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An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression.

Repetitive transcranial magnetic stimulation (rTMS) is currently undergoing active investigation for use in the treatment of major depression. Recent research has indicated that current methods used to localize the site of stimulation in dorsolateral prefrontal cortex (DLPFC) are significantly inaccurate. However, little information is available on which to base a choice of stimulation site. The aim of the current study was to systematically examine imaging studies in depression to attempt to identify whether there is a pattern of imaging results that suggests an optimal site of stimulation localization. We analysed all imaging studies published prior to 2005 that examined patients with major depression. Studies reporting activation in DLPFC were identified. The DLPFC regions identified in these studies were analysed using the Talairach and Rajkowska-Goldman-Rakic coordinate systems. In addition, we conducted a quantitative meta-analysis of resting studies and studies of serotonin reuptake inhibitor antidepressant treatment. There was considerable heterogeneity in the results between studies. Changes in Brodmann area 9 were relatively consistently identified in resting, cognitive activation and treatment studies included in the meta-analysis. However, there was little consistency in the direction of these changes or the hemisphere in which they were identified. At this stage, the results of imaging studies published to date have limited capacity to inform the choice of optimal prefrontal cortical region for the use in rTMS treatment studies.

Antidepressive Agents↗

Transcranial magnetic stimulation over sensorimotor cortex disrupts anticipatory reflex gain modulation for skilled action.

Skilled interactions with new environments require flexible changes to the transformation from somatosensory signals to motor outputs. Transcortical reflex gains are known to be modulated according to task and environmental dynamics, but the mechanism of this modulation remains unclear. We examined reflex organization in the sensorimotor cortex. Subjects performed point-to-point arm movements into predictable force fields. When a small perturbation was applied just before the arm encountered the force field, reflex responses in the shoulder muscles changed according to the upcoming force field direction, indicating anticipatory reflex gain modulation. However, when a transcranial magnetic stimulation (TMS) was applied before the reflex response to such perturbations so that the silent period caused by TMS overlapped the reflex processing period, this modulation was abolished, while the reflex itself remained. Loss of reflex gain modulation could not be explained by reduced reflex amplitudes nor by peripheral effects of TMS on the muscles themselves. Instead, we suggest that TMS disrupted interneuronal networks in the sensorimotor cortex, which contribute to reflex gain modulation rather than reflex generation. We suggest that these networks normally provide the adaptability of rapid sensorimotor reflex responses by regulating reflex gains according to the current dynamical environment.

Adult↗

[Changes in magnetic coil orientation affect the stimulation effects of human peripheral nerve].

Transcranial magnetic stimulation is a non-invasive method for assessing the motor function in humans. It is well established that orientation of the magnetic coil plays an important role on the stimulation effects of the motor cortex. However, there has been a few study regarding the effect of magnetic coil orientation on the efficacy of peripheral nerve stimulation. Therefore, in the present study, I carried out two experiments to clarify the relationship between the magnetic coil orientation and the stimulation effects of human peripheral nerve. First, median nerve was stimulated at the elbow and compound muscle action potentials (CMAPs) of abductor pollicis brevis muscle were recorded in 8 subjects at 4 different directions of the induced current. Two eight-shaped coils, 10 cm and 3.5 cm in outer diameter, were used. Stimulus intensities of big and small coils were 850 V and 90%, respectively. Motor threshold was measured at 4 directions with the big coil by increasing stimulus intensity up to 850 V from 150 V at a step of 50 V. It was found that the amplitude of the CMAP was the greatest in outer direction (toward the radial side) using either the big coil or the small coil. There was no significant difference between the amplitude in outer direction and that of supramaximal electrical stimulation. Motor threshold was the lowest in outer direction. Then, I measured the induced current of the big and small coils in a tank filled with saline that mimicked the forearm. The induced currents by both big and small coils were the largest and the first spatial derivatives of the induced electric field were the greatest in outer direction. These results suggest that the orientation of the eight-shaped coil is important for peripheral nerve magnetic stimulation. The fact that the forearm is a restrictive volume conductor may result in the different effects of coil orientation on the excitement of the peripheral nerve.

Action Potentials↗

Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome.

Hyperkinetic disorders may involve excess excitatory output from thalamus to cerebral cortex. Case-control, neurophysiological studies in persons with Tourette Syndrome (TS), Attention Deficit Hyperactivity Disorder (ADHD), and Obsessive-Compulsive Disorder (OCD) support this model. To compare the strength of association between motor cortex inhibition and tic, ADHD, and OCD severity in TS, we used transcranial magnetic stimulation to measure motor cortex inhibition in 36 children and adults with TS. Current symptom severity was assessed with standard clinical rating scales and compared with neurophysiological measures using correlational and multivariate regression analyses. Severity of ADHD symptoms and motor tics were associated significantly and independently with short interval intracortical inhibition (SICI) (r(2) = 0.50; F[2,27] = 13.7; P < 0.001), particularly in subjects not taking neuroleptics (r(2) = 0.68; F[2,17] = 17.8; P < 0.0001). The correlation of cortical disinhibition was greater with ADHD symptoms severity (r = 0.53; P = 0.003) than with tic severity (r = 0.42; P = 0.02), suggesting that in TS, the association between SICI and ADHD symptoms may be more consistent or direct than the association between SICI and tics.

Adolescent↗

The use of a circumferential cathode improves amplitude of intraoperative electrical transcranial myogenic motor evoked responses.

Measurement of motor evoked responses to transcranial electrical stimulation (tc-MER) is a technique for intraoperative monitoring of motor pathways. Since most anesthetics significantly reduce motoneuronal excitability, optimal stimulation paradigms should be sought. We compared the efficiency of stimulus delivery using two different configurations of the cathode component of the stimulating electrode pair (circumferential: Fz, F3, F4, A1, and A2 versus a single cathode at Fz). The anode was positioned at Cz with both cathode configurations. Fourteen neurologically normal patients undergoing spinal surgery were anesthetized with sufentanil-N2O-ketamine. Partial neuromuscular blockade (single twitch height 25%) was maintained with vecuronium. Compound action potentials to transcranial stimulation with both cathode configurations were recorded from the tibialis anterior muscle. All recordings were completed before spinal manipulation. The median amplitude response using the Fz cathode configuration was 256 microV (10th-90th percentiles: 50-641 microV). With the circumferential cathode configuration, tc-MER amplitude increased to 281 (87-1479) microV (P < 0.01). There was no significant difference in onset latency between electrode configurations. The observed tc-MER amplitude augmentation with the use of a circumferential cathode might allow tc-MER monitoring in those patients who do not have sufficiently reproducible responses when a single cathode is used. A possible explanation is that the circumferential cathode alters the direction of the electrical currents in the cortex, resulting in more efficient depolarization of cortical motor neurons.

Action Potentials↗

Comparison between short train, monophasic and biphasic repetitive transcranial magnetic stimulation (rTMS) of the human motor cortex.

OBJECTIVE: To compare motor evoked potentials (MEPs) elicited by short train, monophasic, repetitive transcranial magnetic stimulations (rTMS) with those by short train, biphasic rTMS. METHODS: Subjects were 13 healthy volunteers. Surface electromyographic (EMG) responses were recorded from the right first dorsal interosseous muscle (FDI) in several different stimulation conditions. We gave both monophasic and biphasic rTMS over the motor cortex at a frequency of 0.5, 1, 2 or 3Hz. To study excitability changes of the spinal cord, we also performed 3Hz rTMS at the foramen magnum level [Ugawa Y, Uesaka Y, Terao Y, Hanajima R, Kanazawa I. Magnetic stimulation of corticospinal pathways at the foramen magnum level in humans. Ann Neurol 1994;36:618-24]. We measured the size and latency of each of 20 MEPs recorded in the different stimulation conditions. RESULTS: 2 or 3Hz stimulation with either monophasic or biphasic pulses evoked MEPs that gradually increased in amplitude with the later MEPs being significantly larger than the earlier ones. Monophasic rTMS showed much more facilitation than biphasic stimulation, particularly at 3Hz. Stimulation at the foramen magnum level at 3Hz elicited fairly constant MEPs. CONCLUSIONS: The enhancement of cortical MEPs with no changes of responses to foramen magnum level stimulation suggests that the facilitation occurred at the motor cortex. We hypothesize that monophasic TMS has a stronger short-term effect during repetitive stimulation than biphasic TMS because monophasic pulses preferentially activate one population of neurons oriented in the same direction so that their effects readily summate. Biphasic pulses in contrast may activate several different populations of neurons (both facilitatory and inhibitory) so that summation of the effects is not so clear as with monophasic pulses. When single stimuli are applied, however, biphasic TMS is thought to be more powerful than monophasic TMS because the peak-to-peak amplitude of stimulus pulse is higher and its duration is longer when the same intensity of stimulation (the same amount of current is stored by the stimulator) is used. SIGNIFICANCE: This means that when using rTMS as a therapeutic tool or in research fields, the difference in waveforms of magnetic pulses (monophasic or biphasic) may affect the results.

Adult↗

Linking physics with physiology in TMS: a sphere field model to determine the cortical stimulation site in TMS.

A fundamental problem of transcranial magnetic stimulation (TMS) is determining the site and size of the stimulated cortical area. In the motor system, the most common procedure for this is motor mapping. The obtained two-dimensional distribution of coil positions with associated muscle responses is used to calculate a center of gravity on the skull. However, even in motor mapping the exact stimulation site on the cortex is not known and only rough estimates of its size are possible. We report a new method which combines physiological measurements with a physical model used to predict the electric field induced by the TMS coil. In four subjects motor responses in a small hand muscle were mapped with 9-13 stimulation sites at the head perpendicular to the central sulcus in order to keep the induced current direction constant in a given cortical region of interest. Input-output functions from these head locations were used to determine stimulator intensities that elicit half-maximal muscle responses. Based on these stimulator intensities the field distribution on the individual cortical surface was calculated as rendered from anatomical MR data. The region on the cortical surface in which the different stimulation sites produced the same electric field strength (minimal variance, 4.2 +/- 0.8%.) was determined as the most likely stimulation site on the cortex. In all subjects, it was located at the lateral part of the hand knob in the motor cortex. Comparisons of model calculations with the solutions obtained in this manner reveal that the stimulated cortex area innervating the target muscle is substantially smaller than the size of the electric field induced by the coil. Our results help to resolve fundamental questions raised by motor mapping studies as well as motor threshold measurements.

Adult↗

Dissociation of the pathways mediating ipsilateral and contralateral motor-evoked potentials in human hand and arm muscles.

1. Growing evidence points toward involvement of the human motor cortex in the control of the ipsilateral hand. We used focal transcranial magnetic stimulation (TMS) to examine the pathways of these ipsilateral motor effects. 2. Ipsilateral motor-evoked potentials (MEPs) were obtained in hand and arm muscles of all 10 healthy adult subjects tested. They occurred in the finger and wrist extensors and the biceps, but no response or inhibitory responses were observed in the opponens pollicis, finger and wrist flexors and the triceps. 3. The production of ipsilateral MEPs required contraction of the target muscle. The threshold TMS intensity for ipsilateral MEPs was on average 1.8 times higher, and the onset was 5.7 ms later (in the wrist extensor muscles) compared with size-matched contralateral MEPs. 4. The corticofugal pathways of ipsilateral and contralateral MEPs could be dissociated through differences in cortical map location and preferred stimulating current direction. 5. Both ipsi- and contralateral MEPs in the wrist extensors increased with lateral head rotation toward, and decreased with head rotation away from, the side of the TMS, suggesting a privileged input of the asymmetrical tonic neck reflex to the pathway of the ipsilateral MEP. 6. Large ipsilateral MEPs were obtained in a patient with complete agenesis of the corpus callosum. 7. The dissociation of the pathways for ipsilateral and contralateral MEPs indicates that corticofugal motor fibres other than the fast-conducting crossed corticomotoneuronal system can be activated by TMS. Our data suggest an ipsilateral oligosynaptic pathway, such as a corticoreticulospinal or a corticopropriospinal projection as the route for the ipsilateral MEP. Other pathways, such as branching of corticomotoneuronal axons, a transcallosal projection or a slow-conducting monosynaptic ipsilateral pathway are very unlikely or can be excluded.

Adolescent↗

Comparison of motor effects following subcortical electrical stimulation through electrodes in the globus pallidus internus and cortical transcranial magnetic stimulation.

Current concepts of transcranial magnetic stimulation (TMS) over the primary motor cortex are still under debate as to whether inhibitory motor effects are exclusively of cortical origin. To further elucidate a potential subcortical influence on motor effects, we combined TMS and unilateral subcortical electrical stimulation (SES) of the corticospinal tract. SES was performed through implanted depth electrodes in eight patients treated with deep brain stimulation (DBS) for severe dystonia. Chronaxie, conduction velocity (CV) of the stimulated fibres and poststimulus time histograms of single motor unit recordings were calculated to provide evidence of an activation of large diameter myelinated fibres by SES. Excitatory and inhibitory motor effects recorded bilaterally from the first dorsal interosseus muscle were measured after SES and focal TMS of the motor cortex. This allowed us to compare motor effects of subcortical (direct) and cortical (mainly indirect) activation of corticospinal neurons. SES activated a fast conducting monosynaptic pathway to the alpha motoneuron. Motor responses elicited by SES had significantly shorter onset latency and shorter duration of the contralateral silent period compared to TMS induced motor effects. Spinal excitability as assessed by H-reflex was significantly reduced during the silent period after SES. No ipsilateral motor effects could be elicited by SES while TMS was followed by an ipsilateral inhibition. The results suggest that SES activated the corticospinal neurons at the level of the internal capsule. Comparison of SES and TMS induced motor effects reveals that the first part of the TMS induced contralateral silent period should be of spinal origin while its later part is due to cortical inhibitory mechanisms. Furthermore, the present results suggest that the ipsilateral inhibition is predominantly mediated via transcallosal pathways.

Adolescent↗

Transcranial stimulation of the leg area of the motor cortex in humans.

We used transcranial magnetic stimulation on nine normal volunteers to establish an effective way to stimulate the leg area of the motor cortex. Three types of coils: a large figure-eight coil, small figure-eight coil, and a round coil were used. Surface electromyographic activities were recorded from the left tibialis anterior muscle, and the latencies and amplitudes compared with those obtained by anodal electrical stimulation. The most stable responses were obtained when the large figure-eight coil was centered over the vertex and backward current was run through it or when the round coil was centered two to three centimeters anterior to the vertex with left-flowing current in it at the posterior widening. The latencies obtained under these stimulation conditions were the same as those obtained by electrical stimulation. We conclude that direct activation of the pyramidal cells occurs in the leg area of the motor cortex in all forms of magnetic and electrical stimulation.

Electric Stimulation↗

[One of the methods of treatment of affective disorders in patients with alcoholism].

It has been demonstrated by a double blind placebo-controlled study that transcranial electric treatment (TET) by means of combination of direct current and pulse current and pulse current at a frequency of 70-80 Hz is an effective method of correcting affective disorders (anxiety, depressions) in patients suffering from alcoholism. The therapeutic effects of TET are coupled with changes in GABA and monoamine metabolism rather than in beta-endorphin as well as with a decrease of the latent period of the occurrence of alpha-rhythm after eyes closing.

Adult↗

Transcranial magnetic stimulation of the facial nerve: intraoperative study on the effect of stimulus parameters on the excitation site in man.

Magnetic stimulation (magStim) of the intracranial facial nerve is performed in clinical and research settings, but the activation site is a matter of controversy. Latencies of nasalis muscle responses to magStim were, therefore, compared with those obtained by direct electrical stimulation of the facial nerve (a) at the root exit zone (REZ); (b) at the porus of the facial canal; and (c) in the stylomastoid fossa during microvascular decompression operations in the cerebellopontine angle (CPA). Measurements of latencies of the nasalis muscle response, obtained while the stimulating coil was placed over the parieto-occipital area of the scalp, indicated that it was the labryinthine segment of the facial canal, 5 to 16 mm distal to the CPA, that was activated. This would be in agreement with studies of physical models reported in the literature that showed (a) the strength of the electrical current generated by a magnetic field is particularly high close to a nerve foramen; and (b) excitation to magStim is most likely to occur where the induced electrical field changes rapidly over distance, i.e., at anatomical boundaries between media of high and low specific resistance. These characteristics are found at the end of the labyrinthine segment of the facial canal, where the facial nerve leaves the low-resistance cerebrospinal fluid and enters the high-resistance petrous bone. The site of neural excitation is robust and unaffected by stimulus intensity and current direction within a wide range, or by large changes in location of the coil.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Magnetic stimuli applied over motor and visual cortex: influence of coil position and field polarity on motor responses, phosphenes, and eye movements.

Transcranial magnetic stimulation was performed over the motor and visual cortex with the Novametrix 12-cm diameter stimulation coil. The influence of coil position on the size of electromyographic responses and on the intensity and position of phosphenes in the binocular visual field was studied. Furthermore, it was investigated whether stimulation over the visual cortex or over the frontal eye field evoked or disturbed eye movements. Coil position was recorded by constructing grids on the skull surface using extracranial bony landmarks, and was then related individually to underlying cerebral sulci by analysis of magnetic resonance images of the brain. Motor responses. Excitatory effects were maximal when the coil windings in the middle of the coil ring lay over the particular motor representation field of area 4. The response size depended on the direction of the coil currents passing over the motor cortex. For example, coil currents passing over the lateral part of the precentral gyrus from the front and transversely to the central sulcus elicited maximal responses in hand muscles. With the currents passing over the same area in the opposite direction, response amplitudes were much smaller, suggesting activation of different inputs to cortical motoneurons. Phosphenes. Fields of fixed, white and unstructured phosphens occurred in the lower half of the visual field when the coil center was placed about 7 cm anterior to the inion on the inion-nasion line. Counterclockwise or clockwise coil currents elicited phosphenes within the left or right lower quadrant of the binocular visual field, respectively, which could be attributed to an activation of the right or left primary visual cortex (area 17). The 'cortical' phosphenes moved with voluntary eye movements, but not during caloric and optokinetic nystagmus. Phosphenes resulting from an excitation of the optic nerve rather than the retina could be evoked by stimulation over frontal parts of the skull. Eye movements. The application of single magnetic field pulses over the frontal eye field or over the visual cortex did not elicit eye movements except for small vertical eye movements as part of a magnetically elicited blink.

Adolescent↗

A lack of effect from transcranial magnetic stimulation (TMS) on the vagus nerve stimulator (VNS).

OBJECTIVE: The effects of transcranial magnetic stimulation (TMS) on vagus nerve stimulation (VNS) are unknown. Understanding these effects is important before exposing individuals with an implanted VNS to TMS, as could occur in epilepsy or depression TMS research. To explore this issue, the TMS-induced current in VNS leads and whether TMS has an effect on the VNS pulse generator was assessed. METHODS: Ex vivo measurement of current in VNS leads during single-pulse TMS and pulse generator function before, during, and after single-pulse TMS was assessed. RESULTS: At the highest intensity and with the TMS coil held approximately 5 mm from the VNS wires, a 200 nA, 1.0 ms current was induced by TMS. This translates to an induced charge density of 3.3 nC/cm2/phase. The function of the pulse generator was unaffected by single-pulse TMS, even when its case was directly stimulated by the coil. CONCLUSIONS: TMS-induced current in VNS electrodes was not only well outside of the range known to be injurious to peripheral nerve, but also below the activation threshold of nerve fibers. SIGNIFICANCE: Using single-pulse TMS in individuals with VNS should not result in nerve stimulation or damage. Furthermore, single-pulse TMS does not affect the VNS pulse generator's function.

Brain↗

Imaging of current density and current pathways in rabbit brain during transcranial electrostimulation.

A magnetic resonance imaging (MRI) method was used for a noninvasive study of current density (CD) and current pathways (CP's) inside the skull during transcranial electrostimulation in rabbits. The transcranial impulse current directions studied were those previously used in transcranial electric treatment either sagittally or bilaterally. MRI data were collected from slices perpendicular to the direction of current application. In these slices, only the perpendicular component of the CD was measured. Computer methods for accurate topographic mapping of the main areas with high CD and for reconstruction of CP's are described. It was revealed that current applied on the head sagittally passed mostly through the cerebrospinal fluid in the basal brain cisternas connected in series, and through the anterior horns of the lateral ventricles, foramina of Monro, ventrocaudal part of the third ventricle, aqueductus, and fourth ventricle. Possible connections between these CP's are suggested. Bilaterally applied current passed through the brain and skull core more diffusely without concentrations in cisternas and ventricles. The results of the present study suggest an explanation for the observation that sagittally applied current more effectively stimulates brain structures with antinociceptive function and elicits more pronounced analgesic effect.

Animals↗

Transcranial magnetic stimulation: language function.

Studies of language using transcranial magnetic stimulation (TMS) have focused both on identification of language areas and on elucidation of function. TMS may result in either inhibition or facilitation of language processes and may operate directly at a presumptive site of language cortex or indirectly through intracortical networks. TMS has been used to create reversible "temporary lesions," similar to those produced by Wada tests and direct cortical electrical stimulation, in cerebral cortical areas subserving language function. Rapid-rate TMS over the left inferior frontal region blocks speech output in most subjects. However, the results are not those predicted from classic models of language organization. Speech arrest is obtained most easily over facial motor cortex, and true aphasia is rare, whereas right hemisphere or bilateral lateralization is unexpectedly prominent. A clinical role for these techniques is not yet fully established. Interfering with language comprehension and verbal memory is currently more difficult than blocking speech output, but numerous TMS studies have demonstrated facilitation of language-related tasks, including oral word association, story recall, digit span, and picture naming. Conversely, speech output also facilitates motor responses to TMS in the dominant hemisphere. Such new and often-unexpected findings may provide important insights into the organization of language.

Cerebral Cortex↗

Repetitive transcranial magnetic stimulation activates specific regions in rat brain.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

Animals↗

Suppression of voluntary motor activity revealed using transcranial magnetic stimulation of the motor cortex in man.

1. Suppression of voluntary muscle activity of hand and arm muscles in response to transcranial magnetic stimulation (TMS) of the motor cortex has been investigated in man. 2. Suppression could be elicited by low levels of TMS without any prior excitatory response. The latency of the suppression was 3-8 ms longer than the excitation observed at a higher stimulus intensity. The duration of the suppression ranged from 8 to 26 ms. 3. A circular stimulating coil was used to determine threshold intensity for excitation and suppression of contraction of thenar muscles in response to TMS at different locations over the motor cortex. The locations for lowest threshold excitation coincided with those for lowest threshold suppression. Suppression was elicited at a lower threshold than excitation at all locations. 4. A figure-of-eight stimulating coil was positioned over the left motor cortex at the lowest threshold point for excitation of the right thenar muscles. The orientation for the lowest threshold excitatory and inhibitory responses was the same for all subjects. That orientation induced a stimulating current travelling in an antero-medial direction. Suppression was invariably elicited at lower thresholds than excitation. 5. When antagonistic muscles (second and third dorsal interosseus) were co-contracted, TMS evoked coincident suppression of voluntary EMG in the two muscles without prior excitation of either muscle. This suggests that the suppression is not mediated via corticospinal activation of spinal interneurones. 6. Test responses to electrical stimulation of the cervical spinal cord were evoked in both relaxed and activated thenar muscles. In the relaxed muscle, prior TMS at an intensity that would suppress voluntary activity failed to influence the test responses, suggesting absence of inhibition at a spinal level. However, in the activated muscle, prior TMS could reduce the test response. This may be explained by disfacilitation of motoneurones due to inhibition of corticospinal output. 7. We propose that suppression of voluntary muscle activity by TMS is due in large part to activation of a mechanism within the motor cortex that reduces the corticospinal output to the muscle. It is concluded that TMS evokes excitation and inhibition via neuronal structures lying close to one another and having similar orientations.

Adult↗