOLD signal and functional connectivity of lower and higher tiers of the visual cortical hierarchy were found to be differentially modulated during eyes closed versus fixation. Fixation was associated with greater mean BOLD signals in primary visual cortex and lower mean BOLD signals in extrastriate visual areas than periods of eyes closed. In addition, analysis of thalamocortical functional connectivity during scans in which participants maintained fixation showed synchronized BOLD fluctuations between those thalamic nuclei whose mean BOLD signal was systematically modulated during alternating epochs of eyes closed and fixation, primary visual cortex and the attention network, while during eyes closed negatively correlated fluctuations were seen between the same thalamic nuclei and extrastriate visual areas. Finally, in all visual areas the amplitude of spontaneous BOLD fluctuations was greater during eyes closed than during fixation. The dissociation between early and late tiers of visual cortex, which characterizes both mean and functionally connected components of the BOLD signal, may depend on the reorganization of thalamocortical networks. Since dissociated changes in local blood flow also characterize transitions between different stages of sleep and wakefulness (Braun AR, Balkin TJ, Wesenten NJ, Gwadry F, Carson RE, Varga M, Baldwin P, Belenky G, Herscovitch P. Science 279: 91-95, 1998), our results suggest that dissociated endogenous neural activity in primary and extrastriate cortex may represent a general aspect of brain function.

Ethanol modulates the neurovascular coupling

In a recent Letter to Nature, Lee and colleagues combined optogenetic stimulation with functional magnetic resonance imaging (ofMRI) to examine the relationship between pyramidal-cell spiking and the blood oxygenation level dependent (BOLD) signal. To do so, they injected an adeno-associated viral vector into the primary motor cortex (M1) of adult rats to drive the expression of channelrhodopsin (ChR2) in cortical projection neurons, thus making them sensitive to light. The authors then used combined light stimulation and functional magnetic resonance imaging (fMRI) to examine the effects of selective activation of the light-sensitive pyramidal cells on the BOLD signal, as well as to probe the value of this methodology for mapping brain connectivity. They found that excitation of these neurons induced positive BOLD signals both in the injected M1 region and in remote target thalamic nuclei receiving direct projections from that region, and concluded that ofMRI reliably links positive BOLD signals with increased local neuronal excitation. However, their analysis neglects the almost immediate activation of other circuits that could lead to the generation of BOLD signals through local perisynaptic rather than spiking activity. Their experiments therefore do not pin down the identity of the specific neuronal signals that give rise to the BOLD signal.

We used EEG-fMRI to study epileptiform activity in a cohort of untreated children with typical absence seizures (AS). Our aim was to identify cortical and subcortical regions involved in spike and wave events and to explore the timing of activity in these regions. Eleven children with AS confirmed on video-EEG underwent EEG-fMRI. An event-related analysis of epileptiform activity was performed. Regions of interest (ROIs), identified in the event-related analysis, were used to study the time course of the blood oxygen level-dependent (BOLD) signal prior to and immediately following events of interest in these ROIs. Group analysis confirmed positive BOLD in the thalamus and negative BOLD in the lateral and mesial parietal lobe, caudate nuclei, and additionally the brainstem reticular formation. The event-related time course differed between the thalamus, the parietal cortex, and the pons and caudate nuclei. In the subcortical structures, BOLD signal change occurred at, or immediately after, electrographic onset. Importantly, in the parietal cortex, but not in other cortical regions, there was a subtle BOLD signal increase for 10 seconds prior to the onset of epileptiform activity. In children with typical AS, we have confirmed a core network of structures involved in generalized epileptiform activity that includes the reticular structures of the brainstem. Furthermore, we have identified changes in parietal BOLD signal which precede the onset of epileptiform activity, suggesting the parietal cortex has a role in the initiation of epileptiform activity.

ObjectivesPrevious fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Experimental designChanges in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250ml) of: 1M glucose+predosing with dexloxiglumide (CCK1 receptor antagonist), 1M glucose+placebo, or 0.9% saline (control)+placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Principal observationsIntragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose+dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. ConclusionsGlucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway.

Transcranial alternating current stimulation (tACS) has emerged as a promising tool for manipulating ongoing brain oscillations. While previous studies demonstrated frequency‐specific effects of tACS on diverse cognitive functions, its effect on neural activity remains poorly understood. Here we asked how tACS modulates regional fMRI blood oxygenation level dependent (BOLD) signal as a function of frequency, current strength, and task condition. TACS was applied over the posterior cortex of healthy human subjects while the BOLD signal was measured during rest or task conditions (visual perception, passive video viewing and motor task). TACS was applied in a blockwise manner at different frequencies (10, 16, 60 and 80 Hz). The strongest tACS effects on BOLD activity were observed with stimulation at alpha (10 Hz) and beta (16 Hz) frequency bands, while effects of tACS at the gamma range were rather modest. Specifically, we found that tACS at 16 Hz induced BOLD activity increase in fronto‐parietal areas. Overall, tACS effects varied as a function of frequency and task, and were predominantly seen in regions that were not activated by the task. Also, the modulated regions were poorly predicted by current density modeling studies. Taken together, our results suggest that tACS does not necessarily exert its strongest effects in regions below the electrodes and that region specificity might be achieved with tACS due to varying susceptibility of brain regions to entrain to a given frequency. Hum Brain Mapp 37:94–121, 2016. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc

The contribution of different frequency bands of fMRI data to the correlation with EEG alpha rhythm

Visual cortex reactivity in sedated children examined with perfusion MRI (FAIR)

Vascular component analysis of hyperoxic and hypercapnic BOLD contrast