Ability of NAD and Sirt1 to epigenetically suppress albuminuria.

The time for diabetic nephropathy (DN) to progress from mild to severe is long. Thus, methods to continuously repress DN are required to exert long-lasting effects mediated through epigenetic regulation. In this study, we demonstrated the ability of nicotinamide adenine dinucleotide (NAD) and its metabolites to reduce albuminuria through Sirt1- or Nampt-dependent epigenetic regulation. We previously reported that proximal tubular Sirt1 was lowered before glomerular Sirt1. Repressed glomerular Sirt1 was found to epigenetically elevate Claudin-1. In addition, we reported that proximal tubular Nampt deficiency epigenetically augmented TIMP-1 levels in Sirt6-mediated pathways, leading to type-IV collagen deposition and diabetic fibrosis. Altogether, we propose that the Sirt1/Claudin-1 axis may be crucial in the onset of albuminuria at the early stages of DN and that the Nampt/Sirt6/TIMP-1 axis promotes diabetic fibrosis in the middle to late stages of DN. Finally, administration of NMN, an NAD precursor, epigenetically potentiates the regression of the onset of DN to maintain Sirt1 and repress Claudin-1 in podocytes, suggesting the potential use of NAD metabolites as epigenetic medications for DN.

The relationships between motor behavior and sensory gating in the ball rotation task.

During voluntary muscle contraction, sensory information induced by electrostimulation of the nerves supplying the contracting muscle is inhibited and the amplitude of the corresponding somatosensory evoked potential (SEP) decreases. This phenomenon is called "gating." The reduction of the SEP amplitude is reportedly significantly larger when task performance is high. However, the relationship between dexterous movement skills and gating remains unclear. In this study, we investigated through a ball rotation (BR) task how dexterous movement skills affect the SEP amplitudes. Thirty healthy subjects performed the BR task comprising the rotation of two wooden balls as quickly as possible. We estimated the median number of ball rotations for each participant and classified the participants into two (fast and slow) groups based on the results. Moreover, we recorded SEPs, while the subjects performed BR tasks or rested. SEP amplitude reduction (P45) was significantly larger in the fast than in the slow group. We also observed that the P45 amplitude during the BR task was attenuated even more so in the case of the participants with better dexterous movement skills. Our results suggest that the participants with better dexterous movement skills might display stronger somatosensory information suppression because of increasing the motor cortex activity and the afferent input during the BR task.

Effects of kinesthetic illusion induced by visual stimulation (KINVIS) therapy on patients with stroke in the subacute phase: a visual analysis based on paralysis severity.

We explored the effect of kinesthetic illusion induced by visual stimulation (KINVIS) therapy on motor function in patients with stroke during the subacute phase based on paralysis severity. The study was performed using an ABAB design (A1, B1, A2, B2; for 10 days each). KINVIS therapy was additionally administered in periods B1 and B2. Ten patients with stroke were classified according to severity. The improvement in upper limb motor function was higher after B1 and B2 than after A1 and A2 in the moderate group. The effect of KINVIS therapy increases the degree of improvement in motor function, especially in the moderate group.

Effect of liraglutide on lipids in patients with type 2 diabetes: a pilot study.

The mechanism for the cholesterol-lowering effect of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) remains unknown in patients with type 2 diabetes. We evaluated the effect of liraglutide on serum lipid profiles, including cholesterol synthesis and absorption markers, during daily clinical practice in Japanese patients with type 2 diabetes. We enrolled 38 patients with type 2 diabetes mellitus who were not treated with a GLP-1 RA (≥20 years of age, HbA1c ≥6.5%). Liraglutide, a GLP-1 RA, was administered subcutaneously once a day for three months to these patients. Blood samples and body weights were collected at 0, 1, and 3 months. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) at 1 month, and non-high-density lipoprotein cholesterol (non-HDL-C) and calculated TC at 1 and 3 months, were decreased, while the cholesterol synthesis and cholesterol absorption markers were unchanged by this treatment. In patients with LDL-C levels over 100 mg/dL, LDL-C, non-HDL-C, TC, and calculated TC levels were decreased significantly by the treatment at 1 and 3 months, and the cholesterol absorption marker, campesterol, was decreased at 3 months. The administration of liraglutide for 3 months decreased non-HDL-C and calculated TC significantly, while the cholesterol synthesis and absorption markers were not changed by this treatment.

Event-related desynchronization possibly discriminates the kinesthetic illusion induced by visual stimulation from movement observation.

Visual stimulation of a repetitive self-movement image can evoke kinesthetic illusion when a virtual body part is set over the actual body part (kinesthetic illusion induced by visual stimulation, KINVIS). KINVIS induces activity in cerebral network, similar to that produced during motor execution, and triggers motor imagery passively. This study sought to identify a biomarker of KINVIS using event-related desynchronization (ERD) to improve the application of KINVIS to brain-machine interface (BMI) therapy of patients with stroke with hemiparesis. We included healthy adults in whom KINVIS could be induced. Scalp electroencephalograms were recorded during the KINVIS condition, where KINVIS was induced using a self-movement image. The findings were compared to signals recorded during an observation (OB) condition where only the self-movement image was viewed. For the signal intensity of the α- and low ß-frequency bands, we calculated ERD during a movie period. The ERD of the α-frequency band in P3 and CP3 during KINVIS was significantly higher than that during OB. Furthermore, using the ERD of the α-frequency band recorded from FC3 and CP3, we could discriminate illusory perception with a 70% success rate. In this study, KINVIS could be detected using the ERD of the α-frequency band recorded from the posterior portion of the sensorimotor cortex. Furthermore, adding ERD recorded from FC3 to that recorded from CP3 may enable the objective discrimination of KINVIS from OB. When applying KINVIS in BMI therapy, the combination ERD of FC3 and CP3 will become a parameter for objectively judging the degree of kinesthetic perception achieved.

Mesangial Cell Mammalian Target of Rapamycin Complex 1 Activation Results in Mesangial Expansion.

Human glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)-S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]. Foxd1ER(+) TSC1 mice showed mesangial expansion with increased production of collagen IV, collagen I, and α-smooth muscle actin in glomeruli, but did not exhibit significant mesangial proliferation or albuminuria. Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed mesangial expansion. Among biopsy specimens from patients with glomerular diseases, analysis of phosphorylated ribosomal protein S6 revealed mesangial cell mTORC1 activation in IgA nephropathy and in lupus mesangial proliferative nephritis but not in the early phase of diabetic nephropathy. In summary, mesangial cell mTORC1 activation can cause mesangial expansion and has clinical relevance for human glomerular diseases. This report also confirms that the tamoxifen-induced mesangium-specific Cre-loxP system is useful for studies designed to clarify the role of the mesangium in glomerular diseases in adults.

Muscular responses appear to be associated with existence of kinesthetic perception during combination of tendon co-vibration and motor imagery.

The afferent inputs from peripheral sensory receptors and efferent signals from the central nervous system that underlie intentional movement can contribute to kinesthetic perception. Previous studies have revealed that tendon vibration to wrist muscles elicits an excitatory response-known as the antagonist vibratory response-in muscles antagonistic to the vibrated muscles. Therefore, the present study aimed to further investigate the effect of tendon vibration combined with motor imagery on kinesthetic perception and muscular activation. Two vibrators were applied to the tendons of the left flexor carpi radialis and extensor carpi radialis. When the vibration frequency was the same between flexors and extensors, no participant perceived movement and no muscle activity was induced. When participants imagined flexing their wrists during tendon vibration, the velocity of perceptual flexion movement increased. Furthermore, muscle activity of the flexor increased only during motor imagery. These results demonstrate that kinesthetic perception can be induced during the combination of motor imagery and co-vibration, even with no experience of kinesthetic perception from an afferent input with co-vibration at the same frequency. Although motor responses were observed during combined co-vibration and motor imagery, no such motor responses were recorded during either co-vibration alone or motor imagery alone, suggesting that muscular responses during the combined condition are associated with kinesthetic perception. Thus, the present findings indicate that kinesthetic perception is influenced by the interaction between afferent input from muscle spindles and the efferent signals that underlie intentional movement. We propose that the physiological behavior resulting from kinesthetic perception affects the process of modifying agonist muscle activity, which will be investigated in a future study.

Successful treatment of highly advanced immunoglobulin G4-related kidney disease presenting renal mass-like regions with end-stage kidney failure: a case study.

BACKGROUND: Immunoglobulin G4-related kidney disease characterized by immunoglobulin G4-positive plasma cell-rich tubulointerstitial nephritis has distinctive serological and radiological findings. Renal prognosis is good because of a good response to glucocorticoids. Here we report a case of successful treatment of highly advanced immunoglobulin G4-related kidney disease presenting renal mass-like regions with end-stage kidney failure. CASE PRESENTATION: A 59-year-old Japanese man was referred to our hospital because of uremia with a creatinine level of 12.36 mg/dL. Urinalysis revealed mild proteinuria and hyperß2microglobulinuria, and blood tests showed hyperglobulinemia with an IgG level of 3243 mg/dL and an IgG4 level of 621 mg/dL. Non-contrast computed tomography revealed renal mass-like regions. Based on the findings, immunoglobulin G4-related kidney disease was suspected, however, further radiological examination showed unexpected results. Ga-67 scintigraphy showed no kidney uptake. T2-weighted magnetic resonance imaging revealed high-intensity signals which corresponded to mass-like regions and multiple patchy low-intensity signals in kidney cortex. Finally, the patient was diagnosed with immunoglobulin G4-related kidney disease by renal pathology of severe immunoglobulin G4-positive plasma cell-rich tubulointerstitial nephritis and characteristic fibrosis. He received 50 mg oral prednisolone, which was tapered with a subsequent decrease of serum creatinine and IgG4 levels. One year after initiation of treatment, he achieved normalization of serum IgG4 level and proteinuria, and remained off dialysis with a creatinine level of 3.50 mg/dL. After treatment with steroids, repeat imaging suggested bilateral severe focal atrophy. However, mass-like regions did not show atrophic change although renal atrophy was evident in patchy low-intensity lesions on T2-weighted magnetic resonance imaging. These findings suggest that multiple patchy low-intensity signals and high-intensity mass-like regions were mildly atrophic lesions of immunoglobulin G4-related kidney disease due to severe fibrosis and normal parts of kidney, respectively. CONCLUSIONS: In immunoglobulin G4-related kidney disease with severe kidney failure, radiological findings should be carefully examined. In addition, renal prognosis may be good despite highly advanced tubulointerstitial nephritis and fibrosis.

The association of motor imagery and kinesthetic illusion prolongs the effect of transcranial direct current stimulation on corticospinal tract excitability.

BACKGROUND: A kinesthetic illusion induced by a visual stimulus (KI) can produce vivid kinesthetic perception. During KI, corticospinal tract excitability increases and results in the activation of cerebral networks. Transcranial direct current stimulation (tDCS) is emerging as an alternative potential therapeutic modality for a variety of neurological and psychiatric conditions, such that identifying factors that enhance the magnitude and duration of tDCS effects is currently a topic of great scientific interest. This study aimed to establish whether the combination of tDCS with KI and sensory-motor imagery (MI) induces larger and longer-lasting effects on the excitability of corticomotor pathways in healthy Japanese subjects. METHODS: A total of 21 healthy male volunteers participated in this study. Four interventions were investigated in the first experiment: (1) anodal tDCS alone (tDCSa), (2) anodal tDCS with visually evoked kinesthetic illusion (tDCSa + KI), (3) anodal tDCS with motor imagery (tDCSa + MI), and (4) anodal tDCS with kinesthetic illusion and motor imagery (tDCSa + KIMI). In the second experiment, we added a sham tDCS intervention with kinesthetic illusion and motor imagery (sham + KIMI) as a control for the tDCSa + KIMI condition. Direct currents were applied to the right primary motor cortex. Corticospinal excitability was examined using transcranial magnetic stimulation of the area associated with the left first dorsal interosseous. RESULTS: In the first experiment, corticomotor excitability was sustained for at least 30 min following tDCSa + KIMI (p < 0.01). The effect of tDCSa + KIMI on corticomotor excitability was greater and longer-lasting than that achieved in all other conditions. In the second experiment, significant effects were not achieved following sham + KIMI. CONCLUSIONS: Our results suggest that tDCSa + KIMI has a greater therapeutic potential than tDCS alone for inducing higher excitability of the corticospinal tract. The observed effects may be related to sustained potentiation of resultant cerebral activity during combined KI, MI, and tDCSa.

Re-evaluation of Pre-pump Arterial Pressure to Avoid Inadequate Dialysis and Hemolysis: Importance of Prepump Arterial Pressure Monitoring in Hemodialysis Patients.

Prepump arterial pressure (PreAP) is monitored to avoid generating excessive negative pressure. The National Kidney Foundation K/DOQI clinical practice guidelines for vascular access recommend that PreAP should not fall below -250 mm Hg because excessive negative PreAP can lead to a decrease in the delivery of blood flow, inadequate dialysis, and hemolysis. Nonetheless, these recommendations are consistently disregarded in clinical practice and pressure sensors are often removed from the dialysis circuit. Thus far, delivered blood flow has been reported to decrease at values more negative than -150 mm Hg of PreAP. These values have been analyzed by an ultrasonic flowmeter and not directly measured. Furthermore, no known group has evaluated whether PreAP-induced hemolysis occurs at a particular threshold. Therefore, the aim of this study was to clarify the importance of PreAP in the prediction of inadequate dialysis and hemolysis. By using different diameter needles, human blood samples from healthy volunteers were circulated in a closed dialysis circuit. The relationship between PreAP and delivered blood flow or PreAP and hemolysis was investigated. We also investigated the optimal value for PreAP using several empirical monitoring methods, such as a pressure pillow. Our investigation indicated that PreAP is a critical factor in the determination of delivered blood flow and hemolysis, both of which occured at pressure values more negative than -150 mm Hg. With the exception of direct pressure monitoring, commonly used monitoring methods for PreAP were determined to be ineffective. We propose that the use of a vacuum monitor would permit regular measurement of PreAP.

Does 20 Hz Transcranial Alternating Current Stimulation over the Human Primary Motor Cortex Modulate Beta Rebound Following Voluntary Movement?

Beta frequency oscillations originating from the primary motor cortex increase in amplitude following the initiation of voluntary movement, a process termed beta rebound. The strength of beta rebound has been reported to predict the recovery of motor function following stroke, suggesting therapeutic applications of beta rebound modulation. The present study examined the effect of 20 Hz transcranial alternating current stimulation (tACS) on the beta rebound induced by self-paced voluntary movement. Electroencephalograms (EEGs) and electromyograms (EMGs) were recorded from 16 healthy adults during voluntary movements performed before and after active or sham tACS. There was no significant change in average beta rebound after active tACS. However, the beta rebound amplitude was significantly enhanced in a subset of participants, and the magnitude of the increase across all participants was negatively correlated with the difference between individual peak beta frequency and tACS frequency. Thus, matching the stimulus frequency of tACS with individual beta frequency may facilitate therapeutic enhancement for motor rehabilitation.

Roxadustat for Treating Anemia in Patients with Advanced Chronic Kidney Disease Not Undergoing Dialysis: A Retrospective Study.

Objective Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, increases the hemoglobin (Hb) levels in patients with chronic kidney disease (CKD). To date, limited clinical studies have focused on the excessive increase in the Hb levels in the early weeks after switching from erythropoiesis-stimulating agents (ESA) to roxadustat in adult non-dialysis patients. We conducted a retrospective study to examine whether early overshoot frequently occurs after switching to roxadustat. Methods This 8-week retrospective pilot study examined patients with anemic, non-dialyzed CKD who switched from ESA (darbepoetin or epoetin beta pegol) to roxadustat or continued ESA. The Hb levels >12.5 g/dL after starting our observation was defined as Hb overshoot. Patients: Twenty-three patients who switched to roxadustat (roxadustat group) and 63 who continued ESA (ESA group) were included. Results The baseline median estimated glomerular filtration rate and mean Hb levels were 15.7 mL/min/1.73 mShizuokax and 10.77 g/dL in roxadustat group and 15.2 mL/min/1.73 m2 and 10.64 g/dL in ESA group, respectively. Eight patients (34.8%) in the roxadustat group and two patients (3.2%) in the ESA group had Hb overshoot within the 8-week visit (odds ratio: 20.2 [95% confidence interval 3.13-130.0, p<0.01] in the background adjusted model). Among the patients with Hb overshoot in the roxadustat group, the Hb levels were maintained close to baseline 4 weeks after roxadustat discontinuation. A younger age and higher baseline Hb and Hct levels were risk factors for Hb overshoot. Conclusions Hb overshoot was frequently observed in patients switched to roxadustat. Clinicians should be aware of Hb overshoot and emphasize the importance of early Hb level checks.

Effects of repetitive practice of motor tasks on somatosensory gating.

Introduction: During voluntary muscle contraction, the amplitude of the somatosensory evoked potential (SEP) is reduced by inhibiting sensory information from a peripheral nerve supplying the contracted muscle. This phenomenon is called "gating." We reported that participants with good motor skills indicated strong suppression of somatosensory information. The present study investigated the effects of motor performance improvement following repetitive practice on the SEP amplitude. Methods: The ball rotation task (BR task) was practiced by 15 healthy participants repetitively. SEPs were recorded before (pre) and after (post) repetitive practice. Results: The BR task performance was significantly improved and the required muscle activation to perform the task was significantly reduced after the repetitive practice. The degree of gating was not significant between pre and post- for the SEP amplitude. A significant correlation was found between changes in SEP amplitude from pre to post and performance improvement. Discussion: After repetitive practice, the degree of gating did not change, but the performance of the BR task improved, and the muscle activity required for the BR task decreased. These results suggest that repetitive practice does not change the degree of gating but changes the mechanism of gating. Furthermore, they indicate that suppression of the somatosensory area may play a role in improving task performance.

Movement of the stimulated finger in a Go/NoGo task enhances attention directed to that finger as evidenced by P300 amplitude modulation.

Somatosensory cues and the optimal allocation of attentional resources are critical for motor performance, but it is uncertain how movement of a body part modulates directed attention and the processing of somatosensory signals originating from that same body part. The current study measured motor reaction time (RT) and the P300 event-related potential during a required movement response to stimulation of the same body part in a Go/NoGo task under multiple response. In the Movement Condition, participants were instructed to extend their right index finger in response to mild electrical stimulation of the same finger (Go signal) or remain still when receiving electrical stimulation to the fifth right finger (NoGo signal). Movement RTs and P300 amplitudes and latencies were measured under varying Go signal 50% probabilities. In other trial blocks, participants were required to count Go signals but not respond with movement or to ignore all signals while engaged in an unrelated task. Mean RT in the Movement Condition was 234.5 ms. P300 response amplitudes at midline electrodes (Fz, Cz, Pz) were the largest in the Movement Condition. The P300 amplitude at parietal electrode site Pz was significantly greater during Movement Condition trials than during Count Condition trials. The increase in P300 amplitude during trials requiring movement of the same body part receiving somatosensory stimulation suggests that movement itself modulates the attentional resources allocated to that body part.

Event-Related Brain Potentials N140 and P300 during Somatosensory Go/NoGo Tasks Are Modulated by Movement Preparation.

The Go/NoGo task requires attention and sensory processing to distinguish a motor action cue or 'Go stimulus' from a 'NoGo stimulus' requiring no action, as well as motor preparation for a rapid Go stimulus response. The neural activity mediating these response phases can be examined non-invasively by measuring specific event-related brain potentials (ERPs) using electroencephalography. However, it is critical to determine how different task conditions, such as the relationship between attention site and movement site, influence ERPs and task performance. In this study, we compared attention-associated ERP components N140 and P300, the performance metrics reaction time (RT) and accuracy (%Error) and movement-related cortical potentials (MRCPs) between Go/NoGo task trials in which attention target and movement site were the same (right index finger movement in response to right index finger stimulation) or different (right index finger movement in response to fifth finger stimulation). In other Count trials, participants kept a running count of target stimuli presented but did not initiate a motor response. The N140 amplitudes at electrode site Cz were significantly larger in Movement trials than in Count trials regardless of the stimulation site-movement site condition. In contrast, the P300 amplitude at Cz was significantly smaller in Movement trials than in Count trials. The temporal windows of N140 and P300 overlapped with the MRCP. This superposition may influence N140 and P300 through summation, possibly independent of changes in attentional allocation.

The Effect of Pedaling at Different Cadence on Attentional Resources.

We investigated the relationship between attentional resources and pedaling cadence using electroencephalography (EEG) to measure P300 amplitudes and latencies. Twenty-five healthy volunteers performed the oddball task while pedaling on a stationary bike or relaxing (i.e., no pedaling). We set them four conditions, namely, (1) performing only the oddball task (i.e., control), (2) performing the oddball task while pedaling at optimal cadence (i.e., optimal), (3) performing the oddball task while pedaling faster than optimal cadence (i.e., fast), and (4) performing the oddball task while pedaling slower than optimal cadence (i.e., slow). P300 amplitudes at Cz and Pz electrodes under optimal, fast, and slow conditions were significantly lower than those under control conditions. P300 amplitudes at Pz under fast and slow conditions were significantly lower than those under the optimal condition. No significant changes in P300 latency at any electrode were observed under any condition. Our findings revealed that pedaling at non-optimal cadence results in less attention being paid to external stimuli compared with pedaling at optimal cadence.

Effect of primary motor cortex excitability changes after quadripulse transcranial magnetic stimulation on kinesthetic sensitivity: A preliminary study.

Muscle spindles provide the greatest contribution to kinesthetic perception. Primary motor cortex (M1) excitability changes in parallel with the intensity of kinesthetic perception inputs from muscle spindles; M1 is therefore involved in kinesthetic perception. However, the causal relationship between changes in kinesthetic sensitivity and M1 excitability is unclear. The purpose of this study was to test whether artificially and sustainably modulated M1 excitability causes changes in kinesthetic sensitivity in healthy individuals. We evaluated motor evoked potentials (MEP) in Experiment 1 and joint motion detection thresholds (JMDT) in Experiment 2 before and after quadripulse transcranial magnetic stimulation (QPS). Nine healthy right-handed male volunteers were recruited. In each experiment, participants received QPS or sham stimulation (Sham) on separate days. MEP amplitude and JMDT were recorded before and at 0, 15, 30, 45, and 60 min after QPS and Sham. Our results showed that M1 excitability and kinesthetic sensitivity increased after QPS, whereas neither changed after Sham. In the five subjects who participated in both experiments, there was a significant moderate correlation between M1 excitability and kinesthetic sensitivity. Thus, the long-lasting change in kinesthetic sensitivity may be due to changes in M1 excitability. In addition, M1 may play a gain adjustment role in the neural pathways of muscle spindle input.

TGF-ß1 is involved in senescence-related pathways in glomerular endothelial cells via p16 translocation and p21 induction.

p16 inhibits cyclin-dependent kinases and regulates senescence-mediated arrest as well as p21. Nuclear p16 promotes G1 cell cycle arrest and cellular senescence. In various glomerular diseases, nuclear p16 expression is associated with disease progression. Therefore, the location of p16 is important. However, the mechanism of p16 trafficking between the nucleus and cytoplasm is yet to be fully investigated. TGF-ß1, a major cytokine involved in the development of kidney diseases, can upregulate p21 expression. However, the relationship between TGF-ß1 and p16 is poorly understood. Here, we report the role of podocyte TGF-ß1 in regulating the p16 behavior in glomerular endothelial cells. We analyzed podocyte-specific TGF-ß1 overexpression mice. Although p16 was found in the nuclei of glomerular endothelial cells and led to endothelial cellular senescence, the expression of p16 did not increase in glomeruli. In cultured endothelial cells, TGF-ß1 induced nuclear translocation of p16 without increasing its expression. Among human glomerular diseases, p16 was detected in the nuclei of glomerular endothelial cells. In summary, we demonstrated the novel role of podocyte TGF-ß1 in managing p16 behavior and cellular senescence in glomeruli, which has clinical relevance for the progression of human glomerular diseases.

Region-dependent bidirectional plasticity in M1 following quadripulse transcranial magnetic stimulation in the inferior parietal cortex.

BACKGROUND: The ability to manipulate the excitability of the network between the inferior parietal lobule (IPL) and primary motor cortex (M1) may have clinical value. OBJECTIVE: To investigate the possibility of inducing long-lasting changes in M1 excitability by applying quadripulse transcranial magnetic stimulation (QPS) to the IPL, and to ascertain stimulus condition- and site-dependent differences in the effects. METHODS: QPS was applied to M1, the primary somatosensory cortex (S1), the supramarginal gyrus (SMG) and angular gyrus (AG) IPL areas, with the inter-stimulus interval (ISI) in the train of pulses set to either 5 ms (QPS-5) or 50 ms (QPS-50). QPS was repeated at 0.2 Hz for 30 min, or not presented (sham condition). Excitability changes in the target site were examined by means of single-pulse transcranial magnetic stimulation (TMS). RESULTS: QPS-5 and QPS-50 at M1 increased and decreased M1 excitability, respectively. QPS at S1 induced no obvious change in M1 excitability. However, QPS at the SMG induced mainly suppressive effects in M1 for at least 30 min, regardless of the ISI length. Both QPS ISIs at the AG yielded significantly different MEP compared to those at the SMG. Thus, the direction of the plastic effect of QPS differed depending on the site, even under the same stimulation conditions. CONCLUSIONS: QPS at the IPL produced long-lasting changes in M1 excitability, which differed depending on the precise stimulation site within the IPL. These results raise the possibility of noninvasive induction of functional plasticity in M1 via input from the IPL.