Continuous theta-burst stimulation modulates tactile synchronization.

BACKGROUND: Temporal order judgement (TOJ) is the ability to detect the order of occurrence of two sequentially delivered stimuli. Previous research has shown that TOJ in the presence of synchronized periodic conditioning stimuli impairs TOJ performance, and this phenomenon is suggested to be mediated by GABAergic interneurons that cause perceptual binding across the two skin sites. Application of continuous theta-burst repetitive TMS (cTBS) over primary somatosensory cortex (SI) alters temporal and spatial tactile perception. The purpose of this study was to examine TOJ perception in the presence and absence of synchronized periodic conditioning stimuli before and after cTBS applied over left-hemisphere SI. A TOJ task was administered on the right index and middle finger (D2 and D3) in two separate sessions in the presence and absence of conditioning stimuli (a background low amplitude sinusoidal vibration). RESULTS: CTBS reduced the impact of the conditioning stimuli on TOJ performance for up to 18 minutes following stimulation while sham cTBS did not affect TOJ performance. In contrast, the TOJ task performed in the absence of synchronized conditioning stimulation was unaltered following cTBS. CONCLUSION: We conclude that cTBS suppresses inhibitory networks in SI that mediate perceptual binding during TOJ synchronization. CTBS offers one method to suppress cortical excitability in the cortex and potentially benefit clinical populations with altered inhibitory cortical circuits. Additionally, TOJ measures with conditioning stimuli may provide an avenue to assess sensory processing in neurologically impaired patient populations.

Theta burst repetitive transcranial magnetic stimulation attenuates somatosensory evoked potentials from the lower limb.

BACKGROUND: Continuous theta burst stimulation (cTBS) is a form of repetitive transcranial magnetic stimulation which has been shown to alter cortical excitability in the upper limb representation of primary somatosensory cortex (SI). However, it is unknown whether cTBS modulates cortical excitability within the lower limb representation in SI. The present study investigates the effects of cTBS over the SI lower limb representation on cortical somatosensory evoked potentials (SEPs) and Hoffmann reflex (H-reflex) following tibial nerve stimulation at the knee. SEPs and H-reflex were recorded before and in four time blocks up to 30 minutes following cTBS targeting the lower limb representation within SI. RESULTS: Following cTBS, the P1-N1 first cortical potential was significantly decreased at 12-16 minutes. CTBS also suppressed the P2-N2 second cortical potential for up to 30 minutes following stimulation. The H-reflex remained statistically unchanged following cTBS although there was a modest suppression observed. CONCLUSION: We conclude that cTBS decreases cortical excitability of the lower limb representation of SI as evidenced by suppressed SEP amplitude. The duration and magnitude of the cTBS after effects are similar to those observed in upper limb studies.

Imaging Striatal Microglial Activation in Patients with Parkinson's Disease.

This study investigated whether the second-generation translocator protein 18kDa (TSPO) radioligand, [18F]-FEPPA, could be used in neurodegenerative parkinsonian disorders as a biomarker for detecting neuroinflammation in the striatum. Neuroinflammation has been implicated as a potential mechanism for the progression of Parkinson's disease (PD). Positron Emission Tomography (PET) radioligand targeting for TSPO allows for the quantification of neuroinflammation in vivo. Based on genotype of the rs6791 polymorphism in the TSPO gene, 16 mixed-affinity binders (MABs) (8 PD and age-matched 8 healthy controls (HCs)), 16 high-affinity binders (HABs) (8 PD and age-matched 8 HCs) and 4 low-affinity binders (LABs) (3 PD and 1 HCs) were identified. Total distribution volume (VT) values in the striatum were derived from a two-tissue compartment model with arterial plasma as an input function. There was a significant main effect of genotype on [18F]-FEPPA VT values in the caudate nucleus (p = 0.001) and putamen (p < 0.001), but no main effect of disease or disease x genotype interaction in either ROI. In the HAB group, the percentage difference between PD and HC was 16% in both caudate nucleus and putamen; in the MAB group, it was -8% and 3%, respectively. While this PET study showed no evidence of increased striatal TSPO expression in PD patients, the current findings provide some insights on the possible interactions between rs6791 polymorphism and neuroinflammation in PD.

30 Hz theta-burst stimulation over primary somatosensory cortex modulates corticospinal output to the hand.

BACKGROUND: The primary somatosensory cortex (SI) is important for hand function and has direct connectivity with the primary motor cortex (M1). Much of our present knowledge of this connectivity and its relevance to hand function is based on animal research. In humans, less is known about the neural mechanisms by which SI influences motor circuitry that outputs to the muscles controlling the hand. OBJECTIVE: The present study investigated the influence of SI on corticospinal excitability, and inhibitory and excitatory intracortical neural circuitry within M1 before and after continuous theta-burst stimulation (cTBS). Motor-evoked potentials (MEPs), short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) were recorded from the first dorsal interosseous (RFDI) muscle of the right hand following 30 Hz cTBS over left-hemisphere SI and M1 delivered in separate sessions. RESULTS: cTBS over SI facilitated MEPs and did not alter ICF or SICI. cTBS delivered over M1 suppressed MEPs and ICF and did not alter SICI. CONCLUSIONS: These findings indicate that SI influences corticospinal output to the hand, possibly via corticocortical projections, and may be one mechanism by which somatosensory information influences hand control.

Image derived input function for [18F]-FEPPA: application to quantify translocator protein (18 kDa) in the human brain.

In [18F]-FEPPA positron emission topography (PET) imaging, automatic blood sampling system (ABSS) is currently the gold standard to obtain the blood time activity curve (TAC) required to extract the input function (IF). Here, we compare the performance of two image-based methods of IF extraction to the ABSS gold standard method for the quantification of translocator protein (TSPO) in the human brain. The IFs were obtained from a direct delineation of the internal carotid signal (CS) and a new concept of independent component analysis (ICA). PET scans were obtained from 18 healthy volunteers. The estimated total distribution volume (V(T)) by CS-IF and ICA-IF were compared to the reference V(T) obtained by ABSS-IF in the frontal and temporal cortex, cerebellum, striatum and thalamus regions. The V(T) values estimated using ICA-IF were more reliable than CS-IF for all brain regions. Specifically, the slope regression in the frontal cortex with ICA-IF was r²â€Š= 0.91 (p<0.05), and r²â€Š= 0.71 (p<0.05) using CS-IF.

Continuous theta-burst stimulation over primary somatosensory cortex modulates short-latency afferent inhibition.

OBJECTIVE: The present study investigated the effects of continuous theta-burst stimulation (cTBS) over primary somatosensory (SI) and motor (M1) cortices on motor-evoked potentials (MEPs) and short-latency afferent inhibition (SAI). METHODS: MEPs and SAI were recorded from the first dorsal interosseous (FDI) muscle of the right hand following 30Hz cTBS over left-hemisphere SI and M1 delivered to the same participants in separate sessions. Measurements were taken before and up to 60min following cTBS. RESULTS: CTBS over M1 suppressed MEPs and did not alter SAI. In contrast cTBS over SI facilitated MEPs and decreased median and digital nerve evoked SAI. CONCLUSIONS: These findings indicate that SAI amplitude is influenced by cTBS over SI but not M1, suggesting an important role for SI in the modulation of this circuit. These data provide further evidence that cTBS over SI versus M1 has opposite effects on corticospinal excitability. SIGNIFICANCE: To date, plasticity-inducing TMS protocols delivered over M1 have failed to modulate SAI, and the present research continues to support these findings. However, in young adults, cTBS over SI acts to reduce SAI and simultaneously increase corticospinal excitability. Future studies may investigate the potential to modulate SAI via targeting neural activity within SI.

Modulation of short-latency afferent inhibition depends on digit and task-relevance.

Short-latency afferent inhibition (SAI) occurs when a single transcranial magnetic stimulation (TMS) pulse delivered over the primary motor cortex is preceded by peripheral electrical nerve stimulation at a short inter-stimulus interval (∼ 20-28 ms). SAI has been extensively examined at rest, but few studies have examined how this circuit functions in the context of performing a motor task and if this circuit may contribute to surround inhibition. The present study investigated SAI in a muscle involved versus uninvolved in a motor task and specifically during three pre-movement phases; two movement preparation phases between a "warning" and "go" cue and one movement initiation phase between a "go" cue and EMG onset. SAI was tested in the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles in twelve individuals. In a second experiment, the origin of SAI modulation was investigated by measuring H-reflex amplitudes from FDI and ADM during the motor task. The data indicate that changes in SAI occurred predominantly in the movement initiation phase during which SAI modulation depended on the specific digit involved. Specifically, the greatest reduction in SAI occurred when FDI was involved in the task. In contrast, these effects were not present in ADM. Changes in SAI were primarily mediated via supraspinal mechanisms during movement preparation, while both supraspinal and spinal mechanisms contributed to SAI reduction during movement initiation.

Continuous theta-burst stimulation over the primary somatosensory cortex modulates interhemispheric inhibition.

One mechanism thought to mediate hand and upper limb control across motor cortices is called interhemispheric inhibition (IHI). Somatosensory cortices are important in the motor control of the hand, although the neural mechanisms by which somatic loci act are not fully understood. In the present study, we study the possibility that the primary somatosensory cortex (SI) influences IHI as one mechanism to modulate hand control. IHI from the motor cortices was measured before and after continuous theta-burst stimulation (cTBS) was delivered over the left-hemisphere SI. IHI was evoked using paired-pulse transcranial magnetic stimulation and measured using electromyography electrodes over the first dorsal interosseous muscles of both hands at short (10 ms) and long (40 ms) intervals to evoke short interval IHI and long interval IHI, respectively. Measures were taken before and for up to 1 h after 600 pulse cTBS was delivered over SI. Results indicate that cTBS over SI increases short interval IHI in the left hand (i.e. ipsilateral to cTBS) for 45-60 min after stimulation. These results indicate that SI is indeed able to modify IHI, and this is therefore one neural mechanism by which SI may influence hand control.

Short-latency afferent inhibition modulation during finger movement.

When somatosensory input via electrical stimulation of a peripheral nerve precedes a transcranial magnetic stimulation (TMS) pulse over the primary motor cortex (M1) the corticospinal output is substantially reduced, a phenomenon known as short-latency afferent inhibition (SAI). The present study investigated SAI during rest and during pre-movement, phasic and tonic components of movement. Participants were required to perform an index finger flexion reaction time task in response to an auditory cue. In a series of experiments, SAI was evoked from the mixed, median nerve at the wrist or the cutaneous, digital nerve stimulation of the index finger. To assess the spinal versus cortical origin of movement-related modulation of SAI, F-wave amplitudes were measured during rest and the three movement components. Results indicated that SAI was reduced during all movement components compared to rest, an effect that occurred for both nerves stimulated. Pre-movement SAI reduction was primarily attributed to reduced cortical inhibition, while increased spinal excitability additionally contributed to reduced SAI during tonic and phasic components of movement. SAI was differentially modulated across movement components with mixed but not cutaneous nerve stimulation. These findings reveal that SAI is reduced during movement and this reduction begins as early as the preparation to move. Further, these data suggest that the degree of SAI reduction during movement may be specific to the volume and/or composition of afferent input carried by each nerve.

Current direction specificity of continuous θ-burst stimulation in modulating human motor cortex excitability when applied to somatosensory cortex.

The present study examines the influence of primary somatosensory cortex (SI) on corticospinal excitability within primary motor cortex (M1) using repetitive transcranial magnetic stimulation. Two groups of subjects participated and both received continuous theta-burst stimulation (cTBS) over SI. One group received cTBS oriented to induce anterior-to-posterior (AP) followed by posterior-to-anterior (PA) current flow in the cortex and the other group received cTBS in the opposite direction (PA-AP). Motor evoked potentials (MEPs) were measured from the first dorsal interosseous muscle of the left and right hand before and at three time points (5, 25, 45 min) following cTBS over left-hemisphere SI. CTBS over SI in the AP-PA direction increased contralateral MEPs at 5 and 45 min with a near significant increase at 25 min. In contrast, PA-AP cTBS decreased contralateral MEPs at 25 min. We conclude that cTBS over SI modulates neural output directed to the hand with effects that depend on the direction of induced current.