Neural activity in trigeminal neuralgia patients with sensory and motor stimulations: A pilot functional MRI study.

OBJECTIVE: Trigeminal neuralgia (TN) is a neuropathic pain syndrome that typically exhibits paroxysmal pain. However, the true mechanism of pain processing is unclear. We aim to evaluate the neural activity changes, before and after radiofrequency rhizotomy, in TN patients using functional MRI (fMRI) with sensory and motor stimulations. METHODS: Six patients with classical TN participated in the study. Each patient underwent two boxcar paradigms of fMRI tasks: air-sensation and jaw-clenching around 1-3 weeks before and after the surgical intervention. McGill Pain Questionnaire (MPQ) was used to evaluate the pain intensity prior to fMRI study. RESULTS: Before rhizotomy, the jaw-clenching stimulation yielded reduced brain activation in primary motor (M1) and primary (SI) and secondary somatosensory (SII) cortices. Following intervention, activation in those regions returned to near normal levels observed in healthy subjects. For air-sensation stimulation, several pain and pain modulation regions such as right thalamus, right putamen, insula, and brainstem, were activated before the intervention, but subsided after the intervention. This correlated well with the change of MPQ scores (p < 0.01). CONCLUSIONS: In our study, we observed significant pain reduction accompanied by increased motor activities after rhizotomy in patients with TN. We hypothesize that the reduced motor activities identified in fMRI may be reversed after the treatment with radiofrequency rhizotomy. More research is warranted.

Rational Design of an ICT-Based Chemodosimeter with Aggregation-Induced Emission for Colorimetric and Ratiometric Fluorescent Detection of Cyanide in a Wide pH Range.

An alkoxy-substituted 1,3-indanedione-based chemodosimeter 1 with an aggregation-induced emission (AIE) characteristic was rationally designed and synthesized for the ultrasensitive and selective sensing of cyanide in a wide pH range of 3.0-12.0. The nucleophilic addition of cyanide to the ß-conjugated carbon of the 1,3-indanedione group obstructs intramolecular charge transfer (ICT) and causes a significant change in the absorption and fluorescence spectra, enabling colorimetric and ratiometric fluorescent detection of cyanide in a 90% aqueous solution. The cyanide-sensing mechanism is supported by single-crystal X-ray diffraction analysis, time-dependent density functional theory (TD-DFT) calculations, and 1H NMR titration experiments. Sensor 1 exhibits strong yellow fluorescence in the solid state due to the AIE effect, and the paper probes containing 1 can be conveniently used to sense cyanide by the naked eye. Furthermore, chemodosimeter 1 was successfully used for sensing cyanide in real environmental water samples.

Evidence for decreased Neurologic Pain Signature activation following thoracic spinal manipulation in healthy volunteers and participants with neck pain.

BACKGROUND CONTEXT: Spinal manipulation (SM) is a common treatment for neck and back pain, theorized to mechanically affect the spine leading to therapeutic mechanical changes. The link between specific mechanical effects and clinical improvement is not well supported. SM's therapeutic action may instead be partially mediated within the central nervous system. PURPOSE: To introduce brain-based models of pain for spinal pain and manual therapy research, characterize the distributed central mechanisms of SM, and advance the preliminary validation of brain-based models as potential clinical biomarkers of pain. STUDY DESIGN: Secondary analysis of two functional magnetic resonance imaging studies investigating the effect of thoracic SM on pain-related brain activity: A non-controlled, non-blinded study in healthy volunteers (Study 1, n = 10, 5 females, and mean age = 31.2 ±â€¯10.0 years) and a randomized controlled study in participants with acute to subacute neck pain (Study 2, n = 24, 16 females, mean age = 38.0 ±â€¯15.1 years). METHODS: Functional magnetic resonance imaging was performed during noxious mechanical stimulation of the right index finger cuticle pre- and post-intervention. The effect of SM on pain-related activity was studied within brain regions defined by the Neurologic Pain Signature (NPS) that are predictive of physical pain. RESULTS: In Study 1, evoked mechanical pain (p < 0.001) and NPS activation (p = 0.010) decreased following SM, and the changes in evoked pain and NPS activation were correlated (rRM2 = 0.418, p = 0.016). Activation within the NPS subregions of the dorsal anterior cingulate cortex (dACC, p = 0.012) and right secondary somatosensory cortex/operculum (rS2_Op, p = 0.045) also decreased following SM, and evoked pain was correlated with dACC activity (rRM2 = 0.477, p = 0.019). In Study 2, neck pain (p = 0.046) and NPS (p = 0.033) activation decreased following verum but not sham SM. Associations between evoked pain, neck pain, and NPS activation, were not significant and less clear, possibly due to inadequate power, methodological limitations, or other confounding factors. CONCLUSIONS: The findings provide preliminary evidence that SM may alter the processing of pain-related brain activity within specific pain-related brain regions and support the use of brain-based models as clinical biomarkers of pain.

Production and characterization of cellulose nanofibril (CNF) from agricultural waste corn stover.

Agricultural waste corn stover has little economic value. Cellulose was extracted from corn stover by the processes of alkali treatment and delignification, resulting in a > 93% purity. The particle size of the extracted cellulose was reduced by mechanical shearing through high pressure homogenization. When passing through a homogenizer thirty times, the cellulose nanofibril (CNF) can be obtained. The diameters of the CNF ranged between 5 and 50 nm, and the lengths were microns. The mechanical properties of the films, made by corn stover cellulose, with and without high pressure homogenization shearing were evaluated using an Instron instrument. The films made by cellulose without shearing exhibited weaker mechanical properties, while the CNF films exhibited stronger mechanical properties. The linear rheological properties of CNF suspensions were also investigated and results show solid-like viscoelastic behavior. Our findings regarding corn stover CNF are similar to those CNF from other sources reported in the literature.

Using functional magnetic resonance imaging to determine if cerebral hemodynamic responses to pain change following thoracic spine thrust manipulation in healthy individuals.

STUDY DESIGN: Case series. OBJECTIVES: To use blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) to determine if supraspinal activation in response to noxious mechanical stimuli varies pre- and post-thrust manipulation to the thoracic spine. BACKGROUND: Recent studies have demonstrated the effectiveness of thoracic thrust manipulation in reducing pain and improving function in some individuals with neck and shoulder pain. However, the mechanisms by which manipulation exerts such effects remain largely unexplained. The use of fMRI in the animal model has revealed a decrease in cortical activity in response to noxious stimuli following manual joint mobilization. Supraspinal mediation contributing to hypoalgesia in humans may be triggered following spinal manipulation. METHODS: Ten healthy volunteers (5 women, 5 men) between the ages of 23 and 48 years (mean, 31.2 years) were recruited. Subjects underwent fMRI scanning while receiving noxious stimuli applied to the cuticle of the index finger at a rate of 1 Hz for periods of 15 seconds, alternating with periods of 15 seconds without stimuli, for a total duration of 5 minutes. Subjects then received a supine thrust manipulation directed to the midthoracic spine and were immediately returned to the scanner for reimaging with a second delivery of noxious stimuli. An 11-point numeric pain rating scale was administered immediately after the application of noxious stimuli, premanipulation and postmanipulation. Blood oxygenation level-dependent fMRI recorded the cerebral hemodynamic response to the painful stimuli premanipulation and postmanipulation. RESULTS: The data indicated a significant reduction in subjects' perception of pain (P<.01), as well as a reduction in cerebral blood flow as measured by the blood oxygenation level-dependent response following manipulation to areas associated with the pain matrix (P<.05). There was a significant relationship between reduced activation in the insular cortex and decreased subjective pain ratings on the numeric pain rating scale (r = 0.59, P<.05). CONCLUSION: This study provides preliminary evidence that suggests that supraspinal mechanisms may be associated with thoracic thrust manipulation and hypoalgesia. However, because the study lacked a control group, the results do not allow for the discernment of the causative effects of manipulation, which may also be related to changes in levels of subjects' fear, anxiety, or expectation of successful outcomes with manipulation. Future investigations should strive to elicit more conclusive findings in the form of randomized clinical trials.

Women's clitoris, vagina, and cervix mapped on the sensory cortex: fMRI evidence.

INTRODUCTION: The projection of vagina, uterine cervix, and nipple to the sensory cortex in humans has not been reported. AIMS: The aim of this study was to map the sensory cortical fields of the clitoris, vagina, cervix, and nipple, toward an elucidation of the neural systems underlying sexual response. METHODS: Using functional magnetic resonance imaging (fMRI), we mapped sensory cortical responses to clitoral, vaginal, cervical, and nipple self-stimulation. For points of reference on the homunculus, we also mapped responses to the thumb and great toe (hallux) stimulation. MAIN OUTCOME MEASURES: The main outcome measures used for this study were the fMRI of brain regions activated by the various sensory stimuli. RESULTS: Clitoral, vaginal, and cervical self-stimulation activated differentiable sensory cortical regions, all clustered in the medial cortex (medial paracentral lobule). Nipple self-stimulation activated the genital sensory cortex (as well as the thoracic) region of the homuncular map. CONCLUSION: The genital sensory cortex, identified in the classical Penfield homunculus based on electrical stimulation of the brain only in men, was confirmed for the first time in the literature by the present study in women applying clitoral, vaginal, and cervical self-stimulation, and observing their regional brain responses using fMRI. Vaginal, clitoral, and cervical regions of activation were differentiable, consistent with innervation by different afferent nerves and different behavioral correlates. Activation of the genital sensory cortex by nipple self-stimulation was unexpected, but suggests a neurological basis for women's reports of its erotogenic quality.

Functional connectivity of the sensorimotor area in naturally sleeping infants.

Patterns of cortical functional connectivity in normal infants were examined during natural sleep by observing the time course of very low frequency oscillations. Such oscillations represent fluctuations in blood oxygenation level and cortical blood flow thus allowing computation of neurophysiologic connectivity. Structural and resting-state information were acquired for 11 infants, with a mean age of 12.8 months, using a GE 1.5 T MR scanner. Resting-state data were processed and significant functional connectivity within the sensorimotor area was identified using independent component analysis. Unilateral functional connectivity in the developing sensory-motor cortices was observed. Power spectral analysis showed that slow frequency oscillations dominated the hemodynamic signal at this age, with, on average, a peak frequency for all subjects of 0.02 Hz. Our data suggest that there is more intrahemispheric than interhemispheric connectivity in the sensorimotor area of naturally sleeping infants. This non-invasive imaging technique, developed to allow reliable scanning of normal infants without sedation, enabled computation of neurophysiologic connectivity for the first time in naturally sleeping infants. Such techniques permit elucidation of the role of slow cortical oscillations during early brain development and may reveal critical information regarding the normative development and lateralization of brain networks across time.

Assessment of functional development in normal infant brain using arterial spin labeled perfusion MRI.

Arterial spin labeled (ASL) perfusion MRI provides a noninvasive approach for longitudinal imaging of regional brain function in infants. In the present study, continuous ASL (CASL) perfusion MRI was carried out in normally developing 7- and 13-month-old infants while asleep without sedation. The 13-month infant group showed an increase (P<0.05) of relative CBF in frontal regions as compared to the 7-month group using a region of interest based analysis. Using a machine-learning algorithm to automatically classify the relative CBF maps of the two infant groups, a significant (P<0.05, permutation testing) regional CBF increase was found in the hippocampi, anterior cingulate, amygdalae, occipital lobes, and auditory cortex in the 13-month-old infants. These results are consistent with current understanding of infant brain development and demonstrate the feasibility of using perfusion MRI to noninvasively monitor developing brain function.

Cortical adaptation following partial glossectomy with primary closure: implications for reconstruction of the oral tongue.

OBJECTIVES: The considerable variability in functional outcomes for speech and swallowing with different reconstruction techniques following partial glossectomy may reflect the ability of patients to adapt to altered tongue structure. The purpose of this study was to determine mechanisms of cortical adaptation in swallowing to partial glossectomy reconstructed with primary closure. METHODS: Four patients treated with partial glossectomy and primary closure underwent functional magnetic resonance imaging at a mean of 6 months after operation, and the data were compared to those from 8 healthy controls. RESULTS: Statistically significant increases in activity occurred predominately in the parietal cortices and the cerebellum. The volume of the resection was most highly correlated with activity in the premotor and parietal cortices and cerebellum. CONCLUSIONS: The adaptive changes in the cortex following partial glossectomy with primary closure reflect adaptation to the biomechanics of tongue movement during swallowing, and not altered sensation in the tongue.

The effect of tumour type and distance on activation in the motor cortex.

Functional MRI has been widely used to identify the eloquent cortex in neurosurgical/radiosurgical planning and treatment of CNS neoplasms and malformations. In this study we examined the effect of CNS tumours on the blood oxygenation level-dependent (BOLD) activation maps in the primary and supplementary motor cortex. A total of 33 tumour patients and five healthy right-handed adults were enrolled in the study. Patients were divided into four groups based on tumour type and distance from primary motor cortex: (1) intra-axial, near, (2) extra-axial, near, (3) intra-axial, far and (4) extra-axial, far. The intra-axial groups consisted of patients with astrocytomas, glioblastomas and metastatic tumours of mixed histology; all the extra-axial tumours were meningiomas. The motor task was a bilateral, self-paced, finger-tapping paradigm. Anatomical and functional data were acquired with a 1.5 T GE Echospeed scanner. Maps of the motor areas were derived from the BOLD images, using SPM99 software. For each subject we first determined the activation volume in the primary motor area and the supplementary motor area (SMA) and then calculated the percentage difference between the hemispheres. Two factors influenced the activation volumes: tumour type (P<0.04) and distance from the eloquent cortex (P<0.06). Patients in group 1 (intra-axial, near) had the smallest activation area in the primary motor cortex, the greatest percentage difference in the activation volume between the hemispheres, and the largest activation volume in the SMA. Patients in group 4 (extra-axial, far) had the largest activation volume in the primary motor cortex, the least percentage difference in volume between the hemispheres, and the smallest activation volume in the SMA. There was no significant change in the volume of the SMA in any group, compared with controls, suggesting that, although there is a gradual decrease in SMA volume with distance from the primary motor area, the effect on motor reorganisation is minimal. All the tumour patients showed a net loss in total activation volumes (both hemispheres plus SMA) compared with controls. The effect of the tumours on interhemispheric volume differences was: group 1>group 3>group 2>group 4. Within the intra-axial tumours, there was no significant effect of tumour type on the results. We conclude that BOLD-imaged activation volume is affected at least by the interplay of two factors: tumour type and distance from the motor cortex. Further, all tumours may be expected to cause some loss of activation volumes in motor areas. We suggest that, with proper precautions and planning, BOLD functional magnetic resonance imaging (fMRI) maps can be useful in minimising damage to the functional areas.

Cerebral activation patterns during working memory performance in multiple sclerosis using FMRI.

Working memory deficits are common in Multi Sclerosis (MS) and have been identified behaviourally in numerous studies. Despite recent advance in functional magnetic resonance imaging (fMRI), few published studies have examined cerebral activations associated with working memory dysfunction in MS. The present study examines brain activation patterns during performance of a working memory task in individual with clinically definite MS, compared to healthy controls (HC). fMRI was performed using a 1.5 Tesla GE scanner during a modified Paced Auditory Serial Addition Test (mPA-SAT). Participants were 6 individuals with MS with working memory impairment as evidenced on neuropsychological testing, 5 individuals with MS without working memory impairment, and 5 HC. Groups were demographically equivalent. Data were analyzed using Statistical Parametric Mapping (SPM99) software, with a stringent significance level (alpha < .005, voxel extent > or =8). Both MS groups and the HC group were able to perform the task, with comparable performance in terms of numbers of correct responses. Activation patterns within the HC and MS not-impaired groups were noted in similar brain regions, consistent with published observations in healthy samples That is, activations were lateralized to the left hemisphere, involving predominantly frontal regions. In contrast, the MS impaired group showed greater right frontal and right parietal lobe activation, when compared with the HC group. Thus, it appears that working memory dysfunction in MS is associated with altered patterns of cerebral activation that are related to the presence of cognitive impairement, and not solely a function of MS.

Brain activation during vaginocervical self-stimulation and orgasm in women with complete spinal cord injury: fMRI evidence of mediation by the vagus nerves.

Women diagnosed with complete spinal cord injury (SCI) at T10 or above report vaginal-cervical perceptual awareness. To test whether the Vagus nerves, which bypass the spinal cord, provide the afferent pathway for this response, we hypothesized that the Nucleus Tractus Solitarii (NTS) region of the medulla oblongata, to which the Vagus nerves project, is activated by vaginal-cervical self-stimulation (CSS) in such women, as visualized by functional magnetic resonance imaging (fMRI). Regional blood oxygen level-dependent (BOLD) signal intensity was imaged during CSS and other motor and sensory procedures, using statistical parametric mapping (SPM) analysis with head motion artifact correction. Physiatric examination and MRI established the location and extent of spinal cord injury. In order to demarcate the NTS, a gustatory stimulus and hand movement were used to activate the superior region of the NTS and the Nucleus Cuneatus adjacent to the inferior region of the NTS, respectively. Each of four women with interruption, or "complete" injury, of the spinal cord (ASIA criteria), and one woman with significant, but "incomplete" SCI, all at or above T10, showed activation of the inferior region of the NTS during CSS. Each woman showed analgesia, measured at the fingers, during CSS, confirming previous findings. Three women experienced orgasm during the CSS. The brain regions that showed activation during the orgasms included hypothalamic paraventricular nucleus, medial amygdala, anterior cingulate, frontal, parietal, and insular cortices, and cerebellum. We conclude that the Vagus nerves provide a spinal cord-bypass pathway for vaginal-cervical sensibility in women with complete spinal cord injury above the level of entry into spinal cord of the known genitospinal nerves.

fMRI study of acupuncture-induced periaqueductal gray activity in humans.

BOLD fMRI was used to study acupuncture-induced activation (increase in the BOLD signal from undetectable) of the periaqueductal gray (PAG) and two somatosensory cortical areas in seven healthy human subjects. Mechanical stimulation (push-pull) was given to the LI4 (Hoku) acupoint or to a non-acupoint. The stimulation paradigm consisted of 5 runs, each consisting of four 30 s On/30 s OFF periods over 30 min. The scan for each ON period was analyzed individually. The PAG and cortical areas showed different activity patterns. PAG activity was episodic and reliably demonstrated after 20-25 min of stimulation; both cortical areas, however, were active > 90% of the time. Stimulation of a non-acupoint (leg) resulted in reduced levels of PAG and cortical activity.

Differential cerebellar activation on functional magnetic resonance imaging during working memory performance in persons with multiple sclerosis.

OBJECTIVE: To explore the potential role of the cerebellum in working memory dysfunction in multiple sclerosis (MS). DESIGN: Blood oxygen level dependent functional magnetic resonance imaging (fMRI) was used to examine cerebellar activation during a working memory task. SETTING: University-affiliated medical rehabilitation facility. PARTICIPANTS: Eight persons with MS and 5 healthy controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Change in hemodynamic response. fMRI data were acquired and subsequently analyzed by using Statistical Parametric Mapping. RESULTS: Both the control and MS groups showed significantly greater activations in the right cerebellar hemisphere as compared with the left side. Persons with MS, however, showed no detectable activations in 4 cerebellar substructures that were significantly active in controls (ie, right vermis, right dentate nucleus, right tonsil, cerebellar peduncle). CONCLUSIONS: The significantly decreased cerebellar activation in the MS group suggests that the cerebellum may play a role in the working memory impairment observed in MS.

Functional imaging of pain in patients with primary fibromyalgia.

OBJECTIVE: To examine the function of the nociceptive system in patients with fibromyalgia (FM) using functional magnetic resonance imaging (fMRI). METHODS: Two groups of women, 9 with FM and 9 pain-free, volunteered to participate. In Experiment 1, we assessed psychophysical responses to painful stimuli and prepared participants for fMRI testing. For Experiment 2, subjects underwent fMRI scanning while receiving painful and nonpainful heat stimuli. Conventional and functional MR images were acquired using a 1.5 T MR scanner. Scanning occurred over 5 conditions. Condition 1 served as a practice session (no stimuli). Conditions 2 and 5 consisted of nonpainful warm stimuli. Conditions 3 and 4 consisted of an absolute thermal pain stimulus (47 degrees C) and a perceptually equivalent pain stimulus delivered in counterbalanced order. RESULTS: Experiment 1 indicated that subjects with FM were significantly more sensitive to experimental heat pain than controls (p < 0.001). In Experiment 2, fMRI data indicated that the FM group exhibited greater activity than controls over multiple brain regions in response to both nonpainful and painful stimuli (p < 0.01). Specifically, in response to nonpainful warm stimuli, FM subjects had significantly greater activity than controls in prefrontal, supplemental motor, insular, and anterior cingulate cortices (p < 0.01). In response to painful stimuli, FM subjects had greater activity in the contralateral insular cortex (p < 0.01). Data from the practice session indicated brain activity in pain-relevant areas for the FM group but not for controls. CONCLUSION: Our results provide further evidence for a physiological explanation for FM pain.

Translocation of Broca's area to the contralateral hemisphere as the result of the growth of a left inferior frontal glioma.

We report a case of a patient with a left inferior frontal glioma in whom language functional magnetic resonance imaging (fMRI) paradigms produced activation of Broca's area on the right and Wernicke's area on the left. We propose that tumor invasion of the left frontal operculum led to cortical reorganization and interhemispheric transfer of Broca's area. This case emphasizes the importance of preoperative fMRI in assessing the location of eloquent cortices adjacent to a tumor and in guiding neurosurgical decision-making.

Functional localization of brainstem and cervical spinal cord nuclei in humans with fMRI.

BACKGROUND AND PURPOSE: To our knowledge, no published functional map of the human lower brainstem exists. Our purpose was to use 1.5-T functional MR imaging (fMRI) to visualize the location of cranial nerve (CN) nuclei and other pontine, bulbar, and cervical spinal cord nuclei by using specific sensory stimulation or motor performance. METHODS: We localized nuclei by using cross-correlation analysis of regional blood oxygen level-dependent (BOLD) signal intensity during specific motor and sensory procedures based on known functions of specific nuclei. Statistical parametric mapping (SPM) analysis was used for comparison. Head, cardiac, and respiratory motion artifact correction was applied. Histologic atlases aided localization. RESULTS: We obtained evidence of localization of the following nuclei by using tests, as follows: main trigeminal sensory (CN V), brushing the face; abducens (CN VI), left-right eye movement; facial (CN VII), smiling and lip puckering; hypoglossal (CN XII), pushing the tongue against the hard palate; nucleus ambiguus, swallowing; nucleus tractus solitarii (NTS), tasting a sweet-sour-salty-bitter mixture; nucleus cuneatus, finger tapping; and cervical spinal cord levels C1-C3, tongue movement to activate the strap muscles. Activation of cortical motor and sensory areas and somatosensory thalamus corresponded with the tasks and sites of brainstem activation. Head movement was minimal, typically less than 1 mm in all three axes. CONCLUSION: With 1.5-T fMRI, the CN nuclei of the pons and medulla, and other nuclei of the lower brainstem and cervical spinal cord, can be localized in awake humans with specific sensory stimulation or motor performance.