Cortical Regions Encoding Hardness Perception Modulated by Visual Information Identified by Functional Magnetic Resonance Imaging With Multivoxel Pattern Analysis

Recent studies have revealed that hardness perception is determined by visual information along with the haptic input. This study investigated the cortical regions involved in hardness perception modulated by visual information using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). Twenty-two healthy participants were enrolled. They were required to place their left and right hands at the front and back, respectively, of a mirror attached to a platform placed above them while lying in a magnetic resonance scanner. In conditions SFT, MED, and HRD, one of three polyurethane foam pads of varying hardness (soft, medium, and hard, respectively) was presented to the left hand in a given trial, while only the medium pad was presented to the right hand in all trials. MED was defined as the control condition, because the visual and haptic information was congruent. During the scan, the participants were required to push the pad with the both hands while observing the reflection of the left hand and estimate the hardness of the pad perceived by the right (hidden) hand based on magnitude estimation. Behavioral results showed that the perceived hardness was significantly biased toward softer or harder in >73% of the trials in conditions SFT and HRD; we designated these trials as visually modulated (SFTvm and HRDvm, respectively). The accuracy map was calculated individually for each of the pair-wise comparisons of (SFTvm vs. MED), (HRDvm vs. MED), and (SFTvm vs. HRDvm) by a searchlight MVPA, and the cortical regions encoding the perceived hardness with visual modulation were identified by conjunction of the three accuracy maps in group analysis. The cluster was observed in the right sensory motor cortex, left anterior intraparietal sulcus (aIPS), bilateral parietal operculum (PO), and occipito-temporal cortex (OTC). Together with previous findings on such cortical regions, we conclude that the visual information of finger movements processed in the OTC may be integrated with haptic input in the left aIPS, and the subjective hardness perceived by the right hand with visual modulation may be processed in the cortical network between the left PO and aIPS

Magnetoenkefalografian ja toiminnallisen magneettikuvauksen vertailu ja yhdistäminen tunto- ja liikejärjestelmän tutkimuksessa

MEG directly measures the neuronal events and has greater temporal resolution than fMRI, which has limited temporal resolution mainly due to the larger timescale of the hemodynamic response. On the other hand fMRI has advantages in spatial resolution, while the localization results with MEG can be ambiguous due to the non-uniqueness of the electromagnetic inverse problem. Thus, these methods could provide complementary information and could be used to create both spatially and temporally accurate models of brain function. We investigated the degree of overlap, revealed by the two imaging methods, in areas involved in sensory or motor processing in healthy subjects and neurosurgical patients. Furthermore, we used the spatial information from fMRI to construct a spatiotemporal model of the MEG data in order to investigate the sensorimotor system and to create a spatiotemporal model of its function. We compared the localization results from the MEG and fMRI with invasive electrophysiological cortical mapping. We used a recently introduced method, contextual clustering, for hypothesis testing of fMRI data and assessed the the effect of neighbourhood information use on the reproducibility of fMRI results. Using MEG, we identified the ipsilateral primary sensorimotor cortex (SMI) as a novel source area contributing to the somatosensory evoked fields (SEF) to median nerve stimulation. Using combined MEG and fMRI measurements we found that two separate areas in the lateral fissure may be the generators for the SEF responses from the secondary somatosensory cortex region. The two imaging methods indicated activation in corresponding locations. By using complementary information from MEG and fMRI we established a spatiotemporal model of somatosensory cortical processing. This spatiotemporal model of cerebral activity was in good agreement with results from several studies using invasive electrophysiological measurements and with anatomical studies in monkey and man concerning the connections between somatosensory areas. In neurosurgical patients, the MEG dipole model turned out to be more reliable than fMRI in the identification of the central sulcus. This was due to prominent activation in non-primary areas in fMRI, which in some cases led to erroneous or ambiguous localization of the central sulcus.Magnetoenkefalografia (MEG) mittaa suoraan aivojen hermosolujen sähköistä toimintaa ja sillä on parempi ajallinen erotuskyky kuin aivojen aktivaation aiheuttamia paikallisen verenkierron muutoksia kuvaava toiminnallinen magneettikuvaus (TMK). TMK:lla on toisaalta etuja paikannuksessa MEG:hen nähden ja MEG:llä saadut paikannustulokset ovat monikäsitteisiä. Nämä menetelmät voivat täydentää toisiaan ja yhdessä niillä voidaan saada tarkempi ajallinen ja paikallinen kuva aivojen toiminnasta. Käytimme näitä kahta menetelmää aivojen tunto- ja liikejärjestelmän toiminnan kuvantamisessa terveillä koehenkilöillä ja neurokirurgisilla potilailla. Tutkimme menetelmillä saatavan paikannustuloksen yhteneväisyyttä ja käytimme TMK:sta saatavaa paikannustietoa MEG:llä mitattujen aivojen magneetisten vasteiden mallinuksessa luoden mallin aivojen tuntojärjestelmän toiminnasta. Neurokirurgisilla potilailla vertasimme kuvantamismenetelmien tuloksia leikkauksenaikaiseen sähköiseen liikeaivokuoren paikannukseen. Tutkimuksessa testattiin ja sovellettin kehittämiämme uusia kuva-analyysimenetelmiä. MEG:llä ja TMK:lla havaitsimme viitteitä aktivaatiosta tuntoärsykkeen kanssa samanpuoleisella primäärillä tuntoaivokuorella. Tuloksemme viittaavat lisäksi siihen että aivojen lateraalisessa fissuurassa on ainakin kaksi erillistä lähdealuetta jotka tuottavat magneettisia tuntoherätevasteita. Mallimme aivojen toiminnasta tuntoarsykkeen käsittelyn aikana vastasi hyvin kirjallisuudessa raportoituja suoraan aivoista mitattuja eri alueiden aktivaatioaikoja. TMK-analyysimenetelmiä vertailtaessa todettiin kuva-alkion naapurustoinformaatiota käyttävien menetelmien tuottavan paremmin toistettavia tuloksia. Kehittämämme menetelmä rajasi tarkemmin aivojen aktivaatioalueen ja oli muita menetelmiä herkempi havaitsemaan heikkoja aktivaatioita. Paikannettaessa aivojen keskusuurretta leikkauksen suunnittelua ja riskien arviointia varten MEG tuotti luotettavamman tuloksen kuin TMK jossa osalla potilaista aktivaatiot muilla kuin primäärillä liikeaivokuorella olivat voimakkaimpia vaikeuttaen tulosten tulkintaa

Functional neuroimaging of the somatosensory system with Ultra-high-field fMRI and MEG

Multimodal neuroimaging using a combination of Magnetoencephalography (MEG) and ultra-high-field fMRI are used in order to gain further insight into the neural oscillations and haemodynamic responses in the somatosensory cortex. Single pulse electrical median nerve stimulation (MNS) with regular and jittered intervals is used in MEG. A preliminary study is used to determine acceptable trial number and length, and highlights points to be considered in paradigm optimization. Time-frequency analysis shows that the largest activities are beta event-related desynchronization (ERD) and event-related synchronization (ERS) between 13Hz and 30Hz. No significant difference in both the induced oscillations and evoked responses are found. Paired pulse MNS with varying ISIs are studied using MEG and 7T fMRI. The beta ERD is suggested to have a gating role with a magnitude irrespective of the starting point of stimulus. Non-linearity effects both in beta ERD/ERS and P35m are shown for ISIs of up to 2s, implying that the non-linear neural responses to the stimulus may still contribute to the BOLD non-linearity even when the evoked response has returned to baseline. Multiple pulse MNS with varying pulse train length and frequency are also investigated using MEG and MEG-fMRI. The gating role of beta ERD is further confirmed and the N160m is suggested to be modulated under this role. No accumulative effect is seen in the ERS with increasing pulse number but the amplitude of the ERS is modulated by the frequency. This can be explained by a Cortical Activation Model (CAM). Efforts to spatially separate the beta ERD and ERS are shown for all three studies. Group averaged SAM images suggest a separation of activation areas along the central gyrus. Significant difference are found in the z MNI coordinate between beta ERD and ERS peak locations, suggesting that these two effects could arise from different generators. In the multiple pulse frequency study, by including the temporal signature of beta ERD and ERS as a regressor in BOLD fMRI analysis, delayed BOLD responses are located posterior to the standard BOLD response. However, the exact nature of the relationship between this delayed BOLD response and the ERS effects requires further work

Functional neuroimaging of the somatosensory system with Ultra-high-field fMRI and MEG

Multimodal neuroimaging using a combination of Magnetoencephalography (MEG) and ultra-high-field fMRI are used in order to gain further insight into the neural oscillations and haemodynamic responses in the somatosensory cortex. Single pulse electrical median nerve stimulation (MNS) with regular and jittered intervals is used in MEG. A preliminary study is used to determine acceptable trial number and length, and highlights points to be considered in paradigm optimization. Time-frequency analysis shows that the largest activities are beta event-related desynchronization (ERD) and event-related synchronization (ERS) between 13Hz and 30Hz. No significant difference in both the induced oscillations and evoked responses are found. Paired pulse MNS with varying ISIs are studied using MEG and 7T fMRI. The beta ERD is suggested to have a gating role with a magnitude irrespective of the starting point of stimulus. Non-linearity effects both in beta ERD/ERS and P35m are shown for ISIs of up to 2s, implying that the non-linear neural responses to the stimulus may still contribute to the BOLD non-linearity even when the evoked response has returned to baseline. Multiple pulse MNS with varying pulse train length and frequency are also investigated using MEG and MEG-fMRI. The gating role of beta ERD is further confirmed and the N160m is suggested to be modulated under this role. No accumulative effect is seen in the ERS with increasing pulse number but the amplitude of the ERS is modulated by the frequency. This can be explained by a Cortical Activation Model (CAM). Efforts to spatially separate the beta ERD and ERS are shown for all three studies. Group averaged SAM images suggest a separation of activation areas along the central gyrus. Significant difference are found in the z MNI coordinate between beta ERD and ERS peak locations, suggesting that these two effects could arise from different generators. In the multiple pulse frequency study, by including the temporal signature of beta ERD and ERS as a regressor in BOLD fMRI analysis, delayed BOLD responses are located posterior to the standard BOLD response. However, the exact nature of the relationship between this delayed BOLD response and the ERS effects requires further work

Mécanismes cérébraux de la régulation de la douleur : perception de la douleur et hypoalgésie induite psychologiquement

Objectif : Cette thèse a pour but de préciser les mécanismes neuropsychologiques de la douleur, de la régulation endogène de la douleur et de l'hypoalgésie induite psychologiquement (HIP) par la synthèse de près de trente ans de recherche imagerie cérébrale fonctionnelle. Méthodologie : Étant donné l'abondance des études sur le sujet et le manque d'intégration de leurs résultats, la technique de métaanalyse quantitative basée sur les coordonnées d'activation cérébrale fut privilégiée dans cette thèse, telle qu’implémentée dans l'algorithme ALE (Activation Likelyhood Estimate). Une force supplémentaire de cette thèse repose sur la rigueur du processus de sélection des articles. En effet, les études incluses dans les métaanalyses devaient satisfaire des critères stricts d'inclusion, ceci dans le but de favoriser la précision et la validité des conclusions subséquentes. Étude 1 : Le premier article visait à identifier les aires cérébrales impliquées dans la réduction de la douleur par des méthodes psychologiques d'interventions. Les articles retenus portent sur une variété de méthodes d'intervention, telles que le placebo, l'hypnose, la méditation, la perception de contrôle sur la stimulation douloureuse et l'induction d'émotions. Les résultats indiquent que l'HIP implique un vaste réseau d'activation qui comprend le cortex cingulaire antérieur, l'insula antérieure, les zones orbitofrontale et préfrontale latérale, ainsi que les régions pariétale, temporale et souscorticales. Ces activations reflèteraient l'implication des mécanismes neuropsychologiques cognitifs et émotionnels sous-tendent les interventions psychologiques ciblées par ces études, incluant la conscience de soi et la motivation. De plus, les divergences de patron d'activation entre les approches ont été explorées, notamment pour le placebo et la distraction. Étude 2 : Le deuxième article a identifié des patrons d'activations préférentiellement associés à la perception de la douleur, à l'HIP, ainsi que des activations communément associées à la douleur et l'HIP. Les résultats indiquent que 1) la perception de la douleur est associée à l'activation d'aires somatosensorielles et motrices, ce qui pourrait être le reflet de la préparation d'une action adaptative, 2) l'HIP est liée à l'engagement de régions préfrontales antéromédianes et orbitales, possiblement en lien avec des processus motivationnels et émotionnels, et 3) la douleur et l'HIP sont associés à l'activation d'aires préfrontales dorsolatérales, de l'insula antérieure et du cortex cingulaire moyen, ce qui pourrait refléter l'engagement spontané pendant la douleur de mécanismes endogènes de régulation descendante. Conclusion : Par ces études, cette thèse fait le point sur les mécanismes cérébraux impliqués différentiellement dans la perception de la douleur, dans sa régulation endogène et dans l'hypoalgésie induite psychologiquement.Objective: This thesis aims to clarify the neuropsychological mechanisms of pain, of the endogenous regulation of pain and of psychologically induced hypoalgesia (PIH), through the synthesis of almost thirty years of functional brain imaging research. Methodology: Given the abundance of studies in this domain and the lack of integration of their results, we used the quantitative meta-analysis technique based on brain activation using the ALE (Activation likelihood Estimate) statistic. The strength of this thesis lies in the globalized perspective of the litterature, and in the rigor of the article selection process from which results were extracted. Indeed, the studies included in the meta-analyses needed to meet strict inclusion criteria in order to strengthen the accuracy and the validity of subsequent conclusions. Study 1: The first article is aimed at identifying brain areas involved in pain reduction through psychological methods of intervention. Chosen articles that covered a variety of approaches, such as placebo, hypnosis, meditation, perception of control over the stimulation, and induction of emotions. Analysis across these various studies indicated that PIH involves a broad network of activation that includes the anterior cingulate cortex, anterior insulae, orbital and lateral prefrontal and frontal areas, as well as parietal, temporal and subcortical regions. This activation network may reflect the involvement of diverse neuropsychological mechanisms in the various affective, self-awareness, cognitive and motivational processes underlying the psychological interventions targeted by these studies. In addition, we explored some specific patterns of brain activity related to placebo and distraction, in comparison to other approaches. We propose several hypotheses regarding the distinctive neuropsychological processes underlying these approaches. Study 2: The second article aimed at investigating patterns of brain activity preferentially associated with pain perception or with PIH. First we assessed patterns of increased and decreased activity during experimental pain in healthy volunteers. Second we determined the brain regions preferentially activated during pain perception or during PIH with subtraction analyses. Using a conjunction analysis, we also determined a set of brain regions possibly involved in regulatory processes activated spontaneously during acute of pain. Our results indicate that 1) somatosensory and motor areas are preferentially related to pain perception, which may reflect the preparation of a motor response, 2) dorsolateral prefrontal areas, anterior insula and the anterior midcingulate cortex were associated with both pain and PIH and may reflect the spontaneous activation of top-down regulation mechanisms during pain, and 3) antero-medial and orbital prefrontal regions were preferentially associated with PIH, which may indicate motivational and emotional processes associated with the engagement of an externally driven hypoalgesic procedure