Grey matter structure within the visual networks in migraine with aura: multivariate and univariate analyses.

BACKGROUND: The visual cortex is involved in the generation of migraine aura. Voxel-based multivariate analyses applied to this region may provide complementary information about aura mechanisms relative to the commonly used mass-univariate analyses. METHODS: Structural images constrained within the functional resting-state visual networks were obtained in migraine patients with (n = 50) and without (n = 50) visual aura and healthy controls (n = 50). The masked images entered a multivariate analysis in which Gaussian process classification was used to generate pairwise models. Generalizability was assessed by five-fold cross-validation and non-parametric permutation tests were used to estimate significance levels. A univariate voxel-based morphometry analysis was also performed. RESULTS: A multivariate pattern of grey matter voxels within the ventral medial visual network contained significant information related to the diagnosis of migraine with visual aura (aura vs. healthy controls: classification accuracy = 78%, p < 0.001; area under the curve = 0.84, p < 0.001; migraine with aura vs. without aura: classification accuracy = 71%, p < 0.001; area under the curve = 0.73, p < 0.003). Furthermore, patients with visual aura exhibited increased grey matter volume in the medial occipital cortex compared to the two other groups. CONCLUSIONS: Migraine with visual aura is characterized by multivariate and univariate patterns of grey matter changes within the medial occipital cortex that have discriminative power and may reflect pathological mechanisms.

An altered reward system characterizes chronic migraine with medication overuse headache.

BACKGROUND: Medication overuse headache shares several characteristics with substance use disorders. However, key features of substance use disorders such as increased impulsivity and alterations in reward processing remain little explored in medication overuse headache. METHODS: Temporal discounting and impulsive decision making behavior and the associated brain mechanisms were assessed in 26 chronic migraine patients with medication overuse headache and in 28 healthy controls. Regions-of-interest analyses were first performed for task-related regions, namely the ventral striatum and the ventromedial and dorsomedial prefrontal cortices. Resting-state functional connectivity between these regions were then explored. An additional 27 chronic migraine patients without medication overuse headache were included for comparison in the latter analysis. RESULTS: Patients with medication overuse headache showed steeper temporal discounting behavior than healthy controls. They also showed weaker subjective value representations in the dorsomedial prefrontal cortex, when accepting larger delayed rewards, and in ventral striatum and ventromedial prefrontal cortex, when accepting the smaller immediate reward. Resting-state functional connectivity was reduced among the valuation regions when comparing patients with medication overuse headache to the other two control groups. CONCLUSIONS: Patients with medication overuse headache were characterized by altered processing and dysconnectivity in the reward system during intertemporal choices and in the resting-state.

Prediction of individual trigeminal pain sensitivity from gray matter structure within the sensorimotor network.

OBJECTIVE: To determine whether multivariate pattern regression analysis based on gray matter (GM) images constrained to the sensorimotor network could accurately predict trigeminal heat pain sensitivity in healthy individuals. BACKGROUND: Prediction of individual pain sensitivity is of clinical relevance as high pain sensitivity is associated with increased risks of postoperative pain, pain chronification, and a poor treatment response. However, as pain is a subjective experience accurate identification of such individuals can be difficult. GM structure of sensorimotor regions have been shown to vary with pain sensitivity. It is unclear whether GM structure within these regions can be used to predict pain sensitivity. METHODS: In this cross-sectional study, structural magnetic resonance images and pain thresholds in response to contact heat stimulation of the left supraorbital area were obtained from 79 healthy participants. Voxel-based morphometry was used to extract segmented and normalized GM images. These were then constrained to a mask encompassing the functionally defined resting-state sensorimotor network. The masked images and pain thresholds entered a multivariate relevance vector regression analysis for quantitative prediction of the individual pain thresholds. The correspondence between predicted and actual pain thresholds was indexed by the Pearson correlation coefficient (r) and the mean squared error (MSE). The generalizability of the model was assessed by 10-fold and 5-fold cross-validation. Non-parametric permutation tests were used to estimate significance levels. RESULTS: Trigeminal heat pain sensitivity could be predicted from GM structure within the sensorimotor network with significant accuracy (10-fold: r = 0.53, p < 0.001, MSE = 10.32, p = 0.001; 5-fold: r = 0.46, p = 0.001, MSE = 10.54, p < 0.001). The resulting multivariate weight maps revealed that accurate prediction relied on multiple widespread regions within the sensorimotor network. CONCLUSION: A multivariate pattern of GM structure within the sensorimotor network could be used to make accurate predictions about trigeminal heat pain sensitivity at the individual level in healthy participants. Widespread regions within the sensorimotor network contributed to the predictive model.

Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind, randomized sham-controlled trial.

BACKGROUND: Bihemispheric transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can simultaneously modulate bilateral corticospinal excitability and interhemispheric interaction. However, how tDCS affects subacute stroke recovery remains unclear. We investigated the effects of bihemispheric tDCS on motor recovery in subacute stroke patients. METHODS: We enrolled subacute inpatients who had first-ever ischemic stroke at subcortical regions and moderate-to-severe baseline Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score 2-56. Participants between 14 and 28 days after stroke were double-blind, randomly assigned (1:1) to receive real (n = 13) or sham (n = 14) bihemispheric tDCS (with ipsilesional M1 anode and contralesional M1 cathode, 20 min, 2 mA) during task practice twice daily for 20 sessions in two weeks. Residual integrity of the ipsilesional corticospinal tract was stratified between groups. The primary efficacy outcome was the change in FMA-UE score from baseline (responder as an increase ≥ 10). The secondary measures included changes in the Action Research Arm Test (ARAT), FMA-Lower Extremity (FMA-LE) and explorative resting-state MRI functional connectivity (FC) of target regions after intervention and three months post-stroke. RESULTS: Twenty-seven participants completed the study without significant adverse effects. Nineteen patients (70%) had no recordable baseline motor-evoked potentials (MEP-negative) from the paretic forearm. Compared with the sham group, the real tDCS group showed enhanced improvement of FMA-UE after intervention (p < 0.01, effect size η2 = 0.211; responder rate: 77% vs. 36%, p = 0.031), which sustained three months post-stroke (p < 0.01), but not ARAT. Interestingly, in the MEP-negative subgroup analysis, the FMA-UE improvement remained but delayed. Additionally, the FMA-LE improvement after real tDCS was not significantly greater until three months post-stroke (p < 0.01). We found that the individual FMA-UE improvements after real tDCS were associated with bilateral intrahemispheric, rather than interhemispheric, FC strengths in the targeted cortices, while the improvements after sham tDCS were associated with predominantly ipsilesional FC changes after adjustment for age and sex (p < 0.01). CONCLUSIONS: Bihemispheric tDCS during task-oriented training may facilitate motor recovery in subacute stroke patients, even with compromised corticospinal tract integrity. Further studies are warranted for tDCS efficacy and network-specific neuromodulation. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov: (ID: NCT02731508).

Brain metabolites in chronic migraine patients with medication overuse headache.

BACKGROUND: Medication overuse headache may be associated with widespread alterations along the thalamocortical pathway, a pathway involved in pain perception and disease progression. This study addressed whether brain metabolites in key regions of the thalamocortical pathway differed between chronic migraine patients with medication overuse headache and without medication overuse headache. METHODS: Magnetic resonance spectroscopic imaging was used to map metabolites in the bilateral anterior cingulate cortices, mid cingulate cortices, posterior cingulate cortices, and the thalami. Sixteen patients with medication overuse headache were compared with 16 matched patients without medication overuse headache and 16 matched healthy controls. RESULTS: Glutamate and glutamine in the right mid cingulate cortex and myo-inositol in the left anterior cingulate cortex were significantly higher in patients with medication overuse headache than patients without medication overuse headache, but similar to healthy controls. Both patient groups exhibited reduced N-acetyl-aspartate and creatine in the thalamus, reduced myo-inositol in the right anterior cingulate cortex, and elevated choline in the right mid cingulate cortex. Finally, a negative association between myo-inositol laterality index in the anterior cingulate cortices and number of days per month with acute medication use was found across all patients. CONCLUSIONS: Patients with medication overuse headache were characterized by a distinct concentration profile of myo-inositol, a glial marker, in the anterior cingulate cortices that may have arisen from medication overuse and could contribute to the development of medication overuse headache.

Cortical morphological changes in chronic migraine in a Taiwanese cohort: Surface- and voxel-based analyses.

BACKGROUND: Previous voxel- or surface-based morphometric analysis studies have revealed alterations in cortical structure in patients with chronic migraine, yet with inconsistent results. The discrepancies may be derived partly from the sample heterogeneity. Employing both methods in a clinically homogenous group may provide a clearer view. METHODS: Structural MRI data from 30 prevention-naïve patients with chronic migraine without medication overuse headache or a history of major depression and 30 healthy controls were analyzed. Vertex-wise (surface-based) or voxel-wise (voxel-based) linear models were applied, after controlling for age and gender, to investigate between-group differences. Averaged cortical thicknesses and volumes from regions showing group differences were correlated with parameters related to clinical profiles. RESULTS: Surface-based morphometry showed significantly thinner cortices in the bilateral insular cortex, caudal middle frontal gyrus, precentral gyrus, and parietal lobes in patients with chronic migraine relative to healthy controls. Additionally, the number of migraine days in the month preceding MRI examination was correlated negatively with right insular cortical thickness. Voxel-based morphometry (VBM) did not show any group differences or clinical correlations. CONCLUSION: Patients with chronic migraine without medication overuse headache, major depression, or prior preventive treatment had reduced cortical thickness in regions within the pain-processing network. Compared to voxel-based morphometry, surface-based morphometry analysis may be more sensitive to subtle structural differences between healthy controls and patients with chronic migraine.

Brain Metabolism and Structure in Chronic Migraine.

PURPOSE OF REVIEW: The purpose of this paper is to review and synthesize current literature in which neurochemical and structural brain imaging were used to investigate chronic migraine (CM) pathophysiology and to further discuss the clinical implications. RECENT FINDINGS: Spectroscopic and structural MRI studies have shown the presence of both impaired metabolism and structural alterations in the brain of CM patients. Metabolic changes in key brain regions support the notion of altered energetics and homeostasis as part of CM pathophysiology. Furthermore, CM, like other chronic pain disorders, may undergo structural reorganization in pain-related brain regions following near persistent endogenous painful input. Finally, both imaging techniques may provide potential biomarkers of disease state and progression and may help guide novel therapeutic interventions or strategies. Spectroscopic and structural MRI have revealed novel aspects of CM pathophysiology. Findings from the former support the metabolic theory of migraine pathogenesis.

Neurochemical changes in the medial wall of the brain in chronic migraine.

Migraine chronification is associated with a dysfunctional thalamocortical pathway. The present study addressed whether abnormal concentrations of neurochemicals exist in key brain regions of this pathway in chronic migraine. Magnetic resonance spectroscopic imaging of the bilateral medial walls of the brain was used to measure choline, creatine, glutamate and glutamine, myo-inositol, and N-acetyl-aspartate in chronic migraine patients and in matched groups of episodic migraine patients and healthy controls. A region of interest analysis was conducted to examine whether N-acetyl-aspartate, a marker of neuronal integrity, was reduced in the thalamus, occipital cortex and anterior cingulate cortex in chronic migraine. Interregional N-acetyl-aspartate correlations among these regions of interest were also examined. Additionally, statistical mapping was performed for all the metabolites throughout the medial walls. Chronic migraine was associated with N-acetyl-aspartate reductions in the bilateral thalami and in the right anterior cingulate. The N-acetyl-aspartate reduction in the right thalamus correlated with disease duration. Compared with healthy controls, patients with chronic migraine had altered interregional N-acetyl-aspartate correlations between the right thalamus-anterior cingulate and thalamus-occipital cortex, and between the left and right anterior cingulate. N-acetyl-aspartate concentrations and interregional correlations in patients with episodic migraine were between those of healthy controls and chronic migraine patients. The unconstrained analyses revealed a reduction of myo-inositol in the left anterior and posterior cingulate in both patient groups as well as a negative association with depression scores for the anterior cingulate in the combined patient group. In addition, migraine patients with headache on the scan day (irrespective of diagnosis) had reduced N-acetyl-aspartate and total creatine concentrations in the right dorsal anterior cingulate. Reduced N-acetyl-aspartate metabolism and altered interregional N-acetyl-aspartate correlations lend support to the role of thalamocortical dysfunction in migraine chronification. It remains to be established if the pattern of changes within the N-acetyl-aspartate network is specific to chronic migraine or can be found in other chronic pain conditions.

Comparison of gray matter volume between migraine and "strict-criteria" tension-type headache.

BACKGROUND: Despite evidently distinct symptoms, tension-type headache (TTH) and migraine are highly comorbid and exhibit many similarities in clinical practice. The purpose of this study was to investigate whether both types of headaches are similar in brain morphology. METHODS: Consecutive patients with TTH and age- and sex-matched patients with migraine and healthy controls were enrolled for brain magnetic resonance imaging examination. Patients with TTH were excluded if they reported any headache features or associated symptoms of migraine. Changes in gray matter (GM) volume associated with headache diagnosis (TTH vs. migraine) and frequency (episodic vs. chronic) were examined using voxel-based morphometry. The correlation with headache profile and the discriminative ability between TTH and migraine were also investigated for these GM changes. RESULTS: In comparison with controls (n = 43), the patients with TTH (25 episodic and 24 chronic) exhibited a GM volume increase in the anterior cingulate cortex, supramarginal gyrus, temporal pole, lateral occipital cortex, and caudate. The patients with migraine (31 episodic and 25 chronic) conversely exhibited a GM volume decrease in the orbitofrontal cortex. These GM changes did not correlate with any headache profile. A voxel-wise 2 × 2 factorial analysis further revealed the substantial effects of headache types and frequency in the comparison of GM volume between TTH and migraine. Specifically, the migraine group (vs. TTH) had a GM decrease in the superior and middle frontal gyri, cerebellum, dorsal striatum, and precuneus. The chronic group (vs. episodic group) otherwise demonstrated a GM decrease in the bilateral insula and anterior cingulate cortex. In receiver operating characteristic analysis, the GM volumes of the left superior frontal gyrus and right cerebellum V combined had good discriminative ability for distinguishing TTH and migraine (area under the curve = 0.806). CONCLUSIONS: TTH and migraine are separate headache disorders with different characteristics in relation to GM changes. The major morphological difference between the two types of headaches is the relative GM decrease of the prefrontal and cerebellar regions in migraine, which may reflect a higher allostatic load associated with this disabling headache.

Hippocampus and amygdala volume in relation to migraine frequency and prognosis.

Objectives To investigate the structural changes of hippocampus and amygdala and their relationships with migraine frequency and prognosis. Methods Hippocampus and amygdala volumes were measured by 3-T brain magnetic resonance imaging (MRI) in 31 controls and 122 migraine patients who were categorized into eight groups by headache frequency: group 1 (1-2 headache days/month), 2 (3-4), 3 (5-7), 4 (8-10), 5 (11-14), 6 (15-19), 7 (20-24), and 8 (25-30). Headache frequency was reassessed 2 years later and a frequency reduction ≥50% was regarded a good outcome. Results Hippocampus and amygdala volumes fluctuated in patient groups but did not differ from the controls. In migraine patients, the bilateral hippocampus volumes peaked in group 3. The volumes and headache frequencies correlated positively in groups 2-3 on bilateral sides (L: r = 0.44, p = 0.007; R: r = 0.35, p = 0.037), and negatively in groups 3-7 on the left side (5-24 days/month; L: r = -0.31, p = 0.004) and groups 3-8 on the right side ( r = -0.31, p = 0.002). The left amygdala volume also peaked in group 3, and correlated with headache frequency in groups 1-3 ( r = 0.34, p = 0.020) and groups 3-6 ( r = -0.30, p = 0.012). The volumetric changes of the right amygdala with headache frequency did not reach statistical significance. At 2-year follow-up, the right hippocampus volume was positively associated with a good migraine outcome after adjustment of headache frequency (OR 4.72, p = 0.024). Conclusions Hippocampus and amygdala display a structural plasticity linked to both headache frequency and clinical outcome of migraine.

Resting GABA concentration predicts inhibitory control during an auditory Go-Nogo task.

Inhibitory control plays an important role in goal-directed behavior. Although substantial inter-individual variability exists in the behavioral performance of response inhibition, the corresponding modulating neurochemical and neurophysiological mechanisms remain unclear. Thus, the present study aimed to explore the relationship between behavioral response inhibition, GABA+ concentrations and automatic sensory gating (SG) in the auditory cortices. We recruited 19 healthy adults to undergo magnetoencephalography, magnetic resonance spectroscopy (MRS), and behavioral experiments. A paired-stimulus paradigm was used to study SG of the auditory cortices, and an auditory-driven Go-Nogo task was used to evaluate the behavioral response inhibition. Resting GABA+ concentrations were measured in the bilateral superior temporal gyri by means of MRS. Neither GABA+ concentrations nor auditory SG showed significant hemispheric asymmetry. However, an enhanced SG (lower ratio) was found to correlate with improved behavioral inhibition. Moreover, a higher GABA+ concentration was strongly related to improved inhibitory control. These findings highlight the important role of automatic neurophysiological processes and inhibitory neurotransmitters in the prediction of the behavioral performance of inhibitory control.

Reduced functional connectivity between salience and visual networks in migraine with aura.

BACKGROUND: Migraine with visual aura (MA) is associated with distinct visual disturbances preceding migraine attacks, but shares other visual deficits in between attacks with migraine without aura (MO). Here, we seek to determine if abnormalities specific to interictal MA patients exist in functional brain connectivity of intrinsic cognitive networks. In particular, these networks are involved in top-down modulation of visual processing. METHODS: Using resting-state functional magnetic resonance imaging, whole-brain functional connectivity maps were derived from seeds placed in the anterior insula and the middle frontal gyrus, key nodes of the salience and dorsal attention networks, respectively. Twenty-six interictal MA patients were compared with 26 matched MO patients and 26 healthy matched controls. RESULTS: The major findings were: connectivity between the anterior insula and occipital areas, including area V3A, was reduced in MA but not in MO. Connectivity changes between the anterior insula and occipital areas further correlated with the headache severity in MA only. CONCLUSIONS: The unique pattern of connectivity changes found in interictal MA patients involved area V3A, an area previously implicated in aura generation. Hypoconnectivity to this and other occipital regions may either represent a compensatory response to occipital dysfunctions or predispose MA patients to the development of aura.

Statistical mapping of metabolites in the medial wall of the brain: a proton echo planar spectroscopic imaging study.

With magnetic resonance spectroscopic imaging (MRSI), it is possible to simultaneously map distributions of several brain metabolites with relatively good spatial resolution in a short time. Although other functional imaging modalities have taken advantage of population-based inferences using spatially extended statistics, this approach remains little utilized for MRSI. In this study, statistical nonparametric mapping (SnPM) was applied to two-dimensional MRSI data from the medial walls of the human brain to assess the effect of normal aging on metabolite concentrations. The effects of different preprocessing steps on these results were then explored. Short echo time MRSI of left and right medial walls was acquired in conjunction with absolute quantification of total choline, total creatine (tCr), glutamate and glutamine, myo-inositol, and N-acetyl-aspartate. Individual images were spatially warped to a common anatomical frame of reference. Age effects were assessed within SnPM as were the effects of voxel subsampling, variance smoothing, and spatial smoothing. The main findings were: (1) regions in the bilateral dorsal anterior cingulate and in the left posterior cingulate exhibited higher tCr concentrations with age; (2) voxel subsampling but not spatial smoothing enhanced the cluster-level statistical sensitivity; and (3) variance smoothing was of little benefit in this study. Our study shows that spatially extended statistics can yield information about regional-specific changes in metabolite concentrations obtained by short echo time MRSI. This opens up the possibility for systematic comparisons of metabolites in the medial wall of the brain.

Effects of far-infrared radiation on heart rate variability and central manifestations in healthy subjects: a resting-fMRI study.

The aim of this study was to investigate the autonomic responses and central manifestations by peripheral FIR stimulation. Ten subjects (mean ± SD age 26.2 ± 3.52 years) received FIR stimulation at left median nerve territory for 40 min. Electrocardiograph was continuously recorded and heart rate variability (HRV) were analyzed. By using a 3 T-MRI scanner, three sessions of resting-state functional magnetic resonance images (fMRI) were acquired, namely, before (baseline-FIR), immediately after (IA-FIR) and 15 min after FIR was turned off (Post-FIR). The fractional amplitude of low-frequency (0.01-0.08 Hz) fluctuation (fALFF) of each session to evaluate the intensity of resting-brain activity in each session was analyzed. Our results showed that FIR stimulation induced significant HRV responses such as an increasing trend of nLF and LF/HF ratio, while FIR increased fALFF in right superior front gyrus, middle frontal gyrus and decreased the resting brain activity at fusiform gyrus, extrastriae cortex, inferior temporal gyrus and middle temporal gyrus, especially 15 min after FIR was turned off. We conclude that the central manifestation and the autonomic responses are prominent during and after FIR stimulation, which provide important mechanistic explanation on human disorder treated by such energy medicine.

Neuromagnetic index of hemispheric asymmetry predicting long-term outcome in sudden hearing loss.

The neuromagnetic index of hemispheric asymmetry in terms of ipsilateral/contralateral ratio at acute stage was previously revealed to prognosticate the 1-month hearing outcome of acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL), showing a dynamic relationship between top- and down-levels of auditory pathway. However, the prognostic effect of reorganization pattern for the long-term results remained elusive. This study aimed to probe the prognosticating relevance of hemispheric asymmetry to the hearing at chronic stage of ISSNHL. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole of N100m responses to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at initial and final (12 months later) stages. Predictive value of hemispheric asymmetry was assessed by correlating hearing level and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m was observed in ISSNHL initially, and remained in three final prognostic subgroups (complete, partial, and no recovery) of ISSNHL. The initial I/C(amplitude) on affected-ear stimulation strongly correlated with the hearing level of final stage in ISSNHL. However, there was no prognostic effect of hemispheric asymmetry pattern for the 12-month hearing improvement. The heterogeneity between neuromagnetic index and hearing levels possibly echoed different pathogeneses of ISSNHL. Since a restored hearing status did not necessarily lead toward a normal functional organization, the dynamics of hemispheric asymmetry could actually index a central resilient reorganization in the brain for sound processing in ISSNHL. Our finding showed not only a clinically relevant measure to predict final hearing of ISSNHL, but also a linkage between central plasticity and cochlear lesion. This finding suggests a new perspective, and perhaps new interventions, to diagnose and treat unilateral ISSNHL.

Short- and long-term quantitation reproducibility of brain metabolites in the medial wall using proton echo planar spectroscopic imaging.

Proton echo planar spectroscopic imaging (PEPSI) is a fast magnetic resonance spectroscopic imaging (MRSI) technique that allows mapping spatial metabolite distributions in the brain. Although the medial wall of the cortex is involved in a wide range of pathological conditions, previous MRSI studies have not focused on this region. To decide the magnitude of metabolic changes to be considered significant in this region, the reproducibility of the method needs to be established. The study aims were to establish the short- and long-term reproducibility of metabolites in the right medial wall and to compare regional differences using a constant short-echo time (TE30) and TE averaging (TEavg) optimized to yield glutamatergic information. 2D sagittal PEPSI was implemented at 3T using a 32 channel head coil. Acquisitions were repeated immediately and after approximately 2 weeks to assess the coefficients of variation (COV). COVs were obtained from eight regions-of-interest (ROIs) of varying size and location. TE30 resulted in better spectral quality and similar or lower quantitation uncertainty for all metabolites except glutamate (Glu). When Glu and glutamine (Gln) were quantified together (Glx) reduced quantitation uncertainty and increased reproducibility was observed for TE30. TEavg resulted in lowered quantitation uncertainty for Glu but in less reliable quantification of several other metabolites. TEavg did not result in a systematically improved short- or long-term reproducibility for Glu. The ROI volume was a major factor influencing reproducibility. For both short- and long-term repetitions, the Glu COVs obtained with TEavg were 5-8% for the large ROIs, 12-17% for the medium sized ROIs and 16-26% for the smaller cingulate ROIs. COVs obtained with TE30 for the less specific Glx were 3-5%, 8-10% and 10-15%. COVs for N-acetyl aspartate, creatine and choline using TE30 with long-term repetition were between 2-10%. Our results show that the cost of more specific glutamatergic information (Glu versus Glx) is the requirement of an increased effect size especially with increasing anatomical specificity. This comes in addition to the loss of sensitivity for other metabolites. Encouraging results were obtained with TE30 compared to other previously reported MRSI studies. The protocols implemented here are reliable and may be used to study disease progression and intervention mechanisms.

Reduced hippocampal glutamate-glutamine levels in irritable bowel syndrome: preliminary findings using magnetic resonance spectroscopy.

OBJECTIVES: Enhanced stress responsiveness is an important pathophysiological factor in irritable bowel syndrome (IBS), suggesting the presence of a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. A possible mechanism involves maladaption of the feedback mechanism of the HPA axis. We hypothesized that hippocampus, a key brain region providing inhibitory feedback to the HPA axis, would exhibit reduced excitatory glutamatergic neurotransmission and reduced N-acetyl-aspartate (NAA; a marker of neuronal integrity) levels in IBS patients. METHODS: In this preliminary study, proton magnetic resonance spectroscopy was used to quantify absolute concentrations of metabolites in bilateral hippocampi of 15 IBS patients without significant psychiatric comorbidity and 15 age-matched controls. RESULTS: The main finding was a reduction in hippocampal glutamate-glutamine (Glx) in IBS patients. Furthermore, Glx concentrations were inversely related to emotional stress indicators in patients only. No difference was found between subject groups for other metabolite concentrations, including NAA. However, an elevated myo-inositol (mI)/NAA ratio was found in IBS patients. CONCLUSIONS: Our results provide preliminary evidence for the presence of abnormal hypofunction of hippocampal glutamatergic neurotransmission in IBS patients without psychiatric comorbidity, possibly as a result of the chronic pain. This supports the notion of an imbalance in regulatory brain regions in this subgroup of IBS patients. The inverse relationship between Glx and emotional stress indicators is in agreement with the inhibitory role of hippocampus on the stress system and suggests a sensitization of the mechanism to emotional arousal. The elevated mI/NAA ratio in IBS patients further suggests the presence of hippocampal glial proliferation and remodeling.

Corticomotor plasticity induced by tongue-task training in humans: a longitudinal fMRI study.

Corticomotor pathways may undergo neuroplastic changes in response to acquisition of new motor skills. Little is known about the motor control strategies for learning new tongue tasks. The aim of this study was to investigate the longitudinal effect of novel tongue-task training on corticomotor neuroplasticity. Thirteen healthy, right-handed men, aged 24-35 years (mean age ± SD: 27.3 ± 0.3 years), performed a training task consisting of standardized tongue protrusion onto a force transducer. The tongue task consisted of a relax-protrude-hold-relax cycle with 1.0 N as the target at the hold phase lasting for 1.5 s. Subjects repeated this task for 1 h. Functional magnetic resonance imaging was carried out before the tongue-task training (baseline), 1-h after the training, and one-day and one-week follow-up. During scanning, the subjects performed tongue protrusion in blocks interspersed with rest. A region-of-interest (ROI) approach and an explorative search were implemented for the analysis of corticomotor activity across conditions. All subjects completed the tongue-task training (mean success rate 43.0 ± 13.2%). In the baseline condition, tongue protrusion resulted in bilateral activity in regions most typically associated with a motor task including medial frontal gyrus (supplementary motor area [SMA]), precentral gyrus (tongue motor cortex), putamen, thalamus, and cerebellum. The ROI analysis revealed increased activity in the precentral gyrus already 1 h post-training. One day after the training, increased activity was observed in the precentral gyrus, SMA, putamen, and cerebellum. No increase was found 1 week after training. Correlation analyses between changes in success rates and changes in the numbers of voxels showed robust associations for left Area 4a in primary motor cortex 1 h, 1 day, and 1 week after the tongue-task training and for the left Area 4p in primary motor cortex and the left lateral premotor cortex 1 day after the training. In the unrestricted analysis, increased activity was found in the parahippocampal gyrus 1 h after the tongue-task training and remained for a week. Decreased activity was found in right post-central and middle frontal gyri 1 h and 1 week post-training. The results verified the involvement of specific corticomotor areas in response to tongue protrusion. Short-term tongue-task training was associated with longer-lasting (up to 1 week) changes in motor-related brain activity. The results suggested that primary motor areas are involved in the early and late stages, while other motor areas mainly are engaged in the later stage of corticomotor neuroplasticity of the tongue.