A comparison of two methods in acquiring stimulus-response curves with transcranial magnetic stimulation

Background
The stimulus–response (S–R) curve is a well accepted constituent in transcranial magnetic stimulation (TMS) studies. However, it has been suggested that parameters of the S–R curve differ when stimuli are provided in a “ramped” (measured steps from low to high intensity), or “random” fashion.

Hypothesis
We hypothesized that there would be no difference in the parameters of the S–R curve between either methodologies.

Methods
Using a randomised cross-over design, 10 healthy participants (29.6 ± 6.4 yrs, 3 f) completed “ramped” or “random” curves in biceps brachii (BB) and first dorsal interosseous (FDI) muscles of both limbs. Curves were compared using mixed-factor ANOVA and correlated between limbs and methodologies.

Results
No differences (P > 0.05) and high correlations (range 0.71–0.97; P < 0.001) were observed in BB and FDI data between curves.

Conclusions
This study demonstrated that either methodology provides similar parameters of the S–R curve in healthy participants.

Calcaneal ultrasound reference ranges for Australian men and women : the Geelong Osteoporosis Study

Summary Heel ultrasound is a more portable modality for assessing fracture risk than dual-energy X-ray absorptiometry and does not use ionising radiation. Fracture risk assessment requires appropriate reference data to enable comparisons. This study reports the first heel ultrasound reference ranges for the Australian population.

Introduction This study aimed to develop calcaneal (heel) ultrasound reference ranges for the Australian adult population using a population-based random sample.

Methods Men and women aged ≥20 years were randomly selected from the Barwon Statistical Division in 2001–2006 and 1993–1997, respectively, using the electoral roll. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were measured at the heel using a Lunar Achilles Ultrasonometer. Gender-specific means and standard deviations for BUA, SOS and SI were calculated for the entire sample (men 20–93 years, n = 1,104; women 20–92 years, n = 914) and for participants aged 20–29 years (men, n = 157; women, n = 151). Associations between ultrasound measures and age were examined using linear regression.

Results For men, mean ± standard deviation BUA, SOS and SI were 118.7 ± 15.8 dB/MHz, 1,577.0 ± 43.7 m/s and 100.5 ± 20.7, respectively; values for women were consistently lower (111.0 ± 16.4 dB/MHz, P < 0.001; 1,571.0 ± 39.0 m/s, P = 0.001; and 93.7 ± 20.3, P < 0.001, respectively). BUA was higher in young men compared with young women (124.5 ± 14.4 vs 121.0 ± 15.1 dB/MHz), but SOS (1,590.1 ± 43.1 vs 1,592.5 ± 35.0 m/s) and SI (108.0 ± 19.9 vs 106.3 ± 17.7) were not. The relationships between age and each ultrasound measure were linear and negative across the age range in men; associations were also negative in women but non-linear.

Conclusion These data provide reference standards to facilitate the assessment of fracture risk in an Australian population using heel ultrasound.

Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation

RUNX2 is an essential transcription factor required for skeletal development and cartilage formation. Haploinsufficiency of RUNX2 leads to cleidocranial displaysia (CCD) a skeletal disorder characterised by gross dysgenesis of bones particularly those derived from intramembranous bone formation. A notable feature of the RUNX2 protein is the polyglutamine and polyalanine (23Q/17A) domain coded by a repeat sequence. Since none of the known mutations causing CCD characterised to date map in the glutamine repeat region, we hypothesised that Q-repeat mutations may be related to a more subtle bone phenotype. We screened subjects derived from four normal populations for Q-repeat variants. A total of 22 subjects were identified who were heterozygous for a wild type allele and a Q-repeat variant allele: (15Q, 16Q, 18Q and 30Q). Although not every subject had data for all measures, Q-repeat variants had a significant deficit in BMD with an average decrease of 0.7SD measured over 12 BMD-related parameters (p = 0.005). Femoral neck BMD was measured in all subjects (−0.6SD, p = 0.0007). The transactivation function of RUNX2 was determined for 16Q and 30Q alleles using a reporter gene assay. 16Q and 30Q alleles displayed significantly lower transactivation function compared to wild type (23Q). Our analysis has identified novel Q-repeat mutations that occur at a collective frequency of about 0.4%. These mutations significantly alter BMD and display impaired transactivation function, introducing a new class of functionally relevant RUNX2 mutants.

Does the longer application of anodal-transcranial direct current stimulaton increase corticomotor excitability further? A pilot study

Introduction: Anodal transcranial direct current stimulation (a-tDCS) of the primary motor cortex (M1) has been shown to be effective in increasing corticomotor excitability.
　
Methods: We investigated whether longer applications of a-tDCS coincide with greater increases in corticomotor excitability compared to shorter application of a-tDCS. Ten right-handed healthy participants received one session of a-tDCS (1mA current) with shorter (10 min) and longer (10+10 min) stimulation durations applied to the left M1 of extensor carpi radialis muscle (ECR). Corticomotor excitability following application of a-tDCS was assessed at rest with transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEP) and compared with baseline data for each participant.
　
Results: MEP amplitudes were increased following 10 min of a-tDCS by 67% (p = 0.001) with a further increase (32%) after the second 10 min of a-tDCS (p = 0.005). MEP amplitudes remained elevated at 15 min post stimulation compared to baseline values by 65% (p = 0.02).
　
Discussion: The results demonstrate that longer application of a-tDCS within the recommended safety limits, increases corticomotor excitability with after effects of up to 15 minutes post stimulation.

Different current intensities of anodal transcranial direct current stimulation do not differentially modulate motor cortex plasticity

Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates the excitability of neurons within the motor cortex (M1). Although the aftereffects of anodal tDCS on modulating cortical excitability have been described, there is limited data describing the outcomes of different tDCS intensities on intracortical circuits. To further elucidate the mechanisms underlying the aftereffects of M1 excitability following anodal tDCS, we used transcranial magnetic stimulation (TMS) to examine the effect of different intensities on cortical excitability and short-interval intracortical inhibition (SICI). Using a randomized, counterbalanced, crossover design, with a one-week wash-out period, 14 participants (6 females and 8 males, 22–45 years) were exposed to 10 minutes of anodal tDCS at 0.8, 1.0, and 1.2 mA. TMS was used to measure M1 excitability and SICI of the contralateral wrist extensor muscle at baseline, immediately after and 15 and 30 minutes following cessation of anodal tDCS. Cortical excitability increased, whilst SICI was reduced at all time points following anodal tDCS. Interestingly, there were no differences between the three intensities of anodal tDCS on modulating cortical excitability or SICI. These results suggest that the aftereffect of anodal tDCS on facilitating cortical excitability is due to the modulation of synaptic mechanisms associated with long-term potentiation and is not influenced by different tDCS intensities.