Dimensionality of semantic meaning and evoked potential fields

Induction of long-lasting potentiation in the secondary somatosensory cortex by thalamic stimulation requires cortico-cortical pathways from the primary somatosensory cortex.

The ability to perceive and withdraw rapidly from noxious environmental stimuli is crucial for survival. When heat stimuli are applied to primate hairy skin, first pain sensation is mediated by type-II A-fibre nociceptors (II-AMHs). In contrast, the reported absence of first pain and II-AMH microneurographical responses when heat stimuli are applied to the hand palm has led to the notion that II-AMHs are lacking in this primate glabrous skin. The aim of this study was to assess the effect of hairy and glabrous skin stimulation on neural transmission of nociceptive inputs elicited by different kinds of thermal heating. We recorded psychophysical and EEG brain responses to radiant (laser-evoked potentials, LEPs) and contact heat stimuli (contact heat-evoked potentials, CHEPs) delivered to the dorsum and the palm of the hand in normal volunteers. Brain responses were analysed at a single-trial level, using an automated approach based on multiple linear regression. Laser stimulation of hairy and glabrous skin at the same energy elicited remarkably similar psychophysical ratings and LEPs. This finding provides strong evidence that first pain to heat does exist in glabrous skin, and suggests that similar nociceptive afferents, with the physiological properties of II-AMHs, mediate first pain to heat stimulation of glabrous and hairy skin in humans. In contrast, when contact heat stimuli were employed, a significantly higher nominal temperature had to be applied to glabrous skin in order to achieve psychophysical ratings similar to those obtained following hairy skin stimulation, and CHEPs following glabrous skin stimulation had significantly longer latencies (N2 wave, +25%; P2 wave, +24%) and smaller amplitudes (N2 wave, -40%; P2 wave, -44%) than CHEPs following hairy skin stimulation. Irrespective of the stimulated territory, CHEPs always had significantly longer latencies (hairy skin N2 wave, +75%; P2 wave, +56%) and smaller amplitudes (hairy skin N2 wave, -42%; P2 wave, -19%) than LEPs. These findings are consistent with the thickness-dependent delay and attenuation of the temperature waveform at nociceptor depth when conductive heating is applied, and suggest that the previously reported lack of first pain and microneurographical II-AMH responses following glabrous skin stimulation could have been the result of a search bias consequent to the use of long-wavelength radiant heating (i.e. CO(2) laser) as stimulation procedure.

Laser-evoked brain potentials in patients with dissociated loss of pain and temperature sensibility

Somatosensory-evoked potentials are influenced differently by isometric muscle contraction of stimulated and non-stimulated hand in humans

Loss of inhibition in ipsilateral somatosensory areas following altered afferent nerve signaling from the hand

One of the widely used paradigms for the brain-computer interface (BCI), the P300 BCI, was proposed by Farwell and Donchin as a variation of the classical visual oddball paradigm, known to elicit the P300 component of the brain event-related potentials (ERP). We show that this paradigm, unlike the standard oddball paradigm, elicit not only the P300 wave but also a strong posterior N1 wave. Moreover, we present evidence that the sensitivity of this ERP component to targets cannot be explained by the variations of the perceived stimuli energy. This evidence is based on comparing the ERP obtained for usual P300 BCI stimuli and for the "inverted" stimulation scheme with low stimulus related variations of light energy (gray letters on the light gray background, "highlighted" by very light darkening). Despite the dramatic difference between the stimuli in the standard and "inverted" schemes, no difference between N1 amplitudes were found, supporting the view that this component's sensitivity to targets cannot be based simply on "foveating" the target, but may be related to spatial attention mechanisms, which involvement is natural for the P300 BCI. Efforts to optimize the P300 BCI should address better use of both P300 and N1 waves.

Differential nociceptive deficits in patients with borderline personality disorder and self-injurious behavior: laser-evoked potentials, spatial discrimination of noxious stimuli, and pain ratings

Neurobiological models of emotion focus traditionally on limbic/paralimbic regions as neural substrates of emotion generation, and insular cortex (in conjunction with isocortical anterior cingulate cortex, ACC) as the neural substrate of feelings. An emerging view, however, highlights the importance of isocortical regions beyond insula and ACC for the subjective feeling of emotions. We used music to evoke feelings of joy and fear, and multivariate pattern analysis (MVPA) to decode representations of feeling states in functional magnetic resonance (fMRI) data of n = 24 participants. Most of the brain regions providing information about feeling representations were neocortical regions. These included, in addition to granular insula and cingulate cortex, primary and secondary somatosensory cortex, premotor cortex, frontal operculum, and auditory cortex. The multivoxel activity patterns corresponding to feeling representations emerged within a few seconds, gained in strength with increasing stimulus duration, and replicated results of a hypothesis-generating decoding analysis from an independent experiment. Our results indicate that several neocortical regions (including insula, cingulate, somatosensory and premotor cortices) are important for the generation and modulation of feeling states. We propose that secondary somatosensory cortex, which covers the parietal operculum and encroaches on the posterior insula, is of particular importance for the encoding of emotion percepts, i.e., preverbal representations of subjective feeling.

Inferring resting-state connectivity patterns from functional magnetic resonance imaging (fMRI) data is a challenging task for any analytical technique. In this paper, we review a probabilistic independent component analysis (PICA) approach, optimized for the analysis of fMRI data, and discuss the role which this exploratory technique can take in scientific investigations into the structure of these effects. We apply PICA to fMRI data acquired at rest, in order to characterize the spatio-temporal structure of such data, and demonstrate that this is an effective and robust tool for the identification of low-frequency resting-state patterns from data acquired at various different spatial and temporal resolutions. We show that these networks exhibit high spatial consistency across subjects and closely resemble discrete cortical functional networks such as visual cortical areas or sensory-motor cortex.

The secondary somatosensory cortex (SII) and posterior insular cortex (pIC) are recognized for processing touch and movement information during hand manipulation in humans and non-human primates. However, their involvement in three-dimensional (3D) object manipulation remains unclear. To investigate neural activity related to hand manipulation in the SII/pIC, we trained two macaque monkeys to grasp three objects (a cone, a plate, and a ring) and engage in visual fixation on the object. Our results revealed that 19.4% (n = 50/257) of the task-related neurons in SII/pIC were active during hand manipulations, but did not respond to passive somatosensory stimuli. Among these neurons, 44% fired before hand-object contact (reaching to grasping neurons), 30% maintained tonic activity after contact (holding neurons), and 26% showed continuous discharge before and after contact (non-selective neurons). Object grasping-selectivity varied and was weak among these neurons, with only 24% responding to fixation of a 3D object (visuo-motor neurons). Even neurons unresponsive to passive visual stimuli showed responses to set-related activity before the onset of movement (42%, n = 21/50). Our findings suggest that somatomotor integration within SII/pIC is probably integral to all prehension sequences, including reaching, grasping, and object manipulation movements. Moreover, the existence of a set-related activity within SII/pIC may play a role in directing somatomotor attention during object prehension-manipulation in the absence of vision. Overall, SII/pIC may play a role as a somatomotor hub within the lateral grasping network that supports the generation of intentional hand actions based on haptic information.

The neuronal mechanisms that contribute to tactile perception were studied using single-unit recordings from the cutaneous hand representation of primate primary (S1) and secondary (S2) somatosensory cortex. This study followed up on our recent observation that S1 and S2 neurons developed a sustained change in discharge during the instruction period of a directed-attention task. We determined the extent to which the symbolic light cues, which signaled the modality (tactile, visual) to attend and discriminate, elicited changes in discharge rate during the instructed delay (ID) period of the attention task and the functional importance of this discharge. ID responses, consisting of a sustained increase or decrease in discharge during the 2-s instruction period, were present in about 40% of the neurons in S1 and S2. ID responses in both cortical regions were very similar in most respects (frequency, sign, latency, amplitude), suggesting a common source. A major difference, however, was related to attentional modulation during the ID period: attentional influences were almost entirely restricted to S2 and these effects were always superimposed on the ID response (additive effect). These findings suggest that the underlying mechanisms for ID discharge and attention are independent. ID discharge significantly modified the initial response to the standard stimuli (competing texture and visual stimuli), usually enhancing responsiveness. We also showed that tactile detection in humans is enhanced during the ID period. Together, the results suggest that ID discharge represents a priming mechanism that prepares cortical areas to receive and process sensory inputs.

We investigated the long-lasting effects of mechanical vibratory stimulation of the skin on the excitability of feline cortical neurons in the forelimb areas of the primary (SI) and secondary (SII) somatosensory cortices. Conditioning mechanical stimuli were 300 bursts of 10 pulses at 200 Hz delivered with a 10-s interburst interval from a mechanical stimulator. Test field potentials and unit discharges were evoked by electrical stimulation to the ventral posterolateral thalamic nucleus (VPL) or by single mechanical stimuli applied to the skin. In SII, the mechanical burst stimulation to the skin increased the amplitudes of field potentials and the frequency of unit discharges elicited by single mechanical stimuli applied to the skin. The vibratory conditioning stimulus also produced a similar potentiation of the VPL-evoked field potentials (126-139% increase in amplitude, P < 0.05) with an associated increase in firing rates of extracellularly recorded neuronal activity (117%, P < 0.001). These potentiations persisted through the entire experimental period of 120 min. The translaminar current source density analysis calculated from the VPL-evoked field potentials increased to 127% of the control value (P < 0.01). In contrast, in SI we observed no significant changes in the field potential amplitudes or in the currents generated in superficial layers (91-117%). Taken together with the previous finding that tetanic electrical stimulation of VPL induces long-lasting potentiation of the VPL-evoked cortical responses in SII but not of those in SI, the present results suggest that SII has a large capacity for the rapid functional plasticity involved in the learning that occurs during repeated tactile experiences.

Neuronal oscillations in the gamma frequency range have been reported in many cortical areas, but the role they play in cortical processing remains unclear. We tested a recently proposed hypothesis that the intensity of sensory input is coded in the timing of action potentials relative to the phase of gamma oscillations, thus converting amplitude information to a temporal code. We recorded spikes and local field potential (LFP) from secondary somatosensory (SII) cortex in awake monkeys while presenting a vibratory stimulus at different amplitudes. We developed a novel technique based on matching pursuit to study the interaction between the highly transient gamma oscillations and spikes with high time-frequency resolution. We found that spikes were weakly coupled to LFP oscillations in the gamma frequency range (40−80 Hz), and strongly coupled to oscillations in higher gamma frequencies. However, the phase relationship of neither low-gamma nor high-gamma oscillations changed with stimulus intensity, even with a ten-fold increase. We conclude that, in SII, gamma oscillations are synchronized with spikes, but their phase does not vary with stimulus intensity. Furthermore, high-gamma oscillations (>60 Hz) appear to be closely linked to the occurrence of action potentials, suggesting that LFP high-gamma power could be a sensitive index of the population firing rate near the microelectrode.

The primary somatosensory cortex (S1) is important for the control of movement as it encodes sensory input from the body periphery and external environment during ongoing movement. Mouse S1 consists of several distinct sensorimotor subnetworks that receive topographically organized corticocortical inputs from distant sensorimotor areas, including the secondary somatosensory cortex (S2) and primary motor cortex (M1). The role of the vibrissal S1 area and associated cortical connections during active sensing is well documented, but whether (and if so, how) non-whisker S1 areas are involved in movement control remains relatively unexplored. Here, we demonstrate that unilateral silencing of the non-whisker S1 area in both male and female mice disrupts hind paw movement during locomotion on a rotarod and a runway. S2 and M1 provide major long-range inputs to this S1 area. Silencing S2→non-whisker S1 projections alters the hind paw orientation during locomotion, whereas manipulation of the M1 projection has little effect. Using patch-clamp recordings in brain slices from male and female mice, we show that S2 projection preferentially innervates inhibitory interneuron subtypes. We conclude that interneuron-mediated S2-S1 corticocortical interactions are critical for efficient locomotion.SIGNIFICANCE STATEMENT Somatosensory cortex participates in controlling rhythmic movements, such as whisking and walking, but the neural circuitry underlying movement control by somatosensory cortex remains relatively unexplored. We uncover a corticocortical circuit in primary somatosensory cortex that regulates paw orientation during locomotion in mice. We identify neuronal elements that comprise these cortical pathways using pharmacology, behavioral assays, and circuit-mapping methods.

Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.