This study was supported by the funding of the Xiangya Boai Rehabilitation Hospital.

This study was carried out in strict accordance with the national standards for human experimentation, and the clinical study was approved by the Ethics Association of Xiangya Boai Rehabilitation Hospital (ethics approval number: 20211223). The children&#39;s guardians agreed to participate in this training program and signed informed consent forms. Children with SCP were recruited in the Xiangya Boai Rehabilitation Hospital and Xiangya Hospital of Central South University from February 2022 to December 2022.
1. Preparation before the experiment
<ol>
	<li>To ensure the accuracy of study results, provide relevant training to rehabilitation therapists and assess their skills in advance to make sure that they can guide the children in the training. 
	NOTE: The rTMS technicians should be trained and qualified to ensure the safety of children.</li>
	<li>Conduct rTMS safety screening with parents before the experiment, including questioning them about evidence of seizures and medications taken. 
	NOTE: Medications can lower the seizure threshold.</li>
</ol>
2. Recruitment
<ol>
	<li>Recruit children with SCP whose clinical diagnosis and classification meet the criteria of China Cerebral Palsy Rehabilitation Treatment Guidelines (2022)21.
	<ol>
		<li>Ensure that the children are between 3 and 6 years old.</li>
		<li>Ensure that the children have Gesell Developmental Diagnostic Scale (GDDS) adaptive behavioral area development quotient (DQ) &#62; 55 so that they can actively participate in training.</li>
		<li>Ensure that the children have Gross motor function classification (GMFCS) I-III.</li>
		<li>Ensure that the children can walk more than 10 m independently or with a walker.</li>
	</ol>
	</li>
	<li>Exclude the following: children with other types of CP; children scheduled for medical rehabilitation or surgery during the study period; children with epilepsy, severe intellectual impairment, visual impairment, or attention deficit; children with cochlear implants or intracranial implants.</li>
	<li>Before the training, obtain informed consent forms from children&#39;s guardians for voluntary participation in this training program 1x a day, 5 days per week for 12 weeks.</li>
</ol>
3. Pretreatment assessment
<ol>
	<li>Analyze the baseline data collected from recruited children with SCP, including name, sex, age, cerebral palsy spasticity type, GMFCS, cognitive level, ankle foot orthosis wear, previous or current medical treatment, and surgical history.</li>
	<li>Rehabilitation assessment 
	NOTE: Studies have shown that the Comprehensive Spasticity Scale (CSS) used to assess the degree of lower limb spasm in children with SCP has good reliability and validity22.
	<ol>
		<li>Determine the degree of spasm by examining the lower limb Achilles tendon reflex, the muscle tension of the ankle plantar flexor group, and the ankle clonus. Use the following evaluation criteria: no spasm, &#60;7; mild spasm, 7-9; moderate spasm, 10-12; and severe spasm, 13-16.</li>
		<li>Assess balance function according to the Pediatric Balance Scale (PBS)23, which includes 14 tested items. Each item is divided into five levels with 0-4 points for each item and 56 points in total. The higher the score, the better the balance function. 
		NOTE: PBS is based on the BBS Children&#39;s Revision, mainly adjusting the order of the tested items, shortening the time for maintaining posture, and clarifying test instructions.</li>
		<li>Assess the children&#39;s walking ability based on the 10 m walking speed (10MWS)24.
		<ol>
			<li>Ask children to walk as fast as possible on a runway with specifications of width x length =20 cm x 15 m, independently or wearing an ankle-foot orthotic or using a walking aid for children with GMFCS class III.</li>
		</ol>
		</li>
		<li>Ask children to start walking at the 15 m marker; start timing at 12 m, and stop at 2 m to measure the time taken for the middle 10 m. Ask the children to perform three consecutive 10MWT tests and calculate the walking speed (m/s). 
		NOTE: The functional level of the children was graded I-III according to GMFCS, meaning they have certain standing and walking ability.</li>
		<li>Evaluate the gross motor function level of the children by selecting a standing position in area D (13 items) and walking, running, and jumping in area E (24 items) in the Gross Motor Function Measure (GMFM). Calculate the score according to the completion degree of each item (0-3 points) and get the total score of Zones D and E. The higher the score, the better the gross motor function.</li>
		<li>Calculate the efficacy rate using equations (1) and (2) and assess the clinical effectiveness of gross motor function interventions by measuring the difference in the scores from the GMFM-88E section before and after treatment. 
		Efficacy rate (%) = <img alt="Equation 1" src="/files/ftp_upload/66013/66013eq01.jpg" style="margin: auto;" />&#160; &#160;(1) 
		&#8203;Efficacy rate = significant effective rate + effective rate&#160; &#160;(2)
		<ol>
			<li>Consider the outcome to be significantly effective if the efficacy rate is &#62;50%.</li>
			<li>Consider the outcome to be effective if the efficacy rate is between 20% and 50%.</li>
			<li>Consider the outcome to be ineffective if the efficacy rate is &#60;20%.</li>
		</ol>
		</li>
	</ol>
	</li>
</ol>
4. Therapeutic method
NOTE: Explain the principles and objectives of the training program, as well as possible adverse effects and safety issues during the training process, to the guardians of the children.
<ol>
	<li>Randomly divide the children with SCP into four different groups: a conventional group, a rTMS group, an AOT group, and a combination intervention group according to the numerical table method (16 cases in each group in this study).</li>
	<li>Ensure that all the children receive conventional rehabilitation treatment, based on which they will be given different rehabilitation treatment measures. The conventional group receives no other rehabilitation treatment; the rTMS group receives rTMS; the AOT group receives AOT; and the study group receives rTMS combined with AOT.
	<ol>
		<li>Explain in detail to the families of the subject children the possibilities of their participation in training programs of conventional rehabilitation, rTMS, AOT, and combined interventions. Ensure that the researchers are blinded to the allocation of the subjects and are not involved in the assessment.</li>
		<li>According to the admission order of these children, generate a numerical list as a spreadsheet. Randomize into groups as follows: numbers 1, 5, 9... for the regular group; numbers 2, 6, 10&#8230; for the rTMS group; numbers 3, 7, 11&#8230; for the AOT group; and numbers 4, 8, 12&#8230; for the combined intervention group. To ensure privacy, use a curtain to provide each child with a separate space during each treatment session.</li>
	</ol>
	</li>
	<li>Conventional rehabilitation
	<ol>
		<li>Exercise therapy
		<ol>
			<li>Explain the principle and purpose of exercise therapy to the guardians of the children and notify them that the duration of treatment is 30 min.</li>
			<li>According to their muscle strength rating, instruct the children to perform muscle strength exercises for the training of hip abductor muscles, hip posterior extensor muscles, and ankle dorsal extensor muscles, 10x per set and three sets per day.</li>
			<li>According to their balance function level, instruct the children to conduct balance training such as standing without support, standing with feet together, and standing on one leg, with a duration of 10 min each time.</li>
			<li>According to their walking ability, instruct the children to carry out walking training such as handholding, independent walking, and crossing obstacles, with a duration of 10 min each time.</li>
		</ol>
		</li>
		<li>Hydrotherapy
		<ol>
			<li>Explain the principle, process, and purpose of hydrotherapy to guardians of the children and notify them that the duration of treatment is 20 min.</li>
			<li>When using the special hydrotherapy machine for children, adjust the water temperature to an appropriate temperature of 37-38 &#176;C.</li>
			<li>Ask the parents to help their children take off their clothes, put on waterproof swimming trunks and hydrotherapy collars, and then get them into the hydrotherapy machine.</li>
			<li>Click on the bubble bath button to start treatment and instruct the children to stand, turn around, and take steps alternately with both feet in the water.</li>
		</ol>
		</li>
		<li>Massage treatment
		<ol>
			<li>Have the children diagnosed first.</li>
			<li>Explain the effects of massage treatment to the guardians of the children and notify them that the duration of treatment is 30 min.</li>
			<li>Place the children in the prone position and apply alternating pinching and pushing techniques 5-10x along both sides of the coronary artery and the bladder meridian.</li>
			<li>Place the children in the prone position and press, using the end of the thumb, the acupuncture points of Futu, Liangqiu, Zusanli, Jiexi, Huantiao, Chengfu, and Wuizhong from the top down.</li>
			<li>Place the children in the supine or prone position and apply rhythmic lifting and pinching 10-20x with the thumb and other four fingers alternately on the quadriceps, hamstrings, and calf triceps muscle at the same time.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>rTMS 
	NOTE: The physical therapist engaged in performing rTMS first participated in the training arranged by the manufacturer. For the safety of the participants, the therapist or other trained medical professionals must supervise the entire treatment process and inform the guardians in advance that the pulse generated by rTMS may cause temporary and mild pain and slight twitching of the face and limbs when it hits the scalp.
	<ol>
		<li>rTMS patient preparation
		<ol>
			<li>At the first visit, let the physical therapist know about the basic information and medical history of the subject children.</li>
			<li>Explain the process of rTMS treatment and possible responses to the guardians of the children and notify them that the duration of treatment is approximately 30 min.</li>
			<li>Place the children in the supine or seated position, degrease their hands with medical alcohol, and choose a suitable positioning cap for each of them according to their head circumference. Place the naso-occipital line on the positioning cap on the median line of the participating children, and the crossing point of the naso-occipital line and the temporal-parietal line at the midpoint of the line between the eyebrow and the occipital posterior carina. 
			NOTE: The appropriate size should be selected according to their head circumferences.</li>
			<li>Affix the recording electrode to the abdominal muscle of the abductor pollicis brevis of the participating children, the reference electrode to the tendon of the abductor pollicis brevis, and the bottom electrode to the wrist.</li>
		</ol>
		</li>
		<li>rTMS operation preparation
		<ol>
			<li>Start the computer application on the rTMS instrument, input the basic information and diagnoses of the participating children, and determine the treatment plan.</li>
			<li>The stimulation coil is a circular air-cooled coil, the center of which coincides with the contralateral M1 area corresponding to the identified abductor pollicis brevis. Place the coil at 45&#176; to the scalp. 
			NOTE: The positioning cap was designed according to the electroencephalography (EEG) 10-20 electrode arrangement system, which could quickly locate the M1 region.</li>
			<li>Select a stimulation intensity of 30% and stimulate the M1 region corresponding to the contralateral abductor pollicis brevis muscle by manual monopulse. 
			NOTE: During the treatment, the participating children should hold their position to avoid deviation of the stimulation target.</li>
			<li>Observe the motor evoked potentials interface graph and gradually reduce the stimulation intensity. Define the RMT as the minimum stimulus intensity that will elicit this response if at least 5 out of 10 consecutive stimulations of the child&#39;s primary motor cortex (M1) induce a motor potential strength of more than 50 mV in the contralateral abductor hallucis brevis muscle (Figure 1A).</li>
			<li>Click on the confirm button, save the RMT record, and then enter the treatment parameter setting page.</li>
		</ol>
		</li>
		<li>rTMS treatment
		<ol>
			<li>Use the following settings to perform low-frequency stimulation on the M1 region of the undamaged cerebral cortex: stimulation frequency 1 Hz, stimulation intensity 80% RMT, stimulation number 10, stimulation time 10 s, the number of repetitions 80, and the total number of pulses 80025,26 (see Figure 1B).</li>
			<li>Use the following settings to perform high-frequency stimulation of the M1 region of the damaged cerebral cortex: stimulation frequency 5 Hz, stimulation intensity 100% RMT, stimulation number 15, stimulation time 3 s, repetition times 80, and the total number of pulses 1,20010(see Figure 1C).</li>
			<li>Observe the responses of the participating children. For example, if the children start crying due to scalp beating, have excessive facial twitching, or show signs of a seizure and other adverse reactions, stop the treatment immediately. 
			NOTE: For children with spastic diplegia/quadriplegia, high-frequency stimulation of the M1 region of the damaged cerebral cortex was performed alternately on both sides of the damaged brain. For those with spastic hemiplegia, the M1 region of the undamaged cerebral cortex was stimulated at a low frequency, while the damaged cerebral cortex of M1 area was stimulated at a high frequency.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>AOT 
	NOTE: AOT requires physical therapists to video subjects&#39; body movements in advance and supervise the safety and training accuracy of the whole treatment process.
	<ol>
		<li>Explain the principle, process, and precautions of AOT to the guardians of the children, and notify them that the duration is 30 min.</li>
		<li>Have two professional physiotherapists shoot videos of body movements from three different angles: front, side, and back, and design six body movements for the purpose of improving lower limb balance and walking function.
		<ol>
			<li>The first movement goes from sitting to standing: move the body forward from the upright sitting position by lifting the pelvis and extending the knee joint, gradually converting to the standing position, and then sit down. Perform this 3x consecutively (Figure 2A).</li>
			<li>The second movement is a standing exercise: move the body weight to the left or right as far as possible and then back to the neutral position. Perform it 3x in turn (Figure 2B).</li>
			<li>The third movement is also a standing exercise: move the body weight forward or backward as far as possible and then return to the neutral position. Perform it 3x in turn (Figure 2C).</li>
			<li>The fourth movement is also a standing exercise: rotate the body to the left or right as far as possible and then return to the neutral position. Perform it 3x in turn (Figure 2D).</li>
			<li>The fifth movement is a standing exercise: walk sideways to the left or right and then return to the neutral position. Perform it 3x in turn (Figure 2E).</li>
			<li>The sixth movement is a standing exercise: alternately step up or down a 10 cm high step with the left and right feet. Perform it 3x in turn (Figure 2F).</li>
		</ol>
		</li>
		<li>Get the children gathered in a quiet room and sitting 5 m away from an 86 inch TV in comfortable positions.</li>
		<li>Have the physiotherapist explain the body movements first so that the children can then focus on watching the video.</li>
		<li>After watching the video, ask the children to imitate these movements.</li>
	</ol>
	</li>
</ol>
5. Post treatment evaluation
NOTE: The pretreatment and 12 week post treatment evaluation for each patient would be completed by the same pediatric rehabilitation doctor.
<ol>
	<li>After 12 weeks of different rehabilitation measures for the four groups of children, have the same pediatric rehabilitation doctor re-evaluate the clinical efficacy of CSS, PBS, 10 MWS, GMFM, and gross motor function.</li>
	<li>Record the guardians&#39; satisfaction and feedback on the treatment plan, including the degree of enjoyment of the treatment and improvement in self-awareness, as well as their wishes and suggestions for continuing the treatment.</li>
</ol>
6. Statistical analysis
<ol>
	<li>Enter the demographics, CSS, PBS, 10 m walking speed (10MWS), GMFM, and effective rate (%) assessment data into the software for statistical analysis.</li>
	<li>Analyze the counting data using the &#967;2 Test or Fisher Probabilistic Precision method.</li>
	<li>Determine whether the data conform to a normal distribution and express normally distributed data as mean &#177; SD.
	<ol>
		<li>Use repetitive measurement deviation analysis for comparison among the four groups and perform repeated measures analysis of variance under the mixed model to verify whether the results and variation scores of each group are consistent with the approximately normal distribution.</li>
	</ol>
	</li>
	<li>Consider time as an intra-group factor and intervention an inter-group factor. If there is any interaction between these two factors, test the inter-group difference at each time point at a= 0.05. If there is no interaction effect, test the main effect. Consider differences to be statistically significant at P &#60; 0.05.</li>
</ol>

Combined Intervention Training for Children with Spastic Cerebral Palsy 

The authors have no conflicts of interest to declare.

For children with SCP, increased activity of &#947; and &#945; neurons leads toinhibition of corticospinal tract input, which results in increased muscle tension known as spasm. As limb spasms significantly affect the development of lower limb motor function of children with SCP, one of the crucial training goals is to reduce spasticity. Currently, stepwise treatment strategies are employed to alleviate spasticity, including rehabilitation nursing, physical therapy, orthopedic brace application, botulinum toxin injection...

Cerebral palsy1 (CP) is one of the most common disabling disorders in children and is a group of persistent syndromes caused by non-progressive brain damage in developing fetuses and infants, including central dyskinesia, abnormal posture, and limited mobility. Currently, there are approximately 17 million children worldwide affected by cerebral palsy2, with over 5 million cases in China. Among various forms of cerebral palsy, spastic cerebral palsy (SCP) accounts for roughly 80%3. Children with SCP suffer from brain damage resulting in muscle spasms, diminished sensory function, impaired muscle coordination, and decreased balance capabilities, all of which hinder independent walking and daily activities. Current rehabilitation measures for enhancing gross motor function in children with SCP encompass activities such as core stability training4, task-oriented training5, constraint-induced movement therapy6, and mirror visual feedback therapy7. These measures can improve clinical symptoms of children by regulating and reshaping the central nervous system from bottom to top by improving the functions of peripheral organs. 
Transcranial magnetic stimulation (TMS)8,9 is a painless, non-invasive, and safe therapeutic method. rTMS refers to the continuous release of stimuli at equal intervals after a single command, which is one of the regular repetitive stimulation patterns. Based on the principle of electromagnetic induction and electromagnetic conversion, it applies transient currents through stimulation coils to form a pulsed magnetic field to penetrate the skull, generate induction current to stimulate neurons and trigger a series of physiological and biochemical responses. rTMS has been applied to the monitoring, evaluation, and treatment of neurological diseases, providing a novel approach to exploring the structure and function of the brain10. Existing studies11,12 have shown that rTMS has varying therapeutic effects on limb spasms and motor function in children with CP. Moreover, the effect of rTMS treatment combined with other rehabilitation techniques is more noticeable. 
AOT is a rehabilitation method that utilizes the Mirror Neuron System (MNS) to establish motor learning and memory13,14. The essence of AOT is to make the observer carefully observe actions in the video and subsequently try their best to imitate what they observed. The observing process might trigger activation in the neural network known as MNS, akin to the activation that occurs when one is personally engaged in executing those actions15, which provides a neurophysiological basis for AOT. AOT has shown success in improving motor skills in patients with movement disorders, yielding positive outcomes in stroke recovery and rehabilitation of upper limb motor function in cerebral palsy patients16,17. 
Our previous studies have found that AOT based on the mirror neuron system could effectively improve the balance and walking ability of children with cerebral palsy18. In addition, studies19 have shown that rTMS can improve muscle spasticity, movement, and gait in children with SCP, but treatment standards of rTMS applied to children with cerebral palsy have not been unified, and it is an urgent problem to explore the influence of different parameters of rTMS on children with CP, to provide a personalized and precise treatment standard. We believe that combining rTMS with AOT has the potential to develop into a valuable physical therapy strategy for the neurological rehabilitation of cerebral palsy. Both rTMS and AOT stimulated the cerebral cortex in children with SCP20, thereby aiding gross motor function development. This study aimed to find out whether the combination of rTMS and AOT could achieve a greater synergistic effect than conventional treatment or rTMS or AOT alone.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>K6 multimedia scene interactive training system</td>
			<td>Hunan Le Jiekang technology Co., LTD</td>
			<td></td>
			<td>Program implementation</td>
		</tr>
		<tr>
			<td>KLW-SLL type spa machine for children</td>
			<td>Nanjing Kanglongwei Technology Industrial Co., LTD</td>
			<td></td>
			<td>Conventional therapy</td>
		</tr>
		<tr>
			<td>Pulse magnetic field stimulator model YRD CCY-II</td>
			<td>Shenzhen Yingzhi technology Co., LTD</td>
			<td></td>
			<td>Program implementation</td>
		</tr>
		<tr>
			<td>SPSS26 software</td>
			<td>IBM</td>
			<td></td>
			<td>Statistic analysis</td>
		</tr>
	</tbody>
</table>

repeated transcranial magnetic stimulation combined with action observation training in children with spastic cerebral palsy

This study presents the results of a randomized controlled trial utilizing a 2 x 2 factorial design, comparing the effects of repeated transcranial magnetic stimulation (rTMS) and action observation training (AOT) intervention methods on spasticity, balance function, and motor function in children with spastic cerebral palsy (SCP). The study aimed to investigate whether the combination of the two interventions produces greater improvement than either treatment alone or conventional treatment.
Subject children in this study, in accordance with the random number table, were randomly divided into four groups: conventional group, rTMS group, AOT group, and combined intervention group. All the children in the four groups received conventional rehabilitation treatment, on the basis of which they were given different therapeutic programs of rehabilitation measures. The conventional group had no other treatment while the rTMS group received rTMS, the AOT group received AOT and the combined intervention group was given a combined intervention of rTMS and AOT. They were trained five days per week for 12 weeks. Changes in scores of spasticity, balance function, walking ability, and gross motor function were assessed at the onset of the training program and upon completion of 12 weeks of treatment.
A total of 64 Children with SCP completed the study, and their results were analyzed. The total gross motor function efficiency of 87.50% in the experimental group was significantly higher than that of 25.00% in the conventional group, 62.50% in the rTMS group, and 68.75% in the AOT group. The preliminary results showed that combined intervention of rTMS and AOT could effectively improve the balance function and motor function of children, and the therapeutic effect of the combined intervention was better than that of conventional treatment, rTMS or AOT alone. Finally, clinical efficacy and optimal treatment parameters of the combined intervention were clarified to provide a clinical basis for therapists to conduct lower limb function rehabilitation for children with SCP.

This paper presents the results of 64 children with SCP (Supplementary Table S1 and Supplementary File 1), who were randomly divided into four groups according to the numerical table method and given different rehabilitation measures for 12 weeks. During the entire process, the participating children had no adverse reactions such as headaches, dizziness, and seizures.
The demographic data of the four groups of children are shown in Table 1. Be...

Author Spotlight: Repetitive Transcranial Magnetic Stimulation Combined with Movement Observation in Cerebral Palsy

Children with spastic cerebral palsy (SCP) have limb spasticity, movement disorders, and abnormal posture due to injury to the cerebral cortex motor area, resulting in inability to stand and walk normally. Therefore, alleviating limb spasticity and enhancing gross motor function in children with SCP have become important therapeutic goals.

Repeated Transcranial Magnetic Stimulation Combined with Action Observation Training in Children with Spastic Cerebral Palsy

This study presents the results of a randomized controlled trial utilizing a 2 x 2 factorial design, comparing the effects of repeated transcranial ...

repeated-transcranial-magnetic-stimulation-combined-with-action

Research

JoVE Journal

Medicine

874 Views.  Xiangya Boai Rehabilitation Hospital. Children with spastic cerebral palsy (SCP) have limb spasticity, movement disorders, and abnormal posture due to injury to the cerebral cortex motor area, resulting in inability to stand and walk normally. Therefore, alleviating limb spasticity and enhancing gross motor function in children with SCP have become important therapeutic goals. 

Video: Author Spotlight: Repetitive Transcranial Magnetic Stimulation Combined with Movement Observation in Cerebral Palsy

Modeling Stroke in Mice - Middle Cerebral Artery Occlusion with the Filament Model

Stroke is among the most frequent causes of death and adult disability, especially in highly developed countries. However, treatment options to date are very limited. To meet the need for novel therapeutic approaches, experimental stroke research frequently employs rodent models of focal cerebral ischaemia. Most researchers use permanent or transient occlusion of the middle cerebral artery (MCA) in mice or rats.
Proximal occlusion of the middle cerebral artery (MCA) via the intraluminal suture technique (so called filament or suture model) is probably the most frequently used model in experimental stroke research. The intraluminal MCAO model offers the advantage of inducing reproducible transient or permanent ischaemia of the MCA territory in a relatively non-invasive manner. Intraluminal approaches interrupt the blood flow of the entire territory of this artery. Filament occlusion thus arrests flow proximal to the lenticulo-striate arteries, which supply the basal ganglia. Filament occlusion of the MCA results in reproducible lesions in the cortex and striatum and can be either permanent or transient. In contrast, models inducing distal (to the branching of the lenticulo-striate arteries) MCA occlusion typically spare the striatum and primarily involve the neocortex. In addition these models do require craniectomy. In the model demonstrated in this article, a silicon coated filament is introduced into the common carotid artery and advanced along the internal carotid artery into the Circle of Willis, where it blocks the origin of the middle cerebral artery. In patients, occlusions of the middle cerebral artery are among the most common causes of ischaemic stroke. Since varying ischemic intervals can be chosen freely in this model depending on the time point of reperfusion, ischaemic lesions with varying degrees of severity can be produced. Reperfusion by removal of the occluding filament at least partially models the restoration of blood flow after spontaneous or therapeutic (tPA) lysis of a thromboembolic clot in humans.
In this video we will present the basic technique as well as the major pitfalls and confounders which may limit the predictive value of this model.

Filamentous occlusion of the Middle cerebral artery is a common model for studying ischemic stroke in mice.

Stroke is among the most frequent causes of death and adult disability, especially in highly developed countries. However, treatment options to date are ...

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

Transcranial magnetic stimulation (TMS) has been in use for more than 20 years 1, and has grown exponentially in popularity over the past decade. While the use of TMS has expanded to the study of many systems and processes during this time, the original application and perhaps one of the most common uses of TMS involves studying the physiology, plasticity and function of the human neuromuscular system. Single pulse TMS applied to the motor cortex excites pyramidal neurons transsynaptically 2 (Figure 1) and results in a measurable electromyographic response that can be used to study and evaluate the integrity and excitability of the corticospinal tract in humans 3. Additionally, recent advances in magnetic stimulation now allows for partitioning of cortical versus spinal excitability 4,5. For example, paired-pulse TMS can be used to assess intracortical facilitatory and inhibitory properties by combining a conditioning stimulus and a test stimulus at different interstimulus intervals 3,4,6-8. In this video article we will demonstrate the methodological and technical aspects of these techniques. Specifically, we will demonstrate single-pulse and paired-pulse TMS techniques as applied to the flexor carpi radialis (FCR) muscle as well as the erector spinae (ES) musculature. Our laboratory studies the FCR muscle as it is of interest to our research on the effects of wrist-hand cast immobilization on reduced muscle performance6,9, and we study the ES muscles due to these muscles clinical relevance as it relates to low back pain8. With this stated, we should note that TMS has been used to study many muscles of the hand, arm and legs, and should iterate that our demonstrations in the FCR and ES muscle groups are only selected examples of TMS being used to study the human neuromuscular system.

Transcranial magnetic stimulation (TMS) is a non-invasive tool to gain insight on the physiology and function of the human nervous system. Here, we present our TMS techniques to study cortical excitability of the upper limb and lumbar musculature.

Transcranial magnetic stimulation (TMS) has been in use for more than 20 years 1, and has grown exponentially in popularity over the past decade.  While ...

Eye Tracking Young Children with Autism

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a direct, detailed and objective measure of gaze behavior, eye-tracking has become a valuable tool for examining abnormal perceptual strategies in clinical populations and has been used to identify disorder-specific characteristics1, promote early identification2, and inform treatment3. In particular, investigators of autism spectrum disorders (ASD) have benefited from integrating eye-tracking into their research paradigms4-7. Eye-tracking has largely been used in these studies to reveal mechanisms underlying impaired task performance8 and abnormal brain functioning9, particularly during the processing of social information1,10-11. While older children and adults with ASD comprise the preponderance of research in this area, eye-tracking may be especially useful for studying young children with the disorder as it offers a non-invasive tool for assessing and quantifying early-emerging developmental abnormalities2,12-13. Implementing eye-tracking with young children with ASD, however, is associated with a number of unique challenges, including issues with compliant behavior resulting from specific task demands and disorder-related psychosocial considerations. In this protocol, we detail methodological considerations for optimizing research design, data acquisition and psychometric analysis while eye-tracking young children with ASD. The provided recommendations are also designed to be more broadly applicable for eye-tracking children with other developmental disabilities. By offering guidelines for best practices in these areas based upon lessons derived from our own work, we hope to help other investigators make sound research design and analysis choices while avoiding common pitfalls that can compromise data acquisition while eye-tracking young children with ASD or other developmental difficulties.

Eye tracking has long been used to study gaze patterns in typically-developing individuals, but recent technological advancements have made its use with clinical populations, including autism, more feasible. While eye-tracking young children with autism can offer insight into early symptom manifestations, it involves methodological challenges. Suggestions for best practices are provided.

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a ...

Utilizing Repetitive Transcranial Magnetic Stimulation to Improve Language Function in Stroke Patients with Chronic Non-fluent Aphasia

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six-month post-stimulation language testing.

We explore the use of repetitive transcranial magnetic stimulation (rTMS) to improve language abilities in patients with chronic stroke and non-fluent aphasia. After identifying a site in the right frontal gyrus for each patient that responds optimally to stimulation, we target this site during ten days of rTMS treatment.

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this ...

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson&#39;s disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.
Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson&#39;s Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

Adaptive deep brain stimulation (aDBS) is effective for Parkinson&#8217;s disease, improving symptoms and reducing power consumption compared to conventional deep brain stimulation (cDBS). In aDBS we track a local field potential biomarker (beta oscillatory amplitude) in real time and use this to control the timing of stimulation.

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time ...

Adapted Resistance Training Improves Strength in Eight Weeks in Individuals with Multiple Sclerosis

Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis (MS). It is known that resistance strength training (RST) can improve strength in individuals with MS, however; it remains unclear the duration of RST that is needed to make strength gains and how to adapt hip strengthening exercises for individuals of varying strength using only resistance bands. This paper describes the methodology to set up and implement an adapted resistance strength training program, using resistance bands, for individuals with MS. Directions for pre- and post-strength tests to evaluate efficacy of the strength-training program are included. Safety features and detailed instructions outline the weekly program content and progression. Current evidence is presented showing that significant strength gains can be made within 8 weeks of starting a RST program. Evidence is also presented showing that resistance strength training can be successfully adapted for individuals with MS of varying strength with little equipment.

Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis. Isolated muscle strengthening is a useful method to target specific weaknesses. This protocol describes a progressive resistance-training program using exercise bands to increase hip muscle strength.

Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis (MS). It is known that resistance strength training (RST) can ...

A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy

As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, standardized battery of neonatal mouse motor tests. These tests can validate injury or disease models, determine treatment efficacy and/or assess motor behaviors in new transgenic strains. This paper presents a series of neonatal motor tests to evaluate general motor function, including ambulation, hindlimb foot angle, surface righting, negative geotaxis, front- and hindlimb suspension, grasping reflex, four limb grip strength and cliff aversion. Mice between the ages of post-natal day 2 to 14 can be used. In addition, these tests can be used for a wide range of neurological and neuromuscular pathologies, including cerebral palsy, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, neurodegenerative diseases, and neuromuscular disorders. These tests can also be used to determine the effects of pharmacological agents, as well as other types of therapeutic interventions. In this paper, motor deficits were evaluated in a novel neonatal mouse model of cerebral palsy that combines hypoxia, ischemia and inflammation. Forty-eight hours after injury, five tests out of the nine showed significant motor deficits: ambulation, hindlimb angle, hindlimb suspension, four limb grip strength, and grasping reflex. These tests revealed weakness in the hindlimbs, as well as fine motor skills such as grasping, which are similar to the motor deficits seen in human cerebral palsy patients.

Presented is a concise battery of mouse neonatal motor tests. Using these tests, neonatal motor deficits can be demonstrated in a variety of neonatal motor disorders. By having a standardized set of tests, results from different studies can be compared, allowing for better and accurate reporting between groups.

As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, ...

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

Updated Technique for Reliable, Easy, and Tolerated Transcranial Electrical Stimulation Including Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a noninvasive method of neuromodulation using low-intensity direct electrical currents. This method of brain stimulation presents several potential advantages compared to other techniques, as it is noninvasive, cost-effective, broadly deployable, and well-tolerated provided proper equipment and protocols are administered. Even though tDCS is apparently simple to perform, correct administration of the tDCS session, especially the electrode positioning and preparation, is vital for ensuring reproducibility and tolerability. The electrode positioning and preparation steps are traditionally also the most time consuming and error-prone. To address these challenges, modern tDCS techniques, using fixed-position headgear and pre-assembled sponge electrodes, reduce complexity and setup time while also ensuring that the electrodes are consistently placed as intended. These modern tDCS methods present advantages for research, clinic, and remote-supervised (at home) settings. This article provides a comprehensive step-by-step guide for administering a tDCS session using fixed-position headgear and pre-assembled sponge electrodes. This guide demonstrates tDCS using commonly applied montages intended for motor cortex and dorsolateral prefrontal cortex (DLPFC) stimulation. As described, selection of the head size and montage-specific headgear automates electrode positioning. Fully assembled pre-saturated snap-electrodes are simply affixed to the set position snap-connectors on the headgear. The modern tDCS method is shown to reduce setup time and reduce errors for both novice and expert operators. The methods outlined in this article can be adapted to different applications of tDCS as well as other forms of transcranial electrical stimulation (tES) such as transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS). However, since tES is application specific, as appropriate, any methods recipe is customized to accommodate subject, indication, environment, and outcome specific features.

When administering transcranial direct current stimulation (tDCS), reproducible electrode preparation and placement are vital for a tolerated and effective session. The purpose of this article is to demonstrate updated modern setup procedures for the administration of tDCS and related transcranial electrical stimulation techniques, such as transcranial alternating current stimulation (tACS).

Transcranial direct current stimulation (tDCS) is a noninvasive method of neuromodulation using low-intensity direct electrical currents. This method of ...

Human Fetal Blood Flow Quantification with Magnetic Resonance Imaging and Motion Compensation

Magnetic resonance imaging (MRI) is an important tool for the clinical assessment of cardiovascular morphology and heart function. It is also the recognized standard-of-care for blood flow quantification based on phase contrast MRI. While such measurement of blood flow has been possible in adults for decades, methods to extend this capability to fetal blood flow have only recently been developed.
Fetal blood flow quantification in major vessels is important for monitoring fetal pathologies such as congenital heart disease (CHD) and fetal growth restriction (FGR). CHD causes alterations in the cardiac structure and vasculature that change the course of blood in the fetus. In FGR, the path of blood flow is altered through the dilation of shunts such that the oxygenated blood supply to the brain is increased. Blood flow quantification enables assessment of the severity of the fetal pathology, which in turn allows for suitable&#160;in utero&#160;patient management and planning for postnatal care.
The primary challenges of applying phase contrast MRI to the human fetus include small blood vessel size, high fetal heart rate, potential MRI data corruption due to maternal respiration, unpredictable fetal movements, and lack of conventional cardiac gating methods to synchronize data acquisition. Here, we describe recent technical developments from our lab that have enabled the quantification of fetal blood flow using phase contrast MRI, including advances in accelerated imaging, motion compensation, and cardiac gating.

Here we present a protocol for measuring fetal blood flow rapidly with MRI and retrospectively performing motion correction and cardiac gating.