Morito Inouchi

Stimulus–Response Profile during Single-Pulse Transcranial Magnetic Stimulation to the Primary Motor Cortex

We examined the stimulus-response profile during single-pulse transcranial magnetic stimulation (TMS) by measuring motor-evoked potentials (MEPs) with electromyographic monitoring and hemodynamic responses with functional magnetic resonance imaging (fMRI) at 3 Tesla. In 16 healthy subjects, single TMS pulses were irregularly delivered to the left primary motor cortex at a mean frequency of 0.15 Hz with a wide range of stimulus intensities. The measurement of MEP proved a typical relationship between stimulus intensity and MEP amplitude in the concurrent TMS-fMRI environment. In the population-level analysis of the suprathreshold stimulation conditions, significant increases in hemodynamic responses were detected in the motor/somatosensory network, reflecting both direct and remote effects of TMS, and also the auditory/cognitive areas, perhaps related to detection of clicks. The stimulus-response profile showed both linear and nonlinear components in the direct and remote motor/somatosensory network. A detailed analysis suggested that the nonlinear components of the motor/somatosensory network activity might be induced by nonlinear recruitment of neurons in addition to sensory afferents resulting from movement. These findings expand our basic knowledge of the quantitative relationship between TMS-induced neural activations and hemodynamic signals measured by neuroimaging techniques.

Amygdalar enlargement in patients with temporal lobe epilepsy

Objective The purpose of the study was to clarify the significance of amygdalar enlargement (AE) in patients with temporal lobe epilepsy (TLE) detected by MRI. Methods 11 TLE patients (eight men, mean age 45.3 (SD 18.2) years) with AE treated at Kyoto University Hospital were studied. Clinical history, ictal semiology, EEG, fluorodeoxyglucose–positron emission tomography (FDG-PET), interictal single photon emission CT (SPECT) and MRI were investigated. Amygdalar volume measured by 3 T MRI and its laterality index (LI) were compared with the three other groups: normal controls, patients with partial epilepsy of non-TLE and mesial TLE with hippocampal sclerosis (HS). Results Average age of onset was 39.8 years (SD 19.5). Eight had complex partial seizures and three had generalised seizures. Epileptiform discharges were found in the temporal area ipsilateral to the AE by EEG. Interictal FDG–PET/SPECT revealed regional hypometabolism or hypoperfusion in the ipsilateral temporal area. MRI showed AE on the right in five patients, on the left in five and bilateral in one, all without apparent HS. Ten of 11 patients were diagnosed as unilateral TLE ipsilateral to the AE by neurophysiological and neuroimaging methods. Enlarged amygdalae showed iso- to slightly high intensity in FLAIR images without enhancement. Unilateral AE was not seen in the other three groups for amygdalar volume and LI (p<0.05). Discussion AE is most likely a subtype of TLE without ipsilateral HS. This possibility of AE should be considered in TLE patients if there is no apparent HS.

Changes in Energy Metabolism after Continuous Positive Airway Pressure for Obstructive Sleep Apnea

RATIONALE Disrupted energy homeostasis in obstructive sleep apnea (OSA) may lead to weight gain. Paradoxically, treating OSA with continuous positive airway pressure (CPAP) may also promote weight gain, although the underlying mechanism remains unclear. OBJECTIVES To explore the underlying mechanism by which patients with OSA gain weight after CPAP. METHODS A comprehensive assessment of energy metabolism was performed in 63 newly diagnosed OSA study participants (51 men; 60.8 ± 10.1 yr; apnea-hypopnea index >20 h(-1)) at baseline, CPAP initiation, and at a 3-month follow-up. Measurements included polysomnography, body weight, body composition, basal metabolic rate (BMR), hormones (norepinephrine, cortisol, leptin, ghrelin, insulin-like growth factor-1), dietary intake, eating behavior, and physical activity. MEASUREMENTS AND MAIN RESULTS BMR significantly decreased after CPAP (1,584 kcal/d at baseline, 1,561 kcal/d at CPAP initiation, and 1,508 kcal/d at follow-up; P < 0.001), whereas physical activity and total caloric intake did not significantly change. In multivariate regression, baseline apnea-hypopnea index, Δurine norepinephrine, and CPAP adherence were significant predictors of ΔBMR. The weight gainers had higher leptin levels, lower ghrelin levels, and higher eating behavior scores than the non-weight gainers, indicating a positive energy balance and disordered eating behavior among the weight gainers. Among the parameters related to energy metabolism, increased caloric intake was a particularly significant predictor of weight gain. CONCLUSIONS Although a reduction in BMR after CPAP predisposes to a positive energy balance, dietary intake and eating behavior had greater impacts on weight change. These findings highlight the importance of lifestyle modifications combined with CPAP. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000012639).

Left anterior temporal cortex actively engages in speech perception: A direct cortical stimulation study

Recent neuroimaging studies proposed the importance of the anterior auditory pathway for speech comprehension. Its clinical significance is implicated by semantic dementia or pure word deafness. Neurodegenerative or cerebrovascular nature, however, precluded precise localization of the cortex responsible for speech perception. Electrical cortical stimulation could delineate such localization by producing transient, functional impairment. We investigated engagement of the left anterior temporal cortex in speech perception by means of direct electrical cortical stimulation. Subjects were two partial epilepsy patients, who underwent direct cortical stimulation as a part of invasive presurgical evaluations. Stimulus sites were coregistered to presurgical 3D-MRI, and then to MNI standard space for anatomical localization. Separate from the posterior temporal language area, electrical cortical stimulation revealed a well-restricted language area in the anterior part of the superior temporal sulcus and gyrus (aSTS/STG) in both patients. Auditory sentence comprehension was impaired upon electrical stimulation of aSTS/STG. In one patient, additional investigation revealed that the functional impairment was restricted to auditory sentence comprehension with preserved visual sentence comprehension and perception of music and environmental sounds. Both patients reported that they could hear the voice but not understand the sentence well (e.g., heard as a series of meaningless utterance). The standard coordinates of this restricted area at left aSTS/STG well corresponded with the coordinates of speech perception reported in neuroimaging activation studies in healthy subjects. The present combined anatomo-functional case study, for the first time, demonstrated that aSTS/STG in the language dominant hemisphere actively engages in speech perception.

Temporal lobe epilepsy with amygdala enlargement: a morphologic and functional study.

Temporal lobe epilepsy (TLE) with nontumoral amygdala enlargement (AE) has been reported to be a possible subtype of TLE without hippocampal sclerosis (HS). The purpose of this study was to clarify morphologic and functional characteristics of TLE with AE (TLE + AE).

Increased cortical hyperexcitability and exaggerated myoclonus with aging in benign adult familial myoclonus epilepsy

The clinical implications of enlarged early cortical components of somatosensory evoked potentials in benign adult familial myoclonus epilepsy remain unknown. Somatosensory evoked potentials following electrical stimulation of the median nerve at the wrist were studied in 16 patients with a clinical diagnosis of benign adult familial myoclonus epilepsy (7 men and 9 women; mean age, 51 ± 18 years) and 19 age‐matched apparently healthy control subjects (11 men and 8 women; mean age, 49 ± 18 years). Giant somatosensory evoked potentials were observed in 13 of the 16 patients. P25 and N35 amplitudes in the patient group were 11.4 ± 6.1 and 19.2 ± 11.5 μV, respectively, and both were significantly larger compared with those in control subjects (P = 0.008 for P25 and P < 0.0001 for N35). There was a significant positive relationship between age at somatosensory evoked potential examination and N20, P25, and N35 amplitudes, both in the patient and in the control groups (P < 0.05). The linear regression gradient of the N35 amplitude with respect to age was significantly larger in the patient group than in the control group (P = 0.04). Furthermore, regression analysis showed a significant positive relationship between the myoclonus rating scale and age at time of somatosensory evoked potential examination (R = 0.645, P = 0.007). Somatosensory evoked potential amplitude increased with age in patients with benign adult familial myoclonus epilepsy to a greater extent than in the control subjects, which suggests a progressive increase in cortical excitability based on progressive pathophysiology in benign adult familial myoclonus epilepsy.

Bereitschaftspotential augmentation by neuro-feedback training in Parkinson's disease

OBJECTIVE Decreased early Bereitschaftspotential (BP) is one of the electrophysiological characteristics in patients with Parkinsons disease (PD). We examined whether PD patients could increase BP amplitude by means of neuro-feedback (NFB) training for their slow cortical potentials (SCPs). METHODS We worked with 10 PD patients and 11 age-matched controls. BP was measured for self-paced button pressing by their right thumb. The subjects were instructed to make the introspective efforts to produce negative SCPs (negativation). The one-day session consisted of three trials, that is, the first BP, NFB training and the second BP, and each patient performed this routine for 2-4 days. Amplitudes of the first and second BPs were compared between the two groups that were divided depending on NFB performance. RESULTS Good NFB performance had the tendency of larger early BP in the second BP recording than in the first one, whereas in the poor NFB performance the early BP was smaller in the second BP recording than in the first one in both patient and normal groups (p < 0.001). CONCLUSIONS Good NFB performance of negativation could increase excitatory field potentials of pyramidal cells for the generation of early BP. SIGNIFICANCE Voluntary regulation of SCPs could enhance BP in PD patients and in aged controls.

Plasma Incretin Levels and Dipeptidyl Peptidase-4 Activity in Patients with Obstructive Sleep Apnea

RATIONALE Incretin hormones, namely glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP), and dipeptidyl peptidase-4 (DPP-4) activity are important factors in glucose metabolism and have not been investigated in patients with obstructive sleep apnea (OSA). OBJECTIVES The objective of this study was to investigate the association between OSA and incretin and DPP-4 activity. METHODS This study included 96 consecutive patients without diabetes who were suspected of having OSA. We investigated the fasting and post-prandial incremental area under the curve (IAUC) of GLP-1, GIP serum levels, and serum DPP-4 activity levels, as well as their association with OSA. Changes in clinical variables were evaluated in the 43 patients who continued continuous positive airway pressure therapy for 3 months. MEASUREMENTS AND MAIN RESULTS Apnea-hypopnea index was an independent determining factor for fasting GLP-1 (β = 0.31; P = 0.0019) and IAUC GIP (β = -0.21; P = 0.037) after adjusting for known confounding factors. In those with very severe OSA (apnea-hypopnea index ≥50), the IAUCs for GLP-1 and GIP were significantly decreased, while fasting GLP-1 and fasting GIP were significantly increased. DPP-4 activity had no relation to OSA parameters or severity, while body mass index was significantly higher in those with severe OSA. Although significant changes in incretin secretion were not seen for 3 months after onset of continuous positive airway pressure therapy, the fasting GLP-1 level in the treated patients with severe OSA decreased to the same level as in untreated patients with normal to moderately severe OSA. CONCLUSIONS OSA is associated with elevated serum levels of the incretin hormones GLP-1 (fasting) and GIP (post-prandial) in patients without diabetes. A significant association between body mass index and DPP-4, which is said to exist in healthy persons, was not found in the patients with OSA. Fasting GLP-1 in patients without diabetes with OSA may influence fasting glucose levels.

Role of posterior parietal cortex in reaching movements in humans: Clinical implication for ‘optic ataxia’

OBJECTIVE To clarify the spatio-temporal profile of cortical activity related to reaching movement in the posterior parietal cortex (PPC) in humans. METHODS Four patients with intractable partial epilepsy who underwent subdural electrode implantation were studied as a part of pre-surgical evaluation. We investigated the Bereitschaftspotential (BP) associated with reaching and correlated the findings with the effect of electrical stimulation of the same cortical area. RESULTS BPs specific for reaching, as compared with BPs for simple movements by the hand or arm contralateral to the implanted hemisphere, were recognized in all patients, mainly around the intraparietal sulcus (IPS), the superior parietal lobule (SPL) and the precuneus. BPs near the IPS had the earlier onset than BPs in the SPL. Electrical stimulation of a part of the PPC, where the reach-specific BPs were recorded, selectively impaired reaching. CONCLUSIONS Intracranial BP recording and cortical electrical stimulation delineated human reach-related areas in the PPC. SIGNIFICANCE The present study for the first time by direct cortical recording in humans demonstrates that parts of the cortices around the IPS and SPL play a crucial role in visually-guided reaching.

Alpha-band desynchronization in human parietal area during reach planning

OBJECTIVE The symptoms with optic ataxia suggest that simple and visually guided hand movements are controlled by 2 different neural substrates. To assess the differential frequency-coded posterior parietal cortex (PPC) role in planning visuo-motor goal-directed tasks, we studied the action specificity of event-related desynchronization (ERD) in this area. METHODS We investigated cortical activity by electroencephalography, while 16 healthy subjects performed self-paced reaching or wrist extension (control) movements. Time-frequency representations were calculated for each movement during the preparatory period. RESULTS ERD dynamics in upper alpha-band indicated that preparing a goal-directed action activates contralateral PPC to the moving hand around 1.2s before starting the movement, while this activation is later (around 0.7s) in preparing a not-goal-directed action. The posterior dominant rhythm had peak frequency of lower alpha-band at bilateral parietal. CONCLUSIONS Posterior parietal cortex encodes goal-directed movement preparation through upper alpha-band activity, whereas general attention is processed via lower alpha-band oscillations. SIGNIFICANCE Preparing to reach an object engages posterior parietal cortex earlier than a not-goal directed movement.