Absence of stimulus-driven synchronization effects on sensory perception in autism: Evidence for local underconnectivity?

<p>Abstract</p> <p>Background</p> <p>A number of neurophysiological characteristics demonstrated in autism share the common theme of under-connectivity in the cerebral cortex. One of the prominent theories of the cause of the dysfunctional connectivity in autism is based on distinct anatomical structures that differ between the autistic and the neurotypical cortex. The functional minicolumn has been identified as occupying a much smaller space in the cortex of people with autism as compared to neurotypical controls, and this aberration in architecture has been proposed to lead to under-connectivity at the local or within-macrocolumn level, which in turn leads to dysfunctional connectivity globally across cortical areas in persons with autism. Numerous reports have indicated reduced synchronization of activity on a large scale in the brains of people with autism. We hypothesized that if the larger-scale aberrant dynamics in autism were due – at least in part – to a widespread propagation of the errors introduced at the level of local connectivity between minicolumns, then aberrations in local functional connectivity should also be detectable in autism.</p> <p>Methods</p> <p>Recently, we reported a method for measuring the perceptual changes that are impacted by the presence of synchronized conditioning stimuli on the skin. In this study, the temporal order judgment (TOJ) and temporal discriminative threshold (TDT) of 10 adult autism subjects were assessed both in the absence and presence of synchronized conditioning vibrotactile stimuli.</p> <p>Results</p> <p>Our previous report demonstrated that delivering simultaneous and synchronized vibrotactile stimuli to near-adjacent skin sites decreases a subject's ability to determine temporal order by 3 to 4-fold. However, results presented in this report show that subjects with autism do not demonstrate such decreased capacity in temporal order judgment (TOJ) in the presence of synchronized conditioning stimuli, although these same subjects do have TOJ thresholds well above that of controls.</p> <p>Conclusion</p> <p>It is speculated that the differences in sensory perceptual capacities in the presence of synchronized conditioning stimuli in autism are due to local under-connectivity in cortex at the minicolumnar organizational level, and that the above-average TOJ thresholds in autism could be attributed to structural differences that have been observed in the frontostrial system of this population.</p

Effects of the N-methyl-D-Aspartate receptor antagonist dextromethorphan on vibrotactile adaptation

<p>Abstract</p> <p>Background</p> <p>Previous reports have demonstrated that short durations of vibrotactile stimuli (less than or equal to 2 sec) effectively and consistently modify both the perceptual response in humans as well as the neurophysiological response in somatosensory cortex. The change in cortical response with adaptation has been well established by a number of studies, and other reports have extended those findings in determining that both GABA- and NMDAR-mediated neurotransmission play a significant role in the dynamic response of somatosensory cortical neurons. In this study, we evaluated the impact that dextromethorphan (DXM), an NMDAR antagonist, had on two distinct vibrotactile adaptation tasks.</p> <p>Results</p> <p>All subjects, both those that ingested 60 mg DXM and those that ingested placebo, were evaluated for their amplitude discriminative capacity between two simultaneously delivered vibrotactile stimuli both with and without 3 conditions of pre-exposure to adapting stimulation. The results demonstrated that the perceptual metrics of subjects who ingested 60 mg DXM were significantly altered from that of controls when the amplitude discrimination task followed one of the conditions of adapting stimulation. Without the condition of pre-exposure to an adapting stimulus (or stimuli), there was little difference between the observations obtained from the subjects that ingested DXM and controls. Peak impact on subject response occurred at 60 min post-ingestion, whereas the scores of controls who ingested placebo were not impacted.</p> <p>Conclusion</p> <p>The results – that DXM blocks vibrotactile adaptation – is consistent with the suggestion that NMDAR-mediated neurotransmission plays a significant role in the perceptual adaptive response. This finding is also consistent with neurophysiological findings that report observations of the effects of NMDAR block on the SI cortical response to repetitive vibrotactile stimulation.</p

Effects of stimulus-driven synchronization on sensory perception

<p>Abstract</p> <p>Background</p> <p>A subject's ability to differentiate the loci of two points on the skin depends on the stimulus-evoked pericolumnar lateral inhibitory interactions which increase the spatial contrast between regions of SI cortex that are activated by stimulus-evoked afferent drive. Nevertheless, there is very little known about the impact that neuronal interactions – such as those evoked by mechanical skin stimuli that project to and coordinate synchronized activity in adjacent and/or near-adjacent cortical columns – could have on sensory information processing.</p> <p>Methods</p> <p>The temporal order judgment (TOJ) and temporal discriminative threshold (TDT) of 20 healthy adult subjects were assessed both in the absence and presence of concurrent conditions of tactile stimulation. These measures were obtained across a number of paired sites – two unilateral and one bilateral – and several conditions of adapting stimuli were delivered both prior to and concurrently with the TOJ and TDT tasks. The pairs of conditioning stimuli were synchronized and periodic, synchronized and non-periodic, or asynchronous and non-periodic.</p> <p>Results</p> <p>In the absence of any additional stimuli, TOJ and TDT results obtained from the study were comparable across a number of pairs of stimulus sites – unilateral as well as bilateral. In the presence of a 25 Hz conditioning sinusoidal stimulus which was delivered both before, concurrently and after the TOJ task, there was a significant change in the TOJ measured when the two stimuli were located unilaterally on digits 2 and 3. However, in the presence of the same 25 Hz conditioning stimulus, the TOJ obtained when the two stimuli were delivered bilaterally was not impacted. TDT measures were not impacted to the same degree by the concurrent stimuli that were delivered to the unilateral or bilateral stimulus sites. This led to the speculation that the impact that the conditioning stimuli – which were sinusoidal, periodic and synchronous – had on TOJ measures was due to the synchronization of adjacent cortical ensembles in somatosensory cortex, and that the synchronization of these cortical ensembles could have been responsible for the degradation in temporal order judgment. In order to more directly test this hypothesis, the synchronized 25 Hz conditioning stimuli that were delivered during the initial TOJ test were replaced with <it>asynchronous </it>non-periodic 25 Hz conditioning stimuli, and these asynchronous conditioning stimuli did not impact the TOJ measures.</p> <p>Conclusion</p> <p>The results give support to the theory that synchronization of cortical ensembles in SI could significantly impact the topography of temporal perception, and these findings are speculated to be linked mechanistically to previously reported co-activation plasticity studies. Additionally, the impact that such synchronizing conditioning stimuli have on TOJ – which can be measured relatively quickly – could provide an effective means to assess the functional connectivity of neurologically compromised subject populations.</p

Response of SI cortex to ipsilateral, contralateral and bilateral flutter stimulation in the cat

BACKGROUND: While SII cortex is considered to be the first cortical stage of the pathway that integrates tactile information arising from both sides of the body, SI cortex is generally not considered as a region in which neuronal response is modulated by simultaneous stimulation of bilateral (and mirror-image) skin sites. RESULTS: Optical intrinsic signal imaging was used to evaluate the response of SI and SII in the same hemisphere to 25 Hz sinusoidal vertical skin displacement stimulation ("skin flutter") applied contralaterally, ipsilaterally, and bilaterally (simultaneously) to the central pads of the forepaws. A localized increase in absorbance in both SI and SII occurred in response to both contralateral and bilateral flutter stimulation. Ipsilateral flutter stimulation evoked a localized increase in absorbance in SII, but little or no change in SI absorbance. In the forepaw representational region of SI, however, bilateral stimulation of the central pads evoked a response substantially smaller (approximately 30–35% smaller) than the response to flutter stimulation of the contralateral central pad. CONCLUSION: The finding that the response of SI cortex to bilateral central pad flutter stimulation is substantially smaller than the response evoked by a contralateral flutter stimulus, together with the recently published observation that a region located posteriorly in SII responds with a substantially larger response to a bilateral flutter stimulus than the response evoked from the contralateral central pad, lead us to propose that the SI activity evoked by contralateral skin stimulation is suppressed/inhibited (via corticocortical connections between SII and SI in the same hemisphere) by the activity a simultaneous ipsilateral skin stimulus evokes in posterior SII

A quantitative method for determining spatial discriminative capacity

<p>Abstract</p> <p>Background</p> <p>The traditional two-point discrimination (TPD) test, a widely used tactile spatial acuity measure, has been criticized as being imprecise because it is based on subjective criteria and involves a number of non-spatial cues. The results of a recent study showed that as two stimuli were delivered simultaneously, vibrotactile amplitude discrimination became worse when the two stimuli were positioned relatively close together and was significantly degraded when the probes were within a subject's two-point limen. The impairment of amplitude discrimination with decreasing inter-probe distance suggested that the metric of amplitude discrimination could possibly provide a means of objective and quantitative measurement of spatial discrimination capacity.</p> <p>Methods</p> <p>A two alternative forced-choice (2AFC) tracking procedure was used to assess a subject's ability to discriminate the amplitude difference between two stimuli positioned at near-adjacent skin sites. Two 25 Hz flutter stimuli, identical except for a constant difference in amplitude, were delivered simultaneously to the hand dorsum. The stimuli were initially spaced 30 mm apart, and the inter-stimulus distance was modified on a trial-by-trial basis based on the subject's performance of discriminating the stimulus with higher intensity. The experiment was repeated via sequential, rather than simultaneous, delivery of the same vibrotactile stimuli.</p> <p>Results</p> <p>Results obtained from this study showed that the performance of the amplitude discrimination task was significantly degraded when the stimuli were delivered simultaneously and were near a subject's two-point limen. In contrast, subjects were able to correctly discriminate between the amplitudes of the two stimuli when they were sequentially delivered at all inter-probe distances (including those within the two-point limen), and improved when an adapting stimulus was delivered prior to simultaneously delivered stimuli.</p> <p>Conclusion</p> <p>Subjects' capacity to discriminate the amplitude difference between two vibrotactile stimulations was degraded as the inter-stimulus distance approached the limit of their two-point spatial discriminative capacity. This degradation of spatial discriminative capacity lessened when an adapting stimulus was used. Performance of the task, as well as improvement on the task with adaptation, would most likely be impaired if the cortical information processing capacity of a subject or subject population were systemically altered, and thus, the methods described could be effective measures for use in clinical or clinical research applications.</p

Stimulus-dependent spatial patterns of response in SI cortex

BACKGROUND: Recently we reported that vibrotactile flutter stimulation of a skin locus at different amplitudes evokes an optical response confined to the same local region of the primary somatosensory cortex (SI), where its overall magnitude varies proportionally to the flutter amplitude. In this report, we characterize the impact of the flutter amplitude on the spatial patterns of activity evoked within the responding SI region. RESULTS: In order to characterize the spatial pattern of activity within the responding SI region, images of the flutter-evoked SI optical response were segmented and analyzed with spatial frequency analysis. The analysis revealed that: (1) dominant spatial frequencies in the optical intrinsic signal emerge within the responding SI region within 3–5 sec of stimulus onset; (2) the stimulus-evoked activity is spatially organized in a form of several roughly parallel, anterior-posteriorly extended waves, spaced 0.4–0.5 mm apart; (3) the waves themselves exhibit spatial periodicities along their long axis; and (4) depending on the flutter stimulus amplitude, these periodicities can range from fine 0.15 mm "ripples" at 50 μm amplitude to well-developed 0.5 mm fluctuations at the amplitude of 400 μm. CONCLUSION: The observed spatiointensive fractionation on a sub-macrocolumnar scale of the SI response to skin stimulation might be the product of local competitive interactions within the stimulus-activated SI region and may be a feature that could yield novel insights into the functional interactions that take place in SI cortex

Response of SII cortex to ipsilateral, contralateral and bilateral flutter stimulation in the cat

BACKGROUND: A distinctive property of SII is that it is the first cortical stage of the somatosensory projection pathway that integrates information arising from both sides of the body. However, there is very little known about how inputs across the body mid-line are processed within SII. RESULTS: Optical intrinsic signal imaging was used to evaluate the response of primary somatosensory cortex (SI and SII in the same hemisphere) to 25 Hz sinusoidal vertical skin displacement stimulation ("skin flutter") applied contralaterally, ipsilaterally, and bilaterally to the central pads of the forepaws. A localized increase in absorbance in both SI and SII was evoked by both contralateral and bilateral flutter stimulation. Ipsilateral flutter stimulation evoked a localized increase in absorbance in SII, but not in SI. The SII region that responded with an increase in absorbance to ipsilateral stimulation was posterior to the region in which absorbance increased maximally in response to stimulation of the contralateral central pad. Additionally, in the posterior SII region that responded maximally to ipsilateral stimulation of the central pad, bilateral central pad stimulation approximated a linear summation of the SII responses to independent stimulation of the contralateral and ipsilateral central pads. Conversely, in anterior SII (the region that responded maximally to contralateral stimulation), bilateral stimulation was consistently less than the response evoked from the contralateral central pad. CONCLUSIONS: The results indicate that two regions located at neighboring, but distinctly different A-P levels of the anterior ectosylvian gyrus process input from opposite sides of the body midline in very different ways. The results suggest that the SII cortex, in the cat, can be subdivided into at least two functionally distinct regions and that these functionally distinct regions demonstrate a laterality preference within SII

Somatosensory Information Processing in the Aging Population

While it is well known that skin physiology – and consequently sensitivity to peripheral stimuli – degrades with age, what is less appreciated is that centrally mediated mechanisms allow for maintenance of the same degree of functionality in processing these peripheral inputs and interacting with the external environment. In order to demonstrate this concept, we obtained observations of processing speed, sensitivity (thresholds), discriminative capacity, and adaptation metrics on subjects ranging in age from 18 to 70. The results indicate that although reaction speed and sensory thresholds change with age, discriminative capacity, and adaptation metrics do not. The significance of these findings is that similar metrics of adaptation have been demonstrated to change significantly when the central nervous system (CNS) is compromised. Such compromise has been demonstrated in subject populations with autism, chronic pain, acute NMDA receptor block, concussion, and with tactile–thermal interactions. If the metric of adaptation parallels cortical plasticity, the results of the current study suggest that the CNS in the aging population is still capable of plastic changes, and this cortical plasticity could be the mechanism that compensates for the degradations that are known to naturally occur with age. Thus, these quantitative measures – since they can be obtained efficiently and objectively, and appear to deviate from normative values significantly with systemic cortical alterations – could be useful indicators of cerebral cortical health