Personalized depth-specific neuromodulation of the human primary motor cortex via ultrasound.

Non-invasive brain stimulation has the potential to boost neuronal plasticity in the primary motor cortex (M1), but it remains unclear whether the stimulation of both superficial and deep layers of the human motor cortex can effectively promote M1 plasticity. Here, we leveraged transcranial ultrasound stimulation (TUS) to precisely target M1 circuits at depths of approximately 5 mm and 16 mm from the cortical surface. Initially, we generated computed tomography images from each participant's individual anatomical magnetic resonance images (MRI), which allowed for the generation of accurate acoustic simulations. This process ensured that personalized TUS was administered exactly to the targeted depths within M1 for each participant. Using long-term depression and long-term potentiation (LTD/LTP) theta-burst stimulation paradigms, we examined whether TUS over distinct depths of M1 could induce LTD/LTP plasticity. Our findings indicated that continuous theta-burst TUS-induced LTD-like plasticity with both superficial and deep M1 stimulation, persisting for at least 30 min. In comparison, sham TUS did not significantly alter M1 excitability. Moreover, intermittent theta-burst TUS did not result in the induction of LTP- or LTD-like plasticity with either superficial or deep M1 stimulation. These findings suggest that the induction of M1 plasticity can be achieved with ultrasound stimulation targeting distinct depths of M1, which is contingent on the characteristics of TUS. KEY POINTS: The study integrated personalized transcranial ultrasound stimulation (TUS) with electrophysiology to determine whether TUS targeting superficial and deep layers of the human motor cortex (M1) could elicit long-term depression (LTD) or long-term potentiation (LTP) plastic changes. Utilizing acoustic simulations derived from individualized pseudo-computed tomography scans, we ensured the precision of TUS delivery to the intended M1 depths for each participant. Continuous theta-burst TUS targeting both the superficial and deep layers of M1 resulted in the emergence of LTD-like plasticity, lasting for at least 30 min. Administering intermittent theta-burst TUS to both the superficial and deep layers of M1 did not lead to the induction of LTP- or LTD-like plastic changes. We suggest that theta-burst TUS targeting distinct depths of M1 can induce plasticity, but this effect is dependent on specific TUS parameters.

Timing of transcranial direct current stimulation at M1 does not affect motor sequence learning.

Administering anodal transcranial direct current stimulation (tDCS) at the primary motor cortex (M1) at various temporal loci relative to motor training is reported to affect subsequent performance gains. Stimulation administered in conjunction with motor training appears to offer the most robust benefit that emerges during offline epochs. This conclusion is made, however, based on between-experiment comparisons that involved varied methodologies. The present experiment addressed this shortcoming by administering the same 15-minute dose of anodal tDCS at M1 before, during, or after practice of a serial reaction time task (SRTT). It was anticipated that exogenous stimulation during practice with a novel SRTT would facilitate offline gains. Ninety participants were randomly assigned to one of four groups: tDCS before practice, tDCS during practice, tDCS after practice, or no tDCS. Each participant was exposed to 15 min of 2 mA of tDCS and motor training of an eight-element SRTT. The anode was placed at the right M1 with the cathode at the left M1, and the left hand was used to execute the SRTT. Test blocks were administered 1 and 24 h after practice concluded. The results revealed significant offline gain for all conditions at the 1-hour and 24-hour test blocks. Importantly, exposure to anodal tDCS at M1 at any point before, during, or after motor training failed to change the trajectory of skill development as compared to the no-stimulation control condition. These data add to the growing body of evidence questioning the efficacy of a single bout of exogenous stimulation as an adjunct to motor training for fostering skill learning.

Effects of transcranial direct current stimulation over human motor cortex on cognitive-motor and sensory-motor functions.

The primary motor cortex (M1) is broadly acknowledged for its crucial role in executing voluntary movements. Yet, its contributions to cognitive and sensory functions remain largely unexplored. Transcranial direct current stimulation (tDCS) is a noninvasive neurostimulation method that can modify brain activity, thereby enabling the establishment of a causal link between M1 activity and behavior. This study aimed to investigate the online effects of tDCS over M1 on cognitive-motor and sensory-motor functions. Sixty-four healthy participants underwent either anodal or sham tDCS while concurrently performing a set of standardized robotic tasks. These tasks provided sensitive and objective assessments of brain functions, including action selection, inhibitory control, cognitive control of visuomotor skills, proprioceptive sense, and bimanual coordination. Our results revealed that anodal tDCS applied to M1 enhances decision-making capacity in selecting appropriate motor actions and avoiding distractors compared to sham stimulation, suggesting improved action selection and inhibitory control capabilities. Furthermore, anodal tDCS reduces the movement time required to accomplish bimanual movements, suggesting enhanced bimanual performance. However, we found no impact of anodal tDCS on cognitive control of visuomotor skills and proprioceptive sense. This study suggests that augmenting M1 activity via anodal tDCS influences cognitive-motor and sensory-motor functions in a task-dependent manner.

C3 in the 10-20 system may not be the best target for the motor hand area.

The C3 region in the international 10-20 system for electroencephalography (EEG) recording is assumed to represent the right motor hand area. Therefore, in the absence of transcranial magnetic stimulation (TMS) or a neuronavigational system, neuromodulation methods, such as transcranial direct current stimulation, target C3 or C4, based on the international 10-20 system, to influence the cortical excitability of the right and left hand, respectively. The purpose of this study is to compare the peak-to-peak motor evoked potential (MEP) amplitudes of the right first dorsal interosseus (FDI) muscle after single-pulse TMS at C3 and C1 in the 10-20 system and at the region between C3 and C1 (i.e., C3h in the 10-5 system). Using an intensity of 110% of the resting motor threshold, 15 individual MEPs from each of C3, C3h, C1, and hotspots were randomly recorded from FDI for sixteen right-handed undergraduate students. Average MEPs were greatest at C3h and C1, with both being larger than those recorded at C3. These data are congruent with recent findings using topographic analysis of individual MRIs that revealed poor correspondence between C3/C4 and the respective hand knob. Implications for the use of scalp locations determined using the 10-20 system for localizing the hand area are highlighted.

Improving consolidation by applying anodal transcranial direct current stimulation at primary motor cortex during repetitive practice.

Engagement of primary motor cortex (M1) is important for successful consolidation of motor skills. Recruitment of M1 has been reported to be more extensive during interleaved compared to repetitive practice and this differential recruitment has been proposed to contribute to the long-term retention benefit associated with interleaved practice. The present study administered anodal direct current stimulation (tDCS) during repetitive practice in an attempt to increase M1 activity throughout repetitive practice with the goal to improve the retention performance of individuals exposed to this training format. Fifty-four participants were assigned to one of three experimental groups that included: interleaved-sham, repetitive-sham, and repetitive-anodal tDCS. Real or sham stimulation at M1 was administered during practice of three motor sequences for approximately 20-min. Performance in the absence of any stimulation was evaluated prior to practice, immediately after practice as well as at 6-hr, and 24-h after practice was complete. As expected, for the sham conditions, interleaved as opposed repetitive practice resulted in superior offline gain. This was manifest as more rapid stabilization of performance after 6-h as well as an enhancement in performance with a period of overnight sleep. Administration of anodal stimulation at M1 during repetitive practice improved offline gains assessed at both 6-h and 24-h tests compared to the repetitive practice sham group. These data are consistent with the claims that reduced activation at M1 during repetitive practice impedes offline gain relative to interleaved practice and that M1 plays an important role in early consolidation of novel motor skills even in the context of the simultaneous acquisition of multiple new skills. Moreover, these findings highlight a possible role for M1 during sleep-related consolidation, possibly as part of a network including the dorsal premotor region, which supports delayed performance enhancement.

Application of anodal tDCS at primary motor cortex immediately after practice of a motor sequence does not improve offline gain.

Tecchio et al. (J Neurophysiology 104: 1134-1140, 2010) reported that the application of anodal tDCS at primary motor cortex (M1) immediately after practice of a procedural motor skill enhanced consolidation, which in turn improved offline gain. Tecchio et al. noted, however, that this study did not account for known after-effects associated with this form of non-invasive stimulation. The present study was designed to explicitly reevaluate Tecchio et al.'s claim. As in the original study, individuals experienced either anodal or sham stimulation at M1 after practice of a serial reaction time task (SRTT) followed by test trials 15-min later. Two additional novel conditions experienced the test trials after 120-min rather than 15-min thus allowing potential stimulation after-effects to dissipate. The expectation was that if anodal stimulation influences post-practice consolidation leading to offline gain, this effect would be present not only at 15-min but also after 120-min. In agreement with the working hypothesis, findings revealed offline gain at both 15-min and the longer 2-h time period. Unexpectedly, we found no interaction between real and sham conditions. The lack of difference between Real and Sham effects weakens confidence in the potential of post-practice tDCS for consolidation enhancement, while it is more consistent with other claims that decoupling practice and anodal tDCS stimulation in time can reduce the effectiveness of exogenous stimulation for procedural skill gain.

Carbon Dioxide Sequestration by Using a Model Carbonic Anhydrase Complex in Tertiary Amine Medium.

Globally, the elevation of carbon dioxide (CO2 ) levels due to the anthropogenic effect poses a serious threat to the ecosystem. Hence, it is important to control and/or mitigate the level of CO2 in the atmosphere, which necessitates novel tools. Herein, it is proposed to improve CO2 sequestration by using model complexes based on the enzyme carbonic anhydrase (CA) in aqueous tertiary amine medium. The effect of substituents on the model CA model complexes on CO2 absorption and desorption was determined by using a stopped-flow spectrophotometer to follow pH changes through coupling to pH indicator and a continuous stirred-tank reactor (CSTR). The CO2 hydration rate constants were determined under basic conditions and compound 6, which contained a hydrophilic group, showed the highest absorption or hydration levels of CO2 (2.860×10(3) L mol(-1) s(-1) ). In addition, CSTR results for the absorption and desorption of CO2 suggest that simple model CA complexes could be used in post-combustion processing.