Youichi Saitoh

Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex

Abstract The precentral gyrus (M1) is a representative target for electrical stimulation therapy of pain. To date, few researchers have investigated whether pain relief is possible by stimulation of cortical areas other than M1. According to recent reports, repetitive transcranial magnetic stimulation (rTMS) can provide an effect similar to that of electrical stimulation. With this in mind, we therefore examined several cortical areas as stimulation targets using a navigation‐guided rTMS and compared the effects of the different targets on pain. Twenty patients with intractable deafferentation pain received rTMS of M1, the postcentral gyrus (S1), premotor area (preM), and supplementary motor area (SMA). Each target was stimulated with ten trains of 10‐s 5‐Hz TMS pulses, with 50‐s intervals in between trains. Intensities were adjusted to 90% of resting motor thresholds. Thus, a total of 500 stimuli were applied. Sham stimulations were undertaken at random. The effect of rTMS on pain was rated by patients using a visual analogue scale (VAS) and the short form of the McGill Pain Questionnaire (SF‐MPQ). Ten of the 20 patients (50%) indicated that stimulation of M1, but not other areas, provided significant and beneficial pain relief (p < 0.01). Results indicated a statistically significant effect lasting for 3 hours after the stimulation of M1 (p < 0.05). Stimulation of other targets was not effective. The M1 was the sole target for treating intractable pain with rTMS, in spite of the fact that M1, S1, preM, and SMA are located adjacently.

Mirror visual feedback alleviates deafferentation pain, depending on qualitative aspects of the pain: a preliminary report

OBJECTIVESnFollowing lesions in somatosensory pathways, deafferentation pain often occurs. Patients report that the pain is qualitatively complex, and its treatment can be difficult. Mirror visual feedback (MVF) treatment can improve deafferentation pain. We sought to classify the qualities of the pain in order to examine whether the potential analgesic effect of MVF depends on these qualities.nnnMETHODSnTwenty-two patients with phantom limb pain, or pain related to spinal cord or nerve injury, performed a single MVF procedure. Before and after the MVF procedure, we evaluated phantom limb awareness, movement representation of the phantom or affected/paralysed limb, pain intensity on an 11-point numerical rating scale (0-10) and the qualities of the pain [skin surface-mediated (superficial pain) vs deep tissue-mediated (deep pain)] using lists of pain descriptors for each of the two categories.nnnRESULTSnFifteen of the patients perceived the willed visuomotor imagery of the phantom or affected/paralysed limb after the MVF procedure. In most of the patients, a reduction in pain intensity and a decrease in the reporting of deep-pain descriptors were linked to the emergence of willed visuomotor imagery.nnnCONCLUSIONSnIn this pilot study, we roughly classified the pain descriptor items into two types for evaluating the qualities of deafferentation pain. We found that visually induced motor imagery by MVF was more effective for reducing deep pain than superficial pain. This suggests that the analgesic effect of MVF treatment does depend on the qualities of the pain. Further research will be required to confirm that this effect is a specific consequence of MVF.

Reduction of intractable deafferentation pain due to spinal cord or peripheral lesion by high-frequency repetitive transcranial magnetic stimulation of the primary motor cortex

OBJECTnThe authors previously reported that navigation-guided repetitive transcranial magnetic stimulation (rTMS) of the precentral gyrus relieves deafferentation pain. Stimulation parameters were 10 trains of 10-second 5-Hz TMS pulses at 50-second intervals. In the present study, they used various stimulation frequencies and compared efficacies between two types of lesions.nnnMETHODSnPatients were divided into two groups: those with a cerebral lesion and those with a noncerebral lesion. The rTMS was applied to all the patients at frequencies of 1, 5, and 10 Hz and as a sham procedure in random order. The effect of rTMS on pain was rated by patients using a visual analog scale.nnnRESULTSnThe rTMS at frequencies of 5 and 10 Hz, compared with sham stimulation, significantly reduced pain, and the pain reduction continued for 180 minutes. A stimulation frequency of 10 Hz may be more effective than 5 Hz, and at 1 Hz was ineffective. The effect of rTMS at frequencies of 5 and 10 Hz was greater in patients with a noncerebral lesion than those with a cerebral lesion.nnnCONCLUSIONSnHigh-frequency (5- or 10-Hz) rTMS of the precentral gyrus can reduce intractable deafferentation pain, but low-frequency stimulation (at 1 Hz) cannot. Patients with a noncerebral lesion are more suitable candidates for high-frequency rTMS of the precentral gyrus.

Diffusion tensor fiber tracking in patients with central post-stroke pain; correlation with efficacy of repetitive transcranial magnetic stimulation.

Abstract Central post‐stroke pain (CPSP) is one of the most common types of intractable pain. We reported that repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex relieves pain for patients who were refractory to medical treatment. But the mechanism is unclear. In the present study, we investigated relations between the characteristics of CPSP and the results of fiber tracking, which is the only noninvasive method of evaluating the anatomical connectivity of white matter pathways. Fiber tracking of the corticospinal tract (CST) and thalamocortical tract (TCT) was investigated in 17 patients with CPSP. The stroke lesion was located in a supratentorial region in all cases (corona radiata, one case; thalamus, seven cases; putamen, nine cases). Relations between the delineation ratio (defined as the ratio of the cross section of the affected side to that of the unaffected side) of the CST and of the TCT, manual muscle test score, pain score, region of pain, and efficacy of rTMS were evaluated. Fiber tracking was successful in 13 patients with the stroke lesion involving the TCT. The rTMS‐effective group had higher delineation ratio of the CST (p = 0.02) and the TCT (p = 0.005) than the rTMS‐ineffective group. Previous studies suggested that an intact CST allows pain control but did not discuss the TCT. Our results suggest that the TCT also plays a role in pain reduction by rTMS of the primary motor cortex and that the efficacy of rTMS for patients with CPSP is predictable by fiber tracking.

Neural decoding using gyral and intrasulcal electrocorticograms

Electrocorticography of the primary motor cortex (M1) is a promising tool for controlling a brain-computer interface (BCI). Electrocorticograms (ECoG) of the human M1 within the central sulcus (intrasulcal ECoG) have been rarely examined. In order to evaluate the usefulness of intrasulcal ECoG for BCI, we examined patients with subdural electrodes placed temporarily inside the central sulcus and over the sensorimotor cortex (gyral ECoG). Five patients were asked to perform or imagine two or three classes of simple upper limb movements. Univariate statistical analysis of the results revealed that the intrasulcal ECoG on M1 showed significant variability across movement classes. A support vector machine was used for classification of single-trial ECoG signals to infer movement class (neural decoding). The movement classes were predicted with 80-90% accuracy (chance level: 33% or 50%). To reveal the relative importance of anatomical areas for neural decoding, the decoding performance was compared between gyral and intrasulcal ECoGs. The intrasulcal ECoG on the motor bank showed higher performance than the equally-sized gyral ECoG or the intrasulcal ECoG on the sensory bank. Analysis using a short time window revealed that movement class could be decoded even before movement onset. These results suggest the usefulness of intrasulcal ECoG on M1 to infer upper limb movements and present a promising application for a practical BCI system.

Electrical stimulation of primary motor cortex within the central sulcus for intractable neuropathic pain.

OBJECTIVEnTo assess the pain-relieving effects of motor cortex electrical stimulation (MCS) within the central sulcus and the predictive factors retrospectively.nnnMETHODSnThirty-four patients with intractable neuropathic pain underwent MCS; 19 patients had cerebral lesions, and 15 had non-cerebral lesions. In selected 12 patients, test electrodes were implanted within the central sulcus and on the precentral gyrus. Twelve patients received both MCS and repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex.nnnRESULTSnPain reduction of > or =50% was observed in 12 of 32 (36%) patients with > or =12 months follow-ups (2 patients were excluded because of short follow-up). In 10 of the 12 patients who received test electrodes within the central sulcus and on the precentral gyrus, the optimal stimulation was MCS within the central sulcus. In 4 of these (40%) patients, positive effects were maintained at follow-ups. The pain reduction of rTMS significantly correlated with that of MCS during test stimulation.nnnCONCLUSIONSnThe test stimulation within the central sulcus was more effective than that of the precentral gyrus. In the selected patients, chronic stimulation within the central sulcus did not significantly improve long-term results.nnnSIGNIFICANCEnThe present findings suggest that an intra-central sulcus is one of the favorable targets for MCS.

Motor cortex stimulation for phantom limb pain

A 62-year-old man was injured in a road-traffic accident 8 years before and his right lower leg was amputated later 1! s years later because of necrotic changes. After amputation, he had phantom limb pain, described as continuous burning and intermittent severe crushing pain. He could not sit still for even 3 min because of pain. He was admitted to the pain clinic and treated with drugs, lumbar sympathetic ganglion block, and dorsal column stimulation but did not get relief from his pain. He was admitted to the department of neurosurgery for motor cortex stimulation. The location of the precentral gyrus was estimated from magnetic resonance images and angiography. On December 10, 1997, an electrode array with four plate electrodes 0·5 cm in diameter, each separated by 0·5 cm (Model 3586, Medtronic, Inc, Minneapolis, Minnesota), was placed on the left interhemispheric motor cortex under general anaesthesia. Test stimulation showed that a visual analogue scale of his pain was reduced from 9 to 2, and that the pain reduction lasted for a day. On Dec 17, 1997, the stimulation system was internalised (XTREL, Medtronic). At follow-up in December, 1998, pain reduction with stimulation is still effective. The mechanism of phantom limb pain is not known; however, both hyperactivity of peripheral nerves and sensitisation of spinal neurons may play a part. Experimental studies have shown that some deafferented dorsal root ganglion cells developed spontaneous activity after dorsal rhizotomy and that prolonged or repetitive input from unmyelinated afferent nociceptors produce progressive increase of neuronal responses in the dorsal horn to subsequent peripheral stimuli. On the other hand, Melzack proposed that the anatomical structure of the body was represented in a neuromatrix extending throughout the brain which is genetically determined and later modified by sensory inputs. Nerve deafferentation can eventually result in neuron damage and pain generated in the brain. Pharmacological treatments of phantom limb pain with tricyclic antidepressants, carbamazepine, and ketamine are effective in some cases. Sympathetic ganglion blockade may work in patients with burning pain. Dorsal column stimulation provides a third of patients with a greater than 50% reduction in pain. Excisions of cortical areas or of the thalamus are effective for a short time, after which pain returns. There are two general targets in the brain (periaqueductal grey and thalamus) for electrical stimulation to treat pain. Only thalamic stimulation has sometimes brought pain relief in deafferentation pain. Motor cortex stimulation is less invasive and effective for approximately half of the patients with central post-stroke deafferentation pain. It was thought that activation of hypothetical sensory neurons through motor cortex stimulation may inhibit deafferentation nociceptive neurons within the cortex.

Motor cortex stimulation in patients with deafferentation pain: activation of the posterior insula and thalamus

OBJECTnThe mechanisms underlying deafferentation pain are not well understood. Motor cortex stimulation (MCS) is useful in the treatment of this kind of chronic pain, but the detailed mechanisms underlying its effects are unknown.nnnMETHODSnSix patients with intractable deafferentation pain in the left hand were included in this study. All were righthanded and had a subdural electrode placed over the right precentral gyrus. The pain was associated with brainstem injury in one patient, cervical spine injury in one patient, thalamic hemorrhage in one patient, and brachial plexus avulsion in three patients. Treatment with MCS reduced pain; visual analog scale (VAS) values for pain were 82 +/- 20 before MCS and 39 +/- 20 after MCS (mean +/- standard error). Regional cerebral blood flow (rCBF) was measured by positron emission tomography with H2(15)O before and after MCS. The obtained images were analyzed with statistical parametric mapping software (SPM99).nnnRESULTSnSignificant rCBF increases were identified after MCS in the left posterior thalamus and left insula. In the early post-MCS phase, the left posterior insula and right orbitofrontal cortex showed significant rCBF increases, and the right precentral gyrus showed an rCBF decrease. In the late post-MCS phase, a significant rCBF increase was detected in the left caudal part of the anterior cingulate cortex (ACC).nnnCONCLUSIONSnThese results suggest that MCS modulates the pathways from the posterior insula and orbitofrontal cortex to the posterior thalamus to upregulate the pain threshold and pathways from the posterior insula to the caudal ACC to control emotional perception. This modulation results in decreased VAS scores for deafferentation pain.

Evoked magnetic fields following noxious laser stimulation of the thigh in humans

Primary somatosensory cortex (SI) and posterior parietal cortex (PPC) are activated by noxious stimulation. In neurophysiological studies using magnetoencephalography (MEG), however, it has been difficult to separate the activity in SI from that in PPC following stimulation of the upper limb, since the hand area of SI is very close to PPC. Therefore, we investigated human pain processing using MEG following the application of a thulium-YAG laser to the left thigh to separate the activation of SI and PPC, and to clarify the time course of the activities involved. The results indicated that cortical activities were recorded around SI, contralateral secondary somatosensory cortex (cSII), ipsilateral secondary somatosensory cortex (iSII), and PPC between 150-185 ms. The precise location of PPC was indicated to be the inferior parietal lobule (IPL), corresponding to Brodmanns area 40. The mean peak latencies of SI, cSII, iSII and IPL were 152, 170, 181, and 183 ms, respectively. This is the first study to clarify the time course of the activities of SI, SII, and PPC in human pain processing using MEG.

Motor cortex stimulation for levodopa-resistant akinesia: Case report

We treated a patient with levodopa‐resistant akinesia with motor cortex stimulation (MCS), and she showed dramatic improvement more than 1 year. On admission, the patient presented severe akinesia and gait disturbance without tremor and rigidity, and did not respond to levodopa test. The patient was suspected pure akinesia and progressive supranuclear palsy. First, high‐frequency rTMS of primary motor cortex was examined, and showed the dramatic improvement. Next, chronic subdural electrodes were implanted over the motor cortex bilaterally. One year after surgery, the Unified Parkinsons Disease Rating Scale had improved remarkably, and she could walk four times faster than before. The H215O PET study showed a significant increase of rCBF in the left SMA and right dorsolateral prefrontal cortex after bilateral MCS. MCS may be an alternative treatment for patients with akinesia, including those with PD, and particularly for levodopa‐resistant patients, who respond well to rTMS.