This work was supported by the General Scientific Research Project of Zhejiang Provincial Education Department, China (Grant No. Y202249231).

This study was approved by the ethical and scientific review board of our hospital. Written informed consent was obtained from the patient. All the treatment procedures were performed by personnel with 10 years of experience in musculoskeletal ultrasound intervention. The operator must have good knowledge of musculoskeletal anatomy. The ultrasound machine used here is mentioned in the Table of Materials and has a high-frequency probe.
1. Instrument setup and patient preparation
<ol>
	<li>Enter the ID number and the patient&#39;s name to save the images.</li>
	<li>Sanitize the ultrasound probe using equipment disinfectant wipes. Perform all the procedures with the probe covered with surgical gloves.</li>
	<li>Set the image with the DBRN in the middle of the screen. To do this, perform cross-sectional scanning along the supinator muscle to find the DBRN. Then, rotate 90&#176; to obtain a long-axis section. Under continuous ultrasound guidance, separate the adhesion between the surrounding tissue of the posterior spin muscles and the DBRN.</li>
	<li>Ask the patient to sit and place their arm in a flexed 20&#176; position on the examination bed. Perform ultrasound to check for DBRN adhesion to the surrounding tissue (Figure 1; Video 1).</li>
</ol>
2. Ultrasound examination and treatment
<ol>
	<li>Use complex iodine to disinfect the patient&#39;s skin three times, and then place a sterile surgical towel on the patient&#39;s arm.</li>
	<li>Provide local anesthesia using a 10 mL aliquot of a mixed solution (5 mL of 2% lidocaine and 5 mL of 0.9% sodium chloride) layer by layer until the DBRN surface is reached (Figure 2). The four layers that are anesthetized include the skin, the subcutaneous soft tissue, the brachioradialis, and the superficial supinator muscle. Confirm the anesthetization of each layer using ultrasound guidance, and check that the tip of the needle passes through each layer.</li>
	<li>Identify the radial nerve by transversely using the probe at the level of the lateral epicondyle of the humerus. The radial nerve is located between the humerus muscle and the brachioradial muscle. Then, move the probe distally to find the deep branch of the radial nerve between the deep and superficial layers of the supinator.</li>
	<li>Use a 5 mL syringe to separate the adhesion between the surrounding tissue of the posterior spin muscles and the DBRN under the continuous ultrasound guidance. Perform needle release from the DBRN distal area to the proximal area. Prick the adhesion tissue back and forth with the tip. Stop when there is resistance between the syringe and the tissues around the DBRN.</li>
	<li>Ensure that the probe and the needle are accurately controlled, keep the tip of the needle visible during the entire operation, and avoid damage to the DBRN.</li>
	<li>After the procedure, inject a mixture of 1 mL of corticosteroid (betamethasone) and 2 mL of 2% lidocaine into the superficial area of the DBRN.</li>
</ol>

Ultrasound-Guided Needle Release Combined with Corticosteroid Injection

<ol>
	<li>Babaei-Ghazani, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasonographic+reference+values+for+the+deep+branch+of+the+radial+nerve+at+the+arcade+of+Frohse.">Ultrasonographic reference values for the deep branch of the radial nerve at the arcade of Frohse.</a> Journal of Ultrasound. 21 (3), 225-231 (2018).</li><li>Ozkan, M., Bacakoglu, A. K., Gul, O., Ekin, A., Magden, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anatomic+study+of+posterior+interosseous+nerve+in+the+arcade+of+Frohse.">Anatomic study of posterior interosseous nerve in the arcade of Frohse.</a> Journal of Shoulder and Elbow Surgery. 8 (6), 617-620 (1999).</li><li>Keefe, D. T., Lintner, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nerve+injuries+in+the+throwing+elbow.">Nerve injuries in the throwing elbow.</a> Clinical Journal of Sports Medicine. 23 (4), 723-742 (2004).</li><li>Konjengbam, M., Elangbam, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Radial+nerve+in+the+radial+tunnel:+anatomic+sites+of+entrapment+neuropathy.">Radial nerve in the radial tunnel: anatomic sites of entrapment neuropathy.</a> Clinical Anatomy. 17 (1), 21-25 (2004).</li><li>Chang, K. V., Wu, W. T., Ozcakar, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound+imaging+for+a+rare+cause+of+postpartum+forearm+pain:+Diffuse+enlargement+rather+than+focal+swelling+of+the+deep+branch+of+the+radial+nerve.">Ultrasound imaging for a rare cause of postpartum forearm pain: Diffuse enlargement rather than focal swelling of the deep branch of the radial nerve.</a> Pain Medicine. 21 (1), 203-205 (2020).</li><li>Dang, A. C., Rodner, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Unusual+compression+neuropathies+of+the+forearm,+part+I:+Radial+nerve.">Unusual compression neuropathies of the forearm, part I: Radial nerve.</a> Journal of Hand Surgery. American Volume. 34 (10), 1906-1914 (2009).</li><li>Sarris, I. K., Papadimitriou, N. G., Sotereanos, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Radial+tunnel+syndrome.">Radial tunnel syndrome.</a> Techniques in Hand &amp; Upper Extremity Surgery. 6 (4), 209-212 (2002).</li><li>Ozcakar, L., Kara, M., Gurcay, E., Onat, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound+imaging+for+prompt+clinical+decision+making+before+interventions.">Ultrasound imaging for prompt clinical decision making before interventions.</a> American Journal of Physical Medicine and Rehabilitation. 96 (3), (2017).</li><li>Domkundwar, S., Autkar, G., Khadilkar, S. V., Virarkar, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound+and+EMG-NCV+study+(electromyography+and+nerve+conduction+velocity)+correlation+in+diagnosis+of+nerve+pathologies.">Ultrasound and EMG-NCV study (electromyography and nerve conduction velocity) correlation in diagnosis of nerve pathologies.</a> Journal of Ultrasound. 20 (2), 111-122 (2017).</li><li>Chang, K. V., Wu, W. T., Han, D. S., Ozcakar, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Static+and+dynamic+shoulder+imaging+to+predict+initial+effectiveness+and+recurrence+after+ultrasound-guided+subacromial+corticosteroid+injections.">Static and dynamic shoulder imaging to predict initial effectiveness and recurrence after ultrasound-guided subacromial corticosteroid injections.</a> Archives of Physical Medicine and Rehabilitation. 98 (10), 1984-1994 (2017).</li><li>Wu, W. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subacromial+motion+metrics+in+painful+shoulder+impingement:+A+dynamic+quantitative+ultrasonography+analysis.">Subacromial motion metrics in painful shoulder impingement: A dynamic quantitative ultrasonography analysis.</a> Archives of Physical Medicine and Rehabilitation. 104 (2), 260-269 (2023).</li><li>Martinoli, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sonography+of+entrapment+neuropathies+in+the+upper+limb+(wrist+excluded).">Sonography of entrapment neuropathies in the upper limb (wrist excluded).</a> Journal of Clinical Ultrasound. 32 (9), 438-450 (2004).</li><li>Cartwright, M. S., Walker, F. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuromuscular+ultrasound+in+common+entrapment+neuropathies.">Neuromuscular ultrasound in common entrapment neuropathies.</a> Muscle and Nerve. 48 (5), 696-704 (2013).</li><li>Rota, E., Morelli, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Entrapment+neuropathies+in+diabetes+mellitus.">Entrapment neuropathies in diabetes mellitus.</a> World Journal of Diabetes. 7 (17), 342-353 (2016).</li><li>Miller, T. T., Reinus, W. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nerve+entrapment+syndromes+of+the+elbow,+forearm,+and+wrist.">Nerve entrapment syndromes of the elbow, forearm, and wrist.</a> American Journal of Roentgenology. 195 (3), 585-594 (2010).</li><li>Zeng, Z., Chen, C. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound-guided+needle+release+plus+corticosteroid+injection+of+superficial+radial+nerve:+A+case+report.">Ultrasound-guided needle release plus corticosteroid injection of superficial radial nerve: A case report.</a> World Journal of Clinical Cases. 10 (4), 1320-1325 (2022).</li><li>Barnum, M., Mastey, R. D., Weiss, A. P., Akelman, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Radial+tunnel+syndrome.">Radial tunnel syndrome.</a> Hand Clinics. 12 (4), 679-689 (1996).</li><li>Spinner, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+arcade+of+Frohse+and+its+relationship+to+posterior+interosseous+nerve+paralysis.">The arcade of Frohse and its relationship to posterior interosseous nerve paralysis.</a> The Journal of Bone and Joint Surgery. British Volume. 50 (4), 809-812 (1968).</li><li>Dufour, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound-guided+perineural+circumferential+median+nerve+block+with+and+without+prior+dextrose+5%+hydrodissection:+A+prospective+randomized+double-blinded+noninferiority+trial.">Ultrasound-guided perineural circumferential median nerve block with and without prior dextrose 5% hydrodissection: A prospective randomized double-blinded noninferiority trial.</a> Anesthesia and Analgesia. 115 (3), 728-733 (2012).</li><li>Wu, Y. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nerve+hydrodissection+for+carpal+tunnel+syndrome:+A+prospective,+randomized,+double-blind,+controlled+trial.">Nerve hydrodissection for carpal tunnel syndrome: A prospective, randomized, double-blind, controlled trial.</a> Muscle and Nerve. 59 (2), 174-180 (2019).</li><li>Lin, C. P., Chang, K. V., Huang, Y. K., Wu, W. T., Ozcakar, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regenerative+injections+including+5%+dextrose+and+platelet-rich+plasma+for+the+treatment+of+carpal+tunnel+syndrome:+A+systematic+review+and+network+meta-analysis.">Regenerative injections including 5% dextrose and platelet-rich plasma for the treatment of carpal tunnel syndrome: A systematic review and network meta-analysis.</a> Pharmaceuticals. 13 (3), (2020).</li></ol>

The authors declare no competing financial interests.

In recent years, ultrasound has become a valuable tool for assessing peripheral nerve entrapments. Ultrasound can be used to observe nerves in real-time and provide dynamic visualization12. The obvious sonographic indicator of entrapment is the increased nerve CSA at the site of entrapment13,14. Other findings such as a hypoechoic texture, nerve flattening, and increased vascularity are also reported in entrapment neuropathy<sup class='xre...

The radial nerve (RN) splits into two main branches at the elbow level: the deep branch (DBRN) and the superficial branch (SBRN). The DBRN originates from the main trunk of the RN at the level of the lateral epicondyle of the humerus1. The DBRN curves around the neck of the radius and then goes through under the tendinous arch of the superficial edge of the supinator muscle, which is called the arcade of Frohse2. This anatomical site is the most common entrapment site of the DBRN at the forearm3,4. In some rare cases, the DBRN can be compressed from the entrance to the exit of supinator5. The entrapment of the DBRN can cause pain in the lateral-dorsal proximal forearm and weakness of the wrist extensor muscles6,7,8.
When a nerve is injured, nerve conduction studies (NCS) and electromyography (EMG) sometimes show abnormal results indicating that the nerve is damaged. Although EMG is an established method and provides functional information about nerve disease, it lacks the ability to detect anatomical and morphological information related to the nerve9. Besides that, the sensitivity and specificity of EMG are not very high at early stages of nerve injury. Ultrasound can easily detect peripheral nerves and show them in sonographic imaging. Many studies have reported the value of high-frequency ultrasound in diagnosing the entrapment of peripheral nerves5. It has great potential as a diagnostic method for finding peripheral nerves. Babaei-Ghazani et al. reported ultrasonographic values for the DBRN at the arcade of Frohse, and they concluded that age was associated with the cross-sectional area (CSA) of DBRN, while other features such as height or gender were not1. Some studies have reported that corticosteroid injections are effective in treating musculoskeletal diseases10,11. However, until now, there have been no reports on ultrasound-guided needle release plus a corticosteroid injection in the DBRN for treating adhesion. Here, we report a method that can separate the adhesion without open surgery. A male patient who had a dorsiflexion limitation in his left ring and little fingers was treated using this method. This patient had injured his left forearm 1 month prior to the treatment. Multiple muscles of the forearm (the extensor digitorum, extensor digiti minimi, and extensor carpi ulnaris) were sutured in another hospital. His DBRN had edema and was thickened, and the exit point of DBRN was deeply adhered to the surrounding tissue. After treatment using US-guided needle release and corticosteroid injection of the DBRN, the patient&#39;s dorsal extension of the ring and the little finger was normal when the joints of the fingers were fully straightened.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Betamethasone</td>
			<td>MSD Merck Sharp &#38; Dohme AG</td>
			<td>B7005-100MG</td>
			<td></td>
		</tr>
		<tr>
			<td>Injection syringe</td>
			<td>Hangzhou Minsheng Pharmaceutical Co., LTD</td>
			<td></td>
			<td>5 mL and 10 mL</td>
		</tr>
		<tr>
			<td>Lidocaine</td>
			<td>Shanghai Zhaohui Pharmaceutical Co., LTD</td>
			<td>H41022244</td>
			<td>7 mL</td>
		</tr>
		<tr>
			<td>Sodium chloride</td>
			<td>Hangzhou Minsheng Pharmaceutical Co., LTD</td>
			<td>http://www.mspharm.com/pro_list.asp?PageNumber=3&#38;info_kind=004001 
			&#38;d_add_date1=&#38;d_add_date2=&#38; 
			skind=&#38;p_keys=</td>
			<td>5 mL</td>
		</tr>
		<tr>
			<td>Ultrasonic diagnostic system</td>
			<td>SIEMENS</td>
			<td></td>
			<td>Type:ACUSON Sequoia</td>
		</tr>
	</tbody>
</table>

ultrasound-guided needle release combined with corticosteroid injection for the treatment of supinator syndrome

The two main branches of the radial nerve (RN) are the deep branch (DBRN) and the superficial branch (SBRN). The RN splits into two main branches at the elbow. The DBRN runs between the deep and shallow layers of the supinator. The DBRN can be easily compressed at the arcade of Frohse (AF) due to its anatomical features. This work focuses on a 42-year-old male patient who had injured his left forearm 1 month prior. Multiple muscles of the forearm (extensor digitorum, extensor digiti minimi, and extensor carpi ulnaris) were sutured in another hospital. After that, he had dorsiflexion limitations in his left ring and little fingers. The patient was reluctant to undergo another operation because he had undergone suture surgeries for multiple muscles 1 month prior. Ultrasound revealed that the deep branch of the radial nerve (DBRN) had edema and was thickened. The exit point of the DBRN had deeply adhered to the surrounding tissue. To relieve this, ultrasound-guided needle release plus a corticosteroid injection were performed on the DBRN. Nearly 3 months later, the dorsal extension in the patient's ring and little fingers was significantly improved (ring finger: &#8722;10&#176;, little finger: &#8722;15&#176;). Then, the same treatment was done for the second time. Nearly 1 month after that, the dorsal extension of the ring and the little finger was normal when the joints of the fingers were fully straightened. Ultrasound could evaluate the condition of the DBRN and its relationship with the surrounding tissues. Ultrasound-guided needle release combined with corticosteroid injection is an effective and safe treatment for DBRN adhesion.

At 1 month after the treatment, the joints of the fingers were fully straightened, and the dorsal extension of the ring and little fingers was significantly improved upon fully straightening the fingers (ring finger: &#8722;15&#176;, little finger: &#8722;25&#176;). At 3 months after the treatment, the patient came back for re-examination of the DBRN. The range of DBRN adhesions, as assessed by ultrasound, was significantly reduced compared to before the treatment. The dorsal extension of the ring and little fingers was ...

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Author Spotlight: Ultrasound-Guided Needle Release Combined with Corticosteroid Injection for the Treatment of Supinator Syndrome  

The deep branch of the radial nerve can easily be compressed at the arcade of Frohse due to its anatomical features. Ultrasound-guided needle release combined with corticosteroid injection is an effective and safe treatment for deep branch radial nerve adhesion.

Ultrasound-Guided Needle Release Combined with Corticosteroid Injection for the Treatment of Supinator Syndrome

The two main branches of the radial nerve (RN) are the deep branch (DBRN) and the superficial branch (SBRN). The RN splits into two main branches at the ...

ultrasound-guided-needle-release-combined-with-corticosteroid

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1.3K Views.  Hangzhou Medical College. The deep branch of the radial nerve can easily be compressed at the arcade of Frohse due to its anatomical features. Ultrasound-guided needle release combined with corticosteroid injection is an effective and safe treatment for deep branch radial nerve adhesion.

Video: Author Spotlight: Ultrasound-Guided Needle Release Combined with Corticosteroid Injection for the Treatment of Supinator Syndrome  

Ultrasound-Guided Microinjection into the Mouse Forebrain In Utero at E9.5

In utero survival surgery in mice permits the molecular manipulation of gene expression during development. However, because the uterine wall is opaque during early embryogenesis, the ability to target specific parts of the embryo for microinjection is greatly limited. Fortunately, high-frequency ultrasound imaging permits the generation of images that can be used in real time to guide a microinjection needle into the embryonic region of interest. Here we describe the use of such imaging to guide the injection of retroviral vectors into the ventricular system of the mouse forebrain at embryonic day (E) 9.5. This method uses a laparotomy to permit access to the uterine horns, and a specially designed plate that permits host embryos to be bathed in saline while they are imaged and injected. Successful surgeries often result in most or all of the injected embryos surviving to any subsequent time point of interest (embryonically or postnatally). The principles described here can be used with slight modifications to perform injections into the amnionic fluid of E8.5 embryos (thereby permitting infection along the anterior posterior extent of the neural tube, which has not yet closed), or into the ventricular system of the brain at E10.5/11.5. Furthermore, at mid-neurogenic ages (~E13.5), ultrasound imaging can be used direct injection into specific brain regions for viral infection or cell transplantation. The use of ultrasound imaging to guide in utero injections in mice is a very powerful technique that permits the molecular and cellular manipulation of mouse embryos in ways that would otherwise be exceptionally difficult if not impossible.

Ultrasound-Guided Microinjection into the Mouse Forebrain In Utero at E9.5

In utero survival surgery in mice permits the molecular manipulation of gene expression during development. Here we describe the use of high-frequency ultrasound imaging to guide the injection of retroviral vectors into the mouse brain at embryonic day (E) 9.5.

In utero survival surgery in mice permits the molecular manipulation of gene expression during development.  However, because the uterine wall is opaque ...

TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS display abnormalities in the expression of FMR1 - a protein required for typical, healthy neural development.3 Recent data has suggested that the loss of this protein can cause the cortex to be hyperexcitable thereby affecting overall patterns of neural plasticity.4,5
In addition, Fragile X shows a strong comorbidity with autism: in fact, 30% of children with FXS are diagnosed with autism, and 2 - 5% of autistic children suffer from FXS.6
Transcranial Magnetic Stimulation (a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses 7,8) represents a unique method of exploring plasticity and the manifestations of FXS within affected individuals. More specifically, Theta-Burst Stimulation (TBS), a specific stimulatory protocol shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations, has already proven an efficacious tool in the exploration of abnormal plasticity.9,10 
Recent studies have shown the effects of TBS last considerably longer in individuals on the autistic spectrum - up to 90 minutes.11 This extended effect-duration suggests an underlying abnormality in the brain's natural plasticity state in autistic individuals - similar to the hyperexcitability induced by Fragile X Syndrome.
In this experiment, utilizing single-pulse motor-evoked potentials (MEPs) as our benchmark, we will explore the effects of both intermittent and continuous TBS on cortical plasticity in individuals suffering from FXS and individuals on the Autistic Spectrum.

In this article, we examine the effects of Theta-Burst TMS stimulation on cortical plasticity in individuals suffering from Fragile X syndrome and individuals on the autistic spectrum.

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS ...

The NeuroStar TMS Device: Conducting the FDA Approved Protocol for Treatment of Depression

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic fields. These rapidly alternating fields induce electrical currents within localized, targeted regions of the cortex which are associated with various physiological and functional brain changes.1,2,3
In 2007, O'Reardon et al., utilizing the NeuroStar device, published the results of an industry-sponsored, multisite, randomized, sham-stimulation controlled clinical trial in which 301 patients with major depression, who had previously failed to respond to at least one adequate antidepressant treatment trial, underwent either active or sham TMS over the left dorsolateral prefrontal cortex (DLPFC). The patients, who were medication-free at the time of the study, received TMS five times per week over 4-6 weeks.4
The results demonstrated that a sub-population of patients (those who were relatively less resistant to medication, having failed not more than two good pharmacologic trials) showed a statistically significant improvement on the Montgomery-Asberg Depression Scale (MADRS), the Hamilton Depression Rating Scale (HAMD), and various other outcome measures. In October 2008, supported by these and other similar results5,6,7, Neuronetics obtained the first and only Food and Drug Administration (FDA) approval for the clinical treatment of a specific form of medication-refractory depression using a TMS Therapy device (FDA approval K061053).
In this paper, we will explore the specified FDA approved NeuroStar depression treatment protocol (to be administered only under prescription and by a licensed medical profession in either an in- or outpatient setting).

In this article, we examine the methodology and considerations relevant to the FDA approved depression treatment protocol using the Neuronetics NeuroStar TMS device.

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic ...

Single Cell Measurement of Dopamine Release with Simultaneous Voltage-clamp and Amperometry

After its release into the synaptic cleft, dopamine exerts its biological properties via its pre- and post-synaptic targets1. The dopamine signal is terminated by diffusion2-3, extracellular enzymes4, and membrane transporters5. The dopamine transporter, located in the peri-synaptic cleft of dopamine neurons clears the released amines through an inward dopamine flux (uptake). The dopamine transporter can also work in reverse direction to release amines from inside to outside in a process called outward transport or efflux of dopamine5. More than 20 years ago Sulzer et al. reported the dopamine transporter can operate in two modes of activity: forward (uptake) and reverse (efflux)5. The neurotransmitter released via efflux through the transporter can move a large amount of dopamine to the extracellular space, and has been shown to play a major regulatory role in extracellular dopamine homeostasis6. Here we describe how simultaneous patch clamp and amperometry recording can be used to measure released dopamine via the efflux mechanism with millisecond time resolution when the membrane potential is controlled. For this, whole-cell current and oxidative (amperometric) signals are measured simultaneously using an Axopatch 200B amplifier (Molecular Devices, with a low-pass Bessel filter set at 1,000 Hz for whole-cell current recording). For amperometry recording a carbon fiber electrode is connected to a second amplifier (Axopatch 200B) and is placed adjacent to the plasma membrane and held at +700 mV. The whole-cell and oxidative (amperometric) currents can be recorded and the current-voltage relationship can be generated using a voltage step protocol. Unlike the usual amperometric calibration, which requires conversion to concentration, the current is reported directly without considering the effective volume7. Thus, the resulting data represent a lower limit to dopamine efflux because some transmitter is lost to the bulk solution.

The amperometric technique measures dopamine release from a single cell by detecting the oxidative current produced by spontaneous dopamine oxidization. Simultaneous voltage clamp and amperometry methodology reveal the mechanistic relationship between the overall "activity" of dopamine transporter and the regulatory role of this activity on the reverse transport of dopamine.

After its release into the synaptic cleft, dopamine exerts its biological properties via its pre- and post-synaptic targets1. The dopamine signal is ...

Olfactory Neurons Obtained through Nasal Biopsy Combined with Laser-Capture Microdissection: A Potential Approach to Study Treatment Response in Mental Disorders

Bipolar disorder (BD) is a severe neuropsychiatric disorder with poorly understood pathophysiology and typically treated with the mood stabilizer, lithium carbonate. Animal studies as well as human genetic studies indicate that lithium affects molecular targets that are involved in neuronal growth, survival and maturation, and notably molecules involved in Wnt signaling. Given the ethical challenge to obtaining brain biopsies for investigating dynamic molecular changes associated with lithium-response in the central nervous system (CNS), one may consider the use of neurons obtained from olfactory tissues to achieve this goal.The olfactory epithelium contains olfactory receptor neurons at different stages of development and glial-like supporting cells. This provides a unique opportunity to study dynamic changes in the CNS of patients with neuropsychiatric diseases, using olfactory tissue safely obtained from nasal biopsies. To overcome the drawback posed by substantial contamination of biopsied olfactory tissue with non-neuronal cells, a novel approach to obtain enriched neuronal cell populations was developed by combining nasal biopsies with laser-capture microdissection. In this study, a system for investigating treatment-associated dynamic molecular changes in neuronal tissue was developed and validated, using a small pilot sample of BD patients recruited for the study of the molecular mechanisms of lithium treatment response.

In this study, a novel platform to investigate intraneuronal molecular signatures of treatment response in bipolar disorder (BD) was developed and validated. Olfactory epithelium from BD patients was obtained through nasal biopsies. Then laser-capture microdissection was combined with Real Time RT PCR to investigate the molecular signature of lithium response in BD.

Bipolar disorder (BD) is a severe neuropsychiatric disorder with poorly understood pathophysiology and typically treated with the mood stabilizer, lithium ...

Preparation of Acute Brain Slices Using an Optimized N-Methyl-D-glucamine Protective Recovery Method

This protocol is a practical guide to the N-methyl-D-glucamine (NMDG) protective recovery method of brain slice preparation. Numerous recent studies have validated the utility of this method for enhancing neuronal preservation and overall brain slice viability. The implementation of this technique by early adopters has facilitated detailed investigations into brain function using diverse experimental applications and spanning a wide range of animal ages, brain regions, and cell types. Steps are outlined for carrying out the protective recovery brain slice technique using an optimized NMDG artificial cerebrospinal fluid (aCSF) media formulation and enhanced procedure to reliably obtain healthy brain slices for patch clamp electrophysiology. With this updated approach, a substantial improvement is observed in the speed and reliability of gigaohm seal formation during targeted patch clamp recording experiments while maintaining excellent neuronal preservation, thereby facilitating challenging experimental applications. Representative results are provided from multi-neuron patch clamp recording experiments to assay synaptic connectivity in neocortical brain slices prepared from young adult transgenic mice and mature adult human neurosurgical specimens. Furthermore, the optimized NMDG protective recovery method of brain slicing is compatible with both juvenile and adult animals, thus resolving a limitation of the original methodology. In summary, a single media formulation and brain slicing procedure can be implemented across various species and ages to achieve excellent viability and tissue preservation.

Preparation of Acute Brain Slices Using an Optimized N-Methyl-D-glucamine Protective Recovery Method

This protocol demonstrates the implementation of an optimized N-methyl-D-glucamine (NMDG) protective recovery method of brain slice preparation. A single media formulation is used to reliably obtain healthy brain slices from animals of any age and for diverse experimental applications.

This protocol is a practical guide to the N-methyl-D-glucamine (NMDG) protective recovery method of brain slice preparation. Numerous recent studies have ...

Extracellular Recording of Neuronal Activity Combined with Microiontophoretic Application of Neuroactive Substances in Awake Mice

Differences in the activity of neurotransmitters and neuromodulators, and consequently different neural responses, can be found between anesthetized and awake animals. Therefore, methods allowing the manipulation of synaptic systems in awake animals are required in order to determine the contribution of synaptic inputs to neuronal processing unaffected by anesthetics. Here, we present methodology for the construction of electrodes to simultaneously record extracellular neural activity and release multiple neuroactive substances at the vicinity of the recording sites in awake mice. By combining these procedures, we performed microiontophoretic injections of gabazine to selectively block GABAA receptors in neurons of the inferior colliculus of head-restrained mice. Gabazine successfully modified neural response properties such as the frequency response area and stimulus-specific adaptation. Thus, we demonstrate that our methods are suitable for recording single-unit activity and for dissecting the role of specific neurotransmitter receptors in auditory processing.
The main limitation of the described procedure is the relatively short recording time (~3 hr), which is determined by the level of habituation of the animal to the recording sessions. On the other hand, multiple recording sessions can be performed in the same animal. The advantage of this technique over other experimental procedures used to manipulate the level of neurotransmission or neuromodulation (such as systemic injections or the use of optogenetic models), is that the drug effect is confined to the local synaptic inputs to the target neuron. In addition, the custom-manufacture of electrodes allows adjustment of specific parameters according to the neural structure and type of neuron of interest (such as the tip resistance for improving the signal-to-noise ratio of the recordings).

We present methods for the construction of electrodes to simultaneously record extracellular neural activity and release multiple neuroactive substances at the vicinity of the recording sites in awake mice. This technique allows the detailed analysis of putative local synaptic inputs to the neuron of interest.

Differences in the activity of neurotransmitters and neuromodulators, and consequently different neural responses, can be found between anesthetized and ...

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic field pulses. The initiation of cortical activation or its modulation depends on the background activation of the neurons of the cortical region activated, the characteristics of the coil, its position and its orientation with respect to the head. TMS combined with simultaneous electrocephalography (EEG) and neuronavigation (nTMS-EEG) allows for the assessment of cortico-cortical excitability and connectivity in almost all cortical areas in a reproducible manner. This advance makes nTMS-EEG a powerful tool that can accurately assess brain dynamics and neurophysiology in test-retest paradigms that are required for clinical trials. Limitations of this method include artifacts that cover the initial brain reactivity to stimulation. Thus, the process of removing artifacts may also extract valuable information. Moreover, the optimal parameters for dorsolateral prefrontal (DLPFC) stimulation are not fully known and current protocols utilize variations from the motor cortex (M1) stimulation paradigms. However, evolving nTMS-EEG designs hope to address these issues. The protocol presented here introduces some standard practices for assessing neurophysiological functioning from stimulation to the DLPFC that can be applied in patients with treatment resistant psychiatric disorders that receive treatment such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST) or electroconvulsive therapy (ECT).

The protocol presented here is for TMS-EEG studies utilizing intracortical excitability test-retest design paradigms. The intent of the protocol is to produce reliable and reproducible cortical excitability measures for assessing neurophysiological functioning related to therapeutic interventions in the treatment of neuropsychiatric diseases such as major depression.

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic ...

Screening of Axonal Degeneration in Carpal Tunnel Syndrome Using Ultrasonography and Nerve Conduction Studies

Axonal degeneration, indicative of surgical decompression, may coexist in carpal tunnel syndrome (CTS) as the disease progresses. However, the current diagnostic and severity gradation system cannot clearly indicate its coexistence, resulting in&#160;confusion of appropriate treatment prescription. There are also constraints in conventional methods for&#160;differentiation as well. This study aims at introducing an innovative, efficient, and quick screening protocol to differentiate axonal degeneration associated with CTS, using ultrasound and nerve conduction studies (NCS). It starts by using NCS to perform orthodromic stimulation at the wrist, to obtain the sensory conduction of the median and the ulnar nerves respectively. Meanwhile, the motor conduction&#160;of the median nerve is collected by stimulating the palm, wrist, and elbow, followed by the stimulation of the ulnar nerve at the wrist,&#160;below and above the elbow. Then, an ultrasound assessment is performed, using a linear array transducer, with cross-sectional area (CSA) and perimeter (P) at the wrist and at the one-third distal forearm calipered. Ratios (R-CSA, R-P) and changes from wrist to one-third distal forearm (&#916;CSA and &#916;P) are calculated according to a standard format. Potential axonal degeneration coexisting in CTS will be screened according to the criteria of NCS and cut-off values of ultrasound measurements established in a previous study. In terms of its noninvasiveness, low cost, convenience, and efficiency, it is easy to apply ultrasound complimentarily in clinical practice to prescreen patients with potential coexisting axonal degeneration. Nevertheless, the ultrasonographic imaging cannot directly reflect axonal degeneration. It still relies on conventional but invasive methods&#160;such as electromyography (EMG) and biopsy&#160;for confirmation if needed.

Here we present a protocol using nerve conduction studies and ultrasound to screen potential axonal degeneration associated with carpal tunnel syndrome. The criteria for differentiation are established. Compared to conventional approaches, this method is noninvasive, convenient, and efficient, with an overall satisfactory accuracy, sensitivity, and specificity.

Axonal degeneration, indicative of surgical decompression, may coexist in carpal tunnel syndrome (CTS) as the disease progresses. However, the current ...