Supported by RF Government grant contract No.14.W03.31.0010. We wish to thank Ekatarina Perikova and Alexander Kirsanov for their support in preparing this publication. We are grateful to Olga Shcherbakova and Margarita Filippova for their help in stimulus selection and to Anastasia Safronova and Pavel Inozemcev for their assistance in the production of video materials.

All procedures were approved by the local research ethics committee of St. Petersburg State University, St. Petersburg, with consent obtained from all participants.
NOTE: All participants must sign the informed consent and fill in a questionnaire to attest the absence of any contraindications for tDCS stimulation (see Technique and Considerations in the Use of 4 x 1 Ring High-definition Transcranial Direct Current Stimulation (HD-tDCS) by Willamar and colleagues12) and to collect other data relevant to the study such as vision acuity, demographics, language experience and handedness. For the latter, the seminal work by Oldfield13 is recommended.
1. Subjects and experimental environment
<ol>
	<li>In a typical language experiment, ensure that all subjects are right-handed and have no record of language deficits, neurological or psychiatric disorders. Their native language and bilingual/multilingual status must be controlled.</li>
	<li>Conduct all measurements in a sound-proof or at least sound-attenuated chamber. Sound insulation is very important, since any extraneous sound, noise, human speech, etc. can significantly affect the performance and thus influence the data (Figure 1).</li>
	<li>To avoid interference by unnecessary subject-experimenter contact, place only the screen, headphones/speakers and any input devices (keyboard, button boxes) inside the chamber. Have all interaction with the experimenter over intercom unless personal contact is required.</li>
	<li>Use the following optimal parameters, based on extensive piloting, for background color and font size: grey background color (RGB: 125, 125, 125), black text color (RGB: 0; 0; 0), Arial font face, size 27.</li>
	<li>To reduce delays and jitter in visual presentation, use a video card and a monitor with a refresh rate of 100 Hz and higher.</li>
	<li>To measure reaction times, use research-grade response pads, which have better ergonomics and more precise timing in comparison with conventional keyboards.</li>
</ol>
2. Stimulus preparation
<ol>
	<li>Choose words of the language in question, which are controlled for their duration, lexical frequency and overall structure (to avoid any basic effects of surface stimulus properties on higher-level processing). Here, all base words were eight phonemes/letters long and consisted of three syllables with the CVCCVCVC structure (where C is consonant, and V is vowel).</li>
	<li>To create multiple lists, divide the words into sets, which should not differ statistically (as measured with, e.g.,&#160;t-tests) on their lemma, bigram and/or trigram as well as&#160;syllabic frequency. These can be obtained from language-specific psycholinguistic databases; here, Russian National Corpus was used (http://www.ruscorpora.ru/en/). Here, one set was used&#160;for creating (through modification) orthographically similar novel words and pseudowords, another set for creating unrelated control pseudowords, and a&#160;further set used as unrelated control words (Figure 2A). This led to&#160;five sets of 10 items each (50 stimuli in total). Modify these procedures in accordance with your exact experimental requirements.</li>
	<li>To minimize any effects of surface forms on newly acquired semantics, counterbalance the sets across the subject sample, such that they play different experimental roles for different subjects.</li>
	<li>Create novel word forms such that they follow the rules of phonology and phonotactics and resemble existing words in terms of orthographic and phonological structure. 
	NOTE: To make sure that the new words can enter into competition with existing words, the current procedures were based on those developed in a series of experiments by Gaskell and colleagues11,14 and aimed at keeping the word onsets (CVCCV-) stable, while rotating their offsets (-CVC) across different items in the set. That is, we preserved the first two syllables of an existing word and varied&#160;the ultimate syllable such that a new, previously unfamiliar novel word form was created (e.g., mandarin -&#62; mandanal*, where the last CVC was taken from another word in the list, cardinal, to create a new item).</li>
	<li>Repeat the procedure described above for creating as many novel word forms as needed. For the current demonstration, we&#160;created&#160;lists of novel word forms to be learnt and of similar unlearnt pseudowords&#160;(e.g. mandarin -&#62; mandanal*, mandaket*, all three potentially entering into a lexical competition post-learning, as neighbors) as well as further control lists of real words and novel pseudowords that did not share this similarity and thus would not produce a lexical competition with the main stimuli&#160;(e.g., circular, muskenal*; Russian examples are used throughout, transliterated from Cyrillic to Latin script for ease of understanding).</li>
</ol>
3. Sentence stimuli for contextual semantic learning
<ol>
	<li>Create novel meanings to be associated with the new words in the process of learning. This could be made-up, obsolete or rare objects or concepts not present in the subjects&#39; native language or culture.</li>
	<li>For contextual learning of novel semantics, the procedures used by&#160;Mestrez-Misse and colleagues15 are&#160;recommended. Create several unique sentences that describe situations through which one can understand the meaning of each of the novel words (e.g., &#34;To control insects in medieval times, people used mandaket&#34;). Use a sequence of such sentences for each of the novel words (here, a total of 5 sentences per word), and&#160;gradually reveal the meaning of each new concept from a more general to more specific sentential context.</li>
	<li>Present novel words ideally in their dictionary form (i.e., uninflected, e.g., singular nominative or accusative case in Russian), such that the surface form is not inflected differently in different sentences (Table 1), unless inflection rule learning is also required.</li>
	<li>Control and balance the length of the sentences and the number of words between conditions. Here, each sentence consisted of 8 words. Always place novel words at the end of the sentences. Such placement allows build-up of necessary contextual information (further, this allows implementing this design, if needed, in an EEG or MEG setting to record evoked brain responses unmasked by further word stimuli).</li>
	<li>Present word-specific sentences in word-specific sub-blocks, gradually revealing the meaning of each new word, without interleaving or randomizing sentences related to different novel words.</li>
	<li>Randomize the order of the sub-blocks across the subject group. Word-by-word sentence presentation is recommended if the visual modality is used.</li>
	<li>Determine the interstimulus interval based on specific stimulus properties to allow their convenient presentation (Figure 2B); make sure to separate different sub-blocks with additional intervals and give regular breaks.</li>
</ol>
4. Tasks to assess acquisition of new word forms and novel meanings
NOTE: Use several tasks to assess different levels of acquisition and comprehension of both surface word forms and lexical semantics. Five tasks are used in the present protocol: free recall, cued recognition, lexical decision, semantic definition and semantic matching. The tasks are applied in the order they are listed below, which was optimized to reduce any carryover between successive tasks.
<ol>
	<li>In the free recall task, have each participant reproduce as many new word forms as they could remember by typing them into the prepared spreadsheet. The instruction is as follows: &#34;Please write down in the column all the new words that you can remember.&#34;</li>
	<li>Include the same stimuli in the recognition and lexical decision (second and third tasks, respectively) and use the same presentation rate.
	<ol>
		<li>These tasks include all items (novel words, real competitor words the novel ones are derived from, untrained pseudoword competitors derived from the same real words, unrelated control pseudowords and unrelated control existing words).</li>
		<li>For the recognition task, use the following instruction: &#34;You will be presented with words sequentially. Press button &#34;1&#34; with the middle finger of the left hand if you have encountered the word during the experiment, or press &#34;2&#34; with the index finger of the left hand if you have not.&#34; Modify the response coding, hand and fingers in accordance with your specific requirements.</li>
		<li>The instruction for the lexical decision task is: &#34;You will be presented with real and meaningless words sequentially. Press &#34;1&#34; with the middle finger of the left hand if the word makes sense, or press &#34;2&#34; with the index finger of the left hand if it does not.&#34; Modify these as necessary.</li>
	</ol>
	</li>
	<li>Use the semantic definition task to estimate the acquisition of novel meaning and the correspondence between the meaning and the surface form.
	<ol>
		<li>Give participants a list of the learnt items (i.e., those presented previously in the learning phase) with the instruction above: &#34;Here is a list of new words presented to you previously. Try to define each of them and type their definitions into the spreadsheet&#34;.</li>
		<li>To assess the completeness and accuracy of the given definitions, engage independent experts to rate the responses; agreement between experts could be tested using, e.g., Kendall&#39;s coefficient of concordance (W).</li>
	</ol>
	</li>
	<li>Use semantic matching task to assess the acquisition of semantics through making explicit links between the newly learnt word forms and their meanings in a simplified manner.
	<ol>
		<li>Use the following instruction: &#34;You will be presented a word and three definitions. You should choose one correct definition for each word by pressing the corresponding button&#34;. Only one of the definitions is correct, with the other two corresponding to the other novel items. In addition to the three optional definitions, including &#34;none of this&#34; or/and &#34;not sure&#34; options is also recommended.</li>
	</ol>
	</li>
</ol>
5. Procedures
<ol>
	<li>Ensure that the tDCS stimulation precedes the behavioral task it is intended to modulate.
	<ol>
		<li>Wernicke&#39;s area. 
		NOTE: The stimulation electrode placement that best corresponds to Wernicke&#39;s area is CP5 according to the extended International 10-20 system for EEG16,17.
		<ol>
			<li>To locate this location in the absence of an electrode cap, follow the standard 10-20 system procedures.</li>
			<li>Measure the head with a tape from the inion to the nasion, and note the middle of this distance. Then, measure the distance from the left preauricular point to the right preauricular point, and mark the crosspoint of the two measurements.</li>
			<li>To find the CP5 location, measure 30% of the distance between the preauricular points from the crosspoint down the left hemisphere and mark it. Measure 10% of the distance between the inion and the nasion from the marked point to the back of the head. This point is the CP5 location for the active electrode (Figure 3).</li>
		</ol>
		</li>
		<li>Broca&#39;s area 
		NOTE: Closest to Broca&#39;s area is the F5 electrode site18&#160;according to the 10-20 system.
		<ol>
			<li>In the absence of an EEG cap, follow the standard 10-20 system procedures to find and mark the crosspoint between inion-nasion and preauricular points, as described above.</li>
			<li>To find the F5 location, measure 20% of the distance between the inion and the nasion from the crosspoint to the front of the head. Measure 30% of the distance between the preauricular points from the recently marked point down the left hemisphere. This point corresponds to the F5 location for the active electrode (Figure 3).</li>
		</ol>
		</li>
		<li>Homologous locations in the right hemisphere: for right-hemispheric homologues of Wernicke&#39;s and Broca&#39;s areas, use the same procedures as above, with the exception of measuring the distance from the midline down the right side of the scalp. Electrode locations are: CP6 for the RH Wernicke homologue and F6 for the Broca homologue.</li>
		<li>Use spongy electrodes measuring 5 cm x 5 cm as this size is a good compromise between focal stimulation (which causes more irritation and discomfort) and larger electrodes that lack focality. Soak the electrodes in physiological saline solution for 5 min before application.</li>
		<li>In order to minimize the effect of stimulation on other areas of the brain, place the reference electrode at the base of the neck on the left (right for homologues) side (see Figure 3 and Figure 4). Use spongy electrodes measuring 5 cm x 5 cm as well. 
		NOTE: Particular attention should be paid to preventing the spreading of the solution beyond the boundaries of the electrode application zone. Special care should be taken to keep the surrounding electrode area dry.</li>
		<li>For optimal cathodal stimulation, use 1.5 mA current for 15 min. At the onset, the current gradually rises from 0 to 1.5 mA over 30 s, and at the end of the stimulation it drops back to zero over 30 s.</li>
		<li>For anodal stimulation, use the same procedure as cathodal stimulation, except the polarity is reversed, and the anodal electrode is placed at the active site, while the cathode is used as the reference electrode located outside the scalp area.</li>
	</ol>
	</li>
	<li>Sham stimulation
	<ol>
		<li>Perform the sham stimulation procedure generally as described above except that the current is only applied briefly in the beginning and the end of the sham session. To this end, during the first and the last 30 s of the session, apply an electric pulse of a triangular shape with a maximum of 1.5 mA, as used in the present protocol.</li>
	</ol>
	</li>
	<li>Main behavioral task: contextual semantic learning
	<ol>
		<li>Present sets with contextual sentences for the novel words in a random order. Start each sentence with a word-by-word presentation.</li>
		<li>After this, display the entire sentence on the screen to ensure its full understanding. Have participants press the spacebar with the index finger of the left hand after reading the whole sentence. Duration of sentence presentation is 5000 ms. 
		NOTE: The sets of the sentences are separated from each other by appearance of three crosshairs (&#34;+++&#34;) for 2000 ms. Each new concept presentation starts with a single fixation cross (&#34;+&#34;) present for 500 ms before the sentence words are flashed. Each word is presented for 500 ms, and the empty screen in the background color between words within one sentence is 300 ms long.</li>
	</ol>
	</li>
	<li>Acquisition assessment procedure
	<ol>
		<li>To assess learning effects both immediately and following the overnight consolidation stage, break the stimulus set into two subsets, equally distributed across stimulus conditions and counterbalanced across the subject group, and run the assessment task immediately after the learning protocol on one subset, and after a 24 h delay on the other one. 
		NOTE: This strategy is based on the literature that highlights the importance of overnight memory consolidation for the acquisition of new words19,20.</li>
		<li>Use all developed tasks in the order described in section 3 above to assess different levels of word/concept acquisition. Choose the order of the tasks to minimize any carryover effects from one task to the following ones.</li>
		<li>For Tasks 1 and 4 use spreadsheets to be filled by subjects (by hand or using a text or spreadsheet processor); present the other tasks using temporally precise simulation software. 
		NOTE: Each stimulus in Tasks 2 and 3 is presented for 600 ms, with a fixation cross (&#34;+&#34;) present in the interstimulus interval (1400 ms); see Figure 3. For the other tasks the response time is not limited.</li>
	</ol>
	</li>
</ol>
6. Data analysis
<ol>
	<li>Perform data analysis using different tests comparing two sets of samples coming from continuous distributions (such as Wilcoxon signed rank test or Mann-Whitney U-test) or medians (two-sample t-test, if the distribution is normal).</li>
</ol>

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The authors have nothing to disclose.

The results highlight a few important points that need to be taken into account when conducting psycholinguistic research in general, and neurolinguistics tDCS studies in particular. Stimulation of language cortices (exemplified here by Wernicke&#39;s area) produces a complex pattern of behavioral outcomes. Unlike the TMS technique, where it is possible to fully disrupt speech processing (e.g., the so-called &#34;speech arrest&#34; protocol)21, this method enables a possibly more complex, graded and subtle influence on the language processing mechanisms. We have found a variety of both accuracy and reaction time differences which diverged substantially between conditions, tests and assessment days. The technical implications of the protocol reported are briefly discussed below.
To disengage the various effects, a battery of different tests is needed, which could test for processes at different levels of short- and long-term memory, lexical access, semantic processing, etc. For example, the effects here include different performance in&#160;recall and recognition for different stimulus types and stimulation conditions, which suggests differential lexical competition effects for novel and old items, and diverging effects of tDCS at lexical and semantic levels. Our results confirm sensitivity of the utilized tasks to efficiency of novel word acquisition at different levels, including recognition, understanding of a word meaning and free recall.
In the same way, a tDCS condition (e.g., anodal, cathodal stimulation) requires a proper control condition (or control group), sham (placebo) stimulation being the most appropriate baseline. Unlike electrical stimulation of the motor cortex, the effects may not always be unambiguous22, they strongly depend on the tests used, or may not appear at all23.
Another very important point is that only one type of stimulation could be applied in each individual subject in the context of a single experimental session. This normally entails a between-group design, for instance, an anodal stimulation group, a cathodal stimulation group, and a placebo (sham) control group. For within-group designs, use different tDCS protocol on different days, at least 24 h apart (in learning studies, this also entails using different linguistic stimuli on different days to avoid contamination of results by repetition effects). The present report uses an experiment with cathodal stimulation of Wernicke&#39;s areas as an example, but similar procedures apply to other polarities/sites.
Contextual presentation of new words significantly expands the possibilities of simultaneous study of acquisition of word form per se and of its semantics. Traditionally, these processes are studied separately focusing either on the acquisition of a new word form or on the correlation of a meaning of a familiar word with other semantic units24,25,26. The proposed protocol combines both aims; therefore, it is possible to compare the dynamics of a new concept acquisition at the level of word form perception and that of mastering its content, which is achieved by using a comprehensive set of tests. The need for such a comparison is emphasized here by diverging dynamics of performance on novel surface forms recall and recognition as opposed to semantic matching.
It is important to remember the main differences between tDCS and other non-invasive brain stimulation methods, such as TMS. Since there is no simple way to determine individual sensitivity to tDCS by threshold assessment, a single protocol is applied for all subjects. It is very difficult to accurately estimate the stimulation area &#8211;&#160;one can only speak about the approximate/hypothetical area being stimulated. It is also difficult to estimate the duration of offline stimulation effects after the current is turned off. Presumably, the main effects of stimulation are observed up to one hour after the termination of stimulation. However, the effects&#160;can sometimes be detected even one day after the stimulation20.
Yet, compared with TMS, the relative ease of application of tDCS, the substantially lower risk of side effects and the absence of acoustic artifacts make this protocol attractive for studying the speech and language function. It is also worth noting that the combination of electrical stimulation with other methods, for example with TMS, fMRI, EEG or&#160;pharmacological intervention, allows studying neuronal mechanisms of tDCS in more detail27,28.
Since tDCS stimulation is not highly localized, a non-specific effect is possible. This is obvious from the existing evidence, where&#160;very different or even opposite protocols may sometimes lead to similar results. This may be due to the general impact on other cognitive functions and processes such as attention, retrieval from memory, and so on. A specialized battery of tests is needed to detect the effects associated with a particular language feature. Following the proposed steps of the stimulus material creation (verification of the surface or lemma frequency of the words, length of words and sentences, etc.), it is necessary to consider the grammatical and phonetic structure of a language. For instance, the number of words in a sentence and the length of the words can vary depending on the exact need. In addition, the words used in the experiment should be controlled for both spelling and sound. In an orthographically transparent language such as Russian, this is relatively straightforward, but it may be difficult to attain in other languages (e.g., English, Danish or Mandarin).
In line with a body of previous studies, we find different effects of acquisition immediately after the learning block and after an overnight sleep, which highlights effects of overnight consolidation. Importantly, we also find group differences (sham versus cathode) on the second day. It is generally accepted that the physical effect of stimulation of the cortex is relatively short-lasting, on the order of minutes to several hours. This implies that the cognitive effects achieved during the transient stimulation phase are nevertheless maintained over a longer period and may therefore be possibly used for modulating word acquisition and processing in practical settings. Obviously, not only the core language areas of Broca and Wernicke are involved in the language function; adoption of the protocol described above is possible for any area of the brain, while a battery of psycholinguistic tests fine-tuned for specific experimental purposes is still needed to assess the stimulation impact on a specific neurolinguistic trait.

The neurobiological mechanisms of human language function are still poorly understood. As the bedrock of our communication ability, this unique human neurocognitive trait plays a particularly important role in our personal and socio-economic lives. Any deficits affecting speech and language are devastating for the sufferers and expensive for the society. At the same time, in the clinic, procedures for treatment of speech deficits (such as aphasia) remain suboptimal, not least due to poor understanding of the neurobiological mechanisms involved1. In research, the recent advent and rapid development of neuroimaging methods have led to multiple discoveries describing activation patterns; yet, causal evidence is often still lacking. Furthermore, language areas of the brain are located somewhat suboptimally for application of mainstream neurostimulation approaches which can provide causal evidence, most importantly the transcranial magnetic stimulation technique (TMS). Whereas offline TMS protocol, such as theta burst stimulation, can cause pain due to the close proximity of the muscles to the point of stimulation, &#34;online&#34; TMS protocols can introduce sound artifacts from stimulation, which is undesirable due to interference&#160;with linguistic stimulus presentation2. Even though TMS is widely used in language studies despite such inconveniences, a welcome alternative may be provided by other stimulation methods, most notably transcranial direct-current stimulation (tDCS). In recent years, tDCS has seen a remarkable growth in its use due to its accessibility, ease of use, relative safety and often rather striking outcomes3. Even though the exact mechanisms underpinning tDCS influence on neural activity are not understood completely, the mainstream view is that, at least at low intensity levels (typically 1-2 mA for 15-60 min), it does not cause any neural excitation or inhibition per se, but instead modulates the resting transmembrane potential in a graded way towards de- or hyperpolarization, shifting the excitation thresholds up or down and thereby making the neural system more or less susceptible to modulations by other events, stimuli, states or behaviors4,5. Whereas most of the applications reported to date have focused on the motor function6 and/or motor system deficits, it has been increasingly applied to higher-level cognitive functions and their respective disabilities. There has been a rise in its application to speech and language, mostly in research aimed at the recovery of post-stroke aphasia7,8,9, even though it has so far led to mixed results with respect to the therapeutic potential, stimulation sites and hemispheres, and optimal current polarity. As this research, and particularly the application of tDCS in cognitive neurobiology of normal language function, is still in its infancy, it is crucial to delineate procedures for stimulating at least the core language cortices (most importantly Wernicke&#39;s and Broca&#39;s areas) using tDCS, which is one of the main aims of the current report.
Here, we will consider application of tDCS to language areas in a word-learning experiment. In general, the case of word learning is taken here as one example of a neurolinguistic experiment, and the tDCS part of the procedure should not change substantially for other types of language experiments targeting the same areas. Yet, we use this opportunity to also highlight major methodological considerations in a word acquisition experiment per se, which is the second main aim of the current protocol description. Brain mechanisms underpinning word acquisition &#8211;&#160;a ubiquitous human capacity at the core of our linguistic communication skill&#160;&#8211;&#160;remain largely unknown10. Complicating the picture, existing literature differs widely in how experimental protocols promote word acquisition, in control over stimulation parameters, and in tasks used to assess learning outcomes (see, e.g., Davis et al.11). Below, we describe a protocol that uses highly controlled stimuli and presentation mode, while ensuring a naturalistic context-driven acquisition of novel vocabulary. Furthermore, we use a comprehensive battery of tasks to assess the outcomes behaviorally at different levels, both immediately after learning and following an overnight consolidation stage. This is combined with sham and cathodal tDCS of language areas (we make a particular example using Wernicke&#39;s area stimulation) which can provide causal evidence on underlying neural processes and mechanisms.

transcranial direct current stimulation (tdcs) of wernicke's and broca's areas in studies of language learning and word acquisition

Language is a highly important yet poorly understood function of the human brain. While studies of brain activation patterns during language comprehension are abundant, what is often critically missing is causal evidence of brain areas&#39; involvement in a particular linguistic function, not least due to the unique human nature of this ability and a shortage of neurophysiological tools to study causal relationships in the human brain noninvasively. Recent years have seen a rapid rise in the use of transcranial direct current stimulation (tDCS) of the human brain, an easy, inexpensive and safe noninvasive technique that can modulate the state of the stimulated brain area (putatively by shifting excitation/inhibition thresholds), enabling a study of its particular contribution to specific functions. While mostly focusing on motor control, the use of tDCS is becoming more widespread in both basic and clinical research on higher cognitive functions, language included, but the procedures for its application remain variable. Here, we describe the use of tDCS in a psycholinguistic word-learning experiment. We present the techniques and procedures for application of cathodal and anodal stimulation of core language areas of Broca and Wernicke in the left hemisphere of the human brain, describe the procedures of creating balanced sets of psycholinguistic stimuli, a controlled yet naturalistic learning regime, and a comprehensive set of techniques to assess the learning outcomes and tDCS effects. As an example of tDCS application, we show that cathodal stimulation of Wernicke&#39;s area prior to a learning session can impact word learning efficiency. This impact is both present immediately after learning and, importantly, preserved over longer time after the physical effects of stimulation wear off, suggesting that tDCS can have long-term influence on linguistic storage and representations in the human brain.

Watch this Scientific Journal Video about Transcranial Direct Current Stimulation tDCS of Wernicke's and Broca's Areas in Studies of Language Learning and Word Acquisition at JoVE.com

Transcranial Direct Current Stimulation tDCS of Wernicke's and Broca's Areas in Studies of Language Learning and Word Acquisition

Here, we describe a protocol for using transcranial direct current stimulation for psycho- and neurolinguistic experiments aimed at studying, in a naturalistic yet fully controlled way, the role of cortical areas of the human brain in word learning, and a comprehensive set of behavioral procedures for assessing the outcomes.

Transcranial Direct Current Stimulation (tDCS) of Wernicke's and Broca's Areas in Studies of Language Learning and Word Acquisition

Language is a highly important yet poorly understood function of the human brain. While studies of brain activation patterns during language comprehension ...

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Nanyang Technological University

Research

JoVE Journal

Behavior

16.8K Views.  St. Petersburg State University. In deze video beschrijven we een eenvoudig tijd- en kostenefficiënt protocol voor het gebruik van transcraniële directe stroomstimulatie voor psycho- en neurolinguïstische experimenten gericht op het bestuderen van een naturalistische, maar volledig gecontroleerde manier van de rol van de corticale gebieden van het menselijk brein in woordleren, en een uitgebreide reeks gedragsprocedures voor het beoordelen van de resultaten. Taal is een zeer belangrijke, maar slecht begrepen functie van h...

Video: Transcranial Direct Current Stimulation tDCS of Wernicke's and Broca's Areas in Studies of Language Learning and Word Acquisition

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 ...

Stimulating the Lip Motor Cortex with Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception. Researchers have used single-pulse and repetitive TMS to stimulate the lip representation in the motor cortex. The excitability of the lip motor representation can be investigated by applying single TMS pulses over this cortical area and recording TMS-induced motor evoked potentials (MEPs) via electrodes attached to the lip muscles (electromyography; EMG). Larger MEPs reflect increased cortical excitability. Studies have shown that excitability increases during listening to speech as well as during&#160;viewing speech-related movements. TMS can be used also to disrupt the lip motor representation. A 15-min train of low-frequency sub-threshold repetitive stimulation has been shown to suppress motor excitability for a further 15-20 min. This TMS-induced disruption of the motor lip representation impairs subsequent performance in demanding speech perception tasks and modulates auditory-cortex responses to speech sounds. These findings are consistent with the suggestion that the motor cortex contributes to speech perception. This article describes how to localize the lip representation in the motor cortex and how to define the appropriate stimulation intensity for carrying out both single-pulse and repetitive TMS experiments.

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception.&#160; This article describes how to record motor evoked potentials (MEPs) from the lip muscles and how to disrupt the motor lip representation using repetitive TMS.

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception. ...

Transcranial Direct Current Stimulation and Simultaneous  Functional Magnetic Resonance Imaging

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp to manipulate cortical excitability and, consequently, behavior and brain function. In the last decade, numerous studies have addressed short-term and long-term effects of tDCS on different measures of behavioral performance during motor and cognitive tasks, both in healthy individuals and in a number of different patient populations. So far, however, little is known about the neural underpinnings of tDCS-action in humans with regard to large-scale brain networks. This issue can be addressed by combining tDCS with functional brain imaging techniques like functional magnetic resonance imaging (fMRI) or electroencephalography (EEG).
In particular, fMRI is the most widely used brain imaging technique to investigate the neural mechanisms underlying cognition and motor functions. Application of tDCS during fMRI allows analysis of the neural mechanisms underlying behavioral tDCS effects with high spatial resolution across the entire brain. Recent studies using this technique identified stimulation induced changes in task-related functional brain activity at the stimulation site&#160;and also in more distant brain regions, which were associated with behavioral improvement. In addition, tDCS administered during resting-state fMRI allowed identification of widespread changes in whole brain functional connectivity.
Future studies using this combined protocol should yield new insights into the mechanisms of tDCS action in health and disease and new options for more targeted application of tDCS in research and clinical settings. The present manuscript describes this novel technique in a step-by-step fashion, with a focus on technical aspects of tDCS administered during fMRI.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique. It has successfully been used in basic research and clinical settings to modulate brain function in humans. This article describes the implementation of tDCS and simultaneous functional magnetic resonance imaging (fMRI), to investigate the neural basis of tDCS effects.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp ...

Transcranial Magnetic Stimulation for Investigating Causal Brain-behavioral Relationships and their Time Course

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily disrupt information processing in a brain region, generating a short-lived &#8220;virtual lesion.&#8221; Stimulation that interferes with task performance indicates that the affected brain region is necessary to perform the task normally. In other words, unlike neuroimaging methods such as functional magnetic resonance imaging (fMRI) that indicate correlations between brain and behavior, TMS can be used to demonstrate causal brain-behavior relations. Furthermore, by varying the duration and onset of the virtual lesion, TMS can also reveal the time course of normal processing. As a result, TMS has become an important tool in cognitive neuroscience. Advantages of the technique over lesion-deficit studies include better spatial-temporal precision of the disruption effect, the ability to use participants as their own control subjects, and the accessibility of participants. Limitations include concurrent auditory and somatosensory stimulation that may influence task performance, limited access to structures more than a few centimeters from the surface of the scalp, and the relatively large space of free parameters that need to be optimized in order for the experiment to work. Experimental designs that give careful consideration to appropriate control conditions help to address these concerns. This article illustrates these issues with TMS results that investigate the spatial and temporal contributions of the left supramarginal gyrus (SMG) to reading.

Transcranial magnetic stimulation (TMS) is a technique for non-invasively disrupting neural information processing and measuring its effect on behavior. When TMS interferes with a task, it indicates that the stimulated brain region is necessary for normal task performance, allowing one to systematically relate brain regions to cognitive functions.

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily ...

Modulating Cognition Using Transcranial Direct Current Stimulation of the Cerebellum

Numerous studies have emerged recently that demonstrate the possibility of modulating, and in some cases enhancing, cognitive processes by exciting brain regions involved in working memory and attention using transcranial electrical brain stimulation. Some researchers now believe the cerebellum supports cognition, possibly via a remote neuromodulatory effect on the prefrontal cortex. This paper describes a procedure for investigating a role for the cerebellum in cognition using transcranial direct current stimulation (tDCS), and a selection of information-processing tasks of varying task difficulty, which have previously been shown to involve working memory, attention and cerebellar functioning. One task is called the Paced Auditory Serial Addition Task (PASAT) and the other a novel variant of this task called the Paced Auditory Serial Subtraction Task (PASST). A verb generation task and its two controls (noun and verb reading) were also investigated. All five tasks were performed by three separate groups of participants, before and after the modulation of cortico-cerebellar connectivity using anodal, cathodal or sham tDCS over the right cerebellar cortex. The procedure demonstrates how performance (accuracy, verbal response latency and variability) could be selectively improved after cathodal stimulation, but only during tasks that the participants rated as difficult, and not easy. Performance was unchanged by anodal or sham stimulation. These findings demonstrate a role for the cerebellum in cognition, whereby activity in the left prefrontal cortex is likely dis-inhibited by cathodal tDCS over the right cerebellar cortex. Transcranial brain stimulation is growing in popularity in various labs and clinics. However, the after-effects of tDCS are inconsistent between individuals and not always polarity-specific, and may even be task- or load-specific, all of which requires further study. Future efforts might also be guided towards neuro-enhancement in cerebellar patients presenting with cognitive impairment once a better understanding of brain stimulation mechanisms has emerged.

Transcranial direct current stimulation (tDCS) over the cerebellum exerts a remote effect on the prefrontal cortex, which can modulate cognition and performance. This was demonstrated using two information-processing tasks of varying complexity, whereby only cathodal tDCS improved performance when the task was difficult, but not easy.

Numerous studies have emerged recently that demonstrate the possibility of modulating, and in some cases enhancing, cognitive processes by exciting brain ...

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

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

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

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

Medicine

Remotely Supervised Transcranial Direct Current Stimulation: An Update on Safety and Tolerability

The remotely supervised tDCS (RS-tDCS) protocol enables participation from home through guided and monitored self-administration of tDCS treatment while maintaining clinical standards. The current consensus regarding the efficacy of tDCS is that multiple treatment sessions are needed to observe targeted behavioral reductions in symptom burden. However, the requirement for patients to travel to clinic daily for stimulation sessions presents a major obstacle for potential participants, due to work or family obligations or limited ability to travel. This study presents a protocol that directly overcomes these obstacles by eliminating the need to travel to clinic for daily sessions.
This is an updated protocol for remotely supervised self-administration of tDCS for daily treatment sessions paired with a program of computer-based cognitive training for use in clinical trials. Participants only need to attend clinic twice, for a baseline and study-end visit. At baseline, participants are trained and provided with a study stimulation device, and a small laptop computer. Participants then complete the remainder of their stimulation sessions at home while they are monitored via videoconferencing software.
Participants complete computerized cognitive remediation during stimulation sessions, which may serve a therapeutic role or as a &#34;placeholder&#34; for other computer-based activity. Computers are enabled for real-time monitoring and remote control by study staff.
Outcome measures that assess feasibility and tolerance are administered remotely with the aid of visual analogue scales that are presented onscreen. Following completion of all RS-tDCS sessions, participants return to clinic for a study end visit in which all study equipment is returned.
Results support the safety, feasibility, and scalability of the RS-tDCS protocol for use in clinical trials. Across 46 patients, 748 RS-tDCS sessions have been completed. This protocol serves as a model for use in future clinical trials involving tDCS.

This manuscript provides an updated remote supervision protocol that enables participation in transcranial direct current stimulation (tDCS) clinical trials while receiving treatment sessions from home. The protocol has been successfully piloted in both patients with multiple sclerosis and Parkinson&#39;s disease.

The remotely supervised tDCS (RS-tDCS) protocol enables participation from home through guided and monitored self-administration of tDCS treatment while ...

Neuroscience

Transcranial Electrical Brain Stimulation in Alert Rodents

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in humans is transcranial direct current stimulation (tDCS). Less frequently, transcranial alternating current stimulation (tACS) or transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range, is used. The increase of noninvasive electrical brain stimulation research in humans, both for experimental and clinical purposes, has yielded an increased need for basic, mechanistic, safety studies in animals. This article describes a model for transcranial electrical brain stimulation (tES) through the intact skull targeting the motor system in alert rodents. The protocol provides step-by-step instructions for the surgical set-up of a permanent epicranial electrode socket combined with an implanted counter electrode on the chest. By placing a stimulation electrode into the epicranial socket, different electrical stimulation types, comparable to tDCS, tACS, and tRNS in humans, can be delivered. Moreover, the practical steps for tES in alert rodents are introduced. The applied current density, stimulation duration, and stimulation type may be chosen depending on the experimental needs. The caveats, advantages, and disadvantages of this set-up are discussed, as well as safety and tolerability aspects.

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in ...

Transcranial Direct Current Stimulation (tDCS) for Memory Enhancement

Memory enhancement is one of the great challenges in cognitive neuroscience and neurorehabilitation. Among various techniques used for memory enhancement, transcranial direct current stimulation (tDCS) is emerging as an especially promising tool for improvement of memory functions in a non-invasive manner. Here, we present a tDCS protocol that can be applied for memory enhancement in healthy-participant studies as well as in aging and dementia research. The protocol uses weak constant anodal current to stimulate cortical targets within cortico-hippocampal functional network engaged in memory processes. The target electrode is placed either on the posterior parietal cortex (PPC) or the dorsolateral prefrontal cortex (DLPFC), while the return electrode is placed extracranially (i.e., on the contralateral cheek). In addition, we outline a more advanced method of oscillatory tDCS, mimicking a natural brain rhythm to promote hippocampus-dependent memory functions, which can be applied in a personalized and non-personalized manner. We present illustrative results of associative and working memory improvement following single tDCS sessions (20 minutes) in which the described electrode montages were used with current intensities between 1.5 mA and 1.8 mA. Finally, we discuss crucial steps in the protocol and methodological decisions that must be made when designing a tDCS study on memory.

Transcranial Direct Current Stimulation tDCS for Memory Enhancement

A protocol for memory enhancement by using transcranial direct current stimulation (tDCS) targeting dorsolateral prefrontal and posterior parietal cortices, as core cortical nodes within hippocampo-cortical network, is presented. The protocol has been well evaluated in healthy-participant studies and is applicable to aging and dementia research as well.

Memory enhancement is one of the great challenges in cognitive neuroscience and neurorehabilitation. Among various techniques used for memory enhancement, ...

Study Design for Navigated Repetitive Transcranial Magnetic Stimulation for Speech Cortical Mapping

The cortical areas involved in human speech should be characterized reliably prior to surgery for brain tumors or drug-resistant epilepsy. The functional mapping of language areas for surgical decision-making is usually done invasively by electrical direct cortical stimulation (DCS), which is used to identify the organization of the crucial cortical and subcortical structures within each patient. Accurate preoperative non-invasive mapping aids surgical planning, reduces time, costs, and risks in the operating room, and provides an alternative for patients not suitable for awake craniotomy. Non-invasive imaging methods like MRI, fMRI, MEG, and PET are currently applied in presurgical design and planning. Although anatomical and functional imaging can identify the brain regions involved in speech, they cannot determine whether these regions are critical for speech. Transcranial magnetic stimulation (TMS) non-invasively excites the cortical neuronal populations by means of electric field induction in the brain. When applied in its repetitive mode (rTMS) to stimulate a speech-related cortical site, it can produce speech-related errors analogous to those induced by intraoperative DCS. rTMS combined with neuronavigation (nrTMS) enables neurosurgeons to preoperatively assess where these errors occur and to plan the DCS and the operation to preserve the language function. A detailed protocol is provided here for non-invasive speech cortical mapping (SCM) using nrTMS. The proposed protocol can be modified to best fit the patient- and site-specific demands. It can also be applied to language cortical network studies in healthy subjects or in patients with diseases that are not amenable to surgery.

Navigated repetitive transcranial magnetic stimulation is a highly efficient non-invasive tool for mapping speech-related cortical areas. It helps in designing brain surgery and speeds up the direct cortical stimulation conducted during the surgery. This report describes how to perform speech cortical mapping reliably for preoperative evaluation and research.

The cortical areas involved in human speech should be characterized reliably prior to surgery for brain tumors or drug-resistant epilepsy. The functional ...

Transcranial Direct Current Stimulation (tDCS) of Wernicke's and Broca's Areas in Studies of Language Learning and Word Acquisition

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