Name: a novel approach to assess motor outcome of deep brain stimulation effects in the hemiparkinsonian rat: staircase and cylinder test
Uploaded: 2016-05-31T13:00:00
Description: Watch this Scientific Journal Video about A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test at JoVE.com

This work was supported by Interdisziplin&#228;res Zentrum f&#252;r Klinische Forschung (IZKF), University Clinics W&#252;rzburg, Germany (project N-215).

Animal experiments were approved by the University of Wuerzburg and the legal state authorities of Lower Franconia in accordance with the animal protection guidelines and European Communities Council guidelines (approval number: 55.2-2531.01 76/11). All efforts were made to minimize pain or discomfort of the animals used.
Note: Electrode implantation was performed as described elsewhere18.
1. Cylinder Test (Figure 2)
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	<li>Prepare a clear plastic gl...

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S., 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=Fully+Implantable+Deep+Brain+Stimulation+System+with+Wireless+Power+Transmission+for+Long-term+Use+in+Rodent+Models+of+Parkinson's+Disease.">Fully Implantable Deep Brain Stimulation System with Wireless Power Transmission for Long-term Use in Rodent Models of Parkinson's Disease.</a> Journal of Korean Neurosurgical Society. 57, 152-158 (2015).</li><li>Gut, N. K., Winn, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+brain+stimulation+of+different+pedunculopontine+targets+in+a+novel+rodent+model+of+parkinsonism.">Deep brain stimulation of different pedunculopontine targets in a novel rodent model of parkinsonism.</a> J. Neurosci. 35, 4792-4803 (2015).</li><li>Whishaw, I. Q., Gorny, B., Foroud, A., Kleim, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-Evans+and+Sprague-Dawley+rats+have+similar+skilled+reaching+success+and+limb+representations+in+motor+cortex+but+different+movements:+some+cautionary+insights+into+the+selection+of+rat+strains+for+neurobiological+motor+research.">Long-Evans and Sprague-Dawley rats have similar skilled reaching success and limb representations in motor cortex but different movements: some cautionary insights into the selection of rat strains for neurobiological motor research.</a> Behavioural brain research. 145, 221-232 (2003).</li><li>Honndorf, S., Lindemann, C., Tollner, K., Gernert, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Female+Wistar+rats+obtained+from+different+breeders+vary+in+anxiety-like+behavior+and+epileptogenesis.">Female Wistar rats obtained from different breeders vary in anxiety-like behavior and epileptogenesis.</a> Epilepsy research. 94, 26-38 (2011).</li><li>Jadavji, N. 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This article describes a detailed training protocol for the cylinder and staircase test. The latter is designed to assess complex grasping behavior and fine motor movement due to skilled reaching in rats16,17. The outcome measurement is expressed as number of pellets eaten during the test, which is an objective measurement. The protocol can be used in rat models for Parkinson&#39;s disease and other motor disease models. The cylinder test involves a simple approach to evaluate paw use in rats. It requires no t...

Deep brain stimulation of the subthalamic nucleus (STN) is an effective treatment option for Parkinson&#39;s disease1 and other movement disorders. The underlying mechanisms are still poorly understood and multifactorial, but a key feature is the modulation of neuronal network activity by repetitive depolarization of axons in the vicinity of the stimulating electrode2-4. High-frequency (&#62;100 Hz) stimulation is required for a beneficial effect in most brain targets and for most indications of DBS. Side effects of deep brain stimulation result from inadvertent coactivation of other fibers, which are covered by the stimulation volume and which subserve different functions, such as the pyramidal tract. Hence, it would be desirable to develop stimulation parameters, which preferentially activate beneficial neural elements, while avoiding the coactivation of side effect elements5,6. Although neurophysiology may offer such fine tuning options of DBS, the scientific progress has been minimal during the past two decades, because programming strategies have primarily been assessed by &#34;trial and error&#34; in patients and restricted by the limited programming options of commercially available DBS devices, rather than using neurophysiological insight and defined experimental settings to systematically explore the full parameter space.
To overcome the translational roadblock in DBS research we are proposing a protocol to screen alternative stimulation parameters in rodent models of Parkinsonism prior to clinical exploration. Unilateral Parkinson&#39;s disease in rats is modeled using 6-hydroxydopamine injections into the right medial forebrain bundle7,8. The resulting lesion, described further as hemiparkinsonian, is assessed in the apomorphine test by evaluation of rotation score after low dose apomorphine injection and confirmed post mortem by tyrosine hydroxylase immunohistochemistry. The method is easy to apply and highly reproducible, while bearing a low mortality and morbidity. The resulting motor deficits are very discrete7,8; the animals exhibit a slight impairment of the contralateral left paw during both spontaneous exploration and complex grasping behavior9,10.
To assess the effectiveness of deep brain stimulation protocols tests are required which allow measuring a quick and reliable change in motor performance and can be repeated over time with different neurostimulation settings. Several groups have proposed different stimulation approaches and different tests to assess the motor functions in rats11 with highly variable and inconsistent outcomes11-14. This forced us to choose a set of tests with high predict validity and complementarity. Additionally, for assessment of motor outcome under deep brain stimulation conditions, tests were favored which could be performed by animals connected via cable to the stimulus generator. For these purposes we established our test battery consisting of one test for paw use asymmetry and one test for skilled reaching. The study design is illustrated in Figure 1.
For spontaneous paw use we performed the cylinder test described by Shallert15, which is a widely used test for paw use during vertical exploration. No training of the animal is required. For the assessment of more complex grasping behavior we established the staircase test according to Montoya16. Our protocol is modified according to Kloth17. The rats are trained for a period of twelve days in reaching pellets from the test box. After the training period the test can be applied to measure the complex grasping behavior by counting the success rate described as number of pellets eaten. The article presents the detailed training in the staircase box as well as the performance of both behavioral tests under na&#239;ve, hemiparkinsonian and deep brain stimulation conditions.

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			<td height="42" style="height:42px;width:216px;">Staircase box witout lid</td>
			<td style="width:71px;">Glas Keil, Germany</td>
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			<td height="42" style="height:42px;width:216px;">Cylinder box</td>
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a novel approach to assess motor outcome of deep brain stimulation effects in the hemiparkinsonian rat: staircase and cylinder test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson&#39;s lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.

All animals underwent a post mortem histological verification of both the dopaminergic lesion and the electrode location. Only animals with correct electrode placement inside the STN (Figure 6) and complete dopaminergic lesion (&#62;90% loss of dopaminergic neurons in substantia nigra) were included into the results section (Figure 7).
The cylinder test performed under lesioned condition showed ...

Watch this Scientific Journal Video about A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test at JoVE.com

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

The overall goal of this behavioral test battery, is to assess paw use assymetry in Hemiparkinsonian rats. This method can help answer key questions in the experimental deep brain stimulation field such as the motor outcome and the different stimulation patterns. The main advantage of this technique is that the cylinder test and the staircase test are complimentary and they can be both used easily in animal stimulated via cable.Demonstrating the procedure will be Dr.Milos Krstic, from my laboratory. Always perform behavioral tests at the same time of day to avoid circadian differences in activity. For the cylinder test, begin with cleaning a 40 centimeter tall, 19 centimeter diameter clear, plastic glass cylinder with a 0.1%acetic acid solution.Once well-cleaned, position two mirrors at a 90 degree angle behind the cylinder. Place the camera in front of the cylinder such are the distance between camera and the cylinder allows for a good view of the animal's paws when in the cylinder. Then, place the rat in the cylinder.If the animal is connected to the stimulus generator, make sure the cable is not twisted. Now, start the recording and flash a card to the camera with the actual date of the experiment and the rat's indentification number. After five minutes of recorded activity, return the rat to its home cage.Then, clean the cylinder again before running the next rat. In the video, count how often the front left and front right paws contact the wall. Also, count how often the rat stands on its hind paws with or without supporting itself with its front paws.These are called rearings. One day prior to the training, familiarize the rats with the staircase apparatus and pellet rewards. First, prepare a clear plastic glass staircase box by cleaning the box with 0.1%acetic acid.The staircase box is a two-compartment box with a raised platform and two stairs in a narrow compartment. The left steps on the stairs can be reached only with the left paw. The right steps can only be reached with the right paw.This is a standard commercially available box, but if the rats are to be stimulated via a cable, use a high box without a lid. Now, remove the staircase and fill the wells on each step with eight 45-milligram pellets. Then, replace the staircase and put eight additional pellets on the heightened platform.Now, place the rat in the box and after five minutes, return the rat to its home cage. Score how many pellets were eaten from the platform. Before the next test, wash the staircase and reload it with pellets.The acquisition phase should be performed once per day for three days. Over the next three days, run the free choice phase of the test. It is executed just like the acquisition phase, but now score how many pellets were eaten from the two staircases.If the animals have problems with grasping the pellet, add some more on the platform where they can be easily reached. Then, for six days, run the forced choice phase of the test. During this phase, only load pellets into the same side of the staircase as the occurred impairment.A lesion of the right hemisphere would require testing the left paw and thus loading the left staircase. Over the first three of these days, load one staircase side with eight pellets per step. But on the fourth through sixth days, only load that side with four pellets per step.For a successful staircase training, it is crucial to motivate a animal during the acquisition phase. It is important that the rat is able to grab some pellets at first grasping approach because the immediate reward resides in good training effect in the later phases. Another critical step of course, when the rat is not interested in the task, it can be then necessary to apply a mild foot restriction until the proper motivation level is reached.Tested animals were given dopaminergic lesions and STN-placed electrodes. Data was only included in the analysis when post-mortem analysis confirmed a correct electrode placement and lesion propagation. The cylinder test revealed that the lesioned paw use decreased to about 15%After 24 hours of deep-brain stimulation delivered to the STN for 60 microseconds, at 130 hertz frequency, the use of the lesioned paw increased to roughly 22%The result was encouraging, but not significant.In the staircase test, normal animals retrieved about half the pellets after 12 days of testing. Lesioned animals could only retrieve about 10%of the pellets. After deep-brain stimulation however, a significant improvement was made and they retrieved about 25%of the pellets.In neither test, did the stimulation cable effect the results. Animals reared as expected and ran the staircase as expected. After watching this video, you should have a good understanding how to train the rats in the staircase test and how to use the presented behavioral test battery to screen different stimulation patterns in rats.While attempting this procedure, it is important to remember that to handle the animals before starting the behavioral test. The test should be always performed by the same experimenter to avoid stress in the animals. Don't forget that while working with animals with implanted deep-brain stimulation electrodes, you should be extremely careful and the animals should be daily controlled for signs of pain or distress during the whole procedure.

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JoVE Journal

Behavior

Stereotactic Injection of MicroRNA-expressing Lentiviruses to the Mouse Hippocampus CA1 Region and Assessment of the Behavioral Outcome

MicroRNAs (miRNAs) are small regulatory single-stranded RNA molecules around 22 nucleotides long that may each target numerous mRNA transcripts and dim an entire gene expression pathway by inducing destruction and/or inhibiting translation of these targets. Several miRNAs play key roles in maintaining neuronal structure and function and in higher-level brain functions, and methods are sought for manipulating their levels for exploring these functions. Here, we present a direct in vivo method for examining the cognitive consequences of enforced miRNAs excess in mice by stereotactic injection of miRNA-encoding virus particles. Specifically, the current protocol involves injection into the hippocampal CA1 region, which contributes to mammalian memory consolidation, learning, and stress responses, and offers a convenient injection site. The coordinates are measured according to the mouse bregma and virus perfusion is digitally controlled and kept very slow. After injection, the surgery wound is sealed and the animals recover. Lentiviruses encoding silencers of the corresponding mRNA targets serve to implicate the specific miRNA/target interaction responsible for the observed effect, with na&iuml;ve mice, mice injected with saline and mice injected with "empty" lentivirus vectors as controls. One month post-injection, the animals are examined in the Morris Water Maze (MWM) for assessing their navigation learning and memory abilities. The MWM is a round tank filled with colored water with a small platform submerged 1 cm below the water surface. Steady visual cues around the tank allow for spatial navigation (sound and the earth's magnetic field may also assist the animals in navigating). Video camera monitoring enables measuring the route of swim and the time to find and amount the platform. The mouse is first taught that mounting the hidden platform offers an escape from the enforced swimming; it is then tested for using this escape and finally, the platform is removed and probe tests examine if the mouse remembers its previous location. Repeated tests over several consecutive days highlight improved performance of tested mice at shorter latencies to find and mount the platform, and as more direct routes to reach the platform or its location. Failure to show such improvement represents impaired learning and memory and/or anxiety, which may then be tested specifically (e.g. in the elevated plus maze). This approach enables validation of specific miRNAs and target transcripts in the studied cognitive and/or stress-related processes.

MicroRNAs have significant roles in brain structure and function. Here we describe a method to enforce hippocampal miRNA over-expression using stereotactic injection of an engineered miRNA-expressing lentivirus. This approach can serve as a relatively rapid way to assess the in vivo effects of over-expressed miRNAs in specific brain regions.

MicroRNAs (miRNAs) are small regulatory single-stranded RNA molecules around 22 nucleotides long that may each target numerous mRNA transcripts and dim an ...

Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore by rearing and touching the walls of the cylinder with their forelimb paws for postural support. Following ischemic injury to the forelimb sensorimotor cortex, rats rely more heavily on their unaffected forelimb paw for postural support resulting in fewer touches with their affected paw which is termed forelimb asymmetry. In contrast, focal ischemic damage in the mouse brain fails to result in comparable consistent deficits in forelimb asymmetry. While forelimb asymmetry deficits are infrequently observed, mice do demonstrate a novel behaviour post stroke termed &#8220;paw-dragging&#8221;. Paw-dragging is the tendency for a mouse to drag its affected paw along the cylinder wall rather than directly push off from the wall when dismounting from a rear to a four-legged stance. We have previously demonstrated that paw-dragging behaviour is highly sensitive to small cortical ischemic injuries to the forelimb motor cortex. Here we provide a detailed protocol for paw-dragging analysis. We define what a paw-drag is and demonstrate how to quantify paw-dragging behaviour. The cylinder test is a simple and inexpensive test to administer and does not require pre-training or food deprivation strategies. In using paw-dragging analysis with the cylinder test, it fills a niche for predicting cortical ischemic injuries such as photothrombosis and Endothelin-1 (ET-1)-induced ischemia &#8211; two models that are ever-increasing in popularity and produce smaller focal injuries than middle cerebral artery occlusion. Finally, measuring paw-dragging behaviour in the cylinder test will allow studies of functional recovery after cortical injury using a wide cohort of transgenic mouse strains where previous forelimb asymmetry analysis has failed to detect consistent deficits.

Classical forelimb asymmetry analysis of the cylinder test is routinely used to assess behavioural deficits in rats following brain injury or stroke; however, it fails to detect consistent deficits in mice. This study demonstrates that quantifying paw-dragging behaviour is a more sensitive analysis of brain injury in mice.

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore ...

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

Vagus nerve stimulation (VNS) has emerged as a tool to induce targeted synaptic plasticity in the forebrain to modify a range of behaviors. This protocol describes how to implement VNS to facilitate the consolidation of fear extinction memory.

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people.  There is a need ...

A Novel Experimental and Analytical Approach to the Multimodal Neural Decoding of Intent During Social Interaction in Freely-behaving Human Infants

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental paradigms and analysis tools have been limited to constrained laboratory tasks and contexts due to technical limitations imposed by the available set of measuring and analysis techniques and the age of the subjects. These limitations severely limit the study of developmental neural dynamics and associated neural networks engaged in cognition, perception and action in infants performing &#8220;in action and in context&#8221;. This protocol presents a novel approach to study infants and young children as they freely organize their own behavior, and its consequences in a complex, partly unpredictable and highly dynamic environment. The proposed methodology integrates synchronized high-density active scalp electroencephalography (EEG), inertial measurement units (IMUs), video recording and behavioral analysis to capture brain activity and movement non-invasively in freely-behaving infants. This setup allows for the study of neural network dynamics in the developing brain, in action and context, as these networks are recruited during goal-oriented, exploration and social interaction tasks.

This protocol presents a novel methodology for the neural decoding of intent from freely-behaving infants during unscripted social interaction with an actor. Neural activity is acquired using non-invasive high-density active scalp electroencephalography (EEG). Kinematic data is collected with inertial measurement units and supplemented with synchronized video recording.

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental ...

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, which is unlike the protocols used for human subjects. We report a successful application of rTMS to the unilateral hemisphere of rat brain. The rTMS was delivered with a low-frequency (1 Hz), high-frequency (20 Hz), or sham stimulation protocol to one side of the brain by using a small 25-mm figure-8 coil. We placed the center of the coil 1 cm lateral to the vertex on the biauricular line and angulated the coil 45&#176; to the ground to minimize a potential direct effect of rTMS on the contralateral cortex. We also used an in-house water cooling system to enable repetitive magnetic stimulation for more than 20 min, even at a 20-Hz stimulation frequency. Increases in the transcriptions of immediate early genes (Arc, Junb, and Egr2) were greater after rTMS than after sham stimulation. After 5 consecutive days of 20-min 1-Hz rTMS, bdnf mRNA expression was significantly higher in stimulated cortex than in contralateral side. The model presented herein will elucidate the molecular mechanisms of rTMS by allowing analysis of the inter-hemispheric difference in its effect.

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45&#176;. An in-house water cooling system was used for rTMS for more than 20 min.

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, ...

Sit-to-stand-and-walk from 120% Knee Height: A Novel Approach to Assess Dynamic Postural Control Independent of Lead-limb

Individuals with sensorimotor pathology e.g., stroke have difficulty executing the common task of rising from sitting and initiating gait (sit-to-walk: STW). Thus, in clinical rehabilitation separation of sit-to-stand and gait initiation - termed sit-to-stand-and-walk (STSW) - is usual. However, a standardized STSW protocol with a clearly defined analytical approach suitable for pathological assessment has yet to be defined.
Hence, a goal-orientated protocol is defined that is suitable for healthy and compromised individuals by requiring the rising phase to be initiated from 120% knee height with a wide base of support independent of lead limb. Optical capture of three-dimensional (3D) segmental movement trajectories, and force platforms to yield two-dimensional (2D) center-of-pressure (COP) trajectories permit tracking of the horizontal distance between COP and whole-body-center-of-mass (BCOM), the decrease of which increases positional stability but is proposed to represent poor dynamic postural control.
BCOM-COP distance is expressed with and without normalization to subjects&#39; leg length. Whilst COP-BCOM distances vary through STSW, normalized data at the key movement events of seat-off and initial toe-off (TO1) during steps 1 and 2 have low intra and inter subject variability in 5 repeated trials performed by 10 young healthy individuals. Thus, comparing COP-BCOM distance at key events during performance of an STSW paradigm between patients with upper motor neuron injury, or other compromised patient groups, and normative data in young healthy individuals is a novel methodology for evaluation of dynamic postural stability.

Here, we present a novel protocol to measure positional stability at key events during the sit-to-stand-to-walk using the center-of-pressure to the whole-body-center-of-mass distance. This was derived from the force platform and three-dimensional motion-capture technology. The paradigm is reliable and can be utilized for the assessment of neurologically compromised individuals.

Individuals with sensorimotor pathology e.g., stroke have difficulty executing the common task of rising from sitting and initiating gait (sit-to-walk: ...

Behavioral Disturbances: An Innovative Approach to Monitor the Modulatory Effects of a Nutraceutical Diet

In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, the traditional ways to monitor behavioral changes in dogs are complicated and not efficient. In the current clinical evaluation, a new, simple monitoring system was used to assess the effectiveness of a specific diet in positively modulating the intense and restless activity of 24 dogs of different ages and breeds. This protocol describes how to easily and rapidly evaluate improvement in a set of symptoms related to generalized anxiety by using a specific sensor, a mobile phone app, a wireless router, and a computer. The results showed that dogs treated with specific diets showed significant improvement in the times spent active and at rest after 10 days (p &lt; 0.01 and p &lt; 0.05, respectively). These dogs also showed an overall significant improvement in clinical and behavioral symptoms. A specific sensor, along with its related hardware, was demonstrated to successfully monitor behavioral changes relating to movement in dogs.

We report a simple approach to evaluate the effectiveness of a specific diet in positively modulating the daily activity and clinical and behavioral symptoms of dogs with evident behavioral disturbances.

In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, ...

A Within-subjects Experimental Protocol to Assess the Effects of Social Input on Infant EEG

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants socially interact. Electroencephalography (EEG) power is an advantageous technique to assess infant functional neural activation. However, many studies record infant EEG only during one baseline condition. This protocol describes a paradigm that is designed to comprehensively assess infant EEG activity in both social and nonsocial contexts as well as tease apart how different types of social inputs differentially relate to infant EEG. The within-subjects paradigm includes four controlled conditions. In the nonsocial condition, infants view objects on computer screens. The joint attention condition involves an experimenter directing the infant's attention to pictures. The joint attention condition includes three types of social input: language, face-to-face interaction, and the presence of joint attention. Differences in infant EEG between the nonsocial and joint attention conditions could be due to any of these three types of input. Therefore, two additional conditions (one with language input while the experimenter is hidden behind a screen and one with face-to-face interaction) were included to assess the driving contextual factors in patterns of infant neural activation. Representative results demonstrate that infant EEG power varied by condition, both overall and differentially by brain region, supporting the functional nature of infant EEG power. This technique is advantageous in that it includes conditions that are clearly social or nonsocial and allows for examination of how specific types of social input relate to EEG power. This paradigm can be used to assess how individual differences in age, affect, socioeconomic status, and parent-infant interaction quality relate to the development of the social brain. Based on the demonstrated functional nature of infant EEG power, future studies should consider the role of EEG recording context and design conditions that are clearly social or nonsocial.

This novel protocol is designed to assess the neural bases of social interaction in infants. The paradigm is designed to tease apart how various social inputs such as language, joint attention, and face-to-face interaction relate to infant neural activation. Infant EEG power is recorded during both social and nonsocial conditions.

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants ...

Application of 3D Printing in the Construction of Burr Hole Ring for Deep Brain Stimulation Implants

3D printing has been widely applied in the medical field since the 1980s, especially in surgery, such as preoperative simulation, anatomical learning and surgical training. This raises the possibility of using 3D printing to construct a neurosurgical implant. Our previous works took the construction of the burr hole ring as an example, described the process of using softwares like computer aided design (CAD), Pro/Engineer (Pro/E) and 3D printer to construct physical products. That is, a total of three steps are required, the drawing of 2D-image, the construction of 3D-image of burr hole ring, and using a 3D printer to print the physical model of burr hole ring. This protocol shows that the burr hole ring made of carbon fiber can be rapidly and accurately molded by 3D printing. It indicated that both CAD and Pro/E softwares can be used to construct the burr hole ring via integrating with the clinical imaging data and further applied 3D printing to make the individual consumables.

Here, we present a protocol to demonstrate 3D printing in the construction of deep brain stimulation implants.

3D printing has been widely applied in the medical field since the 1980s, especially in surgery, such as preoperative simulation, anatomical learning and ...