Granger causal time-dependent source connectivity in the somatosensory network

Peer reviewedPublisher PD

Effects of parietal TMS on somatosensory judgments challenge interhemispheric rivalry accounts

Interplay between the cerebral hemispheres is vital for coordinating perception and behavior. One influential account holds that the hemispheres engage in rivalry, each inhibiting the other. In the somatosensory domain, a seminal paper claimed to demonstrate such interhemispheric rivalry, reporting improved tactile detection sensitivity on the right hand after transcranial magnetic stimulation (TMS) to the right parietal lobe (Seyal, Ro, & Rafal, 1995). Such improvement in tactile detection ipsilateral to TMS could follow from interhemispheric rivalry, if one assumes that TMS disrupted cortical processing under the coil and thereby released the other hemisphere from inhibition. Here we extended the study by Seyal et al. (1995) to determine the effects of right parietal TMS on tactile processing for either hand, rather than only the ipsilateral hand. We performed two experiments applying TMS in the context of median-nerve stimulation; one experiment required somatosensory detection, the second somatosensory intensity discrimination. We found different TMS effects on detection versus discrimination, but neither set of results followed the prediction from hemispheric rivalry that enhanced performance for one hand should invariably be associated with impaired performance for the other hand, and vice-versa. Our results argue against a strict rivalry interpretation, instead suggesting that parietal TMS can provide a pedestal-like increment in somatosensory response

Exploring the role of interhemispheric inhibition in musculoskeletal pain

The overarching aim of this thesis was to determine whether: i) interhemispheric inhibition (IHI) is altered in response to unilateral musculoskeletal pain; and ii) a relationship exists between altered IHI (if any) and the development of bilateral sensorimotor dysfunction. To achieve this, three studies were conducted. These studies provided novel insight into IHI in experimentally induced acute muscle pain and chronic lateral elbow pain. The body of work in this thesis provides an original contribution to the field of musculoskeletal pain that deepens our understanding of IHI, and its potential association with changes in sensorimotor function in the unaffected limb, in unilateral conditions. Study 1 demonstrated a reduction in IHI from the affected to unaffected M1 but no change in IHI from the affected to unaffected S1 was observed in Study 2. In both studies, increased sensitivity to pressure was observed on the affected and unaffected sides. No change in IHI between M1s, and no differences in sensorimotor function were observed between individuals with chronic LE and healthy controls in Study 3. Taken together, the findings presented in this thesis suggest that IHI between M1s is reduced in response to acute muscle pain and altered IHI could contribute to the development of bilateral sensorimotor symptoms soon after pain onset. Conversely, IHI between S1s is preserved in response to acute muscle pain. In a clinical chronic musculoskeletal pain population, IHI is also preserved. However, further research is needed to determine whether the degree of change in IHI is related to various features of clinical pain such as pain severity, or the severity of bilateral sensorimotor dysfunction. The studies in this thesis are amongst the first to investigate: i) IHI in response to musculoskeletal pain of varying durations; and ii) the relationship between altered IHI and the development of bilateral sensorimotor dysfunction. Longitudinal studies that follow individuals from an initial episode of acute musculoskeletal pain to recovery, or to the development of chronic musculoskeletal pain, are required to further explore the relationship between IHI and the development of bilateral sensorimotor symptoms in unilateral musculoskeletal pain conditions

Reorganisation of sensorimotor function in children with brain disease

Introduction: In this study, paradigms were developed for the investigation of sensorimotor function in children using functional MRI (fMRI), somatosensory evoked potential (SEP) recordings and behavioural measures. These techniques were applied both to normal controls subjects and to children with brain disease. A major aim was to investigate the remarkable recovery of function that can take place following brain injury sustained early in life. Methods: Three fMRI paradigms were developed, namely active movement of the hand, passive flexion/extension movement of the fingers and median nerve stimulation. In addition, SEPs of functional cortical responses to stimulation of the median nerve were recorded at high temporal resolution. Finally, the extent of residual or recovered sensory and motor hand function was assessed using behavioural tests, including grip strength and double simultaneous stimulation. In one set of investigations, all three techniques were applied to children following hemispherectomy or children following vascular damage to the middle cerebral artery territory, to examine the pattern of residual sensorimotor function following brain injury. In a second study, fMRI was carried out in pre-surgical paediatric patients for mapping of the sensorimotor cortex in preparation for surgical resection of lesions in the vicinity of this cortical region. Results and Discussion: fMRI was successful in locating the hand cortical sensorimotor area in 11 out of 12 paediatric patients pre-operatively, and was of value to the neurosurgeon in helping to delineate the boundaries of subsequent cortical resection. In patients following stroke and hemispherectomy, a combination of fMRI, SEP and behavioural techniques provided evidence for inter-hemispheric reorganisation of sensorimotor function through ipsilateral sensorimotor pathways, and also suggested an increase in the involvement of ipsilateral secondary sensorimotor areas. The data also indicate that cortical sensorimotor reorganisation and functional recovery can be seen in patient both with congenital disease and with late-onset acquired disease, suggesting that factors additional to age at injury may influence the degree of residual function resulting from cerebral reorganisation. Informed consent was obtained for all patients and controls, and the study was approved by the Great Ormond Street Hospital for Children/Institute of Child Health Research Ethics Committee

Neuromagnetic studies on cortical somatosensory functions in infants and children : Normal development and effect of early brain lesions

Until recently, objective investigation of the functional development of the human brain in vivo was challenged by the lack of noninvasive research methods. Consequently, fairly little is known about cortical processing of sensory information even in healthy infants and children. Furthermore, mechanisms by which early brain insults affect brain development and function are poorly understood. In this thesis, we used magnetoencephalography (MEG) to investigate development of cortical somatosensory functions in healthy infants, very premature infants at risk for neurological disorders, and adolescents with hemiplegic cerebral palsy (CP). In newborns, stimulation of the hand activated both the contralateral primary (SIc) and secondary somatosensory cortices (SIIc). The activation patterns differed from those of adults, however. Some of the earliest SIc responses, constantly present in adults, were completely lacking in newborns and the effect of sleep stage on SIIc responses differed. These discrepancies between newborns and adults reflect the still developmental stage of the newborns’ somatosensory system. Its further maturation was demonstrated by a systematic transformation of the SIc response pattern with age. The main early adult­like components were present by age two. In very preterm infants, at term age, the SIc and SIIc were activated at similar latencies as in healthy fullterm newborns, but the SIc activity was weaker in the preterm group. The SIIc response was absent in four out of the six infants with brain lesions of the underlying hemisphere. Determining the prognostic value of this finding remains a subject for future studies, however. In the CP adolescents with pure subcortical lesions, contrasting their unilateral symptoms, the SIc responses of both hemispheres differed from those of controls: For example the distance between SIc representation areas for digits II and V was shorter bilaterally. In four of the five CP patients with cortico­subcortical brain lesions, no normal early SIc responses were evoked by stimulation of the palsied hand. The varying differences in neuronal functions, underlying the common clinical symptoms, call for investigation of more precisely designed rehabilitation strategies resting on knowledge about individual functional alterations in the sensorimotor networks.Lääketieteellisen teknologian kehitys on vasta viime vuosina mahdollistanut lasten aivotoiminnan tarkan, objektiivisen tutkimuksen. Näin ollen esimerkiksi aistiärsykkeiden aivoprosessoinnista vastasyntyneillä tiedetään varsin vähän, samoin kuin monien aivotoimintojen kehittymisestä lapsen kasvaessa. Myös ymmärrys erilaisten aivovaurioiden vaikutuksesta kehittyviin aivoihin on puutteellista. Magnetoenkefalografialla (MEG) tutkitaan aivohermosolujen toimintaa mittaamalla niissä syntyvien sähkövirtojen tuottamia magneettikenttiä pään ulkopuolelta. Väitöskirjassa MEG:n avulla tutkittiin tuntoaivokuoren toimintaa vastasyntyneillä ja tämän toiminnan kehitystä ensimmäisten elinvuosien aikana. Lisäksi tuntoaivokuoren toimintaa tarkasteltiin pikkukeskosena syntyneillä vauvoilla sekä nuorilla, joilla on varhaisen aivovaurion aiheuttama toispuoleinen CP-vamma. Jo vastasyntyneellä useat aivoalueet aktivoituivat käden alueen kosketusärsykkeen jälkeen. Tuntoaivokuoren aktiivisuus poikkesi kuitenkin oleellisesti aikuisesta: tietyt aikuistyyppiset aivovasteet puuttuivat vastasyntyneiltä täysin heijastaen vastasyntyneen vauvan hermoston keskeneräistä kehitysvaihetta. Tuntoaivovasteet kehittyivät iän myötä järjestelmällisesti siten, että kaksivuotiailla ne alkoivat morfologisesti muistuttaa aikuisten vasteita. Pikkukeskosten primaarisen tuntoaivokuoren vaste oli lasketussa ajassa heikompi kuin terveillä täysaikaisilla vauvoilla, mikä voi johtua pienemmästä aktivoituneesta hermosolujoukosta tai aktivaation epäsynkroniasta. Sekundaarisen tuntoaivokuoren vasteen puuttuminen liittyi poikkeaviin ultraääni- ja magneettikuvauslöydöksiin. Tämän havainnon ennusteellista merkitystä selvitetään parhaillaan seurantatutkimuksella. CP-vammaisilla nuorilla tuntoaivovasteissa havaittiin verrokkeihin nähden useita poikkeavuuksia, jotka olivat osin laaja-alaisempia kuin oli pääteltävissä kliinisistä oireista tai aivojen rakenteellisesta vauriosta. Esimerkiksi potilailla, joiden sairauden taustalla oli subkortikaalinen aivovaurio, etu- ja pikkusormien edustusalueet tuntoaivokuorella olivat verrokkeihin nähden lähempänä toisiaan sekä vaurion puoleisessa että vastakkaisessa aivopuoliskossa. Aivojen erilaisten rakenteellisten vaurioiden aiheuttamien toiminnallisten muutosten tarkempi ymmärtäminen voi osoittautua merkittäväksi CP-potilaiden kuntoutuksen ja hoidon yksilöllisessä räätälöinnissä

Funzioni di alto livello nella corteccia somatosensoriale secondaria (SII)

Le proprietà della corteccia somato-sensoriale secondaria (SII) sono state largamente discusse in molteplici studi sia nella scimmia, sia nell’uomo, suggerendo che quest’area assolva funzioni di alto livello nel processamento dello stimolo tattile, quali, ad esempio, l’apprendimento o la memoria. Recentemente, alcuni studi su scimmia hanno evidenziato che, oltre agli stimoli somato-sensoriali, SII risponde anche alla stimolazione dello spazio peri-personale, all’esecuzione di azioni, alla vista di oggetti in movimento ed all’osservazione di azioni, candidando SII ad essere un’area complessa, non limitata a sole funzioni somato-sensoriali. Partendo dallo studio delle risposte di SII agli stimoli tattili, lo scopo di questa tesi è di investigare la risposta di quest’area a stimoli complessi, con particolare attenzione a task di integrazione visuo-tattile e all’osservazione di azioni nell’uomo. Con queste finalità, gli esperimenti presentati sono stati condotti mediante elettroencefalografia stereotassica (stereo-EEG) su pazienti epilettici farmaco-resistenti, impiantati come parte della loro valutazione pre-chirurgica. In una prima fase, sono stati studiati la distribuzione spaziale ed il profilo temporale delle risposte intra-corticali alla stimolazione del nervo mediano controlaterale ed ipsilaterale. I risultati ottenuti indicano che mentre la corteccia somato-sensoriale primaria (SI), il giro precentrale ed il solco intra-parietale rispondono solo alla stimolazione controlaterale, la corteccia somato-sensoriale secondaria e l’insula posteriore sono attivate bilateralmente. Inoltre, queste ultime sono caratterizzate da una risposta tonica e duratura nel tempo. Questa potrebbe rappresentare un meccanismo di ritenzione temporale dell’informazione tattile ed essere l’espressione di funzioni di alto livello quali appunto la memoria e l’apprendimento degli stimoli. Nella seconda sezione della tesi, per testare il possibile coinvolgimento dell’opercolo parietale nell’integrazione visuo-tattile, la stimolazione del nervo mediano controlaterale è stata somministrata congiuntamente ad una stimolazione visiva (i.e. flash). I risultati ottenuti evidenziano un aumento in ampiezza della componente tonica, se comparato alla sola stimolazione tattile, localizzato nell’insula posteriore e nelle porzioni più rostrali dell’opercolo parietale mentre SII mostra un comportamento del tutto inalterato. Tuttavia, tenendo in considerazione che studi su primati non umani riportano risposte visiva in SII a stimoli biologici, sono necessarie ulteriori indagini per comprendere quale tipologia di stimolazione determina l’attivazione di quest’area. Infine, la terza parte della tesi mostra le risposte intra-corticali di SI e SII ad un task motorio che include compiti di afferramento e manipolazione di oggetti, e all’osservazione delle stesse azioni eseguite da un altro individuo. I risultati evidenziano un’attivazione bilaterale di SII, sia durante l’esecuzione sia durante l’osservazione di azioni, con un profilo temporale sincrono. Al contrario SI è attiva solo durante l’esecuzione: l’input a SI durante l’osservazione non ha dunque una natura somato-sensoriale ma piuttosto deve essere sostenuto da un circuito visuo-motorio capace di operare in maniera simultanea. In conclusione, questa tesi dimostra il ruolo cruciale di SII non solo nel processamento degli stimoli tattili ma anche nell’integrazione di stimoli visuo-motori.The somatosensory properties of the second somatosensory cortex (SII) have been largely described by many studies in both monkeys and humans, suggesting for this area a high-order role in tactile stimulation processing with functions including tactile learning and memory. More interestingly, recent studies on monkeys showed that beyond somatosensory stimuli, SII responds to a wider number of stimuli including peripersonal space stimulation, active movements, observation of objects displacement and action observation. Taking into account these results, SII is a candidate to be more than just a somatosensory area. Starting from its somatosensory properties, this thesis aims to disentangle the role of SII in more complex tasks with particular attention to visuo-tactile integration and action observation in humans. To this purpose, the experiments presented in this thesis are carried with stereotactic electroencephalography (stereo-EEG) on drug-resistant epileptic patients to take advantage of its high temporal and spatial resolution. Firstly, I investigated the spatial distribution and the temporal profile of the intracortical responses to both contralateral and ipsilateral median nerve stimulation. Results indicated that while the primary somatosensory area, precentral gyrus and intra-parietal sulcus respond only to the contralateral stimulation, the secondary somatosensory cortex and posterior insula are activated bilaterally. Furthermore, these regions exhibit a tonic long-lasting temporal profile, which might represent a mechanism of temporal retention of the tactile information, and thus be the signature of high-level somatosensory functions such as tactile memory and awareness. In a second stage of the thesis, to test the possible involvement of parietal operculum in visuo-tactile integration, we administered to patients contralateral median nerve stimulation jointly with visual stimulation (i.e. flash) to about 100 drug-resistant epileptic patients. Results underline an enhancement of the tonic components relative to tactile stimulation only, limited to posterior insula and to the rostral areas of parietal operculum, with SII maintaining an unaltered behavior. Considering previous findings in non-human primates, which reported visual responses in SII in response to biological stimuli, further researches are needed to understand which threshold in the stimulus might determine the eventual activation of this area. With this aim, the third part of this thesis presents the intracortical responses of both SI and SII to a motor task requiring reaching, grasping and manipulation, as well as to the observation of the same actions performed by another individual. The results obtained highlighted that SII activates bilaterally, both during the execution and the observation of actions, with a synchronous temporal profile. Conversely, SI activates only during the execution, leading to the conclusion that the input to SII during the observation condition has not a somatosensory nature, but rather that it is sustained by visuo-motor circuits operating simultaneously. Taking together all the evidence, this thesis demonstrates the pivotal role of SII not only in somatosensory functions, as largely reported in literature, but also in the integration of visuo-motor stimuli

Diffuse Optical Tomography Activation in the Somatosensory Cortex: Specific Activation by Painful vs. Non-Painful Thermal Stimuli

Background: Pain is difficult to assess due to the subjective nature of self-reporting. The lack of objective measures of pain has hampered the development of new treatments as well as the evaluation of current ones. Functional MRI studies of pain have begun to delineate potential brain response signatures that could be used as objective read-outs of pain. Using Diffuse Optical Tomography (DOT), we have shown in the past a distinct DOT signal over the somatosensory cortex to a noxious heat stimulus that could be distinguished from the signal elicited by innocuous mechanical stimuli. Here we further our findings by studying the response to thermal innocuous and noxious stimuli. Methodology/Principal Findings: Innocuous and noxious thermal stimuli were applied to the skin of the face of the first division (ophthalmic) of the trigeminal nerve in healthy volunteers (N = 6). Stimuli temperatures were adjusted for each subject to evoke warm (equivalent to a 3/10) and painful hot (7/10) sensations in a verbal rating scale (0/10 = no/max pain). A set of 26 stimuli (5 sec each) was applied for each temperature with inter-stimulus intervals varied between 8 and 15 sec using a Peltier thermode. A DOT system was used to capture cortical responses on both sides of the head over the primary somatosensory cortical region (S1). For the innocuous stimuli, group results indicated mainly activation on the contralateral side with a weak ipsilateral response. For the noxious stimuli, bilateral activation was observed with comparable amplitudes on both sides. Furthermore, noxious stimuli produced a temporal biphasic response while innocuous stimuli produced a monophasic response. Conclusions/Significance: These results are in accordance with fMRI and our other DOT studies of innocuous mechanical and noxious heat stimuli. The data indicate the differentiation of DOT cortical responses for pain vs. innocuous stimuli that may be useful in assessing objectively acute pain

MEG event-related desynchronization and synchronization deficits during basic somatosensory processing in individuals with ADHD

<p>Abstract</p> <p>Background</p> <p>Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent, complex disorder which is characterized by symptoms of inattention, hyperactivity, and impulsivity. Convergent evidence from neurobiological studies of ADHD identifies dysfunction in fronto-striatal-cerebellar circuitry as the source of behavioural deficits. Recent studies have shown that regions governing basic sensory processing, such as the somatosensory cortex, show abnormalities in those with ADHD suggesting that these processes may also be compromised.</p> <p>Methods</p> <p>We used event-related magnetoencephalography (MEG) to examine patterns of cortical rhythms in the primary (SI) and secondary (SII) somatosensory cortices in response to median nerve stimulation, in 9 adults with ADHD and 10 healthy controls. Stimuli were brief (0.2 ms) non-painful electrical pulses presented to the median nerve in two counterbalanced conditions: unpredictable and predictable stimulus presentation. We measured changes in strength, synchronicity, and frequency of cortical rhythms.</p> <p>Results</p> <p>Healthy comparison group showed strong event-related desynchrony and synchrony in SI and SII. By contrast, those with ADHD showed significantly weaker event-related desynchrony and event-related synchrony in the alpha (8–12 Hz) and beta (15–30 Hz) bands, respectively. This was most striking during random presentation of median nerve stimulation. Adults with ADHD showed significantly shorter duration of beta rebound in both SI and SII except for when the onset of the stimulus event could be predicted. In this case, the rhythmicity of SI (but not SII) in the ADHD group did not differ from that of controls.</p> <p>Conclusion</p> <p>Our findings suggest that somatosensory processing is altered in individuals with ADHD. MEG constitutes a promising approach to profiling patterns of neural activity during the processing of sensory input (e.g., detection of a tactile stimulus, stimulus predictability) and facilitating our understanding of how basic sensory processing may underlie and/or be influenced by more complex neural networks involved in higher order processing.</p