Migraine Type-Dependent Patterns of Brain Activation After Facial and Intranasal Trigeminal Stimulation.

In migraine, the trigeminal nerve is intimately involved in the pathophysiology of the disease. We hypothesized that alterations in the sensory trigeminal activation in migraine would be reflected by EEG-derived event-related potentials (ERP). We aimed to investigate differences in the temporal and spatial processing of trigeminal stimuli between interictal migraine patients and healthy subjects. ERP to trigeminal stimuli were recorded at 128-channels to allow localization of their cortical sources with high temporal resolution. Seventeen patients with episodic migraine without aura, 17 subjects with episodic migraine with aura, and 17 healthy subjects participated in the study. The first branch of the trigeminal nerve was stimulated using intranasal chemical (CO2), cutaneous electrical, and cutaneous mechanical (air puff) stimuli. Analyses were performed with regard to micro-state segmentation, ERP source localization, and correlation with the patients' clinical characteristics. Topographical assessments of EEG configurations were associated with the pathological condition. The source analysis revealed altered trigeminal-sensory response patterns in the precuneus, temporal pole, and cerebellum for both migraine groups during the interictal phase. The estimated current source density was positively correlated with migraine disease duration, indicating brain functional and structural changes as a consequence of the disease. Hyperactivity of the cerebellar posterior lobe was observed as a specific trigeminal response of migraine patients with aura. In conclusion, our results suggest the presence of brain changes accompanying the advancement of migraine as an expression of dysfunctional central pain processing. Hence, we identified EEG patterns in response to mechano-/chemosensory stimuli that can serve as biomarkers of migraine.

Non-invasive peripheral focused ultrasound neuromodulation of the celiac plexus ameliorates symptoms in a rat model of inflammatory bowel disease.

NEW FINDINGS: What is the central question of this study? Does peripheral non-invasive focused ultrasound targeted to the celiac plexus improve inflammatory bowel disease? What is the main finding and its importance? Peripheral non-invasive focused ultrasound targeted to the celiac plexus in a rat model of ulcerative colitis improved stool consistency and reduced stool bloodiness, which coincided with a longer and healthier colon than in animals without focused ultrasound treatment. The findings suggest that this novel neuromodulatory technology could serve as a plausible therapeutic approach for improving symptoms of inflammatory bowel disease. ABSTRACT: Individuals suffering from inflammatory bowel disease (IBD) experience significantly diminished quality of life. Here, we aim to stimulate the celiac plexus with non-invasive peripheral focused ultrasound (FUS) to modulate the enteric cholinergic anti-inflammatory pathway. This approach may have clinical utility as an efficacious IBD treatment given the non-invasive and targeted nature of this therapy. We employed the dextran sodium sulfate (DSS) model of colitis, administering lower (5%) and higher (7%) doses to rats in drinking water. FUS on the celiac plexus administered twice a day for 12 consecutive days to rats with severe IBD improved stool consistency scores from 2.2 ± 1 to 1.0 ± 0.0 with peak efficacy on day 5 and maximum reduction in gross bleeding scores from 1.8 ± 0.8 to 0.8 ± 0.8 on day 6. Similar improvements were seen in animals in the low dose DSS group, who received FUS only once daily for 12 days. Moreover, animals in the high dose DSS group receiving FUS twice daily maintained colon length (17.7 ± 2.5 cm), while rats drinking DSS without FUS exhibited marked damage and shortening of the colon (13.8 ± 0.6 cm) as expected. Inflammatory cytokines such as interleukin (IL)-1ß, IL-6, IL-17, tumour necrosis factor-α and interferon-γ were reduced with DSS but coincided with control levels after FUS, which is plausibly due to a loss of colon crypts in the former and healthier crypts in the latter. Lastly, overall, these results suggest non-invasive FUS of peripheral ganglion can deliver precision therapy to improve IBD symptomology.

Dataset of verbal evaluation of umami taste in Europe.

The data presented here includes verbal descriptors used by Finnish, German and Italian subjects to express the quality of an umami taste solution offered in a blind fashion. The dataset refers to the research article "A cross-cultural survey of Umami Familiarity in European Countries" [1]. Data shows that a total of 106 different classes of words, including synonyms, were used by the Finnish group, 64 different classes of words, including synonyms, were used by the German group, and a total of 70 different classes of words, including synonyms, were used by the Italian group. The descriptors are reported in Excel tables and visualized in a bar graph where the length of the bars indicates the number of given answers for each class.

Early-life dentine manganese concentrations and intrinsic functional brain connectivity in adolescents: A pilot study.

Maturational processes in the developing brain are disrupted by exposure to environmental toxicants, setting the stage for deviant developmental trajectories. Manganese (Mn) is an essential nutrient that is neurotoxic at high levels of exposure, particularly affecting the basal ganglia and prefrontal cortex. Both the intensity and timing of exposure matter; deciduous teeth can be used to retrospectively and objectively determine early-life windows of vulnerability. The aim of this pilot study was to examine associations between prenatal, early postnatal and childhood dentine Mn concentrations and intrinsic functional connectivity (iFC) of adolescents' brains. 14 adolescents (12-18 years; 6 girls) from northern Italian regions with either current, historic or no Mn contamination, completed a 10-minute resting state functional Magnetic Resonance Imaging (MRI) scan in an 1.5T MRI scanner. We estimated prenatal, early postnatal and childhood Mn concentrations in deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses, focusing on six subcortical seeds (left and right caudate, putamen, pallidum) and one cortical seed (bilateral middle frontal gyrus) from Harvard-Oxford atlases. We examined linear and quadratic correlations between log-transformed Mn concentrations and seed-based iFC (Bonferroni-corrected p<0.0023), controlling for either socio-economic status, sex or age. Dentine Mn concentrations (Mn:Calcium ratio) were highest during the prenatal period (median = 0.48) and significantly declined during the early postnatal (median = 0.14) and childhood periods (median = 0.006). Postnatal Mn concentrations were associated with: 1) increased iFC between the middle frontal gyrus and medial prefrontal cortex; 2) decreased iFC between the right putamen and pre- and postcentral gyrus. Together, these findings suggest that early postnatal Mn concentrations are associated with increased iFC within cognitive control brain areas, but decreased iFC between motor areas in adolescents. Future studies should replicate these findings in larger samples, and link brain connectivity measures to cognitive and motor outcomes.

Advances in Understanding Parosmia: An fMRI Study.

INTRODUCTION: A number of patients with a diminished sense of smell also can suffer from parosmia. These patients with such a qualitative smell disorder are often more severely affected than patients exhibiting only a quantitative smell disorder. Qualitative smell disorders have heretofore been poorly investigated. The focus of the present study was, using functional MRI, to compare the central processing of olfactory stimulation in patients with qualitative smell disorders. MATERIAL AND METHODS: A total of 23 patients were investigated, 12 hyposmic patients without parosmia (HYP group) and 11 hyposmic patients with parosmia (PAR group). Both groups were matched with regard to sex and age. The olfactory smells used were peach and coffee odors. RESULTS: The two groups exhibited different patterns of activation. In HYP patients a stronger activation was observed in the medial orbitofrontal cortex, anterior cingulate cortex, and parahippocampal gyrus, whereas in the PAR group stronger activation in the thalamus and putamen was seen. DISCUSSION: These results are consistent with the hypothesis that there are specific patterns in the central processing of olfactory stimuli which differ in hyposmic patients with and without parosmia.

Odor-related brain hyper-reactivity in euthymic bipolar disorder: An fMRI and ERP study.

Previous studies on olfactory function in patients with bipolar disorder (BD) are limited and contradictory. The current study aimed to comprehensively analyze the olfactory function of patients with euthymic BD using psychophysical, electrophysiological and neuroimaging techniques. Twenty-one patients with BD in remission and 20 healthy controls were tested with the "Sniffin' Sticks" olfactory test. Block-design fMRI data to a pleasant and an unpleasant stimulus were acquired while recording intensity and hedonic ratings. Olfactory event-related potentials (OERP) to the same stimuli were additionally recorded. Results show no differences between patients and healthy controls in terms of self-rated olfactory function and tested olfactory domains (odor threshold, discrimination or identification) (p>0.05). Compared to healthy controls, patients showed an increased fMRI activation in multiple cortical and subcortical regions as a response to olfactory stimulation, as well as larger amplitudes of OERPs regardless of the hedonic valence of the odor. All in all, patients with euthymic BD showed a stronger central responsiveness to odorous stimuli in fMRI and OERPs despite of normal psychophysical results, indicating the probable existence of an odor-related over-reactive brain network in the remission phase of BD.

Gustatory pathway in humans: A review of models of taste perception and their potential lateralization.

The focus of this review is to interpret recent advances in human gustatory pathways with respect to the laterality of gustatory responses. Psychophysical, neuroimaging, and clinical anatomical studies published in peer reviewed scientific journals were examined. From the anatomical and neuroimaging studies a total of six models are outlined and discussed in the light of some recent psychophysical and clinical results. In the specific of the salt condition and right preferred hand the outcomes have revealed a predominant left ipsilateral pathway with evidences of ipsilateral projection from the left primary gustatory cortex (PGC) to the orbitofrontal cortex, while a bilateral projection from the right oral cavity to the left and right insula seems to be more consistent. Also, the right side predominance of the chemosensory perception is objected. Additionally, the gustatory response appears to be dependent on the taste quality, supporting the idea of a chemotopical organization of the PGC as well as the Labelled-Line Model theory of peripheral taste quality encoding. However, where the fibers branch along the ascending pathway is not unequivocally established. Interestingly, factors like handedness appear to be remarkable when studying the lateralization of brain functions. Finally we suggest that further studies must include handedness and taste quality as distinctive factors that can help to interpret the results in a unique way.

Explorative analysis of IPA-SPECT data through statistical inference for an automated diagnosis of glioma tumor.

PURPOSE: The identification of a brain tumor imaged with PET or SPECT is usually performed with visual inspection of an expert medical clinician. However an automated diagnostic of such images hasn't been established or applied. In this study, we explored the possibility of establishing an automated statistical analysis for the diagnosis of glioma by means of IPA-SPECT data. METHODS: On the basis of a dataset of 100 patients that have undergone MRI and IPA-SPECT acquisition, in this work, we identify an automated workflow. Three different approaches were explored: I. statistical non-parametric mapping analysis (SnPM), II. statistical non-parametric analysis with an increased number of permutations due to sign-flipping function (PALM) and III. statistical parametric analysis (SPM). The automated methods were compared with the visual inspection. RESULTS: The study proved PALM and SPM approaches to have a high diagnostic power. Compared to the parametric methods, the non-parametric method is the mathematically correct approach for the problem in question. If we take the high resolution structural MRI information into account, the diagnostic power of PALM was not significantly inferior to the visual inspection (P = 0.5150), showing an area under the ROC curve (AUC) smaller only by less than 3%. CONCLUSIONS: The automated diagnostic method based on statistical inference, here applied to diagnose glioma tumors in IPA-SPECT data, seems to be a promising tool that can support the visual investigation in nuclear medicine. Moreover in the foreseeable future, the presented methodology has a big potential in various application like localization of active tumor tissues in surgical resection or stereotactic radiosurgery.

Age-related changes of gustatory function depend on alteration of neuronal circuits.

Studies on age-related gustatory function report a reduction of the taste function, but the degeneration of the peripheral papillae alone cannot explain this reduction. In the present study, we apply psychophysics and gustatory event-related potentials (gERPs) to explore age-related differences in the processing of gustatory information as indicated by the cerebral sources of the gERP. A total of 96 subjects (47 female), subdivided into four groups with increasing age, participated in the study. After olfactory and gustatory screening for normal function, the subjects were invited to two sessions of gERP acquisition. They received a randomized combination of five isointense basic tastants that were presented at a medium level. At the same time, we recorded scalp electroencephalography (EEG) from 128 scalp locations. Psychophysical testing for smell and taste function exhibited a significant decrease with age. Topographical analyses of the EEG delineated four basic topographical maps that explained the processing of taste in the pre-decline age range, with sources inside the relevant gustatory areas. The age-related change of gustatory processing was associated with the absence of a specific map with sources inside the cerebellum and posterior insula, and the temporal broadening of a map with sources in the bilateral inferior frontal gyrus. These results confirm the hypothesis that the reduction of taste function with aging is not only due to degradation of gustatory peripheral tissues but is also related to different neural signatures in the central nervous system.

Olfactory impairment in Parkinson's disease is a consequence of central nervous system decline.

Early diagnosis and timely treatment of Parkinson's disease are essential factors to provide these patients with a longer period of a better quality of life. Olfactory loss is among the first non-motor symptoms of the disease; however, in light of the many causes of smell loss, it is a very unspecific biomarker and should only be used as part of a diagnostic test battery. In this study, we investigated the olfactory response in 71 subjects, consisting of Parkinson's disease patients, hyposmic and anosmic patients of other causes, and normosmic individuals searching for sensitive, distinct biomarkers for which we used scalp event-related 64-channel electroencephalography and psychophysical tests. The analysis of the global field power indicated significant measurable differences between patients with Parkinson's disease and otherwise olfactory dysfunctional and normosmic individuals. The localization of brain sources, in particular, provides evidence for differences in mainly late EEG-components suggesting a decline of central brain networks as a causal factor for olfactory loss in Parkinson's disease. The findings indicate a different pattern of olfactory processing in patients with Parkinson's disease compared to olfactory dysfunctions of other origin, which provide further insights into the mechanisms behind olfactory dysfunction in Parkinson's.

Effects of Manganese Exposure on Olfactory Functions in Teenagers: A Pilot Study.

Long-term exposure to environmental manganese (Mn) affects not only attention and neuromotor functions but also olfactory functions of a pre-adolescent local population who have spent their whole life span in contaminated areas. In order to investigate the effect of such exposure at the level of the central nervous system we set up a pilot fMRI experiment pointing at differences of brain activities between a non-exposed population (nine subjects) and an exposed one (three subjects). We also measured the volume of the olfactory bulb as well as the identification of standard olfactory stimuli. Our results suggest that young subjects exposed to Mn exhibit a reduction of BOLD signal, subjective odor sensitivity and olfactory bulb volume. Moreover a region of interest SPM analysis showed a specifically reduced response of the limbic system in relation to Mn exposure, suggesting an alteration of the brain network dealing with emotional responses.

A gustatory stimulator.

BACKGROUND: In order to elicit gustatory event related potentials (gERPs) a special taste delivery system is needed which allows precise control of stimulus onset and duration. NEW METHOD: Aim of this investigation was to describe the characteristics, namely onset rise-time step and onset delay time of a recently new taste delivery system based on stepper-motor, computer-driven glass syringes, able to spray pulses of liquid solutions into the mouth. RESULTS: The measurement showed that the pulse rise time is less than 100 ms and increases with the pulse duration; the delay of the stimulus on a 12 m hose is between 55 ms and 71 ms. COMPARISON WITH EXISTING METHODS: The gustometer in examination produce a stream of pulses, constituted by a certain number of taste stimuli interleaved among a number of tasteless pulses, moreover the solution is thermos-regulated at internal body temperature. This make the technique appealing for event related procedure in neuroscience investigation related to gustatory tasks. CONCLUSION: These results of the time rise measurements confirm the suitability of this gustometer to elicit ERPs.

Cerebral processing of umami: A pilot study on the effects of familiarity.

AIM: The identification of umami taste among people is extremely variable. Based on functional magnetic resonance imaging (fMRI) the aim of this study was to investigate changes of brain activation in participants before and after they were familiarized with this peculiar taste. MATERIAL AND METHOD: A total of 10 healthy, right-handed subjects (7 women, mean age 25 years) participated in this study. A computer-controlled gustometer was used to deliver the umami stimuli at supra-threshold concentrations. After the first session of fMRI experiments, participants went through two weeks of controlled exposure to umami taste, before the second session of fMRI experimentation. RESULTS: Results from psychophysical assessment showed that umami became more familiar (p < 0.001) among the participants after the gustatory exposure. No significant differences for pleasantness and intensity were observed before and after umami training. FMRI data showed that a broader central-nervous network was activated before "umami training" as compared to imaging after "umami training". Significant activation was found in the primary and high level sensory specific gustatory area (insula and anterior cingulate cortex) before training, whereas, significant activation was observed in memory retrieval areas (parahippocampal gyrus) after training. CONCLUSION: The main finding of the present study suggests that repeated exposure to umami taste over a relatively short period of time does not produce an increased response at the level of taste primary and secondary areas, but that increased familiarity with umami leads to an increased activation of the parahippocampal gyrus.

Time-course of trigeminal versus olfactory stimulation: evidence from chemosensory evoked potentials.

Habituation of responses to chemosensory signals has been explored in many ways. Strong habituation and adaptation processes can be observed at the various levels of processing. For example, with repeated exposure, amplitudes of chemosensory event-related potentials (ERP) decrease over time. However, long-term habituation has not been investigated so far and investigations of differences in habituation between trigeminal and olfactory ERPs are very rare. The present study investigated habituation over a period of approximately 80 min for two olfactory and one trigeminal stimulus, respectively. Habituation was examined analyzing the N1 and P2 amplitudes and latencies of chemosensory ERPs and intensity ratings. It was shown that amplitudes of both components - and intensity ratings - decreased from the first to the last block. Concerning ERP latencies no effects of habituation were seen. Amplitudes of trigeminal ERPs diminished faster than amplitudes of olfactory ERPs, indicating that the habituation of trigeminal ERPs is stronger than habituation of olfactory ERPs. Amplitudes of trigeminal ERPs were generally higher than amplitudes of olfactory ERPs, as it has been shown in various studies before. The results reflect relatively selective central changes in response to chemosensory stimuli over time.

Oral texture influences the neural processing of ortho- and retronasal odors in humans.

Eating implies mutual interactions between different senses. In the present work we aimed at studying relations between food texture and food odor, using both psychophysical and imaging techniques. Eighteen right-handed healthy human subjects participated to both behavioral and fMRI sessions. Fresh, sweetened milk and a more thickened version were delivered orally; in addition, a buttery-cream aroma was presented ortho- or retronasally. Stimuli were applied using a gustometer and or an air-dilution olfactometer, both computer-controlled. In each session subjects rated separately odor-, taste- and thickness intensities of the stimuli. The behavioral data show that odors, presented through either retro- or orthonasal path, induce a significant flavor enhancement with respect to the no-odor condition. Brain functional data indicated a significant enhancement of the activation of olfactory eloquent areas in favor of ortho-nasal odor presentation while activations of mechanosensory areas were favored by the retro-nasal odor route. As effect of oral stimuli we found a significant correlation between the texture intensity rating vs. the BOLD signal in the supplementary motor area, known to drive subconsciously primed movement, putatively associated in this case with the tongue movement required with the handling of the stimulus. Moreover, we found inhibition of the signal in different sensory specific areas as an effect of the mutual interaction between stimulus qualities. In conclusion, ortho- and retronasal odors differentially affect the neural processing of the texture of oral stimuli.

Olfactory short-term memory encoding and maintenance - an event-related potential study.

This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model.

A spatiotemporal comparison between olfactory and trigeminal event-related potentials.

The present study compared the temporal and spatial aspects of human olfactory and trigeminal processing. A relatively selective trigeminal stimulus, CO2, and a relatively selective olfactory stimulus, H2S, were delivered with an olfactometer to young, healthy volunteers. The analysis was performed in a classical (5-electrode, main ERPs peaks) and modern approach (high topographical resolution, inverse solution, source localization). Results of microstate segmentation highlighted 5 maps that generally described the two processes at cerebral level. The trigeminal response differed from the olfactory response up to 300ms after stimulus onset. In this time range, source analysis pointed out that the olfactory stimulation involved olfactory related areas, while trigeminal stimulation involved noxious/somatosensory specific brain areas. Moreover, from 300ms on our data showed a similarity between the two processes. Statistical parametrical mapping of the differences between conditions suggested greater activation in a specific motor/sniffing network for the CO2 stimulation (probably related to a regulation of the potential noxious stimulus) and a greater activation of the ipsilateral primary olfactory cortex for H2S.

Cross-modal integration of emotions in the chemical senses.

Although the brain structures involved in integrating odorant and trigeminal stimuli are well-documented, there is still a need to clarify (1) how emotional response is represented in the human brain during cross-modal interaction between odors and trigeminal stimuli, and (2) whether the degree of congruency between the two types of stimuli influences these emotional responses and their neural processing. These questions were explored combining psychophysics, event-related potentials (ERP) and fMRI in the same group of 17 subjects under a "congruent condition" (intranasal carbon dioxide mixed with the smell of orange, a combination found in soda drinks, for example), and an "incongruent condition" (intranasal carbon dioxide mixed with the smell of rose, a combination not encountered in everyday life). Responses to the 3 constituent stimuli (carbon dioxide, orange, and rose) were also measured. Hedonic and intensity ratings were collected for all stimulations. The congruent bimodal stimulus was rated as more pleasant than the incongruent. This behavioral effect was associated with enhanced neural activity in the hippocampus and anterior cingulate gyrus, indicating that these brain areas mediate reactivation of pleasant and congruent olfactory-trigeminal associations.

The functional neuroanatomy of odor evoked autobiographical memories cued by odors and words.

Behavioral evidence indicates that odor evoked autobiographical memories (OEAMs) are older, more emotional, less thought of and induce stronger time traveling characteristics than autobiographical memories (AMs) evoked by other modalities. The main aim of this study was to explore the neural correlates of AMs evoked by odors as a function of retrieval cue. Participants were screened for specific OEAMs and later presented with the odor cue and its verbal referent in an fMRI paradigm. Because the same OEAM was retrieved across both cue formats (odor and word), potential cue dependent brain activations were investigated. The overall results showed that odor and word cued OEAMs activated regions typically associated with recollection of autobiographical information. Although no odors were presented, a verbal cuing of the OEAMs activated areas associated with olfactory perception (e.g., piriform cortex). However, relative to word cuing, an odor cuing of OEAMs resulted in more activity in MTL regions such as the parahippocampus, and areas involved in visual vividness (e.g., occipital gyrus and precuneus). Furthermore, odor cues activated areas related to emotional processing, such as limbic and tempopolar regions significantly more. In contrast, word cues relative to odor cues recruited a more widespread and bilateral prefrontal activity. Hippocampus activity did not vary as function of the remoteness of the memory, but recollection of OEAMs from the 1(st) vs the 2(nd) decade of life showed specific activation in the right OFC, whereas the 2(nd) reflected a higher activation in the left inferior frontal gyrus.