Kenji Sakuma

Reciprocal modulation of somatosensory evoked N20m primary response and high-frequency oscillations by interference stimulation

OBJECTIVES We examined whether the inverse relation between somatic evoked N20m primary response and high-frequency oscillations during a wake-sleep cycle (Hashimoto, I., Mashiko, T., Imada, T., Somatic evoked high-frequency magnetic oscillations reflect activity of inhibitory interneurons in the human somatosensory cortex, Electroenceph clin Neurophysiol 1996;100:189-203) holds for interference stimulation. METHODS Somatosensory evoked fields (SEFs) from 14 subjects were measured following electric median nerve stimulation at the wrist with, and without, concurrent brushing of the palm and fingers. SEFs were recorded with a wide bandpass (0.1-1200 Hz) and then N20m and high-frequency oscillations were separated by subsequent low-pass (< 300 Hz) and high-pass (> 300 Hz) filtering. RESULTS The N20m decreased dramatically in amplitude during interference stimulation. In contrast, the high-frequency oscillations moderately increased in number of peaks. CONCLUSIONS These results demonstrate the presence of an inverse relation between N20m and high-frequency oscillations for interference stimulation. We speculate that the high-frequency oscillations represent a localized activity of GABAergic inhibitory interneurons of layer 4, characterized by a high-frequency spike burst (200-1000 Hz) without adaptation, and that the continuous interference stimulation induces tonic excitation of the interneurons, leading to a facilitation of responses to the coherent afferent volley elicited by the median nerve stimulation (bottom-up mechanism). On the other hand, refractoriness of the pyramidal neurons caused directly by interference stimulation along with an enhanced feed-forward inhibition from the interneurons will lead to a decrease of N20m amplitude.

Shortened silent period produced by magnetic cortical stimulation in patients with Parkinson's disease

Magnetic cortical stimulation can produce silent periods (SP) following excitatory motor responses. In patients with Parkinsons disease (PD), a shorter SP was observed. The shortened SP in PD patients improved after levodopa administration. This shortened SP in PD patients may be related to the hyperactivity of the motor cortex, and to the dopaminergic system. In control subjects, sound stimulation produced prolongation of the SP at a time interval of 100 ms between sound and magnetic cortical stimulation-increase in the inhibitory function. However, the prolongation of the SP after sound stimulation was not observed in PD patients lack of an increase in the inhibitory function. Even after levodopa administration, sound did not prolong the SP in PD patients. The change of the auditory effects on the SP may be due to the abnormal function of the reticular formation in PD. This change might be independent of the dopaminergic system.

Quantitative electroencephalogram analysis in dementia with Lewy bodies and Alzheimer's disease.

Clinicopathophysiological differences between dementia with Lewy bodies (DLB) and Alzheimers disease (AD) remain obscure. Our goals were to determine whether characteristic findings of electroencephalogram (EEG) power and coherence in DLB and a differential pathophysiological mechanism of quantitative EEG existed between DLB and AD. The group consisted of 15 patients with AD or DLB and 12 age-matched controls. Original EEG signals were recorded from 14 scalp electrodes positioned according to the International 10-20 System, using digitally linked earlobes as a reference. Although EEG power spectral analysis showed increasing EEG power density in patients with DLB in the delta and theta bands, such a difference did not exist in patients with AD. Compared with AD, the delta and theta band intrahemispheric coherence values in the fronto-temporo-central regions were higher in DLB. In the beta band, AD was lower than DLB in almost all temporo-centro-parieto-occipital regions. Comparing the mean power value between patients with/without donepezil treatment, there was a significantly lower EEG power density in the delta and theta bands in DLB subjects taking donepezil than in subjects not taking donepezil, whereas there was no significant difference in AD patients. These results suggest that cholinergic dysfunction is stronger in DLB than AD.

Olfactory evoked potentials in Parkinson's disease, Alzheimer's disease and anosmic patients

Abstract Olfactory evoked potential (OEP) recordings were undertaken using amyl acetate stimulation in 20 patients with Parkinsons disease, nine patients with Alzheimers disease, seven patients with olfactory dysfunction with no other neurological disorder, and 17 control subjects. In order to eliminate the somatosensory factor from the combined somatosensory and olfactory components produced by amyl acetate stimulation, we subtracted the potentials using odorless air from those using amyl acetate. In normal subjects, three components were observed, the mean latencies of which were 309 ± 46, 484 ± 61 and 710 ± 55 ms. In all subjects with anosmia (n= 7), no responses were observed. In the patients with Alzheimers disease, the components were fewer despite having no olfactory dysfunction. In the 20 patients with Parkinsons disease, four patients showed no components, seven patients showed one component and eight patients showed two components. The components rarely were detected in spite of whether the patients had olfactory dysfunction or not. Olfactory evoked potentials are useful in detecting olfactory dysfunction and the early stages of Alzheimers disease and Parkinsons disease.

High-frequency oscillations change in parallel with short-interval intracortical inhibition after theta burst magnetic stimulation

OBJECTIVE Theta burst transcranial magnetic stimulation (TBS) causes changes in motor cortical excitability. In the present study, somatosensory-evoked potentials (SEPs) and high-frequency oscillations (HFOs) were recorded before and after TBS over the motor cortex to examine how TBS influenced the somatosensory cortex. METHODS SEPs following electric median nerve stimulation were recorded, and amplitudes for the P14, N20, P25, and N33 components were measured and analyzed. HFOs were separated by 400-800 Hz band-pass filtering, and root-mean-square amplitudes were calculated from onset to offset. SEPs and HFOs were measured before and after application of either intermittent or continuous TBS (iTBS/cTBS; 600 total pulses at 80% active motor threshold) over the motor cortex. Motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) of the first dorsal interosseous muscle were examined before and after TBS. RESULTS MEPs, SICI, and HFO amplitudes were increased and decreased significantly after iTBS and cTBS, respectively. Wide-band SEPs did not change significantly after TBS. CONCLUSIONS TBS changed the cortical excitability of the sensorimotor cortices. Changes in HFOs after TBS were parallel to those in SICI. SIGNIFICANCE The mechanisms of changes in HFOs after TBS may be the same as those in SICI.

Neural source estimation from a time-frequency component of somatic evoked high-frequency magnetic oscillations to posterior tibial nerve stimulation

OBJECTIVE High frequency oscillations (HFOs) evoked by posterior tibial nerve stimulation were recorded using magnetoencephalography (MEG). Time-frequency domain multiple signal classification (TF-MUSIC) algorithm was applied, and the usefulness of this method was demonstrated. METHODS Ten normal subjects were studied. To localize sources for the HFOs of those somatosensory evoked fields, we applied two kinds of methods: the single moving dipole (SMD) method and the TF-MUSIC method. The SMD method was applied after digitally band-pass filtering the somatosensory response with a bandwidth of 500-800 Hz. To estimate the locations of sources with the TF-MUSIC algorithm, we first set the target region on the spectrogram of the somatosensory responses. Then, the procedure described in Section 2.2 was applied with this target region. RESULTS A clear, isolated region was detected in 6 out of 10 subjects using a time-frequency spectrogram. The averaged distance of the dipole sources between the HFOs and the underlying P37m using the TF-MUSIC algorithm was smaller than using the SMD method. CONCLUSIONS The TF-MUSIC algorithm is suitable for extracting a target response whose spectrum changes significantly during the observation.

Dynamic mediolateral activation of the pyramidal cell population in human somatosensory 3b area can be visualized by magnetic recordings

Dynamic mediolateral activation in the pyramidal cell population of the human somatosensory 3b area was studied non-invasively. Somatosensory evoked fields (SEFs) were recorded over the hand area contralateral to the right median nerve stimulation at the wrist. Localization of an equivalent current dipole (ECD) for N20m primary cortical response was successively calculated for periods of 2.4 ms around N20m peak where the signal-to-noise ratio exceeded 100 and the spatial resolution was approximately 0.3 mm. The ECD moved toward the anterior, lateral and inferior direction for a distance of 8.7 mm at a propagation velocity of 3.6 m/s. This direction was orthogonal to the orientation of apical dendrites of the pyramidal neurons in area 3b and parallel to the surface of the posterior bank of the central sulcus. These findings suggest that the sequential mediolateral activation of the pyramidal cells in the somatosensory cortex is mediated by horizontal connections running parallel to the cortical surface.

Short-interval intracortical inhibition is modulated by high-frequency peripheral mixed nerve stimulation

Cortical excitability can be modulated by manipulation of afferent input. We investigated the influence of peripheral mixed nerve stimulation on the excitability of the motor cortex. Motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in the right abductor pollicis brevis (APB), extensor carpi radialis (ECR) and first dorsal interosseous (FDI) muscles were evaluated using paired-pulse transcranial magnetic stimulation (TMS) before and after high-frequency peripheral mixed nerve stimulation (150 Hz, 30 min) over the right median nerve at the wrist. The MEP amplitude and SICI of the APB muscle decreased transiently 0-10 min after the intervention, whereas the ICF did not change. High-frequency peripheral mixed nerve stimulation reduced the excitability of the motor cortex. The decrement in the SICI, which reflects the function of GABA(A)ergic inhibitory interneurons, might compensate for the reduced motor cortical excitability after high-frequency peripheral mixed nerve stimulation.

Distal-proximal somatotopy in the human hand somatosensory cortex: a reappraisal

Abstract The distal-proximal representation of the finger and palm in the first somatosensory cortex was reexamined. Somatosensory evoked magnetic fields (SEFs) were measured with a 37-channel first-order axial gradiometer system. Sensory stimulus comprising a 20-ms vibration at a frequency of 200 Hz was delivered to five successive sites in 3-cm increments along the distal-proximal direction over the volar surface of the right index finger and palm. Using a single dipole model, the sources and the signal strengths of the main peak (M50) of the SEFs were estimated. All of the sources were located in the 3b area. There were no statistically significant differences between the locations of dipoles evoked by stimulation of different sites. The results support those of our previous study using a 122-channel whole-head planar gradiometer system that orderly distal-proximal representation of the hand, as described in monkeys, is blurred in the adult human somatosensory cortex.

A novel presenilin 1 mutation (Y154N) in a patient with early onset Alzheimer's disease with spastic paraparesis.

Early onset familial Alzheimers disease with spastic paraparesis (FAD-SP) has been associated with mutations of the presenilin 1 gene (PSEN1). We report a pedigree of FAD-SP due to a novel missense mutation of PSEN1 (Y154N). The symptoms of the proband were characterized by presenile dementia in her 40s, preceded by spastic paraparesis in her 30s, whereas the mother of the proband presented with spastic paraparesis in her 40s, followed by symptoms of dementia in her mid 60s. The mutation was found only in the proband, and not in a normal family member, normal Japanese control subjects, patients with sporadic Alzheimers disease or patients with familial spastic paraparesis without dementia. Thus, Y154N is a novel PSEN1 mutation responsible for FAD-SP of Japanese origin.