Event-related fMRI with painful electrical stimulation of the trigeminal nerve

Several functional brain imaging studies of pain using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have shown that painful stimulation causes activation of different brain areas. The aim of the present study was to develop and implement painful stimulation of the trigeminal nerve, which can be applied with event-related paradigms by using MRI. Twelve healthy, right-handed volunteers were examined. Painful electrical stimulation of the first trigeminal branch was performed. In an event-related setting with a 1.5 T clinical scanner with EPI capability, the following fMRI parameters were used: 20 slices, 3 mm thickness, isotropic voxel, 306 measurements with 54 randomized events. Statistical postprocessing was performed with SPM99. Activation of the ipsi- and contralateral secondary somatosensory cortex (SII), and the contralateral insular cortex was observed as well as a contralateral thalamic activation (T=4.45, extension 15 voxels). Six of the 12 volunteers revealed also activation of the cingulate cortex. The investigation demonstrates that painful stimulation of the trigeminal nerve activates the contralateral insular cortex, SII, and thalamus, as well as the ipsilateral SII. In contrast to other studies, the cingulate cortex was only activated inconsistently.     

Functional Magnetic Resonance Imaging of the Basal Ganglia and Cerebellum Using a Simple Motor Paradigm

Activation of cortical and subcortical motor areas of the brain, including primary motor cortex, supplementary motor area, basal ganglia and cerebellum, were successfully investigated in seven right-handed, normal volunteers during a simple, rapid, thumb flexion-extension task using functional magnetic resonance imaging. A multi-slice echo-planar imaging sequence was used to cover the entire brain. A signal increase varying from 2% to 6% was observed for the different regions involved in the motor task. Moving the non-dominant thumb was associated with a more bilateral activation pattern in both putamen and cerebellar regions. This study demonstrates the capability of functional magnetic resonance imaging to delineate simultaneously many activated brain areas that are commonly thought to be involved in the performance of motor tasks.     

Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system.

Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.     

Disuse atrophy alterations in normal and low temperature environments during hindlimb unloading in Syrian hamsters

This study examined whether a hypothermic environment reduces experimentally-induced atrophy of skeletal muscle, as judged by histochemical findings. The hind limbs of hamsters in a hypothermic group were suspended and flexed into plantar positions at the ankle joint, and housed for one week at 8 to 12 degree celsius in a temperature-controlled room, while the normothermic group was housed at 23 to 25 degree celsius. Hypothermia did not significantly alter the average caloric intake, and the animals from the hypothermic group lost a significant amount of body weight when compared with the normothermic group. The hypothermic group retained more muscle wet-weight and myofibers cross-sectional area in the soleus and gastrocnemius muscles compared with the normothermic group. Our results indicate that a hypothermic environment inhibits short-term muscle atrophy. This inhibition may be caused by the increased caloric intake combined with a state similar to hibernation in low-temperature environments.     

Callosal connections of dorsal versus ventral premotor areas in the macaque monkey: a multiple retrograde tracing study

Background  

The lateral premotor cortex plays a crucial role in visually guided limb movements. It is divided into two main regions, the dorsal (PMd) and ventral (PMv) areas, which are in turn subdivided into functionally and anatomically distinct rostral (PMd-r and PMv-r) and caudal (PMd-c and PMv-c) sub-regions. We analyzed the callosal inputs to these premotor subdivisions following 23 injections of retrograde tracers in eight macaque monkeys. In each monkey, 2–4 distinct tracers were injected in different areas allowing direct comparisons of callosal connectivity in the same brain.     

Development of visually evoked cortical activity in infant macaque monkeys studied longitudinally with fMRI

We studied the development of visual activation longitudinally in two infant monkeys aged 103-561 days using the BOLD fMRI technique under opiate anesthesia and compared the results with those obtained in three adult animals studied under identical conditions. Visual activation in primary visual cortex, V1, was strong and reliable in monkeys of the youngest and oldest ages, showing that functional imaging techniques give qualitatively similar results in infants and adults. Visual activation in extrastriate areas involved in processing motion (MT/V5) and form (V4) was not evident in the younger animals, but became more adult-like in the older animals. This delayed onset of measurable BOLD responses in extrastriate visual cortex may reflect delayed development of visual responses in these areas, although at this stage it is not possible to rule out either effects of anesthesia or of changes in cerebral vascular response mechanisms as the cause. The demonstration of visually evoked BOLD responses in young monkeys shows that the BOLD fMRI technique can usefully be employed to address functional questions of brain development.     

Activation of SC during electrical stimulation of LGN: retinal antidromic stimulation or corticocollicular activation?

We have recently used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in lateral geniculate nucleus (LGN) increases the fMRI signal in the regions of primary visual cortex receiving input from that site, but suppresses it in the retinotopically matched regions of extrastriate cortex. Intracortical injection experiments showed that such suppression is due to synaptic inhibition. During these experiments, we have consistently observed activation of superior colliculus (SC) following LGN stimulation. Since LGN does not directly project to SC, the current study investigated the origin of SC activation. By examining experimental manipulations inactivating the primary visual cortex, we present here evidence that the robust SC activation, which follows the stimulation of LGN, is due to the activation of corticocollicular pathway.     

Investigating directed influences between activated brain areas in a motor-response task using fMRI

Localization of cognitive processes is a strength of functional neuroimaging. However, information about functional interactions between brain areas is crucial for a deeper understanding of brain function. We applied vector autoregressive modeling in the context of Granger causality as a method to analyze directed connectivity in a standard event-related fMRI study using a simple auditory-motor paradigm. The basic idea is to use temporal information in stochastic time series of a brain region in order to predict signal time courses in other brain regions. Thus, we predicted that the method should demonstrate causal influence of the auditory cortex and the supplementary motor area (SMA) on primary motor cortex. Eleven right-handed healthy female subjects were instructed to press a ball with either their left or their right hand when hearing the command "left" or "right" in the scanner. Influence to the left motor cortex was found from bilateral auditory cortex as well as from the SMA in 9 of 11 subjects. Granger causality to the right motor cortex existed from bilateral auditory cortex in 5 and from SMA in 6 subjects. Granger causality to the SMA existed from right auditory cortex in 7 subjects and from left auditory cortex in 8 subjects. Our findings in a simple task show that even under suboptimal circumstances (a relatively long TR of 2440 ms), Granger causality can be a useful tool to explore effective connectivity. Temporally optimized scanning should increase that potential.     

Frontoparietal activity with minimal decision and control in the awake macaque at 7 T

Previous imaging work has identified a frontoparietal network in the human brain involved in many different cognitive functions, as well as in simple updates of attended information. To determine whether a similar network is present in the monkey brain and direct future electrophysiological recordings, we examined the activation of frontoparietal areas during visual stimulation in the awake, fixating monkey. We measured activity with BOLD fMRI in three animals and analyzed the data individually for each animal and at group level. We found reliable activations in lateral prefrontal and parietal areas, even though task-related decision making was minimal, as a response to simple update of visual information. These activations were significant for each individual animal, as well as at group level. Similar to human imaging results the update of visual input was enough to activate an extensive network of frontoparietal cortex in the macaque brain, a network which is normally associated with complex cognitive control processes.     

Effect of a gadodiamide contrast agent on the reliability of brain tissue T1 measurements

To determine whether brain spin-lattice relaxation time (T1) can routinely be measured after contrast-agent injection, we measured T1 by a precise and accurate inversion-recovery (PAIR) method in five brain tumor patients, before and again after contrast-agent injection. The T1 in at least 20 regions of interest (ROIs) was measured in each patient, avoiding areas of contrast enhancement visible by conventional MR imaging. Contrast-agent injection reduced T1 in 51 regions of interest in white matter by less than 1% (not significant), and in 50 regions of interest in gray matter by less than 2% (p = 0.001). Pixel-by-pixel plots demonstrate that T1 is reduced substantially in extra-parenchymal tissues, but not in brain tissues. Therefore, T1 mapping with the precise and accurate inversion-recovery method can routinely be done after contrast injection. Our results suggest that the precise and accurate inversion-recovery method is not sensitive to the T1 of blood in the presence of an intact blood-brain barrier, although a substantial T1 reduction does occur in the absence of a blood-brain barrier.     

Imaging brain activity in conscious monkeys following oral MDMA ("ecstasy")

Recreational use of 3,4-methylenedioxymethamphetamine (MDMA;"ecstasy") poses worldwide potential health problems. Clinical studies show that repeated exposure to low oral doses of MDMA has toxic effects on the brain, altering cognitive and psychosocial behavior. Functional magnetic resonance imaging in conscious marmoset monkeys was used to evaluate the sensitivity of the brain to an oral dose of MDMA (1 mg/kg). Following MDMA administration, the midbrain raphe nuclei and substantia nigra, major sources of serotonin and dopamine, were activated as were the hippocampus, hypothalamus and amygdala. The corticostriatal circuit of dorsal thalamus, sensorimotor cortex and basal ganglia showed a robust, coherent activation pattern. Two key reward areas, the nucleus accumbens and prefrontal cortex, and most other cortical regions showed little activation. The visual cortex, however, showed intense activation without applied visual stimuli. These data identify brain areas and functional circuits sensitive to a recreational dose of MDMA, some of which may be vulnerable to long-term intermittent exposure to this drug.     

Anatomical Increased/Decreased Changes in the Brain Area Following Individuals with Chronic Traumatic Complete Thoracic Spinal Cord Injury

Objectives: This study aimed to investigate anatomical changes in the brain following chronic complete traumatic thoracic spinal cord injury (ThSCI) using voxel-based morphometry (VBM). That is, it attempted to examine dynamic physical change following thoracic injury and the presence or absence of regions with decreased and increased changes in whole brain volume associated with change in the manner of how activities of daily living are performed. Methods: Twelve individuals with chronic traumatic complete ThSCI (age; 21-63 years, American Spinal Injury Association Impairment Scale; grade C-D) participated in this study. VBM was used to investigate the regions with increased volume and decreased volume in the brain in comparison with healthy control individuals. Results: Decreases in volume were noted in areas associated with motor and somatosensory functions, including the right paracentral lobule (PCL)―the primary motor sensory area for lower limbs, left dorsal premotor cortex, and left superior parietal lobule (SPL). Furthermore, increased gray matter volume was noted in the primary sensorimotor area for fingers and arms, as well as in higher sensory areas. Conclusions: Following SCI both regions with increased volume and regions with decreased volume were present in the brain in accordance with changes in physical function. Using longitudinal observation, anatomical changes in the brain may be used to determine the rehabilitation effect by comparing present cases with cases with cervical SCI or cases with incomplete palsy.     

A conditional Granger causality model approach for group analysis in functional magnetic resonance imaging

Granger causality model (GCM) derived from multivariate vector autoregressive models of data has been employed to identify effective connectivity in the human brain with functional magnetic resonance imaging (fMRI) and to reveal complex temporal and spatial dynamics underlying a variety of cognitive processes. In the most recent fMRI effective connectivity measures, pair-wise GCM has commonly been applied based on single-voxel values or average values from special brain areas at the group level. Although a few novel conditional GCM methods have been proposed to quantify the connections between brain areas, our study is the first to propose a viable standardized approach for group analysis of fMRI data with GCM. To compare the effectiveness of our approach with traditional pair-wise GCM models, we applied a well-established conditional GCM to preselected time series of brain regions resulting from general linear model (GLM) and group spatial kernel independent component analysis of an fMRI data set in the temporal domain. Data sets consisting of one task-related and one resting-state fMRI were used to investigate connections among brain areas with the conditional GCM method. With the GLM-detected brain activation regions in the emotion-related cortex during the block design paradigm, the conditional GCM method was proposed to study the causality of the habituation between the left amygdala and pregenual cingulate cortex during emotion processing. For the resting-state data set, it is possible to calculate not only the effective connectivity between networks but also the heterogeneity within a single network. Our results have further shown a particular interacting pattern of default mode network that can be characterized as both afferent and efferent influences on the medial prefrontal cortex and posterior cingulate cortex. These results suggest that the conditional GCM approach based on a linear multivariate vector autoregressive model can achieve greater accuracy in detecting network connectivity than the widely used pair-wise GCM, and this group analysis methodology can be quite useful to extend the information obtainable in fMRI.     

Aberrant resting-state cerebral blood flow and its connectivity in primary dysmenorrhea on arterial spin labeling MRI

PurposeThis study aimed to clarify the resting-state cerebral blood flow alteration patterns induced by primary dysmenorrhea, investigate the relationships between cerebral blood flow alterations and clinical parameters of patients with primary dysmenorrhea, and explore whether brain regions with abnormal cerebral blood flow also feature functional connectivity changes.MethodsArterial spin labeling imaging and clinical parameters were acquired in 42 patients with primary dysmenorrhea and 41 healthy controls during their menstrual phases. Differences in cerebral blood flow were compared between the two groups, and the clusters with significant group differences were selected as the regions of interest for further statistical analyses.ResultsCompared to healthy controls, patients with primary dysmenorrhea exhibited increased cerebral blood flow in the bilateral precuneus, left posterior cingulate cortex, and right rolandic operculum. Among patients with primary dysmenorrhea, we identified a negative correlation between the cerebral blood flow in the right rolandic operculum and the visual analogue score for anxiety, and greater correlation between the functional connectivity in the precuneus/posterior cingulate cortex and the right middle cingulate cortex, and between the right rolandic operculum and the left inferior parietal lobule and the bilateral postcentral gyrus.DiscussionCerebral blood flow abnormalities associated with primary dysmenorrhea were mainly concentrated in the areas comprising the default mode network in primary dysmenorrhea patients, which could be involved in the central mechanism of primary dysmenorrhea. Cerebral blood flow alteration in the rolandic operculum may underlie an anxiety-induced compulsive tendency in patients with primary dysmenorrhea. Investigating the enhanced connectivity among various pain-related brain regions could improve understanding of the onset and development of primary dysmenorrhea.     

Reduced susceptibility effects in perfusion fMRI with single-shot spin-echo EPI acquisitions at 1.5 Tesla

Arterial spin labeling (ASL) perfusion contrast is not based on susceptibility effects and can therefore be used to study brain function in regions of high static inhomogeneity. As a proof of concept, single-shot spin-echo echo-planar imaging (EPI) acquisition was carried out with a multislice continuous ASL (CASL) method at 1.5T. A bilateral finger tapping paradigm was used in the presence of an exogenously induced susceptibility artifact over left motor cortex. The spin-echo CASL technique was compared with a regular gradient-echo EPI sequence with the same slice thickness, as well as other imaging methods using thin slices and spin-echo acquisitions. The results demonstrate improved functional sensitivity and efficiency of the spin-echo CASL approach as compared with gradient-echo EPI techniques, and a trend of improved sensitivity as compared with spin-echo EPI approach in the brain regions affected by the susceptibility artifact. ASL images, either with or without subtraction of the control, provide a robust alternative to blood oxygenation level dependant (BOLD) methods for activation imaging in regions of high static field inhomogeneity.     

Ventral and dorsal streams processing visual motion perception (FDG-PET study)

ABSTRACT: BACKGROUND: Earlier functional imaging studies on visually induced self-motion perception (vection) disclosed a bilateral network of activations within primary and secondary visual cortex areas which was combined with signal decreases, i.e., deactivations, in multisensory vestibular cortex areas. This finding led to the concept of a reciprocal inhibitory interaction between the visual and vestibular systems. In order to define areas involved in special aspects of selfmotion perception such as intensity and duration of the perceived circular vection (CV) or the amount of head tilt, correlation analyses of the regional cerebral glucose metabolism, rCGM (measured by fluorodeoxyglucose positron-emission tomography, FDG-PET) and these perceptual covariates were performed in 14 healthy volunteers. For analyses of the visualvestibular interaction, the CV data were compared to a random dot motion stimulation condition (not inducing vection) and a control group at rest (no stimulation at all). RESULTS: Group subtraction analyses showed that the visual-vestibular interaction was modified during CV, i.e., the activations within the cerebellar vermis and parieto-occipital areas were enhanced. The correlation analysis between the rCGM and the intensity of visually induced vection, experienced as body tilt, showed a relationship for areas of the multisensory vestibular cortical network (inferior parietal lobule bilaterally, anterior cingulate gyrus), the medial parieto-occipital cortex, the frontal eye fields and the cerebellar vermis. The "earlier" multisensory vestibular areas like the parieto-insular vestibular cortex and the superior temporal gyrus did not appear in the latter analysis. The duration of perceived vection after stimulus stop was positively correlated with rCGM in medial temporal lobe areas bilaterally, which included the (para-)hippocampus, known to be involved in various aspects of memory processing. The amount of head tilt was found to be positively correlated with the rCGM of bilateral basal ganglia regions responsible for the control of motor function of the head. CONCLUSIONS: Our data gave further insights into subfunctions within the complex cortical network involved in the processing of visual-vestibular interaction during CV. Specific areas of this cortical network could be attributed to the ventral stream ("what" pathway) responsible for the duration after stimulus stop and to the dorsal stream ("where/how" pathway) responsible for intensity aspects.     

Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain

Background

Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8) ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve.

Results

Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG) ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia.

Conclusions

TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.

     

Exploring vision-related acupuncture point specificity with multivoxel pattern analysis

Acupoint specificity is one of the central issues of functional magnetic resonance imaging (fMRI) studies of acupuncture and has been under discussed. However, strong and consistent proof has not been provided for the existence of acupoint specificity, and unsuitable analysis approach applied could be the reason. We observed that previous researches of acupoint specificity were mostly based on model-based methods which were limited to make exploration of acupoint specificity because of the inaccurate specified prior. Here we applied multi-voxel pattern analysis (MVPA) to investigate the specificity of brain activation patterns induced by acupuncture stimulations at a vision-related acupoint (GB37) and a nearby nonacupoint (NAP). Results showed that multiple brain areas could differentiate the central neural response patterns induced by acupuncture stimulation at these two sites with higher accuracy above the chance level. These regions included occipital cortex, limbic-cerebellar areas and somatosensory cortex. Our results support that the characteristic neural response patterns of brain cortex to the acupuncture stimulation at GB37 and a nearby NAP could differ from each other effectively with the application of MVPA approach.     

fMRI assessment of thalamocortical connectivity during attentional performance

Functional magnetic resonance imaging (fMRI) studies have shown dysfunction in key areas associated with the thalamocortical circuit in patients with schizophrenia. This study examined the functional connectivity involving the frontal-thalamic circuitry during a spatial focusing-of-attention task in 18 unmedicated patients with schizophrenia and 38 healthy controls. Functional connectivity was analyzed by assigning seed regions (in the thalamic nuclei (mediodorsal nucleus (MDN), pulvinar, anterior nucleus (AN)), the dorsolateral prefrontal cortex (Brodmann areas 9 and 46), and the caudate), and correlating their respective activity with that in the non-seed regions voxel-wise. Functional connectivity analysis demonstrated that functional connectivity was significantly impaired in patients, e.g., between the right pulvinar and regions such as the prefrontal and temporal cortices and the cerebellum. On the other hand, enhanced functional connectivity was found in patients e.g., between the AN and regions such as the prefrontal and temporal cortices. In addition, the patients had significantly lower task performance and less (but non-significant) brain activation than those of controls. These results revealed disturbed functional integration in schizophrenia, and suggested that the functional connectivity abnormalities in the thalamocortical circuitry, especially the frontal-thalamic circuitry, may underlie the attention deficits in schizophrenia patients. Further, this study suggested that functional connectivity analysis might be more sensitive than brain activation analysis in detecting the functional abnormalities in schizophrenia.     

柠檬醛长时程嗅觉吸入的脑功能活动MEMRI研究

本文使用设计的嗅觉吸入装置使大鼠吸入挥发性柠檬醛或无气味空气，之后使用锰增强磁共振成像（MEMRI）的方法，观察长时程（24 h）吸入柠檬醛之后，大鼠脑功能活动变化情况．基于体素分析和感兴趣区（ROI）分析结果显示，与对照组相比，长时程吸入柠檬醛组大鼠伏隔核中心部（AcbC）、嗅小球层（GL）等脑区功能活动增强；而该组大鼠视皮层（VC）、听觉皮层（AC）、压后皮层（RSC）等脑区锰累积显著减少．且长时程吸入柠檬醛之后，大鼠脑区GL与关联的脑区功能相关性显著增强．从而表明MEMRI可用于长时程嗅觉吸入刺激的脑功能研究，并极具应用前景．