Name: automatic detection of highly organized theta oscillations in the murine eeg
Uploaded: 2017-03-10T13:00:00
Description: Watch this Scientific Journal Video about Automatic Detection of Highly Organized Theta Oscillations in the Murine EEG at JoVE.com

The authors would like to thank Dr. Christina Ginkel (German Center for Neurodegenerative Diseases, DZNE) and Dr. Robert Stark (DZNE) for their assistance with animal breeding and animal healthcare. This work was financially supported by the Federal Institute for Drugs and Medical Devices (Bundesinstitut f&#252;r Arzneimittel und Medizinprodukte, BfArM), Bonn, Germany.

All animal experimentation was performed according to the guidelines of the local and institutional Council on Animal Care (University of Bonn, BfArM, LANUV, Germany). In addition, all animal experimentation was carried out in accordance with superior legislation, e.g., the European Communities Council Directive of 24 November 1986 (86/609/EEC), or individual regional or national legislation. Specific effort was made to minimize the number of animals used, as well as their suffering.
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<ol>
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Theta activity is of central relevance in systemic neurophysiology. It can be observed in various brain regions, particularly in the hippocampus, where it is related to specific behavioral and cognitive states. In addition, hippocampal theta can be pharmacologically differentiated into atropine-sensitive type II and atropine-insensitive type I theta. Type I is thought to be related to locomotion, such as walking or running27,28,29</su...

Theta activity in the brain is related to different cognitive and functional states, including arousal, attention, voluntary movement, exploratory behavior, attention behavior, learning and memory, somatosensory integration, and rapid eye movement (REM) sleep1,2. Principally, theta activity as a rhythmic entity can be generated in various cerebral regions and is highly organized and synchronized as theta oscillations. Below, we will focus on the analysis and quantification of theta activity/oscillations that are generated within the septohippocampal system3,4. Within the septum, GABAergic, glutamatergic, and cholinergic neurons project to the hippocampus and contribute to the initiation and maintenance of theta oscillatory behavior. There is an ongoing discussion on whether hippocampal theta oscillations are initiated in the septum, i.e., the septal pacemaker-hippocampal follower model, (extrahippocampal theory) or intrinsically within the hippocampus (intrahippocampal theory)5,6,7.
Regardless of their origin, hippocampal theta oscillations have been in the focus of interest for years, particularly in transgenic mouse models. These models allow for the implantation of deep EEG electrodes and for the recording of hippocampal theta oscillations under specific cognitive and behavioral tasks8. Hippocampal theta oscillations are heterogenous in nature. Based on the so-called dualistic theory of theta oscillations, one can differentiate between atropine-sensitive type II theta and atropine-insensitive type I theta9,10,11. The latter can typically be induced by muscarinic M1/M3 receptor agonists, e.g., arecoline, pilocarpine, and urethane. However, urethane is a multi-target drug that, besides muscarinic activation, also exerts complex effects on other ion channel entities. For type II theta, the muscarinic pathway includes the activation of M1/M3 and a subsequent Gq/11 (G&#945;)-mediated activation of phospholipase C &#946;1/4 (PLC&#946;1/4), inositol trisphosphate (InsP3), diacylglycerole (DAG), Ca2+, and protein kinase C (PKC). The role of PLC&#946;1 and PLC&#946;4 in thetagenesis has been validated in knock-out studies using PLC&#946;1-/- and PLC&#946;4-/- mice exhibiting a complete loss or significant attenuation of theta oscillation12,13,14. Additional M1, M3, and M5 downstream targets (channels/currents) of the muscarinic signaling cascade include various conductances, such as M-type K+ channel (KM) via voltage-dependent K+ channel (Kv7); slow after hyperpolarization K+ channel (KsAHP); leak K+ channel (Kleak), probably via TWIK-related acid-sensitive K+ channel (TASK1/3); cation current (ICAT), probably via Na+ leak channel (NALCN); and Ih via hyperpolarization and cyclic nucleotide gated channels (HCN). In addition, M2/M4 acetylcholine receptors (AChRs) were reported to interfere with inward rectifier K+ channel 3.1 (Kir3.1) and inward rectifier K+ channel 3.2 (Kir3.2)15.
Currently, commercially-available analytical software allows for fast FFT-based frequency analysis, e.g., analysis of power (P, mV2) or power spectrum density (PSD, mV2/Hz). Power or power spectrum density (PSD) analysis of the theta frequency range only gives a global overview of its activity. However, in order to get a detailed insight into cognitive and behavior-related theta activity, the analysis of highly-organized theta oscillations is mandatory. The assessment of highly-organized theta oscillations is of central importance in the field of neurodegenerative and neuropsychiatric diseases. Most experimental disease studies are carried out in transgenic mouse models using highly-sophisticated neurosurgical approaches to record epidural surface and deep intracerebral EEGs. These techniques include both tether systems16 and radiotelemetric setups17,18. Theta oscillations can be recorded as spontaneous and behavior-related theta oscillations under long-term recording conditions. Additionally, theta oscillations can be recorded following pharmacological induction but also following the exposure of animals to behavioral or cognitive tasks or to sensory stimuli, such as tail pinching.
Early approaches to characterize theta oscillations were described by Csicsvari et al.19. The authors designed a semi-automated tool for short-term theta analysis (15 - 50 min) that is not suitable for long-time EEG recordings. Our method, described here, allows for the analysis of long-term EEG recording &#62; 48 h20. Csicsvari et al.10 also referred to the theta-delta ratio, but no threshold for the determination of highly-organized theta oscillations is provided. The delta and theta range definitions match our frequency range definitions. As it is not explicitly mentioned, we presume that an FFT-based method is used by Csicsvari et al. to calculate the power of the theta-delta frequency bands. This again clearly differs from our method, since we calculate wavelet-based amplitudes on a large number of frequency scales (frequency steps &#916;(f) = 0.05 Hz), resulting in much higher precision. The duration of the individually-analyzed EEG epoch is similar to our definition.
Klausberger et al.21 also make use of theta-delta ratios for the analysis of long-term EEG recordings. However, there are three major differences compared to our approach: i) the EEG epoch duration is much longer, i.e., at least 6 s; ii) the theta-delta ratio is set to 4, which is much higher than our threshold, and is related to different frequency range definitions; and iii) the power definition is likely to be based on an FFT approach, which lacks high precision, particularly for very short time windows (2 s, i.e., 5 cycles for oscillations with a frequency of 2.5 Hz). In such cases, a wavelet-based procedure is more recommendable. A study by Caplan et al.22 solely calculated theta power while ignoring the theta-delta power ratio. Thus, the Caplan approach22 cannot differentiate between cognitive theta-rich processes accompanied by a high or low delta.
In the following protocol, we will present our analytical wavelet-based approach to reliably analyze highly-organized theta oscillations in hippocampal EEG recordings from mice. Since this procedure works automatically, it can be applied to large data sets and long-term EEG measurements.

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			<td>Carprofen (Rimadyl VET - Injektionsl&#246;sung)</td>
			<td>Pfizer</td>
			<td>PZN 0110208208</td>
			<td>20ml</td>
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			<td>binocular surgical magnification microscope</td>
			<td>Zeiss Stemi 2000</td>
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			<td>Dexpanthenole (Bepanthen Wund- und Heilsalbe)</td>
			<td>Bayer</td>
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			<td>70% ethanol</td>
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			<td>0.3% / 3% hydrogene peroxide solution</td>
			<td>Sigma</td>
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			<td>30% stock solution</td>
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			<td>Unigloves</td>
			<td>1570</td>
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			<td>dental glas ionomer cement</td>
			<td>KentDental /NORDENTA</td>
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			<td>heat-based surgical instrument sterilizer</td>
			<td>F.S.T.</td>
			<td>18000-50</td>
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			<td>high-speed dental drill</td>
			<td>Adeor</td>
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			<td>Inhalation narcotic system (isoflurane)</td>
			<td>Harvard Apparatus GmbH</td>
			<td>34-1352, 10-1340, 34-0422, 34-1041, 34-0401, 34-1067, 72-3044, 34-0426, 34-0387, 34-0415, 69-0230</td>
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			<td>Isoflurane</td>
			<td>Baxter 250 ml</td>
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			<td>Pfizer</td>
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			<td>Lactated Ringer&#39;s solution (sterile)</td>
			<td>Braun</td>
			<td>L7502</td>
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			<td>Nissl staining solution</td>
			<td>Armin Baack</td>
			<td>BAA31712159</td>
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			<td>pads (sterile)</td>
			<td>ReWa Krankenhausbedarf</td>
			<td>2003/01</td>
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			<td>Steel and tungsten electrodes parylene coated</td>
			<td>FHC Inc., USA</td>
			<td>UEWLGESEANND</td>
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			<td>stereotaxic frame</td>
			<td>Neurostar</td>
			<td>51730M</td>
			<td>ordered at Stoelting</td>
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			<td>(Stereo Drive-New Motorized Stereotaxic)</td>
			<td></td>
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			<td>tapes (sterile)</td>
			<td>BSN medical GmbH &#38; Co. KG</td>
			<td>626225</td>
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			<td>TA10ETA-F20</td>
			<td>DSI</td>
			<td>270-0042-001X</td>
			<td>Radiofrequency transmitter 3.9 g, 1.9 cc, input voltage range &#177; 2.5 mV, channel bandwidth (B) 1-200 Hz, nominal sampling rate (f) 1000 Hz (f = 5B) temperature operating range 34-41 &#176;C warranted battery life 4 months</td>
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			<td>TL11M2-F20EET</td>
			<td>DSI</td>
			<td>270-0124-001X</td>
			<td>Radiofrequency transmitter 3.9 g, 1.9 cc, input voltage range &#177; 1.25 mV, channel bandwidth (B) 1-50 Hz, nominal sampling rate (f) 250 Hz (f = 5B) temperature operating range 34-41 &#176;C warranted battery life 1.5 months</td>
		</tr>
		<tr>
			<td>Vibroslicer 5000 MZ</td>
			<td>Electron Microscopy Sciences</td>
			<td>5000-005</td>
			<td></td>
		</tr>
		<tr>
			<td>Xylazine (Rompun)</td>
			<td>Bayer</td>
			<td>PZN: 1320422</td>
			<td></td>
		</tr>
		<tr>
			<td>Matlab</td>
			<td>Mathworks Inc.</td>
			<td></td>
			<td>programming, computing and visualization software</td>
		</tr>
		<tr>
			<td>SPSS</td>
			<td>IBM</td>
			<td></td>
			<td>statistical analysis software</td>
		</tr>
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</table>

automatic detection of highly organized theta oscillations in the murine eeg

Theta activity is generated in the septohippocampal system and can be recorded using deep intrahippocampal electrodes and implantable electroencephalography (EEG) radiotelemetry or tether system approaches. Pharmacologically, hippocampal theta is heterogeneous (see dualistic theory) and can be differentiated into type I and type II theta. These individual EEG subtypes are related to specific cognitive and behavioral states, such as arousal, exploration, learning and memory, higher integrative functions, etc. In neurodegenerative diseases such as Alzheimer&#39;s, structural and functional alterations of the septohippocampal system can result in impaired theta activity/oscillations. A standard quantitative analysis of the hippocampal EEG includes a Fast-Fourier-Transformation (FFT)-based frequency analysis. However, this procedure does not provide details about theta activity in general and highly-organized theta oscillations in particular. In order to obtain detailed information on highly-organized theta oscillations in the hippocampus, we have developed a new analytical approach. This approach allows for time- and cost-effective quantification of the duration of highly-organized theta oscillations and their frequency characteristics.

Theta activity can be recorded in a wide range of central nervous system (CNS) regions. Here, we present an analysis of theta oscillations from the murine hippocampus. Such oscillations can occur during different behavioral and cognitive states. It is highly recommended to analyze theta oscillations under both spontaneous long-term, task-related short-term, and pharmacologically-induced conditions. 
Figure 1 illustrates a representative intrahippocampal CA1 recording...

Watch this Scientific Journal Video about Automatic Detection of Highly Organized Theta Oscillations in the Murine EEG at JoVE.com

Automatic Detection of Highly Organized Theta Oscillations in the Murine EEG

Theta activity in the hippocampus is related to specific cognitive and behavioral stages. Here, we describe an analytical method to detect highly-organized theta oscillations within the hippocampus using a time-frequency (i.e., wavelet analysis)-based approach.

Theta activity is generated in the septohippocampal system and can be recorded using deep intrahippocampal electrodes and implantable ...

The overall goal of this procedure is to analyze pharmacologically induced highly organized theta oscillations in mice using implantable EEG radiotelemetry. This message can help answer key questions in the systemic neuroscience field, such as how to induce, detect, and quantify highly organized theta oscillations in the mouse EEG using long term hippocampal EEG radio-telemetric recordings. The main advantage of this technique is that it helps to analyze highly organized theta oscillations in large scale murine hippocampal EEG recordings.The implications of this technique extend to our therapy of neuropsychiatric and neurodegenerative diseases such as Alzheimer's disease, because frequency alterations such as theta dysrhythmia are often associated with it. Though this method can provide insight into murine hippocampal theta dysrhythmia, it can also be applied to EEG recordings from other species, including human following adaptation. Generally, if the ritual is new, this method will struggle, because the detection analysis of theta oscillation requires proper EEG electrode implantation and theta induction.Prior to insertion of the electrodes, scratch the parylene coating from the tip. Next, mechanically clip the extracranial part of an electrode to the stainless steel helix of the transmitter. And shorten them to the required length.To implant the radio frequency transmitter, place an anesthetized mouse on the surgical table, and continue to deliver isoflurane to the animal through a face mask. Ensure the depth of anesthesia by checking the tail pinch reflex, foot pinch reflex, and respiration rate. Next, remove the body hair from the scalp and disinfect the shaved scalp with 70%ethanol and an iodine based scrub.Afterward, make a midline incision on the scalp from the forehead to the nuchial region using a scalpel. Then, prepare a subcutaneous pouch on one side of the back of the animal by performing a blood dissection using surgical scissors. Subsequently, insert the transmitter into the subcutaneous pouch and deposit the excess length of the flexible transmitter leads into the pouch.Following this, fix the skull using a nose clamp. Then place the experimental animal on the stereotaxic frame. And set the ear bars.Apply 0.3 percent hydrogen peroxide to the skull to remove any tissue and to help visualize the cranial sutures and the craniometric landmarks such as bregma and lambda. Next, drill the holes at the coordinates of choice using a high speed neurosurgical drill in a pressure free mode at maximum velocity. Select the appropriate electrodes and sterilize the electrodes using 70%ethanol prior to implantation.The electrode type should be carefully chosen according to experimental requirements. Usually, parylene coated tungsten or stainless steel electrodes are the most common. Afterward, fix the electrodes using the glass ionomer cement and wait until the cement has fully cured.Next, close the scalp using over and over sutures with non-absorbable suture material. For post-operative pain management, administer carprofen subcutaneously once a day for four days post-implantation. Allow the animal to recover for 10 to 14 days before the recordings or injection experiments.In this procedure, activate the radiofrequency transmitter using the magnetic switch. Perform long term hippocampal EEG recordings for at least 24 to 48 hours. The analysis of EEG amplitude and EEG frequency characteristics of long term recordings provides detailed insight into the circadian dependency of theta oscillations and their association with specific behavior and cognitive conditions or tasks.For the pharmacological induction of theta oscillations, pretreat the animal with methscopolamine to avoid peripheral muscarinic reactions. Subsequently, administer a single dose of urethane or a muscarinic receptor agonist to the mouse for theta initiation. After about 60 minutes, inject atropine to differentiate atropine sensitive type two from atropine insensitive type one theta oscillations.And continue recording. To validate the EEG electrode placement, cut the stainless steel electrodes and remove the radio frequency transmitter. Then, sacrifice the mouse and remove the brain from the neurocranium.To validate the electrode placement, mount the extracted brain on the tissue holder of a Vibroslicer using an adhesive. And cut the brain into 100 micrometer coronal slices. Mount the slices onto glass slides and stain them with nissl blue using standard histological procedure.Incorporate the animal for analysis only when it meets the correct EEG electrode placement criteria. For the CA1 region, the tip of the deep electrode should be localized inside the CA1 pyramidal layer. Upload the EEG data.Here is an exemplary 30 minutes EEG segment. Use the complex Morlet wavelet function, displayed here, for time frequency analysis. For time frequency analysis, the frequency range is set between 0.2 to 12 Hz and a step size is set to 0.1 Hz.This color-coded time frequency plot of the EEG segment illustrates the theta and the upper delta frequency ranges.Here, an extracted 2.5 seconds EEG epoch is analyzed for theta segment. Since the maximum amplitude in the theta range divided by that in the upper delta range is larger than 1.5, this segment is classified as a theta oscillatory epoch. This guarantees that the maximum theta amplitude is at least 50%higher than the amplitude in the upper delta band in the calculated EEG epoch.This figure shows the correlation of the highly organized theta oscillations and the theta detection measure in EEG recording, in which the theta oscillatory segments can be quantified and analyzed statistically. Here are two 2.5 seconds EEG epochs, visually classified as non-theta and theta segments respectively. And here are the time frequency analysis of the CA1 EEG segments, displayed in the corresponding graphs above in the range of 0.2 to 12 Hz.With the amplitude being color-coded, the time frequency analysis of the non-theta EEG segment exhibits a regular fluctuating theta architecture regarding frequencies in time.Whereas the segment with highly synchronized theta oscillations is characterized by a regular non-fluctuating high amplitude theta of a nearly constant frequency of six Hz.The ratio of maximum theta to maximum delta amplitude is 1.25 in this map and 4.67 in this map. Clearly classifying this EEG epoch as a theta oscillation EEG segment. Once mastered, this technique can be done in one hour if it is performed properly.Following this procedure, other methods like time frequency analysis of other frequency bands or automated seizure detection can be performed in order to answer questions like if other EEG bands are affected, how they are coupled and are related to neural hyperexcitability. After its development, this technique paved the way for researchers in the field of systemic neuroscience to explore alterations in hippocampal theta architecture in transgenic mouse models, such as Alzheimer's disease mouse models. After watching this video, you should have a good understanding of how to induce, detect, and analyze highly organized theta oscillations.

automatic-detection-highly-organized-theta-oscillations-murine

Research

JoVE Journal

Behavior

Simultaneous EEG Monitoring During Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a technique that delivers weak electric currents through the scalp. This constant electric current induces shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Although tDCS has most of its neuromodulatory effects on the underlying cortex, tDCS effects can also be observed in distant neural networks. Therefore, concomitant EEG monitoring of the effects of tDCS can provide valuable information on the mechanisms of tDCS. In addition, EEG findings can be an important surrogate marker for the effects of tDCS and thus can be used to optimize its parameters. This combined EEG-tDCS system can also be used for preventive treatment of neurological conditions characterized by abnormal peaks of cortical excitability, such as seizures. Such a system would be the basis of a non-invasive closed-loop device. In this article, we present a novel device that is capable of utilizing tDCS and EEG simultaneously. For that, we describe in a step-by-step fashion the main procedures of the application of this device using schematic figures, tables and video demonstrations. Additionally, we provide a literature review on clinical uses of tDCS and its cortical effects measured by EEG techniques.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has shown initial therapeutic effects in several neurological conditions. The main mechanism underlying these therapeutic effects is the modulation of cortical excitability. Therefore, online monitoring of cortical excitability would help guide stimulation parameters and optimize its therapeutic effects. In the present article we review the use of a novel device that combines simultaneous tDCS and EEG monitoring in real time.

Transcranial  direct current stimulation (tDCS) is a technique that delivers weak electric  currents through the scalp. This constant electric current ...

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST

Prolonged and comprehensive monitoring of mice in a home-cage environment provides a deeper understanding of aberrant behavior in murine models of brain diseases. This paper describes the Integrated Behavioral Station (INBEST) as the key component of contemporary behavioral analysis.

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of ...

Cortical Source Analysis of High-Density EEG Recordings in Children

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and signal processing make it possible to exploit information from other imaging modalities like structural MRI that provide high spatial resolution to overcome this constraint1. This is especially useful for investigations that require high resolution in the temporal as well as spatial domain. In addition, due to the easy application and low cost of EEG recordings, EEG is often the method of choice when working with populations, such as young children, that do not tolerate functional MRI scans well. However, in order to investigate which neural substrates are involved, anatomical information from structural MRI is still needed. Most EEG analysis packages work with standard head models that are based on adult anatomy. The accuracy of these models when used for children is limited2, because the composition and spatial configuration of head tissues changes dramatically over development3.&#160;
In the present paper, we provide an overview of our recent work in utilizing head models based on individual structural MRI scans or age specific head models to reconstruct the cortical generators of high density EEG. This article describes how&#160;EEG recordings are acquired, processed, and analyzed with pediatric populations at the London Baby Lab, including laboratory setup, task design, EEG preprocessing, MRI processing, and EEG channel level and source analysis.&#160;

In recent years, there has been increasing interest in estimating the cortical sources of scalp measured electrical activity for cognitive neuroscience experiments. This article describes how high density EEG is acquired and how recordings are processed for cortical source estimation in children from the age of 2 years at the London Baby Lab.

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and ...

Infant Auditory Processing and Event-related Brain Oscillations

Rapid auditory processing and acoustic change detection abilities play a critical role in allowing human infants to efficiently process the fine spectral and temporal changes that are characteristic of human language. These abilities lay the foundation for effective language acquisition; allowing infants to hone in on the sounds of their native language. Invasive procedures in animals and scalp-recorded potentials from human adults suggest that simultaneous, rhythmic activity (oscillations) between and within brain regions are fundamental to sensory development; determining the resolution with which incoming stimuli are parsed. At this time, little is known about oscillatory dynamics in human infant development. However, animal neurophysiology and adult EEG data provide the basis for a strong hypothesis that rapid auditory processing in infants is mediated by oscillatory synchrony in discrete frequency bands. In order to investigate this, 128-channel, high-density EEG responses of 4-month old infants to frequency change in tone pairs, presented in two rate conditions (Rapid: 70 msec ISI and Control: 300 msec ISI) were examined. To determine the frequency band and magnitude of activity, auditory evoked response averages were first co-registered with age-appropriate brain templates. Next, the principal components of the response were identified and localized using a two-dipole model of brain activity. Single-trial analysis of oscillatory power showed a robust index of frequency change processing in bursts of Theta band (3 - 8 Hz) activity in both right and left auditory cortices, with left activation more prominent in the Rapid condition. These methods have produced data that are not only some of the first reported evoked oscillations analyses in infants, but are also, importantly, the product of a well-established method of recording and analyzing clean, meticulously collected, infant EEG and ERPs. In this article, we describe our method for infant EEG net application, recording, dynamic brain response analysis, and representative results.

High-density electroencephalography (dEEG) is being used increasingly to study brain development and plasticity in the early years of life. Here we present an application of sophisticated analysis techniques that builds on traditional EEG recording to understand the oscillatory dynamics of rapid auditory processing in the infant brain.

Rapid auditory processing and acoustic change detection abilities play a critical role in allowing human infants to efficiently process the fine spectral ...

Measurement of Vibration Detection Threshold and Tactile Spatial Acuity in Human Subjects

Tests that allow the precise determination of psychophysical thresholds for vibration and grating orientation provide valuable information about mechanosensory function that are relevant for clinical diagnosis as well as for basic research. Here, we describe two psychophysical tests designed to determine the vibration detection threshold (automated system) and tactile spatial acuity (handheld device). Both procedures implement a two-interval forced-choice and a transformed-rule up and down experimental paradigm. These tests have been used to obtain mechanosensory profiles for individuals from distinct human cohorts such as twins or people with sensorineural deafness.

Here, we present protocols to determine vibration detection thresholds and tactile acuity using psychophysical methods in man.

Tests that allow the precise determination of psychophysical thresholds for vibration and grating orientation provide valuable information about ...

The Social Dimension of Stress: Experimental Manipulations of Social Support and Social Identity in the Trier Social Stress Test

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations supportive behavior of other people as well as positive social relationships can act as powerful resources to cope with stress. In order to study the interplay between these variables, this protocol describes two effective experimental manipulations of social relationships and supportive behavior in the laboratory. In the present article, these two manipulations are implemented in the Trier Social Stress Test (TSST)&#8212;a standard stress induction paradigm in which participants are subjected to a simulated job interview. More precisely, we propose (a) a manipulation of the relationship between different protagonists in the TSST by making a shared social identity salient and (b) a manipulation of the behavior of the TSST-selection committee, which acts either supportively or unsupportively. These two experimental manipulations are designed in a modular fashion and can be applied independently of each other but can also be combined. Moreover, these two manipulations can also be integrated into other stress protocols and into other standardized social interactions such as trust games, negotiation tasks, or other group tasks.

Previous research on the social dimension of stress has focused on two important variables: social identity and social support. This protocol introduces an effective experimental manipulation of these two social variables and describes their implementation in a standard stress induction paradigm (Trier Social Stress Test).

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations ...

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of current interventions to adequately treat fatigue in all patients leaves a need for new treatment options. Despite the therapeutic need and importance of preclinical research in helping identify promising novel treatments, few preclinical assays of fatigue are available. Moreover, the most common preclinical assay used to assess fatigue-like behavior, voluntary wheel running, is not suitable for use with some strains of mice, may not be sensitive to drugs that reduce fatigue, and has relatively low throughput. The current protocol describes a novel, non-voluntary preclinical assay of fatigue-like behavior, the treadmill fatigue test, and provides evidence of its efficacy in detecting fatigue-like behavior in mice treated with a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in animals. This assay may be a beneficial alternative to wheel running, as fatigue-like behavior and potential interventions can be assessed in a greater number of mice over a shorter time frame, thus permitting faster discovery of new therapeutic options.

Fatigue is a common, undertreated and frequently poorly-understood symptom in many diseases and disorders. New preclinical assays of fatigue may help to improve current understanding and future treatment of fatigue. To that end, the current protocol provides a novel means of measuring fatigue-like behavior in the mouse.

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of ...

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 ...

Continuous Theta Burst Stimulation of the Posterior Medial Frontal Cortex to Experimentally Reduce Ideological Threat Responses

Decades of behavioral science research have documented functional shifts in attitudes and ideological adherence in response to various challenges, but little work to date has illuminated the neural mechanisms underlying these dynamics. This paper describes how continuous theta burst transcranial magnetic stimulation may be employed to experimentally assess the causal contribution of cortical regions to threat-related ideological shifts. In the example protocol provided here, participants are exposed to a threat prime-an explicit reminder of their own inevitable death and bodily decomposition-following a downregulation of the posterior medial frontal cortex (pMFC) or a sham stimulation. Next, disguised within a series of distracter tasks, participants' relative degree of ideological adherence is assessed-in the present example, with regard to coalitional prejudice and religious belief. Participants for whom the pMFC has been downregulated exhibit less coalitionally biased responses to an immigrant critical of the participants' national in-group, and less conviction in positive afterlife beliefs (i.e., God, angels, and heaven), despite having recently been reminded of death. These results complement prior findings that continuous theta burst stimulation of the pMFC influences social conformity and sharing and illustrate the feasibility of investigating the neural basis of high-level social cognitive shifts using transcranial magnetic stimulation.

Threats reliably evoke shifts in high-level ideological investment, but little work to date has explored the neural mechanisms underlying these dynamics. This paper describes how continuous theta burst transcranial magnetic stimulation may be employed to test the contribution of the posterior medial frontal cortex (and/or other regions) to threat-related ideological shifts.

Decades of behavioral science research have documented functional shifts in attitudes and ideological adherence in response to various challenges, but ...

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and dementia. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to some Parkinson&#8217;s-like symptoms by destroying dopaminergic neurons in the substantia nigra of the brain. It has been thus used to establish PD models in various animal studies. Here, mice receive MPTP injections (20 mg/kg/day) for seven days and the behavioral tests are performed on the eighth day. This model is adapted efficiently in the study of PD. The behavioral tests here include the cylinder test and the open field test. The cylinder experiment is used to detect the animals&#8217; ability to lift their front paws when put into a different environment. As the PD model mice show arching&#8212;the mouse arches its back&#8212;the number of paw liftings decrease. This test is easy to execute. The open field test is used to detect the amount of time the mice spend on running, walking, and remaining immobile. We analyze animals&#8217; movements in open field using software and obtain data. Lastly, we use L-DOPA, one of the most commonly used PD drugs, as one example to show how to apply this model to the study of PD drugs. Our results indicate that MPTP neurotoxicity induces motor deficit which can be mitigated by L-DOPA.

We describe establishment of a murine model for Parkinson's disease using MPTP, and behavioral assessments using cylinder and open field tests to measure motor function. We then use L-DOPA as one example to show how to apply this model in the study of PD drugs.

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and ...