Fig. 23.1
Basic principles of transcranial magnetic stimulation. The magnetic coil, represented as a figure-of-eight device, is placed on top of the cerebral cortex and pulses a magnetic field that induces electrical currents across the six layers of the cerebral cortex (indicated by numbers at left). The excitatory cells (green with blue axons) and the inhibitory cells (gray with black axons) have the potential to be activated at the level of their axons, which contain the highest density of ion channels. The incoming axons from other cortical areas and the thalamus (indicated in red) are also activated. The end result of the magnetic pulse is the synaptic activation of a chain of neurons, which generate feed-forward and feedback loops of excitation and inhibition. Source: Huerta PT and Volpe B. Transcranial magnetic stimulation, synaptic plasticity and network oscillations. Journal of NeuroEngineering and Rehabilitation 2009, 6:7 doi:10.1186/1743-0003-6-7. Creative Commons License CC-BY
When the coil is placed on the head, the electric field can reach neurons located at distances that vary according to the type of coil and the intensity of stimulation. Figure-of-eight coils are typically more focal than round coils. Round and figure-of-eight coils typically are able to stimulate cortical neurons at a depth of about 2–3 cm, while H-coils are able to induce currents in deeper structures [5, 6].
Techniques
When a single TMS pulse is applied, neuronal stimulation is short-lived. For instance, if the sensorimotor cortex is stimulated, a movement can be elicited contralateral to the stimulation. This movement occurs because either cortical interneurons projecting to corticospinal neurons are depolarized or corticospinal neurons are directly depolarized by the induced electric field (Fig. 23.2). Action potentials are then induced in axons of the corticospinal tract, leading to depolarization of motor neurons in the spinal cord and hence to activation of motor units and movement.
Fig. 23.2
Transcranial magnetic stimulation of the primary motor cortex. Electric currents induced by a changing magnetic field (in pink) depolarize interneurons (in blue). Excitation of cortical neurons in the motor cortex leads to depolarization of axons in the corticospinal tract and activation of motor units in the spinal cord. Motor-evoked potentials are registered with surface electrodes in target muscles contralateral to the stimulated hemisphere. EMG electromyography, MEP motor-evoked potential, TMS transcranial magnetic stimulation
Depending on the coil position on the head, proximal or distal muscles in the contralateral upper or lower limbs can be activated.
When surface electrodes are placed on the target muscles, motor-evoked potentials (MEPs) can be recorded. A number of measures of excitability can be obtained by analysis of MEPs after administration of one pulse (single-pulse TMS) or two pulses (paired-pulse TMS), among other paradigms. These measures can aid in understanding changes that occur in the brain after lesions such as stroke [7–9]. In addition, the motor threshold, a measure obtained by analysis of MEPs, is often used to individualize doses of TMS in rTMS studies [10].
The motor cortex is the area most frequently targeted by single-pulse TMS, because evoking and analyzing MEPs are objective and straightforward procedures. However, other areas can be stimulated. TMS of the visual cortex can induce phosphenes, and administration of single pulses to non-motor areas during cognitive tasks can induce “noise” in neuronal activity, leading to transient disruption in task performance when the targeted neurons are relevant to the task [7]. This way, the functional relevance of different brain areas can be evaluated.
Another strategy to transiently disrupt task performance is by the use of rTMS pulses at specific frequencies. Typically, rTMS is administered over several minutes. In contrast with single pulses that only lead to immediate effects, rTMS can down- or up-regulate neuronal excitability. The duration of the change in excitability produced by rTMS can outlast the stimulation period. When several sessions of rTMS are administered over days or weeks, cumulative effects lasting for weeks or months may be observed.
Typically, low-frequency (≤1 Hz) rTMS leads to inhibition, and high-frequency (>1 Hz) rTMS leads to excitation. However, these effects can be state dependent; that is, different outcomes may be observed after rTMS is delivered to neurons that have different levels of baseline excitability. Cortical excitability can be changed by administration of drugs such as calcium- or sodium-channel blockers, and also by lesions. Therefore, rTMS can promote dissimilar alterations of excitability in healthy subjects and in patients [11, 12].
In 2005, a particular paradigm named theta-burst stimulation (TBS) was presented [13]. In TBS, three pulses at 50 Hz are administered in trains that are repeated every 200 ms (5 Hz). These trains can be delivered continuously (cTBS), usually leading to inhibition of corticomotor excitability or intermittently (iTBS), resulting in excitation. These patterned TBS paradigms are based on animal models of long-term potentiation (LTP) and depression (LTD). Shorter durations of TBS (20–190 s) can modulate excitability to an extent comparable to that produced by “traditional” rTMS paradigms delivered over 15–25 min.
In summary, single-pulse and paired-pulse TMS are examples of techniques used to evaluate changes in excitability and mechanisms of plasticity after stroke, while rTMS and TBS are used to modulate neural function. RTMS and TBS are promising therapeutic strategies for stroke rehabilitation. We will review results of studies about the effects of these NIBS interventions on motor function, language, neglect, and depression.
Potential Therapeutic Applications of rTMS and TBS
Motor Function
Upper Limb
Upper limb paresis is very common and significantly contributes to disability after stroke [14, 15]. Most studies devoted to the use of rTMS to enhance stroke recovery have focused on upper limb motor function. The rationale behind the use of NIBS to improve motor function has mainly concentrated on the hypothesis of modulation of interhemispheric inhibition [4, 16]. According to this hypothesis, excessive inhibition of the affected hemisphere by the unaffected hemisphere may worsen performance of the paretic hand, as a form of maladaptive plasticity after stroke (Fig. 23.3). This hypothesis bloomed after the observation that, in well-recovered patients, motor performance of the paretic hand worsened after low-frequency rTMS of the affected but not the unaffected hemisphere [17]. Later, abnormally increased inhibition from the motor cortex of the affected hemisphere by the unaffected hemisphere was documented [18].
Fig. 23.3
Schematic representation, hypothesis of imbalance in interhemispheric inhibition after stroke. A lesion (left) would lead to decreased interhemispheric inhibition of the unaffected hemisphere by the affected hemisphere (right). The disinhibited unaffected hemisphere would then excessively inhibit the affected hemisphere. Motor dysfunction in the paretic hand (right) would then depend not only on the affected motor cortex or corticospinal tract, but also on excessive inhibition of surviving motor neurons by the unaffected hemisphere through interhemispheric connections
Either downregulation of excitability of the motor cortex of the unaffected hemisphere or up-regulation of excitability of intact neurons of the affected hemisphere might improve motor function of the paretic upper limb. Along this line, inhibition of the unaffected hemisphere with low-frequency rTMS (Table 23.1) or excitation of the affected hemisphere with high-frequency rTMS (Table 23.2) have been performed in a number of studies. In some of them, rTMS was applied as an add-on therapy to motor training/physical/occupational therapy while in others, it was the only intervention administered.
Table 23.1
Low-frequency repetitive magnetic stimulation (rTMS)
First author, reference | n | Time from stroke | Lesion location | Severity of motor impairment | Number of sessions | Associated intervention | Design | Main outcome(s) | Main result(s) |
|---|---|---|---|---|---|---|---|---|---|
Early stage | |||||||||
Pomeroy [19] | 27 | 7–85 days | CS, S | Mild to moderate | 8 | VMC | Randomized SB SC | Muscle function, ARAT | No difference |
Liepert [20] | 12 | <14 days | S | Mild | 1 | None | Crossover DB SC | NHPT, grip | Active > sham (NHPT) |
No difference in grip | |||||||||
Grefkes [21] | 11 | 1–3 months | S | Mild | 1 | None | Crossover SC | Frequency of fist closure | Active > sham |
Chang [22] | 28 | 7–26 days | S | Mild to severe | 10 | PT, OT | Randomized SC | BBT, MI-A, FMA-UL, GS | Active > sham |
Conforto [23] | 30 | 5–45 days | CS, S | Mild to severe | 10 | PT | Randomized DB SC | JTT, force | Active > sham |
Seniow [24] | 40 | ≤90 days | CS, S | Moderate (plegic were excluded) | 15 | PT | Randomized DB SC | WMFT, FM-M, NIHSS | No difference |
Chronic stage | |||||||||
Takeuchi [25] | 20 | ≥6 months | S | Mild | 1 | Motor training | Randomized DB SC | Pinch acceleration | Active > sham |
Fregni [26] | 15 | >12 months | CS, S | Mild to moderate | 5 | None | Randomized DB SC | JTT, RT, NHPT | Active > sham |
Mally [27] | 64 | >5 years | CS | Not reported | 10 | Not reported | Not reported | “Expenditure and detection” of movements, spasticity | ↑ “motor performance” |
No sham | ↓ spasticity (post > pre) | ||||||||
Takeuchi [28] | 20 | >6 months | S | Mild to moderate | 1 | Motor training | Randomized DB SC | Pinch force, acceleration | Active > sham |
Kakuda [29] | 5 | >12 months | S | Mild | 10 | Intensive OT | No sham, UB | WFMT, FM, TST | Post > pre |
Kakuda [30] | 15 | >12 months | CS, S | Mild to moderate | 22 | Intensive OT | No sham, UB | WFMT, FM | Post > pre |
Avenanti [31] | 30 | >6 months | CS, S (M1-) | Mild | 10 | PT | Randomized DB SC | Dexterity, force | Active > sham if rTMS before PT |
Kakuda [32] | 204 | >1 years | NS | Mild to moderate | 22 | Intensive OT | No sham, UB | WFMT, FM | Post > pre |
Etoh [33] | 18 | >5 months | CS, S | Mild to moderate | 10 | Motor training | Randomized DB SC | FM, ARAT, STEF, spasticity | Active > sham (except for spasticity) |
Higgins [34] | 11 | >3 months | NS | Mild to severe | 8 | Task-specific training | Randomized DB SC | BBT, WMFT, MAL | No difference |
Early and chronic stages | |||||||||
Mansur [35] | 10 | <12 months | CS, S | Mild | 1 | None | Crossover DB SC | RT, NHPT | Active > sham |
Nowak [36] | 15 | 4 weeks to 4 months | S | Mild | 1 | None | Crossover SC | Kinematics | Active > sham |
Dafotakis [37] | 12 | >1 months | S | Mild | 1 | None | Crossover SC | Grasping and lifting | Active > sham |
Emara [38] | 60 | >1 months | CS, S | Mild to moderate | 10 | PT | Randomized DB SC | FT, AI, MRS | Active > sham |
Theilig [39] | 24 | 2 weeks to 58 monhts | CS, S | Severe | 10 | Motor training | Randomized DB SC | WMFT, spasticity | No difference |
Table 23.2
High-frequency repetitive transcranial stimulation (rTMS)
First author, reference | n | Time from stroke | Lesion location | Severity of motor impairment | Number of sessions | Associated intervention | Design | Main outcome(s) | Main result(s) |
|---|---|---|---|---|---|---|---|---|---|
Early stage | |||||||||
Khedr [40] | 52 | 5–10 days | CS, S | Severe (plegic) | 10 | Physical therapy | Randomized DB SC | NIHSS, BI | Active > sham |
Khedr [41] | 36 | 7–20 days | CS, S | Not specified, excluded flaccid hemiplegia | 5 | Physical therapy | Randomized DB SC | NIHSS, BI | Active > sham |
Khedr [42] | 48 | 5–15 days | CS, S | Mild to moderate | 5 | Physical therapy | Randomized DB SC | HSSMP, NIHSS, mRS | Active > sham |
Chronic stage | |||||||||
Richards [43] | 39 | >6 months | NS | At least 10° of extension—wrist, fingers, and thumb | 10 | CI-therapy | Randomized DB SC (secondary analysis) | WMFT, MAL | Not superior to CI-therapy + donepezil |
Kim [44] | 15 | >3 months | CS, S | Mild to moderate | 2 | Motor practice | Crossover SC SB | MA, MT | Active > sham |
Lomarev [45] | 7 | 1–5 years | CS, S | Mild to moderate | 5 | None | Crossover SC | PF | No difference |
Malcolm [46] | 19 | >1 years | NS | At least 20° of wrist extension, 10° of finger extension | 10 | CI therapy | Randomized DB SC | WMFT, MAL | No add-on effect to CI therapy |
Takeuchi [47] | 30 | >6 months | S
Related posts: Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Get Clinical Tree app for offline access
| ||||||
