Vinay Tannan

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

BackgroundA 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.MethodsRecently, 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.ResultsOur previous report demonstrated that delivering simultaneous and synchronized vibrotactile stimuli to near-adjacent skin sites decreases a subjects 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.ConclusionIt 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.

Amplitude-dependency of response of SI cortex to flutter stimulation

BackgroundIt is established that increasing the amplitude of a flutter stimulus increases its perceived intensity. Although many studies have examined this phenomenon with regard to the responding afferent population, the way in which the intensity of a stimulus is coded in primary somatosensory cortex (SI) remains unclear.ResultsOptical intrinsic signal (OIS) imaging was used to study the evoked responses in SI of anesthetized squirrel monkeys by 25 Hz sinusoidal vertical skin displacement stimulation. Stimuli were 10 sec duration with a 50 sec inter-stimulus interval. Stimulus amplitude ranged from 50 to 400 microns and different amplitudes were interleaved. Control levels of activity were measured in the absence of stimulation, and used to compare with activation levels evoked by the different stimulus amplitudes. Stimulation of a discrete skin site on the forelimb evoked a prominent increase in absorbance within the forelimb representational region in cytoarchitectonic areas 3b and 1 of the contralateral hemisphere. An increase in stimulus amplitude led to a proportional increase in the magnitude of the absorbance increase in this region of areas 3b and 1 while surrounding cortex underwent a decrease in absorbance. Correlation maps revealed that as stimulus amplitude is increased, the spatial extent of the activated region in SI remains relatively constant, and the activity within this region increases progressively. Additionally, as stimulus amplitude is increased to suprathreshold levels, activity in the surround of the activated SI territory decreases, suggesting an increase in inhibition of neuronal activity within these regions.ConclusionIncreasing the amplitude of a flutter stimulus leads to a proportional increase in absorbance within the forelimb representational region of SI. This most likely reflects an increase in the firing rate of neurons in this region of SI. The relatively constant spatial extent of this stimulus-evoked increase in absorbance suggests that an increase in the amplitude of a 25 Hz skin stimulus does not evoke a larger area of SI neuronal activation due to an amplitude-dependent lateral inhibitory effect that spatially funnels the responding SI neuronal population.

Perceptual metrics of individuals with autism provide evidence for disinhibition

Adults with autism exhibit inhibitory deficits that are often manifested in behavioral modifications, such as repetitive behaviors, and/or sensory hyper‐responsiveness. If such behaviors are the result of a generalized deficiency in inhibitory neurotransmission, then it stands to reason that deficits involving localized cortical–cortical interactions—such as in sensory discrimination tasks—could be detected and quantified. This study exemplifies a newly developed method for quantifying sensory testing metrics. Our novel sensory discrimination tests may provide (a) an effective means for biobehavioral assessment of deficits specific to autism and (b) an efficient and sensitive measure of change following treatment. The sensory discriminative capacity of ten subjects with autism and ten controls was compared both before and after short duration adapting stimuli. Specifically, vibrotactile amplitude discriminative capacity was obtained both in the presence and absence of 1 sec adapting stimuli that were delivered 1 sec prior to the comparison stimuli. Although adaptation had a pronounced effect on the amplitude discriminative capacity of the control subjects, little or no impact was observed on the sensory discriminative capacity of the subjects with autism. This lack of impact of the adapting stimuli on the responses of the subjects with autism was interpreted to be consistent with the reduced GABAergic‐mediated inhibition described in previous reports. One significant aspect of this study is that the methods could prove to be a useful and efficient way to detect specific neural deficits and monitor the efficacy of pharmacological or behavioral treatments in autism.

Effects of adaptation on the capacity to differentiate simultaneously delivered dual-site vibrotactile stimuli

The capacity of 20 healthy adult subjects for detecting differences in the amplitude of two simultaneously delivered 25 Hz vibrotactile stimuli was assessed both in the absence and presence of prior exposure to different conditions of adapting stimulation. Results obtained from this study demonstrate that increasing durations of adapting stimulation at one of the two skin sites, in the range of 0.2 to 2.0 s, lead to a systematic and progressive decrease in a subjects ability to accurately discriminate between the two different amplitudes. Delivery of adapting stimuli to both of the sites of skin stimulation prior to simultaneous delivery of the test and standard stimuli, however, leads to an improvement in amplitude discrimination performance--a finding which is consistent with prior published psychophysical studies that demonstrate improvements in discriminatory capacity with much longer durations of adaptation. Striking parallels between the results obtained in this study and those reported in a prior study of the effects of vibrotactile adaptation on the optical response of squirrel monkey contralateral SI cortex to vibrotactile stimulation [Simons, S.B., Chiu, J., Favorov, O.V., Whitsel, B.L., Tommerdahl, M., 2007. Duration-dependent response of SI to vibrotactile stimulation in squirrel monkey. J Neurophysiol. 97, 2121-9, Simons, S.B., Tannan, V., Chiu, J., Favorov, O.V., Whitsel, B.L., Tommerdahl, M., 2005. Amplitude-dependency of response of SI cortex to flutter stimulation. BMC Neurosci. 6, 43] suggest that the perceptual effects detected in this study could be attributable to adaptation-induced alterations of SI response.

Effects of stimulus-driven synchronization on sensory perception

BackgroundA subjects 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.MethodsThe 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.ResultsIn 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 asynchronous non-periodic 25 Hz conditioning stimuli, and these asynchronous conditioning stimuli did not impact the TOJ measures.ConclusionThe 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.

A portable tactile sensory diagnostic device

Current methods for applying multi-site vibratory stimuli to the skin typically involve the use of two separate vibrotactile stimulators, which can lead to difficulty with positioning of stimuli and in ensuring that stimuli are delivered perfectly in phase at the same amplitude and frequency. Previously, we reported a two-point stimulator (TPS) that was developed in order to solve the problem of delivering two-point stimuli to the skin at variable distances between the sites of stimulation. Because of the success of the TPS, we designed and fabricated a new stimulator with four significant improvements over our original device. First, the device is portable, lightweight and can be used in a variety of non-laboratory settings. Second, the device consists of two independently controlled stimulators which allow delivery of stimuli simultaneously to two distinct skin sites with different amplitude, frequency and/or phase. Third, the device automatically detects the skin surface and thus allows for much better automated control of stimulus delivery. Fourth, the device is designed for rapid manufacture and, therefore, can be made readily available to other research (non-laboratory) settings. To demonstrate the device, a modified Bekesy tracking method was used to evaluate the simultaneous amplitude discrimination capacity of 20 subjects.

A novel device for delivering two-site vibrotactile stimuli to the skin

Current methods for applying two-site vibration stimuli to the skin typically involve the use of two separate vibrotactile stimulators, which can lead to difficulty with positioning of stimuli and in ensuring that stimuli are delivered perfectly in phase at the same amplitude and frequency. This report describes the Two-Point Stimulator (TPS) that was developed in order to deliver two-point stimuli to the skin at variable distances between the sites of stimulation on a trial-by-trial basis. The apparatus attaches to a vibrotactile stimulator, modifying it from the standard single probe tip to two probe tips. Each of the two probe tips can be independently positioned to set the tip-to-tip spacing. Both points of the TPS are driven by the single vibrotactile stimulator and distances between the two sites can be varied on a trial-by-trial basis. To test the device, a modified Bekesy tracking method was developed and used for two-point limen testing under stimulus conditions of varying amplitude and frequency. Data collected were consistent with previously published reports, suggesting that one possible use of the device would be to provide a means for improved measures of spatio-tactile acuity.

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

BackgroundPrevious 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.ResultsAll 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.ConclusionThe 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.