The study was funded by China Postdoctoral Science Foundation funded project (2019M652854) and Natural Science Foundation of Guangdong, China (Grant No. 2020A1515010077).

Inform all participants about the study and ask them to sign the informed consent form prior to the start of the study. The present protocol was approved by the Research Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University.
NOTE: In this double-blind study, patients with depression were randomly divided into two groups. In the experimental group, stimulation targets are located by the DLPFC-sgACC-based individualized location method (Please see 3.3 for detailed description). The targets of the control group are obtained by the average 5-cm method (i.e. (-41, 16, 54))22.
1. Participants&#39; selection
<ol>
	<li>Recruit patients with a diagnosis of MDD as confirmed by an expert psychiatrist. 
	NOTE: Confirm the diagnosis with the standardized MINI-International Neuropsychiatric Interview (M.I.N.I.)23 . The total score of Montgomery-Asberg Depression Rating Scale (MADRS)24 should be no less than 22.</li>
	<li>Exclude patients who meet the exclusion criteria: (1) serious physical diseases such as malignant tumor, acute heart failure, multiple organ failure, or severe neurological conditions including but not limited to epilepsy, stroke, encephalitis, brain trauma; (2) comorbidity of other mental illness, or a history of substance use disorder; (3) having metallic implants, especially in brain or heart; (4) women during pregnancy or lactation; (5) had suicidal behaviors or attempted suicide in the past six months; and (6) a diagnosis of bipolar depression or psychotic depression. 
	&#8203;NOTE: Recruit at least 36 subjects for each group to ensure statistical power. A balanced demographic profile between the two groups is recommended.</li>
</ol>
2. Preparation of Magnetic Resonance Imaging (MRI) and TMS
<ol>
	<li>Obtain fMRI images by a 3T MRI scanner before performing TMS.
	<ol>
		<li>Reconfirm that the patient has no contraindications before an MRI scanning. Instruct the patient to try to lie still and think of nothing during the scan.</li>
		<li>Conduct a resting-state fMRI (rs-fMRI) scan using the FFE-EPI sequence with the following parameters: TR/TE = 2000/30 ms, FA = 90&#176;, field-of-view = 220 x 220 x 256 mm3, matrix = 64 x 64, voxel size = 3.44 x 3.44 x 4 mm3, gap = 0.6 mm, number of signal averages = 1, volumes = 240, number of slices = 33.</li>
		<li>Conduct a structural MRI scan using the sagittal T1 weighted 3D turbo field echo (T1W 3D TFE) sequence with the following parameters: field of view = 256 x 256 mm2, TR/TE = 8.2/3.8 ms, view matrix= 256 x 256, slice thickness= 1 mm.</li>
	</ol>
	</li>
	<li>Set TMS parameters. 
	NOTE: The protocol of TMS in our study is the intermittent theta-burst stimulation (iTBS). A daily treatment session includes 60 cycles of 10 bursts of 3 pulses at 50 Hz delivered at 100% RMT in 2-s trains, with an interval of 8 s. The whole treatment consists of 10 sessions carried out on weekdays of two consecutive weeks.</li>
</ol>
3. Treatment (Figure 1)
<ol>
	<li>Conduct MRI scans and clinical assessments of symptoms and cognitive performance one day before the treatment.</li>
	<li>Assign the patient randomly to one of the two groups, after scanning.</li>
	<li>For the experimental group, identify the subregion of DLPFC that shows strongest functional anti-connectivity with sgACC. For the control group, simply locate the target in the standard-space using the average 5-cm method, then convert it to the individual space coordinates.
	<ol>
		<li>rs-fMRI data preprocessing
		<ol>
			<li>Preprocess the rs-fMRI data using an MRI analysis software: (a) remove the first 10 volumes; (b) conduct&#160; the slice timing correction; (c) correct the head motion; (d) co-register EPI images to T1 images; (e) perform segmentation; (f) perform normalization using T1 images; (g) smooth the normalized images with a 6-mm Gaussian kernel of full-width half maximum (FWHM); (h) band-pass filter (0.01 - 0.08 Hz); and (i) perform nuisance regression (head motion effects, linear trends, white matter, cerebrospinal fluid, and global mean time course).</li>
		</ol>
		</li>
		<li>Functional connectivity (FC) of the sgACC
		<ol>
			<li>Select the sgACC (MNI coordinate: 6, 16, &#8722;10; Fox et al.) as the region of interest (ROI)25 with a 10-mm radius.</li>
			<li>Remove the white matter and cerebrospinal fluid in the ROI based on the Harvard-Oxford cortical atlas (http://www.cma.mgh.harvard.edu/),&#160;using a gray matter probability threshold of 0.25.</li>
			<li>Extract the average time course of the ROI.</li>
			<li>To generate FC map, compute Pearson&#39;s correlation coefficients between the ROI (sgACC) and DLPFC in a voxel-wise manner. Normalize each correlation coefficient using the Fisher&#39;s r-to-z Transformation. 
			NOTE: The DLPFC mask is a combination of 20mm radius spheres centered along the left hemisphere at BA9 (x=-36, y=39, z=43), BA46 (x=-44, y=40, z=29), the 5-cm approach site (x=-41, y=16, z=54), and the F3 Beam group-average stimulation site (x=-39, y=26, z=49)26.</li>
			<li>According to the FC map, identify the peak coordinate in DLPFC that has the largest Pearson&#39;s anti-correlation coefficient with sgACC. This is the subregion of DLPFC with the strongest negative FC with sgACC, which will be later targeted in the TMS treatment for the experimental group.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Determine the resting motor threshold (RMT) for each subject and record the hotspot.
	<ol>
		<li>Instruct the patient to sit back and relax, then put two recording electrodes on the thenar of the right hand and a reference electrode on the bony part of the wrist.</li>
		<li>Stimulate the motor hotspot with 10 consecutive stimulations with different intensities; in the meanwhile, record the times of thenar muscle contraction.</li>
		<li>Identify the minimum TMS intensity at which a motor evoked potential (MEP) &#8805; 50 &#181;V is recorded at least 5 times. Define it as the patient&#39;s RMT.</li>
	</ol>
	</li>
	<li>Assess the severity of depression using clinical scales as described in Clinical Data Collection.</li>
	<li>Perform TMS treatment twice a day for 10 days. 
	NOTE: For a subject who did not receive treatments as planned, perform additional stimulations after the end of treatment course as needed. However, any subject who misses the treatment for more than four consecutive days should be excluded.
	<ol>
		<li>Create a new patient entry.
		<ol>
			<li>Select the option Create New Patient. Input the patient&#39;s ID number or name in the textbox.</li>
		</ol>
		</li>
		<li>Overlay the structural MRI images onto the navigation system.
		<ol>
			<li>Select Import patient MRI, and then import the structural image of the patient and select the image type.</li>
		</ol>
		</li>
		<li>Create individual head model and define the stimulation target.
		<ol>
			<li>Press the button Specify MRI Fiducials.</li>
			<li>Place the crosshair on these spots in the MRI image: (1) Fiducial Markers: nasion, both left and right tragi; (2) AC-PC Markers for Talairach: anterior commissure, posterior commissure, inter-hemispheric point; (3) Talairach Markers: anterior point, posterior point, superior point, inferior point, left point, and right point. 
			NOTE: The &#34;Talairach Markers&#34; mark the borders of the brain.</li>
			<li>Press Create Head Model. Select Manual Brain Segmentation and adjust the threshold of the scalp, the lower brain, and the upper brain.</li>
			<li>Click Define Target to proceed.</li>
			<li>Select Target Marker page. Click &#8230; to input the coordinate of the treatment target as identified in step 3.3, and then press Go to. Press Add Marker to name the point. 
			NOTE: The coordinates of the control group will be (-41, 16, 54).</li>
		</ol>
		</li>
		<li>Coil calibration
		<ol>
			<li>Click Proceed to Neuronavigation. In the textbox, select the right type of tools to be used in the treatment. Ensure all the tools of reference are in the view of the infrared camera.</li>
			<li>Press Validate Coil. Put the tip of pointer on the marked coil point. Press Validate (or the green button on the remote control) when the indicator of each tool turns green.</li>
		</ol>
		</li>
		<li>Select patient and target.
		<ol>
			<li>Select patient&#39;s name or ID on the Select Patient page. Click Select Targets on the next page.</li>
			<li>Choose Read target markers to browse the file of targets. Import the file and select the target as in step 3.6.3.5.</li>
		</ol>
		</li>
		<li>Define the coordinate system.
		<ol>
			<li>Click Define Coordinate System. Put a headband with a reference tool on the patient. Make sure the coil tracker and the reference tool are in the vision of the navigation system.</li>
			<li>Place pointer&#39;s tip on the nasion and both tragi in turn. Press the green button on the remote control each time when the indicator of a marker turns green.</li>
		</ol>
		</li>
		<li>Head shape generation
		<ol>
			<li>Continuously move the pointer&#39;s tip on the top of the head. Press the button on the remote control (or Fit) to continue. 
			NOTE: One can press Pause to stop the process, and resume by pressing the Start button again, once the pointer has been placed correctly.</li>
		</ol>
		</li>
		<li>Neuronavigation and stimulation
		<ol>
			<li>Press Neuronavigation. On the Active Coil page, set the stimulation intensity to 100% RMT. Choose Stimulate at targets to see the target on the head model online.</li>
			<li>When the coil matches the target crosshair, that is, when the indicator text turns green, stimulate.</li>
		</ol>
		</li>
		<li>Prepare and start the treatment from step 3.6.4 directly if the patient&#39;s entry had been created before.</li>
	</ol>
	</li>
	<li>Conduct follow-up assessments on Day 1, Day 28, and Day 56 after the whole treatment course.</li>
</ol>
4. Clinic data collection (Figure 1b)
<ol>
	<li>Perform clinical assessments using MADRS24, Hamilton Depression Rating Scale (HAMD)27, Beck Depression Inventory-II (BDI-II)28, Hamilton Anxiety Scale (HAMA)29, Clinical Global Impression (CGI)30 and MATRICS Consensus Cognitive Battery (MCCB)31,32. 
	NOTE: MINI and MADRS are used for the screening. All the above scales are applied for pre- and post-treatment clinical assessment.</li>
</ol>

Authors have no disclosures to report.

The sgACC is responsible for emotional processing and plays an important role in stress regulation16,17,18. A study suggests that targeting on a subregion of DLPFC that shows strongest functional anti-connectivity with sgACC (6, 16, -10) may enhance the antidepressant effect25. Therefore, precisely locating this target is the critical step of this protocol. Before the stimulation, the borders of the brain...

Major depressive disorder (MDD) is characterized by significant and persistent depression, and in more severe cases, patients can encounter hallucinations and/or delusions1,2. Compared with the general population, the risk of suicide among MDD patients is approximately 20 times higher3. While medication is currently the most used treatment for MDD, 30% - 50% of the patients lack adequate response to antidepressants4. For the responders, the symptom improvement tends to appear after a relatively long latent period and is accompanied by side effects. Psychotherapy, although effective for some patients, is costly and time-consuming. A safer and more effective treatment for MDD is therefore urgently required.
Repetitive transcranial magnetic stimulation (rTMS)is a non-invasive and safe technique and has been approved for the treatment of various mental disorders5,6,7. Although its therapeutic mechanism remains unclear, rTMS was speculated to work by regulating the activity of the stimulated brain regions and the neural plasticity8,9,10, thus normalizing specific functional networks10,11,12. rTMS also causes network effect, which evokes changes in remote brain areas through connection pathways, leading to an amplified therapeutic effect13. Although rTMS changes brain activity immediately and robustly, its response rate in the treatment of MDD is only about 18%14. The main reason may be the inaccurate location of stimulation targets15.
The subgenual anterior cingulate cortex (sgACC) is mainly responsible for emotional processing and plays a role in regulating the response to stressful events, emotional response to internal and external stimuli, and emotional expression16,17,18. This subregion of ACC shares substantial structural and functional connectivity with the cerebral cortex and the limbic system19,20. Interestingly, studies have shown that the post-stimulation activity of this area is closely related to the clinical efficacy of TMS. For instance, the blood flow of sgACC decreased after a course of TMS targeted on the right dorsolateral prefrontal cortex (DLPFC), which was associated with the alleviation of depressive symptoms21. Vink et al.8 found that stimulation targeted on DLPFC was propagated to sgACC, and suggested that sgACC activity can be a biomarker of the treatment response of TMS. According to previous researches, Fox and colleagues22&#160;proposed that targeting on a subregion of DLPFC that shows strongest functional anti-connectivity with sgACC (MNI coordinate: 6, 16, -10) enhances the antidepressant effect. Here, we demonstrate a study protocol aimed to examine this hypothesis.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3T Philips Achieva MRI scanner</td>
			<td>Philips</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Harvard/Oxford cortical template</td>
			<td>http://www.cma.mgh.harva rd.edu/</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>MATLAB</td>
			<td>MathWorks</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>SPM12</td>
			<td>http://www.fil.ion.ucl.ac.uk/spm</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>The Visor2 system</td>
			<td>ANT Neuro</td>
			<td></td>
			<td>The Visor2 software, the optical tracking system, tracking tools and calibration board are part of the visor2 system.</td>
		</tr>
		<tr>
			<td>TMS device</td>
			<td>Magstim, Carmarthenshire, UK</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

individualized rtms treatment for depression using an fmri-based targeting method

To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe neuromodulation technique that immediately changes brain activity. Despite its wide application in the treatment for MDD, the treatment response remains different among individuals, which may be attributable to the inaccurate positioning of the stimulation target. Our study aims to examine whether the functional magnetic resonance imaging (fMRI)-assisted positioning improves the efficacy of rTMS in treating depression. We intend to identify and stimulate the subregion of dorsolateral prefrontal cortex (DLPFC) in MDD with strongest anti-correlation with the subgenual anterior cingulate cortex (sgACC), and to conduct a comparative investigation of this novel method and the traditional 5-cm rule. To achieve more precise stimulation, both methods were applied under the guidance of neuronavigation system. We expected that the TMS treatment with individualized positioning based on resting state functional connectivity may show better clinical efficacy than the 5-cm method.

ROI-wise FC analysis should show that sgACC is significantly anti-correlated with DLPFC, in which the strongest negative correlation is the stimulus target to be chosen. Significant anti-correlation between the sgACC-DLPFC functional connectivity and the treatment response should be found in the correlation analysis33.
The current protocol is based on an innovative TMS targeting method that no previous studies have applied. Here we present results from an fMRI-guided TM...

Watch this Scientific Journal Video about Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method at JoVE.com

Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

The present protocol describes the application of repetitive transcranial magnetic stimulation (rTMS), where a subregion of the dorsolateral prefrontal cortex (DLPFC) with the strongest functional anticorrelation with the subgenual anterior cingulate cortex (sgACC) was located as the stimulation target under the assistance of a fMRI-based neuronavigation system.

To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial ...

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3.3K Views.  Affiliated Brain Hospital of Guangzhou Medical University. The present protocol describes the application of repetitive transcranial magnetic stimulation (rTMS), where a subregion of the dorsolateral prefrontal cortex (DLPFC) with the strongest functional anticorrelation with the subgenual anterior cingulate cortex (sgACC) was located as the stimulation target under the assistance of a fMRI-based neuronavigation system.

Video: Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals and humans. However, many animal models of depression were developed in males and are not applicable or effective in studies of postpartum females. Recent studies have reported significant effects of chronic social stress during lactation, an ethologically relevant and effective stressor, on maternal behavior, growth, and behavioral neuroendocrinology. This manuscript will describe this chronic social stress paradigm using repeated exposure of a lactating dam to a novel male intruder, and the assessment of the behavioral, physiological, and neuroendocrine effects of this model. Chronic social stress (CSS) is a valuable model for studying the effects of stress on the behavior and physiology of the dam as well as her offspring and future generations. The exposure of pups to CSS can also be used as an early life stress that has long term effects on behavior, physiology, and neuroendocrinology.

This article describes the use of chronic resident intruder social stress as an ethologically relevant paradigm to model postpartum depression and anxiety in lactating rodents.

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals ...

Design and Implementation of an fMRI Study Examining Thought Suppression in Young Women with, and At-risk, for Depression

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the frequency of their negative thoughts by actively suppressing them. We aim to identify the neural correlates underlying thought suppression in at-risk and depressed individuals. Three groups of women were studied; a major depressive disorder group, an at-risk group (having a first degree relative with depression) and controls. Participants performed a mixed block-event fMRI paradigm involving thought suppression, free thought and motor control periods. Participants identified the re-emergence of &#8220;to-be-suppressed&#8221; thoughts (&#8220;popping&#8221; back into conscious awareness) with a button press. During thought suppression the control group showed the greatest activation of the dorsolateral prefrontal cortex, followed by the at-risk, then depressed group. During the re-emergence of intrusive thoughts compared to successful re-suppression of those thoughts, the control group showed the greatest activation of the anterior cingulate cortices, followed by the at-risk, then depressed group. At-risk participants displayed anomalies in the neural regulation of thought suppression resembling the dysregulation found in depressed individuals. The predictive value of these changes in the onset of depression remains to be determined.

We aim to identify the neural correlates underlying sustained and transient thought suppression, and thought re-emergence in controls, at-risk and depressed individuals. Activation was greatest for controls compared to the at-risk and the depressed group in the dorsolateral prefrontal cortex during thought suppression and anterior cingulate cortex during thought re-emergence.

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the ...

Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression.
Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.

Here we present a protocol outlining the methodology for treatment of Major Depressive Disorder using the deep Transcranial Magnetic Stimulation (dTMS) system.

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses ...

How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The coils are made of soft copper windings in multiple planes that lie adjacent to the skull. They are located within a special helmet so that their magnetic fields combine and improve depth penetration. The H1 dTMS coil is designed to stimulate bilateral prefrontal cortices with greater effective stimulation over the left than the right. By positioning the left side of the coil close to the left dorsolateral prefrontal cortex (DLPFC), the H1 coil was used in a multisite study, leading to FDA approval for treatment-resistant depression. In this same position, the H1 coil was also explored as a possible treatment for negative symptoms of schizophrenia, bipolar depression, and migraine. When moved to different positions over the subject's skull, the H1 coil was also explored as a possible treatment for other conditions. Such manipulation of the H1 coil was demonstrated for PTSD and alcohol dependence by positioning it over the medial prefrontal cortex (mPFC), for anxiety by positioning it over the right prefrontal cortex (rPFC), for auditory hallucinations and tinnitus by positioning it over the temporoparietal junction (TPJ), and for Parkinson's and fatigue from multiple sclerosis (MS) by positioning it over the motor cortex (MC) and PFC. Corresponding electrical field diagrams measured with an oscilloscope through a saline-filled head are included.

The H1 deep transcranial magnetic stimulation coil is FDA-cleared for the treatment of depression. We demonstrate how to utilize the H1 for other conditions, such as auditory hallucinations and PTSD, by moving the helmet to different locations over the subject's skull.

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The ...

A New Method for Inducing a Depression-Like Behavior in Rats

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is no existing format for studying the mechanism of action, prevention, containment, and treatment of contagious depression. The purpose of this study, therefore, was to establish the first animal model of contagious depression.
Healthy rats can contract depressive behaviors if exposed to depressed rats. Depression is induced in rats by subjecting them to several manipulations of chronic unpredictable stress (CUS) over 5 weeks, as described in the protocol. A successful sucrose preference test confirmed the development of depression in the rats. The CUS-exposed rats were then caged with na&#239;ve rats from the contagion group (1 na&#239;ve rat/2 depressed rats in a cage) for an additional 5 weeks. 30 social groups were created from the combination of CUS-exposed rats and na&#239;ve rats.
This proposed depression-contagion protocol in animals consists mainly of cohabiting CUS-exposed and healthy rats for 5 weeks. To ensure that this method works, a series of tests are carried out - first, the sucrose preference test upon inducing depression to rats, then, the sucrose preference test, alongside the open field and forced-swim tests at the end of the cohabitation period. Throughout the experiment, rats are given tags and are always returned to their cages after each test.
A few limitations to this method are the weak differences recorded between the experimental and control groups in the sucrose preference test and the irreversible traumatic outcome of the forced swim test. These may be worth considering for suitability before any future application of the protocol. Nonetheless, following the experiment, na&#239;ve rats developed contagion depression after 5 weeks of sharing the same cage with the CUS-exposed rats.

This protocol describes a new model by which healthy rats could contract depression over a given time periodthrough contagion by exposure to chronic unpredictable stressed (CUS) rats.

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is ...

Evaluating the Anti-depression Effect of Xiaoyaosan on Chronically-stressed Mice

In addition to the standardized use of antidepressant medications and psychotherapy, the usage of traditional Chinese medicine has lead to an overall improvement of patients with major depressive disorder (MDD). Therefore, the purpose of this study was to establish the mouse depressive model, observe the behavior changes associated with chronic unpredictable mild stress (CUMS), and then evaluate the anti-depression effect of Xiaoyaosan. Mice were randomly divided into four groups: a control group, a model group, a treatment group with Xiaoyaosan, and a treatment group with fluoxetine. All mice were individually kept in cages, and depression was induced in the mice by exposing them to several designed manipulations of CUMS for 21 days, as described in the protocol. Mice in the control group and model group received 0.5 mL of distilled water, while mice in the treatment groups received either Xiaoyaosan (0.25 g/kg/day) or fluoxetine (2.6 mg/kg/day). The drugs used in the study were given intragastrically daily during the entire three weeks. To estimate the depressive-like behaviors, a series of parameters including the coat state, body weight, open field test score, and sucrose preference test score were recorded. Data analysis showed that behaviors of model mice were significantly changed compared to behaviors of mice in the control group, which were improved by the treatment of Xiaoyaosan and fluoxetine. The current findings demonstrated the anti-depression effects of Xiaoyaosan on the behaviors of CUMS-induced mice and revealed that compounds from the Xiaoyaosan prescription may be worthwhile for treating depression, considering their beneficial effects on depressive-like behaviors.

Here, we present a protocol to establish the mouse depressive model, observe the behavior changes associated with chronic unpredictable mild stress (CUMS), and evaluate the anti-depression effect of Xiaoyaosan.

In addition to the standardized use of antidepressant medications and psychotherapy, the usage of traditional Chinese medicine has lead to an overall ...

A Middle Cerebral Artery Occlusion Technique for Inducing Post-stroke Depression in Rats

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of all ischemic stroke patients suffer from PSD, a disorder considered to be an ischemic stroke-related precursor for increased death and degradation in health. The pathophysiology of PSD is still obscure. To study the mechanism of development and occurrence of PSD further, and to find out a therapy, we attempted to develop a new protocol that requires occluding the middle cerebral artery (MCA) via the internal carotid artery (ICA) in rats. This protocol describes a model of PSD induced in rats through the middle cerebral artery occlusion (MCAO). Also used in the experiment are the Porsolt forced swim test and the sucrose preference test to confirm and evaluate the depressive mood of the rats under investigation. Rather than inserting the catheter through the external carotid artery (ECA), as stipulated for the original procedure, this MCAO technique has the monofilament passing directly through the ICA. This MCAO technique was developed a few years ago and leads to a reduction in mortality and variability. It is generally accepted that the criteria used are preferred in the selection of biological models. The data obtained with this protocol show that this model of MCAO could be a way of inducing PSD in rats and could potentially lead to the understanding of the pathophysiology and the future development of new drugs and other neuroprotective agents.

Here we present a protocol to induce post-stroke depression in rats by occluding the middle cerebral artery via the internal carotid artery. We use the Porsolt forced swim test and the sucrose preference test to confirm and evaluate induced depressive moods.

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of ...

A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice

Depression is not yet fully understood, but various causative factors have been reported. Recently, the prevalence of depression has increased. However, therapeutic treatments for depression or research on depression is scarce. Thus, in the present paper, we propose a mouse model of depression induced by movement restriction. Chronic mild stress (CMS) is a well-known technique to induce depressive-like behavior. However, it necessitates a complex procedure consisting of a combination of various mild stresses. In contrast, chronic immobilization stress (CIS) is a readily accessible chronic stress model, modified from a restraint model that induces depressive behavior by restricting movement using a restrainer for a certain period. To evaluate the depressive-like behaviors, the sucrose preference test (SPT), the tail suspension test (TST), and the ELISA assay to measure stress marker corticosterone levels are combined in the present experiment. The described protocols illustrate the induction of CIS and evaluation of the changes in behavior and physiological factors for the validation of depression.

This article provides a simplified and standardized protocol for induction of depressive-like behavior in chronically immobilized mice by using a restrainer. In addition, behavior and physiological techniques to verify induction of depression are explained.

Depression is not yet fully understood, but various causative factors have been reported. Recently, the prevalence of depression has increased. However, ...

Animal Models of Depression - Chronic Despair Model (CDM)

Major depressive disorder is one of the most prevalent forms of mental illnesses and causes tremendous individual suffering and socioeconomic burden. Despite its importance, current pharmacological treatment is limited, and novel treatment options are urgently needed. One key factor in the search for potential new drugs is evaluating their anti-depressive potency in appropriate animal models. The classical Porsolt forced swim test was used for this purpose for decades to induce and assess a depressive-like state. It consists of two short periods of forced swimming: the first to induce a depressed state and the second on the following day to evaluate the antidepressant effect of the agent given in between the two swim sessions. This model might be suitable as a screening tool for potential antidepressive agents but ignores the delayed onset of action of many antidepressants. The CDM was recently established and represented a modification of the classical test with notable differences. Mice are forced to swim for 5 consecutive days, following the idea that in humans, depression is induced by chronic rather than by acute stress. In a resting period of several days (1-3 weeks), animals develop sustained behavioral despair. The standard read-out method is the measurement of immobility time in an additional delayed swim session, but several alternative methods are proposed to get a broader view of the mood status of the animal. Multiple analysis tools can be used targeting behavioral, molecular, and electrophysiological changes. The depressed phenotype is stable for at least 4 weeks, providing a time window for rapid but also subchronic antidepressant treatment strategies. Furthermore, alterations in the development of a depressive-like state can be addressed using this approach. CDM, therefore, represents a useful tool to better understand depression and to develop novel treatment interventions.

Animal Models of Depression - Chronic Despair Model CDM

The chronic despair mouse model (CDM) of depression consists of repetitive forced swim sessions and another delayed swim phase as a read-out. It represents a suitable model for induction of a chronic depressive-like state stable for at least 4 weeks, amendable to evaluate subchronic and acute treatment interventions.

Major depressive disorder is one of the most prevalent forms of mental illnesses and causes tremendous individual suffering and socioeconomic burden. ...

Investigating Migraine-Like Behavior Using Light Aversion in Mice

Migraine is a complex neurological disorder characterized by headache and sensory abnormalities, such as hypersensitivity to light, observed as photophobia. Whilst it is impossible to confirm that a mouse is experiencing migraine, light aversion can be used as a behavioral surrogate for the migraine symptom of photophobia. To test for light aversion, we utilize the light/dark assay to measure the time mice freely choose to spend in either a light or dark environment. The assay has been refined by introducing two critical modifications: pre-exposures to the chamber prior to running the test procedure and adjustable chamber lighting, permitting the use of a range of light intensities from 55 lux to 27,000 lux. Because the choice to spend more time in the dark is also indicative of anxiety, we also utilize a light-independent anxiety test, the open field assay, to distinguish anxiety from light-aversive behavior. Here, we describe a modified test paradigm for the light/dark and open field assays. The application of these assays is described for intraperitoneal injection of calcitonin gene-related peptide (CGRP) in two mouse strains and for optogenetic brain stimulation studies.

Rodents are not able to report migraine symptoms. Here, we describe a manageable test paradigm (light/dark and open field assays) to measure light aversion, one of the most common and bothersome symptoms in patients with migraines.