Preliminary Results of Branch Level, Brachial Plexus Peripheral Nerve Stimulation on a Non-Human Primate.

Restoring functional hand control is a priority for those suffering from neurological impairments. Functional electrical stimulation (FES) is commonly applied to assist with rehabilitation. However, FES applied intramuscularly typically results in complex surgeries requiring many implants. This paper presents the preliminary findings from a feasibility study focused on evaluating the potential to access the upper extremity peripheral nerves through a single surgical approach (axillary approach). A single Japanese macaque (macaca fuscata) monkey was used to validate the feasibility of this study. Four of the five peripheral nerves which control the upper extremity were exposed, and had multi-contact epineural cuffs implanted: median, radial, ulnar and musculocutaneous. The axillary nerve was not accessible for epineural cuff placement with the current surgical approach used in this study. Electrical stimuli were used to produce movement contraction patterns of muscles relevant to the innervated peripheral nerves. In addition, to assist in quantifying the outcome, evoked potentials were simultaneously recorded from five extrinsic forearm flexors during median nerve stimulation. This feasibility study demonstrated that the axillary approach enables electrode placement to four of the five peripheral nerves required for upper extremity control through a single skin incision.Clinical relevance- This study demonstrated that the electrode placement to most of the peripheral nerves that control the arm and hand can be done by a single surgical approach: axillary approach.

Masked diabetes insipidus in pituitary metastasis from breast cancer after thalamic biopsy: a case report.

BACKGROUND: Symptomatic pituitary metastasis is rare; furthermore, it can result in diabetes insipidus and panhypopituitarism. Since diabetes insipidus is masked by concurrent panhypopituitarism, it can impede the diagnosis of pituitary dysfunction. CASE PRESENTATION: A 68-year-old Japanese female suffering from pituitary and thalamic metastases caused by untreated breast cancer, underwent a biopsy targeting the thalamus, not the pituitary. She lacked prebiopsy pituitary dysfunction symptoms; however, these symptoms unexpectedly occurred after biopsy. Diabetes insipidus was masked by corticosteroid insufficiency, and she showed normal urinary output and plasma sodium levels. Upon commencement of glucocorticoid replacement therapy, the symptoms of diabetes insipidus appeared. CONCLUSIONS: In this case, thalamic biopsy, as opposed to pituitary biopsy, was performed to preserve pituitary function. However, pituitary dysfunction could not be avoided. Caution is necessary for asymptomatic patients with pituitary metastases as invasive interventions, such as surgery, may induce pituitary dysfunction. Moreover, with respect to masked diabetes insipidus, there is a need to carefully consider pituitary dysfunction to avoid misdiagnosis and delayed treatment.

Why brain-controlled neuroprosthetics matter: mechanisms underlying electrical stimulation of muscles and nerves in rehabilitation.

Delivering short trains of electric pulses to the muscles and nerves can elicit action potentials resulting in muscle contractions. When the stimulations are sequenced to generate functional movements, such as grasping or walking, the application is referred to as functional electrical stimulation (FES). Implications of the motor and sensory recruitment of muscles using FES go beyond simple contraction of muscles. Evidence suggests that FES can induce short- and long-term neurophysiological changes in the central nervous system by varying the stimulation parameters and delivery methods. By taking advantage of this, FES has been used to restore voluntary movement in individuals with neurological injuries with a technique called FES therapy (FEST). However, long-lasting cortical re-organization (neuroplasticity) depends on the ability to synchronize the descending (voluntary) commands and the successful execution of the intended task using a FES. Brain-computer interface (BCI) technologies offer a way to synchronize cortical commands and movements generated by FES, which can be advantageous for inducing neuroplasticity. Therefore, the aim of this review paper is to discuss the neurophysiological mechanisms of electrical stimulation of muscles and nerves and how BCI-controlled FES can be used in rehabilitation to improve motor function.

Kinetic Study of Singlet-Oxygen Quenching and Aroxyl-Radical Scavenging Activities of Vitamin E Homologs and Fatty Acids Present in Vegetable Oils.

Recently, singlet-oxygen (1O2) quenching and aroxyl-radical (ArO·) scavenging rates (kQ and kS, respectively) of eight vegetable oils were measured in the ethanol/chloroform/D2O solution. Furthermore, the kQ and kS values and concentrations of four tocopherols and four tocotrienols contained in the vegetable oils were measured. In this study, the concentrations of nine fatty acids (including stearic, oleic, linoleic, and linolenic acids) comprising the above-mentioned eight vegetable oils were determined by gas chromatography. The kQ and kS values for ethyl stearate, ethyl oleate, ethyl linoleate, methyl linolenate, and glyceryl trioleate in the ethanol/chloroform/D2O solution were measured by UV-vis spectrophotometry. Based on the results obtained for the above-mentioned fatty acid esters, the kQ and kS values were estimated for nine fatty acids. Furthermore, comparisons of kQ values observed for the vegetable oils with the sum of the product {∑kQAO-i [AO-i]} of the kQAO-i values obtained for each antioxidant-i (AO-i) and the concentrations ([AO-i]) of AO-i (i.e., four tocopherols (& four tocotrienols) and nine fatty acids) contained in vegetable oils were performed. Based on the results, a detailed comparison of the contributions of the tocopherols (and tocotrienols) and the fatty acids to the 1O2-quenching rate constants (kQ) was performed. This indicated that both the tocopherols (and tocotrienols) and the fatty acids contribute to the 1O2- quenching. A similar comparison was conducted for the ArO· -scavenging rate constants (kS). The results suggested that only the tocopherols (and tocotrienols) contained in the oils contributed to the ArO· -scavenging, with negligible contribution from the fatty acids.

Kinetic Study of the Quenching Reaction of Singlet Oxygen by Eight Vegetable Oils in Solution.

A kinetic study of the reaction of singlet oxygen (1O2) with eight vegetable oils 1-8 containing different concentrations of tocopherols (Tocs) and tocotrienols (Toc-3s) was performed. The second-order rate constants (kQ) for the reaction of 1O2 with vegetable oils 1-8 (rice bran, perilla, rape seed, safflower, grape seed, sesame, extra virgin olive, and olive oils) were measured in ethanol/chloroform/D2O (50:50:1, v/v/v) solution at 35°C using UV-vis spectrophotometry. Furthermore, comparisons of kQ values determined for the above oils 1-8 with the sum of the product {∑kQAO-i [AO-i]/105} of the kQAO-i values obtained for each antioxidant (AO-i) and concentration (in mg/100 g) ([AO-i]/105) of AO-i (Tocs and Toc-3s) contained in the oils 1-8 were performed. The observed kQ values were not reproduced by the kQ values calculated using only the concentrations of the four Tocs and Toc-3s. These results suggest that the contribution of fatty acids contained in the oils 1-8 is also necessary to fully explain the kQ values. Recently, the second-order rate constants (kS) for the reaction of aroxyl radical (ArO・) with the same vegetable oils 1-8 were measured in the same solvent at 25℃ using stopped-flow spectrophotometry (Ref. 23). The kS values obtained could be well explained as the sum of the product {Σ kSAO-i [AO-i]/105} of the kSAO-i and the [AO-i]/105 of AO-i (Tocs and Toc-3s) contained in the vegetable oils.

Induced sensorimotor brain plasticity controls pain in phantom limb patients.

The cause of pain in a phantom limb after partial or complete deafferentation is an important problem. A popular but increasingly controversial theory is that it results from maladaptive reorganization of the sensorimotor cortex, suggesting that experimental induction of further reorganization should affect the pain, especially if it results in functional restoration. Here we use a brain-machine interface (BMI) based on real-time magnetoencephalography signals to reconstruct affected hand movements with a robotic hand. BMI training induces significant plasticity in the sensorimotor cortex, manifested as improved discriminability of movement information and enhanced prosthetic control. Contrary to our expectation that functional restoration would reduce pain, the BMI training with the phantom hand intensifies the pain. In contrast, BMI training designed to dissociate the prosthetic and phantom hands actually reduces pain. These results reveal a functional relevance between sensorimotor cortical plasticity and pain, and may provide a novel treatment with BMI neurofeedback.

Progressively increased M50 responses to repeated sounds in autism spectrum disorder with auditory hypersensitivity: a magnetoencephalographic study.

The aim of this study was to investigate the differential time-course responses of the auditory cortex to repeated auditory stimuli in children with autism spectrum disorder (ASD) showing auditory hypersensitivity. Auditory-evoked field values were obtained from 21 boys with ASD (12 with and 9 without auditory hypersensitivity) and 15 age-matched typically developing controls. M50 dipole moments were significantly increased during the time-course study only in the ASD with auditory hypersensitivity compared with those for the other two groups. The boys having ASD with auditory hypersensitivity also showed more prolonged response duration than those in the other two groups. The response duration was significantly related to the severity of auditory hypersensitivity. We propose that auditory hypersensitivity is associated with decreased inhibitory processing, possibly resulting from an abnormal sensory gating system or dysfunction of inhibitory interneurons.

[Communication with ALS patients: neurosurgical approach].

By progression of the disease, motor neurons degenerate in patients with amyotrophic lateral sclerosis (ALS) eventually lose nearly all voluntary muscles in the body. They are awake and aware but cannot move or communicate (locked-in state). Since the function of the brain is preserved, one possible measure to support their communication is to interpret their motor intention by decoding (deciphering) brain signals and present it with external devices. This technology called "brain-machine interface (BMI)" is now close to clinical use in Japan and USA.In our system, we record electrocorticogram (ECoG) obtained with subudural electrodes during their motor imagery, decode it and determine the movement they intended. So far, one patient of ALS with severe paralysis, implanted with this electrodes, successfully operated the PC communication tool only by thinking.

Differential responses of primary auditory cortex in autistic spectrum disorder with auditory hypersensitivity.

The aim of this study was to investigate the differential responses of the primary auditory cortex to auditory stimuli in autistic spectrum disorder with or without auditory hypersensitivity. Auditory-evoked field values were obtained from 18 boys (nine with and nine without auditory hypersensitivity) with autistic spectrum disorder and 12 age-matched controls. Autistic disorder with hypersensitivity showed significantly more delayed M50/M100 peak latencies than autistic disorder without hypersensitivity or the control. M50 dipole moments in the hypersensitivity group were larger than those in the other two groups [corrected]. M50/M100 peak latencies were correlated with the severity of auditory hypersensitivity; furthermore, severe hypersensitivity induced more behavioral problems. This study indicates auditory hypersensitivity in autistic spectrum disorder as a characteristic response of the primary auditory cortex, possibly resulting from neurological immaturity or functional abnormalities in it.

Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H(2)15O PET study.

Spinal cord stimulation (SCS) is an effective therapy for chronic neuropathic pain. However, the detailed mechanisms underlying its effects are not well understood. Positron emission tomography (PET) with H(2)(15)O was applied to clarify these mechanisms. Nine patients with intractable neuropathic pain in the lower limbs were included in the study. All patients underwent SCS therapy for intractable pain, which was due to failed back surgery syndrome in three patients, complex regional pain syndrome in two, cerebral hemorrhage in two, spinal infarction in one, and spinal cord injury in one. Regional cerebral blood flow (rCBF) was measured by H(2)(15)O PET before and after SCS. The images were analyzed with statistical parametric mapping software (SPM2). SCS reduced pain; visual analog scale values for pain decreased from 76.1+/-25.2 before SCS to 40.6+/-4.5 after SCS (mean+/-SE). Significant rCBF increases were identified after SCS in the thalamus contralateral to the painful limb and in the bilateral parietal association area. The anterior cingulate cortex (ACC) and prefrontal areas were also activated after SCS. These results suggest that SCS modulates supraspinal neuronal activities. The contralateral thalamus and parietal association area would regulate the pain threshold. The ACC and prefrontal areas would control the emotional aspects of intractable pain, resulting in the reduction of neuropathic pain after SCS.

Cortical oscillatory power changes during auditory oddball task revealed by spatially filtered magnetoencephalography.

OBJECTIVE: To investigate the neural sources and associated changes in oscillatory activity involved in auditory attention and memory updating processing using spatially filtered magnetoencephalography. METHODS: We recorded magnetic responses during an auditory oddball task in 12 normal subjects. Synthetic aperture magnetometry (SAM)-permutation analysis was used to visualize the multiple brain regions associated with event-related magnetic fields (ERFs), and event-related oscillations during target detection processing. RESULTS: SAM-permutation results showed the topographical distribution of N1m over the bilateral primary auditory cortex. Post-stimulus delta (1.5-4 Hz) activity sources, likely related to the P300 slow-waveform, were distributed over the right frontocentral and parietal regions. Source locations of theta (4-8 Hz) and alpha (8-13 Hz) event-related synchronization (ERS) were identified over the dorsolateral and medial prefrontal cortex. We visualized bilateral central-Rolandic suppresions for mu (8-15 Hz), beta (15-30 Hz), and low-gamma (30-60 Hz) activities, more dominant in the hemisphere contralateral to the moving hand (button-pressing in response to target stimuli). CONCLUSIONS: Prefrontal theta and alpha ERS, and frontocentral-parietal delta ERS are functionally engaged in auditory attention and memory updating process. SIGNIFICANCE: Spatially filtered MEG is valuable for detection and source localization of task-related changes in the ongoing oscillatory activity during oddball tasks.

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

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.

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

OBJECTIVE: To assess the pain-relieving effects of motor cortex electrical stimulation (MCS) within the central sulcus and the predictive factors retrospectively. METHODS: Thirty-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. RESULTS: Pain 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. CONCLUSIONS: The 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. SIGNIFICANCE: The present findings suggest that an intra-central sulcus is one of the favorable targets for MCS.

Bilateral cortical stimulation for deafferentation pain after spinal cord injury. Case report.

The relief of intractable pain after spinal cord injury (SCI) is very difficult to obtain, even with dorsal root entry zone lesioning, spinal cord stimulation, and thalamic stimulation. Using bilateral motor cortex stimulation (MCS) the authors successfully treated a woman who experienced deafferentation pain 4 years after sustaining an SCI. To the authors' knowledge, this is the first report of bilateral MCS for pain relief after SCI. The success they achieved using this method indicates that MCS could be a new treatment option for deafferentation pain following SCI.