Spatiotemporal integration of tactile information in human somatosensory cortex

BACKGROUND: Our goal was to examine the spatiotemporal integration of tactile information in the hand representation of human primary somatosensory cortex (anterior parietal somatosensory areas 3b and 1), secondary somatosensory cortex (S2), and the parietal ventral area (PV), using high-resolution whole-head magnetoencephalography (MEG). To examine representational overlap and adaptation in bilateral somatosensory cortices, we used an oddball paradigm to characterize the representation of the index finger (D2; deviant stimulus) as a function of the location of the standard stimulus in both right- and left-handed subjects. RESULTS: We found that responses to deviant stimuli presented in the context of standard stimuli with an interstimulus interval (ISI) of 0.33s were significantly and bilaterally attenuated compared to deviant stimulation alone in S2/PV, but not in anterior parietal cortex. This attenuation was dependent upon the distance between the deviant and standard stimuli: greater attenuation was found when the standard was immediately adjacent to the deviant (D3 and D2 respectively), with attenuation decreasing for non-adjacent fingers (D4 and opposite D2). We also found that cutaneous mechanical stimulation consistently elicited not only a strong early contralateral cortical response but also a weak ipsilateral response in anterior parietal cortex. This ipsilateral response appeared an average of 10.7 ± 6.1 ms later than the early contralateral response. In addition, no hemispheric differences either in response amplitude, response latencies or oddball responses were found, independent of handedness. CONCLUSION: Our findings are consistent with the large receptive fields and long neuronal recovery cycles that have been described in S2/PV, and suggest that this expression of spatiotemporal integration underlies the complex functions associated with this region. The early ipsilateral response suggests that anterior parietal fields also receive tactile input from the ipsilateral hand. The lack of a hemispheric difference in responses to digit stimulation supports a lack of any functional asymmetry in human somatosensory cortex

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

Modulation of human corticospinal excitability by paired associative stimulation

Paired Associative Stimulation (PAS) has come to prominence as a potential therapeutic intervention for the treatment of brain injury/disease, and as an experimental method with which to investigate Hebbian principles of neural plasticity in humans. Prototypically, a single electrical stimulus is directed to a peripheral nerve in advance of transcranial magnetic stimulation (TMS) delivered to the contralateral primary motor cortex (M1). Repeated pairing of the stimuli (i.e., association) over an extended period may increase or decrease the excitability of corticospinal projections from M1, in manner that depends on the interstimulus interval (ISI). It has been suggested that these effects represent a form of associative long-term potentiation (LTP) and depression (LTD) that bears resemblance to spike-timing dependent plasticity (STDP) as it has been elaborated in animal models. With a large body of empirical evidence having emerged since the cardinal features of PAS were first described, and in light of the variations from the original protocols that have been implemented, it is opportune to consider whether the phenomenology of PAS remains consistent with the characteristic features that were initially disclosed. This assessment necessarily has bearing upon interpretation of the effects of PAS in relation to the specific cellular pathways that are putatively engaged, including those that adhere to the rules of STDP. The balance of evidence suggests that the mechanisms that contribute to the LTP- and LTD-type responses to PAS differ depending on the precise nature of the induction protocol that is used. In addition to emphasizing the requirement for additional explanatory models, in the present analysis we highlight the key features of the PAS phenomenology that require interpretation

Cortical plasticity in response to median nerve trauma

Median nerve injuries in adults, repaired with nerve suture, lead to incomplete functional recovery despite improved surgical technique. This results in a reduction in quality of life, poorer working ability and a considerable expense for society. Misrouting of axons at the suture site connects regenerating axons to the wrong distal end organs. When distorted signals are conveyed to the dorsal root ganglia, spinal cord, thalamus and the somatosensory cortex, somatotopic maps at all levels become reorganised in a disorderly fashion. Children often regain full sensory function after median nerve injury and repair despite impaired conduction across the injured segment. There is growing evidence that cortical plasticity is the main mechanism behind the superior recovery seen in young patients, but the exact pattern of reorganisation and its impact on functional recovery are not fully understood. The general aim of this thesis was to investigate various aspects of cortical plasticity, in particular the response to median nerve injury. To this end we used two non-invasive brain imaging techniques, functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). In Paper I we investigated the concept of audio-tactile interaction in a healthy population. We found an increased overlap between cortical activation areas (fMRI) in patients trained with coupled tactile and auditory stimuli indicating modulation of cortical plasticity induced by cross-modal training. In Paper II we studied ageand time-dependent effects on cortical activity patterns in patients with median nerve injury by correlating age at the time of injury and time passed since injury to sensory function, and cortical activation. We found a time-dependent decline in the size of the cortical activation area during stimulation of both the median and the ulnar nerve (fMRI). Furthermore, there was greater ipsilateral activation in the patient group than in a control group from a previous study. However, the results were not conclusive on this point because the stimulation paradigms differed between the two studies (event-related in the present and block paradigm in the previous study). Paper III was performed using MEG in order to further study cortical plasticity in patients with median nerve injury. We found decreased N1 and P1 amplitudes during stimulation of the injured median nerve, and an increase in these amplitudes during ulnar nerve stimulation. Paper IV was designed to reveal any possible differences in lateralisation of cortical activation after median nerve injury and to see if this was influenced by the stimulus paradigm used. By means of a laterality index (LI) the extent of contra- and ipsilateral activation was calculated. LI is decreased (more ipsilateral activation) in patients with a median nerve injury compared to controls. This means that median nerve injury causes a shift of activity from the contralateral to the ipsilateral SI. The type of stimulus paradigm (event-related or block) did not affect LI. Our findings add to the evolving knowledge of the cortical plasticity following median nerve injury

Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task

Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia

Brain Cortical Mapping by Simultaneous Recording of Functional Near Infrared Spectroscopy and Electroencephalograms from the Whole Brain During Right Median Nerve Stimulation

To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5–15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity

Activity in somatosensory cortices during stroke recovery

The aim of the thesis was to examine how activity in somatosensory cortex changes during stroke recovery by analysing previously-recorded magnetoencephalographic (MEG) responses to tactile pneumatic stimulation and passive movement of the right and left index fingers. The measurements were made for 23 stroke patients with upper limb paresis at acute phase, one month and 12 months after stroke. To our knowledge, this is the first follow-up study to research somatosensory evoked responses to passive movement in several stroke patients. The activity in somatosensory cortices evoked by both tactile and passive stimuli increased significantly from the acute phase to 12 months post-stroke in both affected and unaffected hemispheres. In addition, the activity was stronger in patients than in healthy control subjects at 12 months after the stroke symptoms in both hemispheres. In healthy subjects, the SEF-response amplitudes are approximately equal in two hemispheres whereas the patients had weaker responses to tactile stimuli in the affected (AH) than the unaffected hemisphere (UH) at one month after the stroke. In contrast to tactile stimuli, no significant differences between the contralateral affected and unaffected hemispheres in the passive movement were observed. However, both tactile and passive stimuli elicited enhanced activity in the ipsilateral unaffected hemisphere with respect to the impaired hand stimulation during the whole follow-up year. In conclusion, the results confirmed that a stroke changes both proprioceptive and tactile information processing and a unilateral stroke affects both hemispheres. Moreover, the results indicate that the activity changes during one-year follow-up, which refers that neural changes occur within first three months but can continue significantly up to 12 months. Enhanced activity in the healthy hemisphere may be associated with incomplete functional recovery

The effect of water immersion on short-latency somatosensory evoked potentials in human

<p>Abstract</p> <p>Background</p> <p>Water immersion therapy is used to treat a variety of cardiovascular, respiratory, and orthopedic conditions. It can also benefit some neurological patients, although little is known about the effects of water immersion on neural activity, including somatosensory processing. To this end, we examined the effect of water immersion on short-latency somatosensory evoked potentials (SEPs) elicited by median nerve stimuli. Short-latency SEP recordings were obtained for ten healthy male volunteers at rest in or out of water at 30°C. Recordings were obtained from nine scalp electrodes according to the 10-20 system. The right median nerve at the wrist was electrically stimulated with the stimulus duration of 0.2 ms at 3 Hz. The intensity of the stimulus was fixed at approximately three times the sensory threshold.</p> <p>Results</p> <p>Water immersion significantly reduced the amplitudes of the short-latency SEP components P25 and P45 measured from electrodes over the parietal region and the P45 measured by central region.</p> <p>Conclusions</p> <p>Water immersion reduced short-latency SEP components known to originate in several cortical areas. Attenuation of short-latency SEPs suggests that water immersion influences the cortical processing of somatosensory inputs. Modulation of cortical processing may contribute to the beneficial effects of aquatic therapy.</p> <p>Trial Registration</p> <p>UMIN-CTR (UMIN000006492)</p

Effects of Hand Transplantation on Cortical Organization

Amputation induces substantial reorganization of the body part somatotopy in primary sensory cortex (S1), and these effects of deafferentation increase with time. Determining whether these changes are reversible is critical for understanding the potential to recover from deafferenting injuries. Here, we report evidence that the representation of a transplanted hand and digits can actually recapture the pre-amputation S1 hand territory in two transplant patients. With limited sensation 4 months post operation, one of the patient's (D.S.) palmar tactile stimulation evoked contralateral S1 responses that were indistinguishable in location and amplitude from those detected in healthy matched controls. The other patient (M.S.) demonstrated not only much improved sensation but also recovered ability to localize tactile stimuli 120+ months after the operation. The results described suggest that even decades after complete deafferentation, restoring afferent input to S1 leads to re-establishment of the gross hand and digits representations within their original territory. Stimulation of the deafferented cortical maps may play an important role in maintaining their viability until the afferent input is restored. Motor imagery and creation of virtual visual feedback of the absent hand with a mirror have been proposed as stimuli. We used fMRI to record neural activity while 11 unilateral hand amputees and matched controls performed aurally-paced thumb-finger sequencing movements with their intact hand (matching hand in case of controls) under visual guidance during four conditions: 1) intact hand (ME), 2) ME with motor imagery of the amputated hand, 3) ME with virtual visual feedback of the amputated hand, and 4) ME with motor imagery and the virtual visual feedback of the amputated hand. In contrast to controls, amputees showed increases in activity during all four conditions within the former functionally-defined sensorimotor hand territory. Movements of the intact hand likely increase activity in the former hand territory as a result of decreased interhemispheric inhibition. This stimulation may maintain deafferented hand representations that can recover soon after the afferent input is restored by hand transplantation