Autism is a pervasive developmental disorder that affects many aspects of the central nervous system, including sensory and motor deficits. For example, a number of autism studies have described Parkinson-like motor characteristics and/or postural control problems which could be attributed to deficits of the basal ganglia portion of the frontostriatal system [1
]. These deficits in sensorimotor control could be derived, in part, from the role that the frontostriatal system plays in an individual's timing perception as well as the coordination that is required between cortical regions during sensorimotor tasks. One relatively simple measure that can be used for the evaluation of a subject's timing perception is ATemporal Order Judgment (TOJ). TOJ is a measure obtained from determining the minimal inter-stimulus interval necessary for a subject to detect the temporal order of two sequentially delivered peripheral stimuli. This metric of timing perception has been shown to be sensitive to lesions to the supplementary motor area (SMA), posterior parietal cortex, and basal ganglia [3
]. Additionally, these cortical areas have been implicated from significantly elevated TOJ thresholds (worse performance) in subjects with dyslexia [5
], dystonia [6
], and Parkinson's Disease [9
]. One goal of our study was to determine if timing perception in subjects with autism would be elevated in a similar fashion.
Although the sensory aspect of an individual's timing perception could play a distinct role in sensorimotor coordination, the lack of larger scale across-cortex integration and coordination of activity across multiple cortical regions has been demonstrated as being characteristic of autism [2
]. Recently, the role of synchronization (or lack of synchronization) in autism has gained a certain degree of prominent attention. Uhlhaas and Singer [13
] recently reviewed the experimental evidence that suggests that functional connectivity is reduced in autism, primarily based on fMRI studies [10
] that examine the coordinated activity between different areas of the cerebral cortex. Uhlhaas and Singer [13
] argued that these data predict that measures of neural synchrony in subjects with autism should be reduced, yet they also pointed out that there are only a small number of studies that actually address such comparisons of synchronization between neurotypical adults and individuals with autism (e.g., [17
]). From another perspective, there is a large body of evidence that the cerebral cortex of subjects with autism is significantly modified at the minicolumnar level [19
]. Casanova and colleagues suggest that this aberrant minicolumnar structure results in the disruption of the inhibitory architecture [20
] that is required for normal function in local neural circuitry. They suggest that disruption of functional connectivity at the local minicolumnar level could be responsible for, or strongly correlated with, the dysfunctional connectivity that has been observed across large scale cortical areas, as described in the neural synchrony studies noted above. In this study, we sought to obtain measures addressing the impact that coordinated somatosensory activity in a local cortical region has on subjects with autism.
We recently investigated the impact that stimulus-driven neuronal interactions, evoked by vibrotactile stimuli at dual skin sites which project to adjacent and near-adjacent cortical ensembles, could have on TOJ [21
]. In that study, it was reported that delivering weak intensity (low amplitude) but synchronized and periodic vibrotactile stimuli unilaterally to two adjacent digit tips (D2 and D3) significantly and robustly (3–4 fold) degraded a subject's TOJ performance. However, delivery of the same stimulus conditions to bilateral skin sites showed that there was little or no impairment in TOJ performance. One of the conclusions that was drawn from that study was that the stimulus-driven effect of the synchronized conditioning stimuli coordinated the activity of near-adjacent cortical ensembles (such as those representing two fingers used in normal everyday tasks) and consequently, made it more difficult to distinguish one cortical locus from the other as the two stimulus sites were effectively perceptually bound by the stimulus-driven synchronization.
The above-described method that we recently reported involves "forcing" adjacent cortical regions to become synchronized (via stimulus-drive), and then measuring the impact that the cortical-cortical interactions generated by such synchronized activity has on sensory percepts known to be modulated by activity in those same cortical regions. In other words, if the activity in the cortical regions that represent D2 and D3 in somatosensory cortex become synchronized and/or coordinated, it should be more difficult to perform a TOJ task – assuming normal functional connectivity (as was observed in our previous report). If neurologically compromised individuals – such as those with autism – have distinct systemic cortical deficits, and that these deficits extend to local neuronal circuitry connectivity, then the abnormal functional connectivity between adjacent and/or near adjacent cortical ensembles would decrease the effect that stimulus-driven synchronization has on the TOJ task (i.e., performance on the task would not degrade). Therefore, one goal of this study was to determine if synchronized conditioning stimuli would have an impact on TOJ performance in subjects with autism.