Cortical fMRI Research Articles

Su2104 Effect of Vagotomy on Cortical FMRI Activity Induced by Esophageal Acid Stimulation in Rats: Further Validation of the Model

Su2104 Effect of Vagotomy on Cortical FMRI Activity Induced by Esophageal Acid Stimulation in Rats: Further Validation of the Model

Cortical fMRI activation to opponents’ body kinematics in sport-related anticipation: Expert-novice differences with normal and point-light video

Badminton players of varying skill levels viewed normal and point-light video clips of opponents striking the shuttle towards the viewer; their task was to predict in which quadrant of the court the shuttle would land. In a whole-brain fMRI analysis we identified bilateral cortical networks sensitive to the anticipation task relative to control stimuli. This network is more extensive and localised than previously reported. Voxel clusters responding more strongly in experts than novices were associated with all task-sensitive areas, whereas voxels responding more strongly in novices were found outside these areas. Task-sensitive areas for normal and point-light video were very similar, whereas early visual areas responded differentially, indicating the primacy of kinematic information for sport-related anticipation.

W11.4 Relationship between cortical fMRI activity and functional measures in amyotrophic lateral sclerosis

W11.4 Relationship between cortical fMRI activity and functional measures in amyotrophic lateral sclerosis

A stand-alone method for anatomical localization of NIRS measurements

Near-infrared spectroscopy (NIRS) is a non-invasive cortical imaging technique that provides many of the advantages of cortical fMRI with additional benefits of low cost, portability, and increased temporal resolution—features that make it potentially ideal for clinical diagnostic applications. However, the usefulness of NIRS is contingent on the ability to reliably localize the measured signal cortically. Although this can be achieved by supplementing NIRS data collection with an MRI scan, a much more appealing alternative is to use a portable magnetic measuring system to record the locations of optodes. Previous work has shown that optode skull measurements can be projected to the brain consistently within reasonable error bounds. Yet, as we show, if this is done without explicitly modeling the geometry of the holder securing the NIR optodes to participants' heads, considerable bias in the projection loci results. Here, we describe an algorithm that not only overcomes this bias but also corrects for measurement error in both optode position and skull reference points (which are used to register the measurements to standard brain templates) by applying geometric constraints. This method has been implemented as part of our NIRS Analysis Package (NAP), a public domain Matlab toolbox for analysis of NIRS data.

Modulation of Visually Evoked Cortical fMRI Responses by Phase of Ongoing Occipital Alpha Oscillations

Using simultaneous electroencephalography as a measure of ongoing activity and functional magnetic resonance imaging (fMRI) as a measure of the stimulus-driven neural response, we examined whether the amplitude and phase of occipital alpha oscillations at the onset of a brief visual stimulus affects the amplitude of the visually evoked fMRI response. When accounting for intrinsic coupling of alpha amplitude and occipital fMRI signal by modeling and subtracting pseudo-trials, no significant effect of prestimulus alpha amplitude on the evoked fMRI response could be demonstrated. Regarding the effect of alpha phase, we found that stimuli arriving at the peak of the alpha cycle yielded a lower blood oxygenation level-dependent (BOLD) fMRI response in early visual cortex (V1/V2) than stimuli presented at the trough of the cycle. Our results therefore show that phase of occipital alpha oscillations impacts the overall strength of a visually evoked response, as indexed by the BOLD signal. This observation complements existing evidence that alpha oscillations reflect periodic variations in cortical excitability and suggests that the phase of oscillations in postsynaptic potentials can serve as a mechanism of gain control for incoming neural activity. Finally, our findings provide a putative neural basis for observations of alpha phase dependence of visual perceptual performance.

The contrast dependence of the cortical fMRI deficit in amblyopia; a selective loss at higher contrasts

Although there is general agreement that the fMRI cortical response is reduced in humans with amblyopia, the deficit is subtle and has little correlation with threshold-based psychophysics. From a purely contrast sensitivity perspective, one would expect fMRI responses to be selectively reduced for stimuli of low contrasts. However, to date, all fMRI stimuli used in studies of amblyopia have been of high contrast. Furthermore, if the deficit is selective for low contrasts, one would expect it to reflect a selective M-cell loss, because M-cells have much higher contrast gain than P-cells and make a larger contribution to the threshold detection of stimuli of low spatial and medium temporal frequencies. To test these two predictions, we compared % BOLD response between the eyes of normals and amblyopes for low- and high-contrast stimuli using a phase-encoded design. The results suggest that the fMRI deficit in amblyopia depends upon stimulus contrast and that it is greater at high contrasts. This is consistent with a selective P-cell contrast deficit at a precortical or early cortical site.

M1297 Viscero-Visceral Inhibition of Cortical FMRI Activity is Associated With Alteration of Effective Brain Connectivity Pathways; the Role of Insula

M1297 Viscero-Visceral Inhibition of Cortical FMRI Activity is Associated With Alteration of Effective Brain Connectivity Pathways; the Role of Insula

Instruction dependent activation during optokinetic nystagmus (OKN) stimulation: An FMRI study at 3 T

Modifying experimental conditions of optokinetic nystagmus (OKN) result in different outcomes and may not optimally translate into clinical testing. The purpose of this study was to assess the influence of subject instruction on the anatomical correlates of OKN. The instructions were to voluntarily look or stare at the same moving grating with fixed contrast and spatial and temporal frequencies. Look and stare OKN were generated under identical stimulus “ON” conditions (vertical sine wave grating of 1.14 c/deg drifting right to left at 11.4 c/s with binocular viewing). FMRI was undertaken utilizing a 3.0 T GE system and the BOLD technique. Subjects included 6 normal adults ranging in age from 18 to 54 years with normal visual acuity (20/20 or better) and normal stereoacuity (40 s of arc or better). The results reveal that look OKN generated significantly more cortical FMRI activation than stare OKN. Look OKN areas included the culmen, parahippocampal, lingual, middle temporal gyri, inferior and superior parietal lobules and precuneus, all of which were unilaterally activated in the left hemisphere. The middle occipital gyrus was unilaterally activated in the right hemisphere while the cuneus was bilaterally activated. These results show that the activation sites for OKN studies are dependent on subject instruction which influence the type of OKN generated. Specifically, voluntary look OKN involved more brain sites than stare OKN. In so doing, we illustrate the importance of subject instruction and recommend that FMRI investigators of OKN be cognizant of these effects. The anatomical correlates of the look versus stare are discussed.

Cortical fMRI maps in response to 3D morphs between head and house

Cortical fMRI maps in response to 3D morphs between head and house

Evidence of altered posteromedial cortical FMRI activity in subjects at risk for Alzheimer disease.

The posteromedial cortices and other regions of the "default network" are particularly vulnerable to the pathology of Alzheimer disease (AD). In this study, we performed functional magnetic resonance imaging (fMRI) to investigate whether the presence of apolipoprotein E (APOE) epsilon allele and degree of memory impairment were associated with the dysfunction of these brain regions. Seventy-five elderly subjects ranging from cognitively normal to mild AD, divided into epsilon carriers and noncarriers, underwent fMRI during a memory-encoding task. Across all subjects, posteromedial and ventral anterior cingulate cortices (key components of the default network) as well as right middle and inferior prefrontal regions demonstrated reduced task-induced deactivation in the epsilon carriers relative to noncarriers. Even among cognitively normal subjects, epsilon carriers demonstrated reduced posteromedial deactivation compared with the noncarriers in the same regions which demonstrated failure of deactivation in AD patients. Greater failure of posteromedial deactivation was related to worse memory performance (delayed recall) across all subjects and within the range of cognitively normal subjects. In summary, the posteromedial cortical fMRI response pattern is modulated both by the presence of APOE epsilon and episodic memory capability. Altered fMRI activity of the posteromedial areas of the brain default network may be an early indicator of risk for AD.

Ipsilateral cortical fMRI responses after peripheral nerve damage in rats reflect increased interneuron activity.

In the weeks following unilateral peripheral nerve injury, the deprived primary somatosensory cortex (SI) responds to stimulation of the ipsilateral intact limb as demonstrated by functional magnetic resonance imaging (fMRI) responses. The neuronal basis of these responses was studied by using high-resolution fMRI, in vivo electrophysiological recordings, and juxtacellular neuronal labeling in rats that underwent an excision of the forepaw radial, median, and ulnar nerves. These nerves were exposed but not severed in control rats. Significant bilateral increases of fMRI responses in SI were observed in denervated rats. In the healthy SI of the denervated rats, increases in fMRI responses were concordant with increases in local field potential (LFP) amplitude and an increased incidence of single units responding compared with control rats. In contrast, in the deprived SI, increases in fMRI responses were associated with a minimal change in LFP amplitude but with increased incidence of single units responding. Based on action potential duration, juxtacellular labeling, and immunostaining results, neurons responding to intact forepaw stimulation in the deprived cortex were identified as interneurons. These results suggest that the increases in fMRI responses in the deprived cortex reflect increased interneuron activity.

A current density map of language: Comparison of cortical stimulation mapping and fMRI

A current density map of language: Comparison of cortical stimulation mapping and fMRI

A toolbox for the visualization and meta-analysis of functional brain organization of the cortical surface using an anatomical database

The recently introduced MatLab toolbox VAMCA (Visualization And Meta-analysis on Cortical Anatomy) [1] provides surface-based visualization of mean cortical functional activations that are published as stereotaxic 3D coordinates (www/ebire.org/hcnlab). VAMCA uses a database of cortices from 72 healthy subjects to locate activations on a standardized cortical surface by extending the technique of multi-fiducial mapping [2] in order to perform meta-analyses. We demonstrate that the multifiducial method should be able to reproduce cortical locations of functional activations. Non-parametric statistical tests are provided for determining (a) whether two groups of foci are in the same cortical location; (b) the extent of overlap of the two groups’ foci; and (c) whether two groups of foci are differentially concentrated in any of the anatomically defined regions of interest (ROI) as defined using FreeSurfer [3]. We explore extending VAMCA’s functionality in two ways. First, we perform a proof-of-principle on the inclusion of studies in meta-analyses that do not report results in stereotaxic coordinates. E.g., electronic journal images can be captured, normalized to 3D space in a semi-automated fashion, and then projected to the cortical surface and used in meta-analyses. Second, a new distance metric, the “least axon distance (LAD)”, is introduced. LAD reflects the minimum distance passing through brain matter between any pair of cortical surface points and provides a functionally relevant alternative to the 3D and 2D distance metrics currently used in VAMCA’s statistical tests. Multi-fiducial Database: VAMCA helps users visualize probable cortical locations associated with MNI/Talairach 3D coordinates by enhancing the technique of multi-fiducial mapping [2]. A cortical database is used to map 3D locations to multiple control subjects’ cortical surfaces in order to assist cortical localization. Subject database: Brain anatomical data from young (18-48 y.o.) healthy subjects: 60 right-handed (33 male) and 12 left-handed (6 male) subjects are included. Processing: Freesurfer [3] renders cortical surfaces and registers them to a mean cortical surface. SPM5 segments and normalizes the T1 images to MNI-152 space using affine-only coregistration. Multi-fiducial map database: 72 Normalized cortical surface space 3D MNI space maps. ROI identification: Freesurfer [3] also identifies 3 different sets of anatomical-based ROIs on each of the 72 cortical surfaces: Lobar ROIs (6 ROIs), Gryal/Sulcal-based ROIs (82 ROIs), and intermediate-sized ROIs (36 ROIs). Flatmaps generated from the mean registered cortical anatomy Multi-fiducial mapping of a 3D foci (circled yellow) to 60 individual cortical locations (red). Green cross is the 2D median location of the 60 points – the likely surface location that is used in subsequent processing. Stereotaxic coordinates in text files processed in MatLab. An occipital lobe coordinate is circled. Cortical surface identification and rendering – gyri (green) and sulci (red) shown Cortical inflation and surface registration to a common cortical coordinate system ROIs marked out on mean cortical anatomy associated with MNI space Mapping a stereotaxic location to the cortical surface Anatomical (sulci=black) shows that most (65%) individuals place the coordinate in Lingual/OccTemp Sulc rather than in Calcarine. Monte Carlo analysis verifies how well noisy, simulated cortical fMRI activations processed in MNI space might be identified: (a) Simulated fMRI activations are centered in various locations across the normalized cortical hemisphere and mapped to the cortex for randomly selected database subjects. (b) Location noises are added to activation locations: on the cortical surface to simulate functional/anatomical colocation variability, surface registration errors, etc. in 3D after converting to individual subjects’ MNI coordinates to simulate fMRI/anatomy coregistration error, MNI normalization error, and cluster maxima location variability, etc. (c) Computed MNI coordinates are processed using VAMCA to estimate cortical activation displacement upon reconstruction.

The effect of intravenous lidocaine on brain activation during non-noxious and acute noxious stimulation of the forepaw: a functional magnetic resonance imaging study in the rat.

Lidocaine can alleviate acute as well as chronic neuropathic pain at very low plasma concentrations in humans and laboratory animals. The mechanism(s) underlying lidocaine's analgesic effect when administered systemically is poorly understood but clearly not related to interruption of peripheral nerve conduction. Other targets for lidocaine's analgesic action(s) have been suggested, including sodium channels and other receptor sites in the central rather than peripheral nervous system. To our knowledge, the effect of lidocaine on the brain's functional response to pain has never been investigated. Here, we therefore characterized the effect of systemic lidocaine on the brain's response to innocuous and acute noxious stimulation in the rat using functional magnetic resonance imaging (fMRI). Alpha-chloralose anesthetized rats underwent fMRI to quantify brain activation patterns in response to innocuous and noxious forepaw stimulation before and after IV administration of lidocaine. Innocuous forepaw stimulation elicited brain activation only in the contralateral primary somatosensory (S1) cortex. Acute noxious forepaw stimulation induced activation in additional brain areas associated with pain perception, including the secondary somatosensory cortex (S2), thalamus, insula and limbic regions. Lidocaine administered at IV doses of either 1 mg/kg, 4 mg/kg or 10 mg/kg did not abolish or diminish brain activation in response to innocuous or noxious stimulation. In fact, IV doses of 4 mg/kg and 10 mg/kg lidocaine enhanced S1 and S2 responses to acute nociceptive stimulation, increasing the activated cortical volume by 50%-60%. The analgesic action of systemic lidocaine in acute pain is not reflected in a straightforward interruption of pain-induced fMRI brain activation as has been observed with opioids. The enhancement of cortical fMRI responses to acute pain by lidocaine observed here has also been reported for cocaine. We recently showed that both lidocaine and cocaine increased intracellular calcium concentrations in cortex, suggesting that this pharmacological effect could account for the enhanced sensitivity to somatosensory stimulation. As our model only measured physiological acute pain, it will be important to also test the response of these same pathways to lidocaine in a model of neuropathic pain to further investigate lidocaine's analgesic mechanism of action.

P1-264: Impaired posteromedial cortical FMRI activity is related to medial temporal atrophy in early Alzheimer's disease

P1-264: Impaired posteromedial cortical FMRI activity is related to medial temporal atrophy in early Alzheimer's disease

Sparse linear regression for reconstructing muscle activity from human cortical fMRI

In humans, it is generally not possible to use invasive techniques in order to identify brain activity corresponding to activity of individual muscles. Further, it is believed that the spatial resolution of non-invasive brain imaging modalities is not sufficient to isolate neural activity related to individual muscles. However, this study shows that it is possible to reconstruct muscle activity from functional magnetic resonance imaging (fMRI). We simultaneously recorded surface electromyography (EMG) from two antagonist muscles and motor cortices activity using fMRI, during an isometric task requiring both reciprocal activation and co-activation of the wrist muscles. Bayesian sparse regression was used to identify the parameters of a linear mapping from the fMRI activity in areas 4 (M1) and 6 (pre-motor, SMA) to EMG, and to reconstruct muscle activity in an independent test data set. The mapping obtained by the sparse regression algorithm showed significantly better generalization than those obtained from algorithms commonly used in decoding, i.e., support vector machine and least square regression. The two voxel sets corresponding to the activity of the antagonist muscles were intermingled but disjoint. They were distributed over a wide area of pre-motor cortex and M1 and not limited to regions generally associated with wrist control. These results show that brain activity measured by fMRI in humans can be used to predict individual muscle activity through Bayesian linear models, and that our algorithm provides a novel and non-invasive tool to investigate the brain mechanisms involved in motor control and learning in humans.

High-frequency (600 Hz) population spikes in human EEG delineate thalamic and cortical fMRI activation sites

Functional magnetic resonance imaging (fMRI) measures neural activity indirectly via its slow vascular/metabolic consequences. At a temporal resolution on the order of seconds, fMRI does not reveal the real ‘language of neurons’, spelt out by fast electrical discharges (‘spikes’) which occur on a time scale of milliseconds. In animal studies, these limitations have been addressed by adding invasive electrode measurements to fMRI. Here, we propose to circumvent this ‘inverse problem of fMRI’ by deriving a noninvasive spike measure from recordings of ultrafast electroencephalography (EEG) signals during fMRI. We demonstrate how in response to median nerve stimulation 600 Hz oscillatory EEG signals can be measured reliably during fMRI. These high-frequency bursts (HFBs) are supposed to reflect population spikes in the thalamus and the somatosensory cortex, respectively. We show that distinct fMRI activations in these two generator structures can be attributed to spontaneous HFB fluctuations. Thus, our approach allowed the noninvasive identification of neural processes along the thalamocortical pathway unfolding at a millisecond time scale.

Quantification of venous blood signal contribution to BOLD functional activation in the auditory cortex at 3 T

Most modern techniques for functional magnetic resonance imaging (fMRI) rely on blood-oxygen-level-dependent (BOLD) contrast as the basic principle for detecting neuronal activation. However, the measured BOLD effect depends on a transfer function related to neurophysiological changes accompanying electrical neural activation. The spatial accuracy and extension of the region of interest are determined by vascular effect, which introduces incertitude on real neuronal activation maps. Our efforts have been directed towards the development of a new methodology that is capable of combining morphological, vascular and functional information; obtaining new insight regarding foci of activation; and distinguishing the nature of activation on a pixel-by-pixel basis. Six healthy volunteers were studied in a parametric auditory functional experiment at 3 T; activation maps were overlaid on a high-resolution brain venography obtained through a novel technique. The BOLD signal intensities of vascular and nonvascular activated voxels were analyzed and compared: it was shown that nonvascular active voxels have lower values for signal peak (P<10(-7)) and area (P<10(-8)) with respect to vascular voxels. The analysis showed how venous blood influenced the measured BOLD signals, supplying a technique to filter possible venous artifacts that potentially can lead to misinterpretation of fMRI results. This methodology, although validated in the auditory cortex activation, maintains a general applicability to any cortical fMRI study, as the basic concepts on which it relies on are not limited to this cortical region. The results obtained in this study can represent the basis for new methodologies and tools that are capable of adding further characterization to the BOLD signal properties.

Comparing surface-based and volume-based analyses of functional neuroimaging data in patients with schizophrenia

A major challenge in functional neuroimaging is to cope with individual variability in cortical structure and function. Most analyses of cortical function compensate for variability using affine or low-dimensional nonlinear volume-based registration (VBR) of individual subjects to an atlas, which does not explicitly take into account the geometry of cortical convolutions. A promising alternative is to use surface-based registration (SBR), which capitalizes on explicit surface representations of cortical folding patterns in individual subjects. In this study, we directly compare results from SBR and affine VBR in a study of working memory in healthy controls and patients with schizophrenia (SCZ). Each subject's structural scan was used for cortical surface reconstruction using the SureFit method. fMRI data were mapped directly onto individual cortical surface models, and each hemisphere was registered to the population-average PALS-B12 atlas using landmark-constrained SBR. The precision with which cortical sulci were aligned was much greater for SBR than VBR. SBR produced superior alignment precision across the entire cortex, and this benefit was greater in patients with schizophrenia. We demonstrate that spatial smoothing on the surface provides better resolution and signal preservation than a comparable degree of smoothing in the volume domain. Lastly, the statistical power of functional activation in the working memory task was greater for SBR than for VBR. These results indicate that SBR provides significant advantages over affine VBR when analyzing cortical fMRI activations. Furthermore, these improvements can be even greater in disorders that have associated structural abnormalities.

Touch or pain? Spatio-temporal patterns of cortical fMRI activity following brief mechanical stimuli

Most imaging studies on the human pain system have concentrated so far on the spatial distribution of pain-related activity. In the present study, we investigated similarities and differences between the spatial and temporal patterns of brain activity related to touch vs. pain perception. To this end, we adopted an event-related functional magnetic resonance imaging (fMRI) paradigm allowing us to separately assess the activity related to stimulus anticipation, perception, and coding. The fMRI signal increases following brief mechanical noxious or non-noxious stimulation of the hand dorsum were largely overlapping in the contralateral and ipsilateral hemispheres, including portions of the parietal, insular, frontal and cingulate cortices. Higher activity following noxious stimulation was found in the contralateral mid-anterior insular cortex, in the anterior mid-cingulate cortex (aMCC) and in the adjacent dorso-medial frontal cortex. Significant decreases in fMRI signals following both tactile and painful stimuli were found in perigenual cingulate (pACC)/medial prefrontal cortex (MPF) and in the posterior cingulate/precuneus/paracentral lobule; more intense decreases were found in the pACC/MPF following painful stimuli. fMRI signal increases in the contralateral insula and in aMCC, but not in the parietal cortex, were more prolonged following painful than tactile stimuli. Moreover, a second peak of signal increases (albeit of lower intensity) was found in anterior insula and aMCC during pain intensity rating. These results show specific spatio-temporal patterns of cortical activity related to processing noxious vs. non-noxious mechanical stimuli.