Theta-Burst Stimulation-Induced Plasticity over Primary Somatosensory Cortex Changes Somatosensory Temporal Discrimination in Healthy Humans

BACKGROUND: The somatosensory temporal discrimination threshold (STDT) measures the ability to perceive two stimuli as being sequential. Precisely how the single cerebral structures contribute in controlling the STDT is partially known and no information is available about whether STDT can be modulated by plasticity-inducing protocols. METHODOLOGY/PRINCIPAL FINDINGS: To investigate how the cortical and cerebellar areas contribute to the STDT we used transcranial magnetic stimulation and a neuronavigation system. We enrolled 18 healthy volunteers and 10 of these completed all the experimental sessions, including the control experiments. STDT was measured on the left hand before and after applying continuous theta-burst stimulation (cTBS) on the right primary somatosensory area (S1), pre-supplementary motor area (pre-SMA), right dorsolateral prefrontal cortex (DLPFC) and left cerebellar hemisphere. We then investigated whether intermittent theta-burst stimulation (iTBS) on the right S1 improved the STDT. After right S1 cTBS, STDT values increased whereas after iTBS to the same cortical site they decreased. cTBS over the DLPFC and left lateral cerebellum left the STDT statistically unchanged. cTBS over the pre-SMA also left the STDT statistically unchanged, but it increased the number of errors subjects made in distinguishing trials testing a single stimulus and those testing paired stimuli. CONCLUSIONS/SIGNIFICANCE: Our findings obtained by applying TBS to the cortical areas involved in processing sensory discrimination show that the STDT is encoded in S1, possibly depends on intrinsic S1 neural circuit properties, and can be modulated by plasticity-inducing TBS protocols delivered over S1. Our findings, giving further insight into mechanisms involved in somatosensory temporal discrimination, help interpret STDT abnormalities in movement disorders including dystonia and Parkinson's disease

Changes in somatosensory temporal discrimination thresholds (STDT) induced by continuous theta-burst stimulation (cTBS) over pre-supplementary motor area (pre-SMA) in healthy subjects.

<p>Each point represents the mean; bars represent standard error. Upper panel: X axis: time: T0 (before cTBS), T1 (5 minutes after cTBS) and T2 (15 minutes after cTBS). Y axis: STDT expressed in millisecond<b>s</b>. Lower panel: cTBS-induced changes in the number of errors subjects made during the experimental procedures.</p

Changes in somatosensory temporal discrimination thresholds (STDT) induced by continuous theta-burst stimulation (cTBS) and intermittent theta-burst stimulation (iTBS) over primary somatosensory cortex (S1) in healthy subjects.

<p>Each point represents the mean; bars represent standard error. X axis: time: T0 (before cTBS/iTBS), T1 (5 minutes after cTBS/iTBS) and T2 (15 minutes after cTBS/iTBS). Y axis: STDT expressed in millisecond<b>s</b>. Asterisks indicate statistical significance.</p

Changes in somatosensory temporal discrimination thresholds (STDT) induced by continuous theta-burst stimulation (cTBS) over left lateral cerebellum in healthy subjects.

<p>Upper panel: X axis: time: T0 (before cTBS), T1 (5 minutes after cTBS) and T2 (15 minutes after cTBS). Y axis: STDT expressed in millisecond<b>s</b>. Each point represents the mean; bars represent standard error. Lower panel: cTBS-induced changes in motor evoked potential (MEP) size evoked in the right primary motor area (M1). X axis time T0 (before cTBS), T1 (10 minutes after cTBS). Y axis: MEP amplitude expressed as percentage of the MEP at T0.</p

Pathophysiology of somatosensory abnormalities in Parkinson disease.

Changes in sensory function that have been described in patients with Parkinson disease (PD) can be either 'pure' disorders of conscious perception such as elevations in sensory threshold, or disorders of sensorimotor integration, in which the interaction between sensory input and motor output is altered. In this article, we review the extensive evidence for disrupted tactile, nociceptive, thermal and proprioceptive sensations in PD, as well as the influences exerted on these sensations by dopaminergic therapy and deep brain stimulation. We argue that abnormal spatial and temporal processing of sensory information produces incorrect signals for the preparation and execution of voluntary movement. Sensory deficits are likely to be a consequence of the dopaminergic denervation of the basal ganglia that is the hallmark of PD. A possible mechanism to account for somatosensory deficits is one in which disease-related dopaminergic denervation leads to a loss of response specificity, resulting in transmission of noisier and less-differentiated information to cortical regions. Changes in pain perception might have a different explanation, possibly involving disease-related effects outside the basal ganglia, including involvement of peripheral pain receptors, as well as structures such as the periaqueductal grey matter and non-dopaminergic neurotransmitter systems