Neuromodulation

1. 1Neurostimulation: purposeful stimulation of the nervous system ([blank_start]both CNS and PNS[blank_end]) with non-invasive (TMS, TES) or invasive (e.g. implanted micro-electrodes) techniques.
   
   NON-INVASIVE NEUROSTIMULATION: stimulation from outside the head. There are two types: [blank_start]magnetic[blank_end] and [blank_start]electric[blank_end]. Both for magnetic and electric stimulation the effect is [blank_start]always[blank_end] electric.
   > [blank_start]Transcranial Magnetic Stimulation (TMS)[blank_end]: classical method, transcranially applied [blank_start]magnetic currents[blank_end] that stimulate the underlying neural tissue (cortex/nerves).
   > Transcranial Electric Stimulation (TES): classical method, transcranially applied [blank_start]electric currents[blank_end] that stimulate the underlying neural tissue (cortex/nerves).
   
   [blank_start]INVASIVE NEUROSTIMULATION[blank_end]: neurosurgeon implants electrodes for both input and output (also for monitoring purposes).
   > [blank_start]Deep brain stimulation (DBS)[blank_end]: neurosurgical implant of electrodes, this helps precise modulation of the activity of an area. This might have cognitive side effects. There are ongoing studies about clinical potentiality for AD, depression, Tourette’s syndrome.
   

   1. ATranscranial Magnetic Stimulation (TMS)
   2. Bboth CNS and PNS
   3. Cmagnetic
   4. Delectric
   5. Ealways
   6. Fmagnetic currents
   7. Gelectric currents
   8. HDeep brain stimulation (DBS)
   9. IINVASIVE NEUROSTIMULATION
2. 2TMS is a technique of neural stimulation, interference and neuromodulation.
   • It allows to temporarily change the functioning of circumscribed regions of the cerebral cortex, and thus the related cognitive functions. Through TMS, [blank_start]excitation[blank_end] or [blank_start]inhibition[blank_end] of processes can be achieved.
   • It is NOT a [blank_start]neuroimaging technique[blank_end] has but functional resolution as it allows to infer causal relationships.
   • It is used for both research and [blank_start]clinical applications[blank_end] (diagnosis, therapy).
   
   There are two approaches: "virtual lesion" vs. "neuromodulation"
   
   “Virtual lesion” approach
   • TMS allows to interfere with the normal functioning of specific brain areas, and to observe the effects at the level of behavior
   and/or mental processes. For instance, if stimulated, a group of neurons cannot perform other tasks.
   [Applied as time-locked single pulses or trains of repetitive magnetic stimuli (rTMS) at certain stimulation parameters, TMS can be used to transiently disrupt the function of a target cortical area and consequently its associated behavior. This creates a temporary “virtual lesion” (VL) in an otherwise healthy brain].
   
   "Neuromodulation" approach
   • Another use of TMS is to slowly modulate neural excitability, for example by potentiating some neural processing (e.g., repetitive TMS-induced entrainment).
   []

   1. Aclinical applications
   2. Bexcitation
   3. Cinhibition
   4. Dneuroimaging technique
3. 3DRAWBACKS OF OTHER TECHNIQUES THAT INVESTIGATE BRAIN FUNCTION (vs TMS):
   
   Neuroimaging and Electrophysiology:
   These techniques allow to correlate activation of brain areas with behavior. They cannot demonstrate that a given brain area is necessary for a function ([blank_start]correlation, not causality[blank_end]). These techniques are typically good only for either spatial or temporal resolution, thus they lack functional resolution.
   
   Lesion studies:
   The lesion studies are methodologically problematic.
   • Dependence on [blank_start]serendipity of nature[blank_end] (e.g. precuneus rarely lesioned by strokes = functions not very well known) or experimental animal models
   • [blank_start]Lesion may be larger[blank_end] than the brain area under study, and often include areas functionally and/or morphologically different.
   • Cognitive abilities may be globally impaired (untestable patients).
   • The damaged region cannot be reintegrated to obtain control measures that circumscribe the lesion-induced effect.
   • Comparisons must be made to [blank_start]healthy controls[blank_end]; within-ss double dissociations are not possible.
   • [blank_start]Given brain plasticity[blank_end], connections might be modified following lesions (chronicity issues).
   
   Cortical stimulation:
   • [blank_start]Limited to the study of patients[blank_end] with brain pathologies requiring neurosurgical interventions
   • [blank_start]Stressful situation[blank_end] in the operative room and medications (e.g., mild anesthesia) might affect patient’s performance
   • [blank_start]Time constraints[blank_end] limit the experimental paradigms
   • [blank_start]Retesting is (usually) not possible[blank_end]
   
   ADVANTAGES OF TMS IN THE STUDY OF BRAIN FUNCTIONING
   • Causal vs. correlational data = > high functional resolution
   • Focused on small cortical area of interest (cf. Bestmann et al. 2003)
   • Acute studies (single session or few sessions) minimize the possibility of plastic reorganization of brain function
   • Flexibility in choosing [blank_start]within-subject vs. between-ss designs[blank_end]
   • Flexibility in studying different types of within-ss dissociations (control site, control condition)
   • Cortico-cortical connections (inter/intrahemispheric, networks, paired-pulse TMS)
   • [blank_start]Neural Chronometry[blank_end]
   TMS ultimately stimulates the cortex but does it [blank_start]indirectly through magnetic pulses[blank_end] but some other techniques do this directly such as [blank_start]TES: tDCS, tACS, tRNS.[blank_end] They implement low voltage current administered directly over the area of interest with electrodes.
   
   Bickford & Freeming (1965) and then Barker (1974) were able to elicit muscle contractions with magnetic stimulations of peripheral nerves. Modern TMS was developed in the 80s by [blank_start]Barker, Freeston & Jalinous[blank_end].

   1. ABarker, Freeston & Jalinous
   2. Bcorrelation, not causality
   3. Cwithin-subject vs. between-ss designs
   4. DNeural Chronometry
   5. Ehealthy controls
   6. FRetesting is (usually) not possible
   7. Gserendipity of nature
   8. HGiven brain plasticity
   9. ILimited to the study of patients
   10. Jindirectly through magnetic pulses
   11. KTES: tDCS, tACS, tRNS.
   12. LStressful situation
   13. MTime constraints
   14. NLesion may be larger
4. 4HOW DOES TMS WORK?
   It aims sending an electric pulse on a small portion of cortical tissue non-invasively. This works based on [blank_start]Faraday-Neumann-Lenz law[blank_end] of electromagnetism.
   
   [blank_start]The direction of the magnetic field[blank_end] can be determined from the direction of the electric field with the right hand rule.
   
   If a coil is above the head and a continuous current flows on the coil, no effect will be produced on the underlying cortex (law of EM induction, Faraday). However, if the current on the coil changes abruptly (e.g. burst suddenly generated), an electric field will be produced on the underlying cortex, with intensity directly proportional to intensity of magnetic field and inversely proportional to time for generating magnetic field.
   
   TMS IN SHORT:
   1) [blank_start]brief electric pulse to a coil[blank_end] 2) [blank_start]brief but intense magnetic pulse[blank_end] perpendicular to the orientation of the electric pulse 3) [blank_start]induction of a temporary electric[blank_end] current on the underlying cortical surface, causing neuronal depolarization, mainly of those neurons located closer to the skull and to the coil.
   
   **Effects actually depend on the stimulation parameters: intensity, duration, number of pulses,…
   

   1. Abrief electric pulse to a coil
   2. Binduction of a temporary electric
   3. Cbrief but intense magnetic pulse
   4. DFaraday-Neumann-Lenz law
   5. EThe direction of the magnetic field
5. 5STIMULATION WAVEFORMS
   [blank_start]Monophasic[blank_end]: the current is allowed to run in a single direction.
   [blank_start]Biphasic[blank_end]: complete cycle of a sine wave.
   
   Monophasic vs. Biphasic
   - Monophasic needs [blank_start]more intensity[blank_end] to reach the same efficacy as the biphasic compared to Biphasic.
   - Biphasic can retrieve about half of the energy spent for each pulse (more efficiency) allowing a faster capacitor’s recharge. This allows [blank_start]repetitive stimulation at higher[blank_end] frequencies.
   - Monophasic stimulation primarily activates a neuronal population oriented in the same direction, thus [blank_start]effects are easily summed.[blank_end] Compared to this, Biphasic stimulation may have both excitatory and inhibitory effects on many sub-populations, therefore [blank_start]summation effects are less clear[blank_end].

   

   1. AMonophasic
   2. BBiphasic
   3. Cmore intensity
   4. Drepetitive stimulation at higher
   5. Esummation effects are less clear
   6. Feffects are easily summed.
6. 6CONSEQUENCES AT THE NEURAL LEVEL
   At the microscopic level, local depolarization/hyperpolarization can
   occur depending on orientation of neurons in respect to electric flux.
   
   At the macroscopic level, changes that can be observed include evoked neuronal activity (EEG co-registration), changes in blood flow and metabolism (PET, fMRI, NIRS, SPECT), muscle twitches (EMG), changes in behavior (online vs offline).
   
   HOW DEEP?
   The magnetic field crosses the skin and the skull with little reduction in intensity and produces a current on the brain [blank_start]mainly at the cortical level[blank_end]. Specifically, the magnetic pulse reaches a depth of about [blank_start]2cm[blank_end] that may result with stimulation of the cortical surface (gyri) or peripheral nerves. Thus, it is difficult to stimulate [blank_start]medial (e.g., sulci)[blank_end] or sub-cortical areas with standard coils. Thus, it is impossible to stimulate [blank_start]sub-cortical[blank_end] structures, except with specific and innovative coils.

   1. Asub-cortical
   2. Bmainly at the cortical level
   3. C2cm
   4. Dmedial (e.g., sulci)
7. 7[blank_start]SPATIAL[blank_end] RESOLUTION OF TMS
   - This [blank_start]depends on the geometry of the coil[blank_end] that determines the focality of the magnetic field and of the induced current.
   - Spatial resolution also depends on [blank_start]coil orientation[blank_end]. Stimulation efficacy is best at 45° in respect to the considered gyrus. Spatial resolution also linearly depends on [blank_start]stimulation intensity.[blank_end]
   
   Circular coil: [blank_start]stimulates a larger surface.[blank_end]
   [blank_start]Figure-of-8 coil[blank_end]: more focal and more powerful.
   **Important to pay attention to the direction of the current flow (in the coil) and to the side of the coil used for stimulation: changing side of the coil = change polarity of the current in the cortex.
   Double-cone coil: [blank_start]allows stimulation on deeper structures[blank_end] (e.g. inside fissures/sulci) -> e.g.motor cortex controlling muscles of lower torso & limbs
   
   
   
   

   1. Astimulation intensity.
   2. BSPATIAL
   3. Cdepends on the geometry of the coil
   4. Dcoil orientation
   5. Eallows stimulation on deeper structures
   6. Fstimulates a larger surface.
   7. GFigure-of-8 coil
8. 8HOW TO FIND RIGHT SPOT?
   - [blank_start]Find functional effect[blank_end]: muscular twitch (M1, measurable also with MEPs) – static phosphenes (V1) – moving phosphenes (V5/MT).
   
   - [blank_start]Find anatomical landmarks[blank_end]: inion/nasion – ear/ear vertex, EEG 10/20 system
   
   - Move towards a certain distance to [blank_start]already localized areas[blank_end]: e.g. FEF: 1.5-4cm rostral to motor hand area.
   
   - [blank_start]Neuro-navigation[blank_end]: coordinates taken from neuroimaging literature/ad-hoc fMRI study.

   1. AFind functional effect
   2. BNeuro-navigation
   3. CFind anatomical landmarks
   4. Dalready localized areas
9. 9EFFECTS OF INTENSITY
   TMS can have two types of effect:
   - [blank_start]Above threshold[blank_end]: produces neuronal discharge. This generates action potential.
   - [blank_start]Below threshold[blank_end]: brings the resting potential closer to the threshold of action potentials, thus increasing the probability of neuronal discharge. This results with modifications of the resting potential.

   1. AAbove threshold
   2. BBelow threshold
10. 10METHODOLOGICAL ISSUES WITH TMS
    > Variability:
    o Variability across subjects/inter-brain anatomical variability: current density varies due to differences in impedance of various tissues and to the geometry of tissue.
    o Variability due to pathological substrate/inter-pathology variability: current density flowing in a healthy vs pathological tissue are not equivalent.
    
    > Types of Pulses and Timing: TMS's effect varies depending on [blank_start]type of[blank_end] pulse applied and [blank_start]timing[blank_end] of pulse.
    o [blank_start]Single pulse TMS[blank_end]: Allow to study neural chronometry, that is when a given area becomes important for a given task (or a given cognitive function). TMS single pulse returns to zero within 1 ms.
    Single pulse cognitive paradigms are [blank_start]more difficult to use[blank_end] as a need to find the exact time for delivering pulses.
    ** The pulse effect varies according to the moment in which neurons involved in a given task are mostly activated. Thus, the effect of single pulse TMS depends on the timing of the neural process under investigation!
    
    o [blank_start]Double or paired-pulse TMS (ppTMS)[blank_end]: allow to study neural chronometry that is, when a given area becomes important for a given task/cognitive function.
    
    o [blank_start]Repetitive TMS (rTMS)[blank_end]: This does not need a precise timing of the function we want to study, and it is more effective. However, this is not useful for [blank_start]neural chronometry[blank_end]. It can be used online vs offline.
    ** Repetitive [blank_start]offline[blank_end] TMS is used to activate or inhibit a given region before the administration of the task (exploiting carry over effects...). Stimulation frequencies ≤ 1 Hz (1 pulse per second) are typically [blank_start]inhibitory[blank_end], whereas stimulation frequencies 5-20 Hz are typically [blank_start]excitatory.[blank_end]
    **Repetitive offline TMS can have [blank_start]short-term and long term effects[blank_end]:
    - Short term effects: usually last half the time of stimulation, even though some effects have been observed with EEG for up to 70-90 minutes after stimulation.
    - Long-term effects: hardly ethical for research purposes, highly desirable for possible therapeutic effects in patients. They involve mechanisms of [blank_start]synaptic plasticity[blank_end] (longterm potentiation and long-term depression).
    
    o Theta burst stimulation (TBS): This is specifc type of rTMS and involves [blank_start]offline stimulation[blank_end] of a given area at very high rates for brief periods (3 pulses @50Hz repeated @5Hz) Its name comes from theta
    rhythm in EEG which is around 5Hz. It has different forms:
    - [blank_start]Intermittent TBS (iTBS)[blank_end]: a 2 sec train of TBS is repeated every 10s for a total of 190 sec (600 pulses). It causes an increase of cortical excitability (excitatory), at least in the motor cortex.
    - [blank_start]Continuous TBS (cTBS)[blank_end]: A 40 sec train of uninterrupted TBS is given (600 pulses). It produces a decrease of cortical excitability (inhibitory).
    
    SUMMARY
    - TMS: generic term for any type of transcranial magnetic stimulation;
    
    - rTMS: repetitive stimulation (in any case > 0.3 Hz);
    
    - Single-pulse TMS: [blank_start]non repetitive TMS[blank_end];
    
    - Low-frequency (slow) TMS: rTMS with frequencies ≤ 1 Hz;
    
    - High-frequency (fast) TMS: rTMS with frequencies typically ≥ 5Hz;
    
    - [blank_start]Dual-pulse TMS[blank_end]: stimulation with 2 distinct pulses generated on the same coil (& brain area) at different time interval; stimulation intensity can be set independently for each of the two pulse;
    
    - [blank_start]Double-pulse/paired-pulse TMS[blank_end]: stimulation with 2 coils over 2 different cortical regions; timing and intensity of stimulation can be set independently;
    
    - [blank_start]Multichannel (aka, multi-coil) TMS[blank_end]: TMS with multiple (N≥2) coils;
    
    - TMS functional mapping: achieved by changing coil position on the skull and assessing the effects on behavior.
    
    ONLINE MODALITY:
    To use TMS to obtain a change in performance during the process of interest, a researcher needs to hypothesize when the processing starts, how long it lasts, whether it is distributed/parallel over multiple areas, whether it is lateralized or bilateral, whether it is a feedforward processing or involves backward processing. Depending on the type of target processing, the researcher should choose the most convenient paradigm (single pulse, paired pulse, rTMS) and the most effective control conditions.
    

    1. ARepetitive TMS (rTMS)
    2. BSingle pulse TMS
    3. Cmore difficult to use
    4. Dneural chronometry
    5. EDouble or paired-pulse TMS (ppTMS)
    6. Foffline
    7. Ginhibitory
    8. Hexcitatory.
    9. Isynaptic plasticity
    10. Jshort-term and long term effects
    11. Ktype of
    12. Ltiming
    13. Moffline stimulation
    14. NIntermittent TBS (iTBS)
    15. OContinuous TBS (cTBS)
    16. Pnon repetitive TMS
    17. QDual-pulse TMS
    18. RDouble-pulse/paired-pulse TMS
    19. SMultichannel (aka, multi-coil) TMS

11. 11AT WHICH INTENSITY, TMS SHOULD BE USED?
    1) [blank_start]Fixed intensity[blank_end]: we set an a priori intensity value that is high enough, and we use it with every subject.
    
    2) [blank_start]Threshold-based Intensity[blank_end]: we find the individual threshold (i.e., different values for different subjects) & use a proportion or % of that threshold. This allows us to distinguish above vs. below threshold stimulations.
    
    Intensity is also regulated as a function of the stimulation paradigm (safety/effectiveness trade off):
    • Single pulse: 60-80% maximum stimulator output (MSO) / 100 -120% motor threshold (MT)
    • Repetitive: 50-70% MSO / 80-110% MT
    • Theta-burst: 35-50% MSO / 70-90% MT
    
    Ideally one should administer the same amount of energy to the same neural tissue in each subject. To try to do so, use of individual psychophysical threshold is needed. Two types:
    > [blank_start]Motor[blank_end] threshold: lowest TMS intensity able to elicit the movement of a specific muscle.
    > Phosphene/visual threshold: lowest TMS intensity able to elicit visual phosphenes.
    
    Stewart et al. (2001) compared individual motor and visual thresholds. Accordingly, TMS motor thresholds cannot be used as proxy of visual cortex excitability or of other non-motor areas. [blank_start]Phosphene thresholds[blank_end] proposed as a potential standard for inter-individual comparison in visual TMS experiments.

    1. AMotor
    2. BFixed intensity
    3. CThreshold-based Intensity
    4. DPhosphene thresholds
12. 12VIRTUAL LESION APPROACH
    In case of a virtual lesion approach;
    1) TMS temporarily interferes with a cortical area
    2) The function operated by this area is compromised
    3) behavioral performance worsens (e.g. longer RTs, lower accuracy)
    
    This disturbance is [blank_start]different from an actual lesion[blank_end] as it has milder and transitory effects. Its direction can also differ from actual lesion since TMS can result with [blank_start]faciliatation[blank_end] processes as well as interference. This depends on many factors:
    • [blank_start]Stimulation parameters[blank_end] (e.g., iTBS vs. cTBS; high frequency vs. low frequency rTMS)
    • Targeted area
    • The activity state of the targeted area or of the targeted neurons
    
    TMS effects have been classically interpreted as “brain virtual lesion”, that is a transitory lesion due to a temporary inactivation of a neuronal population.
    • However, often results obtained with TMS [blank_start]did not entirely correspond to[blank_end] what predicted by real lesion studies.
    • This suggests that TMS may not induce an interruption of neuronal activity; rather, effects could be due to the increase in [blank_start]neural noise[blank_end] produced by TMS.
    
    The effect of TMS seems to also depend on the neural state (activity vs rest). A recent theory, in fact, postulates that TMS effects on
    neurons are state-dependent:
    • TMS would mostly excite those neurons that are less active (Silvanto et al., 2008).
    
    

    1. AStimulation parameters
    2. Bdifferent from an actual lesion
    3. Cfaciliatation
    4. Ddid not entirely correspond to
    5. Eneural noise
13. 13[blank_start]RHYTHMIC NON-INVASIVE TRANSCRANIAL[blank_end] STIMULATION APPROACH: stimulation targets a specific oscillatory frequency promoting the respective oscillatory network.
    
    [blank_start]MULTI-CHANNEL (E.G. DOUBLE PULSE)[blank_end] APPROACH: the use of multiple coils enables selective stimulation of connectivity between 2 or more brain areas.
    

    1. AMULTI-CHANNEL (E.G. DOUBLE PULSE)
    2. BRHYTHMIC NON-INVASIVE TRANSCRANIAL
14. 14ARTIFACTS IN TMS
    TMS can produce various artifacts and side effects that could affect data collection and interpretation:
    • Auditory click
    • Mechanical vibrations on the skull
    • Stimulation of cranial nerves or muscles (twitches, pain)
    
    1) [blank_start]AUDITORY CLICK[blank_end]
    TMS is noisy and involves a rhythmic patterns, therefore it can be annoying/distracting. It may even trigger startle/orientation reflex. A solution is effects can be controlled/reduced by using earplugs, white noise or administration of similar noise in control conditions.
    
    2) [blank_start]MECHANICAL VIBRATIONS ON THE SKULL[blank_end]
    TMS coil generates a mechanical vibration on the skull, and this allows participants to discriminate intensity and guess the locus of stimulation. Solution is a) shock absorbers (e.g. thin rubber between coil and skull) or b) control condition with sham stimulation but similar vibration.
    
    3) [blank_start]STIMULATION OF CRANIAL NERVES OR MUSCLES[blank_end] (TWITCHES, PAIN)
    TMS also stimulates cranial nerves and cranio-facial muscles that may lead to producing pain and/or distracting twitches. Solution is a) manipulating coil orientation (change in stimulated site?) b) offline stimulation ( no timing info) c) selecting least susceptible, non-naïve subjects but (selection bias)
    
    CONTROL OF TMS ARTIFACTS:
    Because of the already mentioned noise factors, TMS might produce non-specific effects. Solution is to have [blank_start]different control conditions[blank_end] to assess the real effect of stimulation:
    o [blank_start]Control site[blank_end]: another cortical site that is not believed to be specifically involved in the studied process (e.g. vertex).
    o [blank_start]Control task[blank_end]: A baseline (high- or low-level) task condition.
    o [blank_start]Control stimulation[blank_end]: sham (90° flipped or inverted coil, same orientation with a thick filler between coil and scalp) or lower intensity stimulation (but may produce some effects).
    
    Sensory side effects of TMS:
    • Auditory and somato-sensory perception during application of TMS
    pulses; • distraction; • multi-sensory experiences; • shifts of spatial attention; • Increase alertness.
    - Such effects should be solved by sham TMS which involves positioning the coil so that it loses power (tilted, shifted or with a small board in between). In that case, most of the magnetic pulse will not reach the cortex but the coil will produce the same sound and similar (although not identical) mechanical vibrations. However, sham might not be enough. Althpugh, it offers better control than
    no-TMS condition but sensations produced by sham are often different from the ones produced by the real stimulation (especially for non-naïve subjects). Therefore, [blank_start]control task/site[blank_end] is recommended.
    
    - Also possible to use a [blank_start]placebo coil[blank_end] for sensory effects fo TMS. This has a magnetic shield that provides a 80% field reduction, with the same mechanical outline and sound level as a real coil.

    1. AAUDITORY CLICK
    2. BMECHANICAL VIBRATIONS ON THE SKULL
    3. CSTIMULATION OF CRANIAL NERVES OR MUSCLES
    4. Ddifferent control conditions
    5. EControl site
    6. FControl task
    7. GControl stimulation
    8. Hcontrol task/site
    9. Iplacebo coil
15. 15SAFETY AND TMS
    Overall, it is a safe technique. Side effects are extremely rare. The most dangerous one are [blank_start]seizures[blank_end], which were reported only in patients or already predisposed people (and usually in protocols pushing the boundaries of security guidelines).
    
    1) [blank_start]Seizure induction[blank_end]:
    This was caused by spread of excitation.
    - Single-pulse TMS has produced seizures in patients, but not in healthy subjects.
    - rTMS has caused seizures in patients and (very rarely) in healthy volunteers. To prevent this, visual and/or EMG or EEG monitoring for after-discharges and spreading excitation. Plus, pre-TMS checklist reduces risk.
    
    2) [blank_start]Hearing loss[blank_end]: TMS produces loud clicks in the most sensitive frequency range (rTMS more sustained). It can be reduced considerably with earplugs.
    
    3) Heating of the brain: low risk.
    
    4) Scalp burns from EEG electrodes:
    
    5) [blank_start]Effect on cognition[blank_end]: slight trend toward e.g. better motor RT.
    
    6) [blank_start]Local neck pain and headaches[blank_end]: due to stimulation of local muscles and nerves, depends on site and intensity.
    
    7)Effect on mood in healthy subjects: subtle changes in mood are site- and frequency-dependent.
    
    CONTRAINDICATIONS:
    1) [blank_start]Metallic hardware[blank_end] near coil: pacemakers, implantable medical pumps, ventriculo-peritoneal shunts (case studies with implanted brain stimulators and abdominal devices have not shown complications).
    2) History of seizures or history of epilepsy in first degree relative.
    3) Medicines which reduce seizure threshold.
    4) Subjects who are [blank_start]pregnant[blank_end] (although case studies have not shown complications).
    5) History of serious head trauma.
    6) History of [blank_start]substance abuse[blank_end] (unless targeted with TMS).
    7) Stroke (unless targeted with TMS).
    8) Brain Surgery.
    9) Other medical/neurologic conditions either associated with epilepsy or in whom a seizure would be particularly hazardous (e.g. increased intracranial pressure).

    1. ASeizure induction
    2. Bseizures
    3. CHearing loss
    4. DEffect on cognition
    5. ELocal neck pain and headaches
    6. FMetallic hardware
    7. Gpregnant
    8. Hsubstance abuse
16. 16TRANSCRANIAL ELECTRIC STIMULATION (TES)
    TES has been re-discovered only recently, after the growing success of TMS but has a different effect. It causes an [blank_start]increase/decrease in neural activity[blank_end] (mostly).
    > [blank_start]TMS and tACS[blank_end] are more powerful -> can induce APs (vs tDCS: small membrane potential changes).
    > [blank_start]tDCS[blank_end] is safer (even more unlikely to induce seizures in predisposed patients).
    > TMS [blank_start]has better spatial resolution[blank_end]: with tDCS and tACS current propagates over much larger areas.
    
    TRANSCRANIAL ELECTRIC STIMULATION (TES)
    It works based on flow of electrical current on the scalp, from a [blank_start]positive pole[blank_end] (anode) to a [blank_start]negative pole[blank_end] (cathode). [blank_start]There are many different types[blank_end]:
    
    [blank_start]Transcranial direct current stimulation[blank_end] (tDCS): [blank_start]most common TES technique[blank_end], application of a direct (i.e., constant) electrical current, usually between 1 and 2 mA. Does not induce APs but [blank_start]can modulate excitability[blank_end] of neurons.
    
    Transcranial alternating current stimulation (tACS): Stimulation currents are time-dependent and follow a sinusoidal shape. Different stimulation frequencies are possible (e.g., Alpha ~10 Hz, Beta ~20 Hz...)
    
    Transcranial random noise stimulation (tRNS): Alternating current is varied randomly and induces random activity in the system.
    
    Transcranial pulsed current stimulation (tPCS): Current is unidirectional and pulsatile.

    1. ATranscranial direct current stimulation
    2. Bincrease/decrease in neural activity
    3. CTMS and tACS
    4. DtDCS
    5. Ehas better spatial resolution
    6. FThere are many different types
    7. Gmost common TES technique
    8. Hcan modulate excitability
    9. Ipositive pole
    10. Jnegative pole
17. 17Transcranial direct current stimulation (tDCS):
    - Evidence from MEPs: with tDCS over M1, anodal stimulation causes [blank_start]increased neural excitability[blank_end] vs cathodal stimulation (usually) causes [blank_start]decreased excitability[blank_end].
    - Evidence from BOLD: anodal tDCS tends to [blank_start]increase the BOLD signal[blank_end], whereas cathodal stimulation decreases it.
    - Evidence from Neurotransmiters: Anodal stimulation causes depolarization whereas Cathodal stimulation causes [blank_start]hyperpolarization[blank_end].
    
    Factors Influencing TDCS Effects:
    - [blank_start]Intensity of the stimulation[blank_end]
    - Protocol type
    - Task used
    - Neuronal excitability
    - Intra & inter-individual variability
    - [blank_start]Electrode montage[blank_end]
    
    * Electrode size [blank_start]negatively affects spatial resolution[blank_end] and focality of tDCS effects. A review by Fertonani, Ferrari & Miniussi (2015) concluded that larger electrodes induce stronger side effects and higher intensities are more strongly perceived.
    
    [blank_start]Compared to TMS[blank_end], tDCS is more portable, cheaper, no noise (sham easier to employ and more effective), no tactile/somatosensory stimulation (apart from the beginning at times).
    
    tDCS like [blank_start]all the Non-invasive Brain Stimulation[blank_end] (NIBS) techniques, allows causal inferences. tDCS and all NIBS largely used for basic research, clinical trials and rehabilitation programs.
    
    [blank_start]No serious side effects[blank_end] wereever found for tDCS. On the other hand, when delivered on an active neural system might [blank_start]synaptic plasticity[blank_end] (animal models / humans). Therefore, it is recommended to couple tDCS with [blank_start]interventions / neurorehabilitation[blank_end].
    
    In [blank_start]HD-tDCS[blank_end], one center ring electrode (anode OR cathode) overlying the target cortical region is surrounded by four return electrodes. Pros of HD-tDCS are a) [blank_start]higher spatial resolution[blank_end] (but still lower than with TMS) and b) unidirectional modulation concentrated on the central electrode increasing interpretability of effects (higher internal validity).
    
    Some counter-indications for tDCS:
    • [blank_start]age >= 18 years old[blank_end]
    • metals in head (except dental fillings)
    • history of seizures or 1st degree relative with history of seizures
    • medications that lower seizure threshold (tricyclic antidepressant
    and antiepileptic drugs)
    • a serious medical, neurological, or psychiatric illness (if we are not
    working with patients)
    • headaches, neck aches
    • hearing threshold shifts
    • syncope (fainting)
    • pregnancy

    1. AIntensity of the stimulation
    2. Bincreased neural excitability
    3. Cdecreased excitability
    4. Dincrease the BOLD signal
    5. Ehyperpolarization
    6. FElectrode montage
    7. Gnegatively affects spatial resolution
    8. Hall the Non-invasive Brain Stimulation
    9. Isynaptic plasticity
    10. Jinterventions / neurorehabilitation
    11. Khigher spatial resolution
    12. LCompared to TMS
    13. MNo serious side effects
    14. NHD-tDCS
    15. Oage >= 18 years old

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Master Principles of Cognitive Neuroscience&Neuroimaging Quiz on Neuromodulation, created by Süleyman Öztürk on 26/12/2023.

Author

Süleyman Öztürk

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English

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principles of cognitive neuroscience&neuroimagingmaster

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