Induced and Evoked Properties of Vibrotactile Adaptation in the Primary Somatosensory Cortex.

Prolonged exposure to afferent stimulation ("adaptation") can cause profound short-term changes in the responsiveness of cortical sensory neurons. While several models have been proposed that link adaptation to single-neuron dynamics, including GABAergic inhibition, the process is currently imperfectly understood at the whole-brain level in humans. Here, we used magnetoencephalography (MEG) to examine the neurophysiological correlates of adaptation within SI in humans. In one condition, a 25 Hz adapting stimulus (5 s) was followed by a 1 s 25 Hz probe ("same"), and in a second condition, the adapting stimulus was followed by a 1 s 180 Hz probe ("different"). We hypothesized that changes in the mu-beta activity band (reflecting GABAergic processing) would be modulated differently between the "same" and "different" probe stimuli. We show that the primary somatosensory (SI) mu-beta response to the "same" probe is significantly reduced (p = 0.014) compared to the adapting stimulus, whereas the mu-beta response to the "different" probe is not (p = n.s.). This reduction may reflect sharpening of the spatiotemporal pattern of activity after adaptation. The stimulus onset mu-beta response did not differ between a 25 Hz adapting stimulus and a 180 Hz probe, suggesting that the mu-beta response is independent of stimulus frequency. Furthermore, we show a sustained evoked and induced desynchronization for the duration of the adapting stimulus, consistent with invasive studies. Our findings are important in understanding the neurophysiology underlying short-term and stimulus-induced plasticity in the human brain and shows that the brain response to tactile stimulation is altered after only brief stimulation.

GABA Levels in Left and Right Sensorimotor Cortex Correlate across Individuals.

Differences in γ-aminobutyric acid (GABA) levels measured with Magnetic Resonance Spectroscopy have been shown to correlate with behavioral performance over a number of tasks and cortical regions. These correlations appear to be regionally and functionally specific. In this study, we test the hypothesis that GABA levels will be correlated within individuals for functionally related regions-the left and right sensorimotor cortex. In addition, we investigate whether this is driven by bulk tissue composition. GABA measurements using edited MRS data were acquired from the left and right sensorimotor cortex in 24 participants. T1-weighted MR images were also acquired and segmented to determine the tissue composition of the voxel. GABA level is shown to correlate significantly between the left and right regions (r = 0.64, p < 0.03). Tissue composition is highly correlated between sides, but does not explain significant variance in the bilateral correlation. In conclusion, individual differences in GABA level, which have previously been described as functionally and regionally specific, are correlated between homologous sensorimotor regions. This correlation is not driven by bulk differences in voxel tissue composition.

Transcranial electric stimulation (tES) and NeuroImaging: the state-of-the-art, new insights and prospects in basic and clinical neuroscience.

Transcranial electric stimulation (tES) of the brain has attracted an increased interest in recent years. Yet, despite remarkable research efforts to date, the underlying neurobiological mechanisms of tES' effects are still incompletely understood. This Special Issue aims to provide a comprehensive and up-to-date overview of the state-of-the-art in studies combining tES and neuroimaging, while introducing most recent insights and outlining future prospects related to this new and rapidly growing field. The findings reported here combine methodological advancements with insights into the underlying mechanisms of tES itself. At the same time, they also point to the many caveats and specific challenges associated with such studies, which can arise from both technical and biological sources. Besides promising to advance basic neuroscience, combined tES and neuroimaging studies may also substantially change previous conceptions about the methods of action of electric or magnetic stimulation on the brain.

Transcranial modulation of brain oscillatory responses: A concurrent tDCS-MEG investigation.

Despite the increasing use of transcranial direct current stimulation (tDCS), the physiological mechanisms underlying its effects are still largely unknown. One approach to directly investigate the effects of the neuromodulation technique on the brain is to integrate tDCS with non-invasive neuroimaging in humans. To provide new insight into the neurobiology of the method, DC stimulation (1mA, 600s) was applied concurrently with Magnetoencephalography (MEG), while participants engaged in a visuomotor task before, during and after a period of tDCS. Responses in the motor beta band (15-30Hz) and visual gamma band (30-80Hz) were localised using Synthetic Aperture Magnetometry (SAM). The resulting induced and evoked oscillatory responses were subsequently analysed. A statistically significant reduction of average power in the visual gamma band was observed for anodal compared to sham stimulation. The magnitude of motor evoked responses was also found to be significantly modulated by anodal stimulation. These results demonstrate that MEG can be used to derive inferences on the cortical mechanisms of tDCS.

Stimulating somatosensory psychophysics: a double-blind, sham-controlled study of the neurobiological mechanisms of tDCS.

The neuromodulation technique transcranial direct current stimulation (tDCS) is thought to produce its effects on behavior by altering cortical excitability. Although the mechanisms underlying the observed effects are thought to rely on the balance of excitatory and inhibitory neurotransmission, the physiological principles of the technique are not completely understood. In this study, we examine the influence of tDCS on vibrotactile adaptation, using a simple amplitude discrimination paradigm that has been shown to exhibit modifications in performance due to changes in inhibitory neurotransmission. Double-blind tDCS (Anodal/Sham) of 1 mA was delivered for 600 s to electrodes positioned in a somatosensory/contralateral orbit montage. Stimulation was applied as part of a pre/post design, between blocks of the behavioral tasks. In accordance with previous work, results obtained before the application of tDCS indicated that amplitude discrimination thresholds were significantly worsened during adaptation trials, compared to those achieved at baseline. However, tDCS failed to modify amplitude discrimination performance. Using a Bayesian approach, this finding was revealed to constitute substantial evidence for the null hypothesis. The failure of DC stimulation to alter vibrotactile adaptation thresholds is discussed in the context of several factors that may have confounded the induction of changes in cortical plasticity.

Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA.

There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the detection of GABA in the human brain. At a recent meeting held at Cardiff University, a number of spectroscopy groups met to discuss the acquisition, analysis and interpretation of GABA-edited MR spectra. This paper aims to set out the issues discussed at this meeting, reporting areas of consensus around parameters and procedures in the field and highlighting those areas where differences remain. It is hoped that this paper can fulfill two needs, providing a summary of the current 'state-of-the-art' in the field of GABA-edited MRS at 3T using MEGA-PRESS and a basic guide to help researchers new to the field to avoid some of the pitfalls inherent in the acquisition and processing of edited MRS for GABA.

Subtraction artifacts and frequency (mis-)alignment in J-difference GABA editing.

PURPOSE: To compare the repeatability of γ-aminobutyric acid (GABA) measurements using J-difference editing, before and after spectral realignment-a technique which has previously been demonstrated to improve the quality of J-difference GABA spectra. MATERIALS AND METHODS: We performed in vivo measurements in three brain regions (occipital, sensorimotor, and dorsolateral prefrontal cortex [DLPFC]), and analyzed these using alternative alignment approaches to evaluate the impact of alignment on repeatability: "Independent alignment" (aligning each subspectrum independently) and "Pairwise alignment" (aligning each on and off subspectrum as a pair) were compared. RESULTS: Pairwise alignment improved the group mean coefficient of variation in all regions; 0.4% in occipital, 1.1% in sensorimotor, and 1.1% in DLPFC. Independent alignment resulted in subtraction artifacts in the majority of cases, and increased the coefficient of variation in the DLPFC by 9.4%. Simulations demonstrate that the GABA quantification error in datasets with high B0 drift, is 4.5% without alignment, but <1% with optimal alignment. CONCLUSION: Pairwise alignment improves the repeatability of GABA spectroscopy data. However, independently aligning all on and off subspectra can lead to artifacts and worse repeatability when compared with nonaligned data.

Test-retest reliability in fMRI: Or how I learned to stop worrying and love the variability.

This paper briefly recounts the details of one of the first studies of whole brain, single subject variability in functional Magnetic Resonance Imaging (fMRI). In this paper I will not attempt to provide an overview of fMRI reliability, but will instead revisit the choices we made in performing our experiment as we did.

Regionally specific human GABA concentration correlates with tactile discrimination thresholds.

The neural mechanisms underlying variability in human sensory perception remain incompletely understood. In particular, few studies have attempted to investigate the relationship between in vivo measurements of neurochemistry and individuals' behavioral performance. Our previous work found a relationship between GABA concentration in the visual cortex and orientation discrimination thresholds (Edden et al., 2009). In the present study, we used magnetic resonance spectroscopy of GABA and psychophysical testing of vibrotactile frequency thresholds to investigate whether individual differences in tactile frequency discrimination performance are correlated with GABA concentration in sensorimotor cortex. Behaviorally, individuals showed a wide range of discrimination thresholds ranging from 3 to 7.6 Hz around the 25 Hz standard. These frequency discrimination thresholds were significantly correlated with GABA concentration (r = -0.58; p < 0.05) in individuals' sensorimotor cortex, but not with GABA concentration in an occipital control region (r = -0.04). These results demonstrate a link between GABA concentration and frequency discrimination in vivo, and support the hypothesis that GABAergic mechanisms have an important role to play in sensory discrimination.

Integration of sensory and motor representations of single fingers in the human cerebellum.

The cerebellum is thought to play a key role in the integration of sensory and motor events. Little is known, however, about how sensory and motor maps in the cerebellum superimpose. In the present study we investigated the relationship between these two maps for the representation of single fingers. Participants made isometric key presses with individual fingers or received vibratory tactile stimulation to the fingertips while undergoing high-resolution functional magnetic resonance imaging (fMRI). Using multivariate analysis, we have demonstrated that the ipsilateral lobule V and VIII show patterns of activity that encode, within the same region, both which finger pressed and which finger was stimulated. The individual finger-specific activation patches are smaller than 3 mm and only show a weak somatotopic organization. To study the superposition of sensory and motor maps, we correlated the finger-specific patterns across the two conditions. In the neocortex, sensory stimulation of one digit led to activation of the same patches as force production by the same digit; in the cerebellum, these activation patches were organized in an uncorrelated manner. This suggests that, in the cerebellum, a movement of a particular finger is paired with a range of possible sensory outcomes. In summary, our results indicate a small and fractured representation of single digits in the cerebellum and suggest a fundamental difference in how the cerebellum and the neocortex integrate sensory and motor events.

Between- and within-scanner variability in the CaliBrain study n-back cognitive task.

Psychiatric neuroimaging techniques are likely to improve understanding of the brain in health and disease, but studies tend to be small, based in one imaging centre and of unclear generalisability. Multicentre studies have great appeal but face problems if functional magnetic resonance imaging (fMRI) data from different centres are to be combined. Fourteen healthy volunteers had two brain scans on different days at three scanners. Considerable effort was first made to use similar scanning sequences and standardise task implementation across centres. The n-back cognitive task was used to investigate between- and within-scanner reproducibility and reliability. Both the functional imaging and behavioural results were in good accord with the existing literature. We found no significant differences in the activation/deactivation maps between scanners, or between repeat visits to the same scanners. Between- and within-scanner reproducibility and reliability was very similar. However, the smoothness of images from the scanners differed, suggesting that smoothness equalization might further reduce inter-scanner variability. Our results for the n-back task suggest it is possible to acquire fMRI data from different scanners which allows pooling across centres, when the same field strength scanners are used and scanning sequences and paradigm implementations are standardised.

Functional Magnetic Resonance Imaging (fMRI) reproducibility and variance components across visits and scanning sites with a finger tapping task.

Multicentre MRI studies offer great potential to increase study power and flexibility, but it is not yet clear how reproducible the results from multiple centres may be. Here we present results from the multicentre study 'CaliBrain', examining the reproducibility of fMRI data within and between three sites. Fourteen subjects were scanned twice on three 1.5 T GE scanners using an identical scanning protocol. We present data from a motor task with three conditions, sequential and random finger tapping and rest. Similar activation maps were obtained for each site and visit; brain areas consistently activated during the task included the premotor, primary motor and supplementary motor areas, the striatum and cerebellum. Reproducibility was evaluated within and between sites by comparing the extent and spatial agreement of activation maps at both the subject and group levels. The results were within the range previously reported for similar tasks on single scanners and both measures were found to be comparable within and between sites, with between site reproducibility similar to the within site measures. A variance components analysis was used to examine the effects of site, subject and visit. The contributions of site and visit were small and reproducibility was similar between and within sites, whereas the variance between subjects, and unexplained variance was large. These findings suggest that we can have confidence in combined results from multicentre fMRI studies, at least when a consistent protocol is followed on similar machines in all participating scanning sites and care is taken to select homogeneous subject groups.

Diurnal stability of gamma-aminobutyric acid concentration in visual and sensorimotor cortex.

PURPOSE: To establish the diurnal stability of edited magnetic resonance spectroscopy measurements of gamma-aminobutyric acid (GABA) in visual and sensorimotor regions of the brain. MATERIALS AND METHODS: GABA measurements were made in two regions of the brain (an occipital, "visual" region and a "sensorimotor" region centered on the precentral gyrus) using the MEGA-PRESS editing method, scanning eight healthy adults at five timepoints during a single day. GABA concentration was quantified from the ratio of the GABA integral to the unsuppressed water signal. RESULTS: No significant effect of time on GABA concentration was seen (P = 0.35). GABA was shown to be significantly more concentrated in visual regions than in sensorimotor regions (1.10 i.u. and 1.03 i.u., respectively; P = 0.050). Coefficients of variability (CVs) across all subjects of 9.1% and 12% (visual and sensorimotor) were significantly higher than mean within-subjects CVs of 6.5% and 8.8. CONCLUSION: This study demonstrates the excellent reproducibility of MEGA-PRESS detection of GABA, demonstrating that the method is sufficiently sensitive to detect inter-subject variability, and suggests that (within the sensitivity limits of current measurements) time of day can be ignored in the design of MRS studies of visual and sensorimotor regions.

Loss of imagery phenomenology with intact visuo-spatial task performance: a case of 'blind imagination'.

The capacity for imagery, enabling us to visualise absent items and events, is a ubiquitous feature of our experience. This paper describes the case of a patient, MX, who abruptly lost the ability to generate visual images. He rated himself as experiencing almost no imagery on standard questionnaires, yet performed normally on standard tests of perception, visual imagery and visual memory. These unexpected findings were explored using functional MRI scanning (fMRI). Activation patterns while viewing famous faces were not significantly different between MX and controls, including expected activity in the fusiform gyrus. However, during attempted imagery, activation in MX's brain was significantly reduced in a network of posterior regions while activity in frontal regions was increased compared to controls. These findings are interpreted as suggesting that MX adopted a different cognitive strategy from controls when performing the imagery task. Evidence from experimental tasks thought to rely on mental imagery, such as the Brooks' matrices and mental rotation, support this interpretation. Taken together, these results indicate that successful performance in visual imagery and visual memory tasks can be dissociated from the phenomenal experience of visual imagery.

Rhythms of the brain: an examination of mixed mode oscillation approaches to the analysis of neurophysiological data.

In the nervous system many behaviorally relevant dynamical processes are characterized by episodes of complex oscillatory states, whose periodicity may be expressed over multiple temporal and spatial scales. In at least some of these instances the variability in oscillatory amplitude and frequency can be explained in terms of deterministic dynamics, rather than being purely noise-driven. Recently interest has increased in studying the application of mixed-mode oscillations (MMOs) to neurophysiological data. MMOs are complex periodic waveforms where each period is comprised of several maxima and minima of different amplitudes. While MMOs might be expected to occur in brain kinetics, only a few examples have been identified thus far. In this article, we review recent theoretical and experimental findings on brain oscillatory rhythms in relation to MMOs, focusing on examples at the single neuron level but also briefly touching on possible instances of the phenomenon across local and global brain networks.

Overactivation of fear systems to neutral faces in schizophrenia.

BACKGROUND: The amygdala plays a central role in detecting and responding to fear-related stimuli. A number of recent studies have reported decreased amygdala activation in schizophrenia to emotional stimuli (such as fearful faces) compared with matched neutral stimuli (such as neutral faces). We investigated whether the apparent decrease in amygdala activation in schizophrenia could actually derive from increased amygdala activation to the neutral comparator stimuli. METHODS: Nineteen patients with schizophrenia and 24 matched control participants viewed pictures of faces with either fearful or neutral facial expressions, and a baseline condition, during functional magnetic resonance imaging scanning. RESULTS: Patients with schizophrenia showed a relative decrease in amygdala activation to fearful faces compared with neutral faces. However, this difference resulted from an increase in amygdala activation to the neutral faces in patients with schizophrenia, not from a decreased response to the fearful faces. CONCLUSIONS: Patients with schizophrenia show an increased response of the amygdala to neutral faces. This is sufficient to explain their apparent deficit in amygdala activation to fearful faces compared with neutral faces. The inappropriate activation of neural systems involved in fear to otherwise neutral stimuli may contribute to the development of psychotic symptoms in schizophrenia.

Spatiotemporal integration of tactile information in human somatosensory cortex.

BACKGROUND: Our goal was to examine the spatiotemporal integration of tactile information in the hand representation of human primary somatosensory cortex (anterior parietal somatosensory areas 3b and 1), secondary somatosensory cortex (S2), and the parietal ventral area (PV), using high-resolution whole-head magnetoencephalography (MEG). To examine representational overlap and adaptation in bilateral somatosensory cortices, we used an oddball paradigm to characterize the representation of the index finger (D2; deviant stimulus) as a function of the location of the standard stimulus in both right- and left-handed subjects. RESULTS: We found that responses to deviant stimuli presented in the context of standard stimuli with an interstimulus interval (ISI) of 0.33 s were significantly and bilaterally attenuated compared to deviant stimulation alone in S2/PV, but not in anterior parietal cortex. This attenuation was dependent upon the distance between the deviant and standard stimuli: greater attenuation was found when the standard was immediately adjacent to the deviant (D3 and D2 respectively), with attenuation decreasing for non-adjacent fingers (D4 and opposite D2). We also found that cutaneous mechanical stimulation consistently elicited not only a strong early contralateral cortical response but also a weak ipsilateral response in anterior parietal cortex. This ipsilateral response appeared an average of 10.7 +/- 6.1 ms later than the early contralateral response. In addition, no hemispheric differences either in response amplitude, response latencies or oddball responses were found, independent of handedness. CONCLUSION: Our findings are consistent with the large receptive fields and long neuronal recovery cycles that have been described in S2/PV, and suggest that this expression of spatiotemporal integration underlies the complex functions associated with this region. The early ipsilateral response suggests that anterior parietal fields also receive tactile input from the ipsilateral hand. The lack of a hemispheric difference in responses to digit stimulation supports a lack of any functional asymmetry in human somatosensory cortex.

Gastric fundic distension activates fronto-limbic structures but not primary somatosensory cortex: a functional magnetic resonance imaging study.

INTRODUCTION: The brain representation of visceral stimulation bears important similarities to that of somatic stimulation. However, the role of the primary (S1) and secondary (S2) somatosensory cortices in mediating gastric sensation is uncertain. MATERIALS AND METHODS: Eighteen healthy, right-handed volunteers (age 32 years+/-6.5 years; 14 men) underwent dynamic assessment of the relationship between sensation and fundic barostat distending pressure and volume, and then brain functional magnetic resonance imaging (fMRI) during noxious fundic distension. Cytoarchitectonic probability maps were used to examine in detail the null hypothesis that fundic distension did not produce significant activation of S1 or S2. RESULTS: Distending volume explained 74% of the variance in gastric sensation, compared to 64% with distending pressure. Incorporating distending volume into the regressor function for our fMRI analyses, we found that noxious fundic distension activated a widespread network of brain regions, including the pontine brainstem, thalami, cerebellum, insular cortex bilaterally, anterior and posterior cingulate cortex, right frontal lobe, and inferior parietal lobules. In detailed analyses, we found no evidence of activation of S1, but did find activation in one region of S2. DISCUSSION: Our findings suggest that an extensive, predominantly fronto-limbic network of brain regions, including the insular cortex, mediates perception of noxious gastric fundic distension in healthy humans, without significant participation by the primary somatosensory cortex. This and other recent studies lay the groundwork for investigations comparing brain processing of visceral stimuli between healthy volunteers and patients with functional dyspepsia.

Anatomical evidence for an anticonvulsant relay in the rat ventromedial medulla.

Pharmacological manipulation of the ventrolateral pontine reticular formation (vlPRF) of rats has an anticonvulsant effect in the maximal electroshock model of epilepsy. This study presents three anatomical experiments that determine the efferent projections from this region likely to mediate this anticonvulsant effect. In the first, the anterograde tracer biotinylated dextran amine (BDA) was injected into the vlPRF. A strong projection to the ventromedial medullary reticular formation (vmMRF) was revealed which continued only weakly to the spinal cord. In the second experiment, double-label procedures were used to indicate whether the BDA-labelled terminals from the vlPRF make contacts with neurons in vmMRF, retrogradely labelled with cholera-toxin B subunit from the lumbar spinal cord. Sections of the vmMRF were examined by: (i) light microscopy which showed significant overlap between terminals from vlPRF and retrogradely-labelled reticulospinal cells; (ii) confocal microscopy which showed labelled terminals in close association with reticulospinal cell bodies; and (iii) electron microscopy which showed vlPRF terminals making synaptic contact with reticulospinal neurons. Finally, immunohistochemical procedures in combination with anterograde tracing revealed that significant numbers of terminals labelled from vlPRF were also positive for markers of glutamatergic or GABAergic neurotransmission. This suggests that the projection from the vlPRF to the vmMRF is likely to include several different functional components. These connections could represent a final critical link of an anticonvulsant circuit that originates in the dorsal midbrain and projects via relays in the vlPRF and the vmMRF to interact with the low-level motor circuitry in the spinal cord.

Variability in fMRI: a re-examination of inter-session differences.

We revisit a previous study on inter-session variability (McGonigle et al. [2000]: Neuroimage 11:708-734), showing that contrary to one popular interpretation of the original article, inter-session variability is not necessarily high. We also highlight how evaluating variability based on thresholded single-session images alone can be misleading. Finally, we show that the use of different first-level preprocessing, time-series statistics, and registration analysis methodologies can give significantly different inter-session analysis results.