Technical Considerations in Endoscopic Lumbar Decompression.

With technical development and evolution of endoscopic instruments, endoscopic spinal surgery has become one of the standard treatments for various lumbar spinal diseases ranging from a simple contained disc to complicated cases such as highly migrated disc herniation and other pathology combined with bony degeneration to produce foraminal and canal stenosis. Favorable clinical results of endoscopic decompression for lumbar stenotic disease were reported by several authors. However, studies have also reported limitations, such as steep learning curves and a relatively high complication rate compared with conventional techniques. The endoscopic lumbar decompression technique consists of many essential skills to manage different endoscopic anatomic structures of the spine. From the perspective of surgical completion and safety, this article discusses issues related to technical considerations in endoscopic lumbar decompression.

Deactivation of anterior cingulate cortex during virtual social interaction in obsessive-compulsive disorder.

Studies about social functioning in obsessive-compulsive disorder (OCD) are lacking, even though neuroimaging studies and metacognition evaluation results suggest abnormal neural responses during social interactions. This study examined neural responses of OCD patients during handshakes with a virtual avatar. Because of the nature of the handshaking task, we expected that OCD patients with predominantly contamination/washing symptoms (CON) would show different neural responses compared to healthy controls (HCs) and to disease-controlled (NCON) patients. Thirteen CON, 13 NCON, and 18 HC participants performed handshake tasks with clean or dirty virtual avatars while undergoing functional magnetic resonance imaging. During handshakes with a clean avatar, deactivation in the left anterior cingulate cortex was found in CON patients compared to NCON and HC subjects. This cortical deactivation also occurred with dirty-avatar handshakes, but the difference was significant only between the two OCD groups and HC patients. Deactivation in the left anterior cingulate cortex was correlated with both OCD symptom severity and social anxiety traits. This cortical deactivation in OCD, especially in CON patients, suggests that social dysfunction in OCD may be due to interactions between OCD symptoms and impairment in social cognition, including emotional processing.

Comparative Analysis between Three Different Lumbar Decompression Techniques (Microscopic, Tubular, and Endoscopic) in Lumbar Canal and Lateral Recess Stenosis: Preliminary Report.

PURPOSE: The purpose of our study is to compare the results of spinal decompression using the full-endoscopic interlaminar technique, tubular retractor, and a conventional microsurgical laminotomy technique and evaluate the advantages and clinical feasibility of minimally invasive spinal (MIS) lumbar decompression technique in the lumbar canal and lateral recess stenosis. METHODS: The authors retrospectively reviewed clinical and radiological data from 270 patients who received microsurgical (group E: 72 patients), tubular (group T: 34 patients), or full-endoscopic decompression surgery (group E: 164 patients) for their lumbar canal and lateral recess stenosis from June 2016 to August 2017. Clinical (VAS, ODI, and Mcnab criteria), radiologic (spinal canal diameter, segmental dynamic angle, and disc height), and surgical outcome parameters (CPK level, Operative time, blood loss, and hospital stay) were evaluated pre- and postoperatively and compared among the three groups by means of statistical analysis. Failed cases and complications were reviewed in all groups. RESULTS: The mean follow-up period was 6.38 months. The Overall clinical success rate was 89.4%. All groups showed favorable clinical outcome. The clinical and radiologic results were similar in all groups. Regarding surgical outcome, group E showed longer operation time than group M and T (group E: 84.17 minutes/level, group M: 52.22 minutes/level, and group T: 66.12 minutes/level) (p<0.05). However, groups E and T showed minimal surgical invasiveness compared with group M. Groups E and T showed less immediate postoperative back pain (VAS) (group E: 3.13, group M: 4.28, group T: 3.54) (p<0.05), less increase of serum CPK enzyme (group E: 66.38 IU/L, group M: 120 IU/L, and group T: 137.5 IU/L) (p<0.05), and shorter hospital stay (group E: 2.12 days, group M: 4.85 days, and group T: 2.83 days) (p<0.05). The rates of complications and revisions were not significantly different among the three groups. CONCLUSIONS: MIS decompression technique is clinically feasible and safe to treat the lumbar canal and lateral recess stenosis, and it has many surgical advantages such as less muscle trauma, minimal postoperative back pain, and fast recovery of the patient compared to traditional open microscopic technique.

Percutaneous Endoscopic Decompression in Lumbar Canal and Lateral Recess Stenosis - The Surgical Learning Curve.

OBJECTIVE: The purpose of this study is to characterize the learning curve of endoscopic lumbar decompression based on peri- and postoperative parameters and to suggest the potential of full endoscopic decompression as a primary treatment option for lumbar canal and lateral recess stenosis. METHODS: The records of 223 consecutive patients who underwent percutaneous endoscopic decompression by a single surgeon for their lumbar canal and lateral recess stenosis were reviewed. Patients were stratified into group 1 (n=100) and group 2 (n=123), depending on their case number. After the 100th case, the procedural time reached a plateau and subsequent patients were assigned to the second group. Demographics and surgical outcomes, including operative times, change in dural sac dimensions, length of hospital stay, and intraoperative complication rates were compared between the 2 groups. Postoperative clinical outcomes, including the visual analogue scale (VAS), the Oswestry Disability Index (ODI) and reoperation rates were compared between the 2 groups (group 1, n=90; group 2, n=110) by follow-up evaluation. RESULTS: Procedural times were greater in group 1 than group 2 (group 1, 105.26 minutes; group 2, 67.65 minutes; p<0.05) and they had higher complication rates (group 1, 16% [16 of 100]; group 2, 8.3% [8 of 123]; p<0.05). The length of hospitalization, postoperative improvement in VAS and ODI, and reoperation rates were not different between the groups. In both groups, stenotic spinal canals were effectively decompressed. CONCLUSION: Continued surgical experience was associated with a reduction in operative times and less intraoperative complications. Although the learning curve was steep and additional surgical experience may be needed to overcome the learning curve, percutaneous full endoscopic lumbar decompression is a safe, clinically-feasible, and effective surgical technique and can be adopted as the primary treatment for lumbar canal and lateral recess stenosis.

The Usefulness of Percutaneous Endoscopic Technique in Multifocal Lumbar Pathology.

Introduction. The multifocal lumbar pathology including disc herniation and stenosis in the spinal canal or foramen has been considered the most difficult to approach surgically. It often requires mandatory dual approaches and/or fusion techniques. Traditional percutaneous endoscopic lumbar transforaminal and interlaminar approach has been focused on unifocal disc herniation. However, the development of endoscopic spinal instruments and surgical technique has broadened surgical indication and therapeutic boundary in endoscopic spine surgery. Cases Presentation. The authors present outcomes of four patients with multilumbar pathology including highly inferior migrated disc combined with lateral recess stenosis, multifocal disc herniation, bilateral disc herniations in spinal canal and foraminal disc herniation combined with central canal stenosis. They were successfully treated by percutaneous uniportal full endoscopic approach with single incision. Conclusion. Percutaneous endoscopic spine surgery is a safe and effective tool to figure out multilumbar pathology in a minimal invasive way.

Percutaneous Endoscopic Laminotomy with Flavectomy by Uniportal, Unilateral Approach for the Lumbar Canal or Lateral Recess Stenosis.

OBJECTIVE: To evaluate clinical feasibility and safety of percutaneous endoscopic decompression by a uniportal, unilateral approach for lumbar canal or lateral recess stenosis. METHODS: In this retrospective study, the procedure was performed with endoscopic instruments in the same way as conventional microscopic laminotomy and flavectomy. Clinical outcomes (visual analog scale, Oswestry Disability Index, modified MacNab criteria) were evaluated. Surgical outcomes, including operative time, hospital stay, and complications, were recorded. RESULTS: Decompression was performed in 213 patients (232 lumbar levels) for spinal canal or lateral recess stenosis (unilateral laminotomy, n = 80; bilateral laminotomy, n = 152). Mean follow-up period was 26.45 months. Mean visual analog scale for leg pain, and back pain and mean Oswestry Disability Index improved from 8.24%, 5.35%, and 67.8% at baseline to 1.93% (P < 0.001), 2.05% (P < 0.001), and 17.14% (P < 0.001) at final follow-up. Based on modified MacNab criteria, excellent or good results were obtained in 93.8% of patients. Average operative time was 105.3 ± 56 minutes. In the late period of the learning curve, mean operative time was shortened by two thirds, and mean hospital stay was 2.45 days. There were 12 cases of transient postoperative dysesthesia, 3 cases of motor weakness, and 6 cases of dural tear. No patient had postoperative infection, hematoma, or need for revision surgery for incomplete decompression. CONCLUSIONS: Percutaneous endoscopic decompression by a uniportal, unilateral approach is a safe, clinically feasible, and effective surgical technique for treatment of lumbar stenosis.

Which Approach Is Advantageous to Preventing Development of Adjacent Segment Disease? Comparative Analysis of 3 Different Lumbar Interbody Fusion Techniques (ALIF, LLIF, and PLIF) in L4-5 Spondylolisthesis.

OBJECTIVE: The purpose of this study was to compare radiologic and clinical outcomes in patients with L4-5 lumbar spondylolisthesis who have undergone either instrumented anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), or posterior lumbar interbody fusion (PLIF), especially with regard to the development of adjacent segment disease (ASD). METHODS: Eighty-two patients with preoperative L4-5 spondylolisthesis and minimal ASD who underwent instrumented L4-5 fusion were divided into 3 groups according to the surgical approach used for treatment (ALIF: 27 patients, LLIF: 24 patients, PLIF: 31 patients). Radiographic measurements including preoperative and postoperative foraminal and disk height, segmental and lumbar lordosis, percentage of vertebral slippage, and reduction rate were reviewed. The incidence of ASD and clinical outcomes were evaluated and compared between the 3 groups. RESULTS: ASD was found in 37.0% (10/27), 41.7% (10/24), and 64.5% (20/31) of the patients in the ALIF, LLIF, and PLIF groups, respectively (mean follow-up duration: 35.42 ± 9.35 months). The ALIF and LLIF groups had significantly increased disk and foraminal height compared with the PLIF group. The ALIF group had significantly improved lordosis compared with the PLIF and LLIF groups. There were no statistically significant intergroup differences in clinical outcomes assessed by visual analog scale and Oswestry Disability Index. CONCLUSION: The 3 different fusion techniques investigated can all produce good outcomes in treating lumbar spondylolisthesis in L4-5, but ALIF and LLIF are more advantageous in preventing the development of ASD.

Suppression of AIMP1 protects cognition in Alzheimer's disease model mice 3xTg-AD.

Neuroinflammation has been raised as a candidate of unifying pathogenesis and a target of a disease-modifying strategy for Alzheimer's disease (AD). Aminoacyl-tRNA synthetase complex (ARS)-interacting multifunctional protein 1 (AIMP1) is a cytokine that is known to amplify the actions of tumor necrosis factor-α and to be involved in microglial activation and neuronal death. In this respect, AIMP1 could be a plausible target for the treatment of AD. Therefore, we aimed to examine whether anti-AIMP1 antibody could exert therapeutic effects against cognitive impairment using 3xTg-AD mice. Through the passive avoidance test, we found that an intraperitoneal injection of anti-AIMP1 antibody over 4 weeks was effective in protecting memory function in 3xTg-AD mice (16 weeks old). In addition, to address the translational implications of AIMP1, we measured blood AIMP1 levels in patients with AD (n=22), mild cognitive impairment (n=25), and normal cognition (n=23). Blood AIMP1 levels were associated negatively with global cognitive function and were significantly higher in individuals with a higher degree of medial temporal lobe atrophy, which is one of the representative clinical markers of AD. Our results suggested a possible association of AIMP1 with AD pathogenesis, as well as the potential of the anti-AIMP1 antibody as a novel therapeutic option for AD.

Tauroursodeoxycholic acid improves viability of artificial RBCs.

Tauroursodeoxycholic acid (TUDCA) is known to prevent apoptosis through the Bax pathway and to promote neovascularization by enhancing the mobilization of stem cells, their differentiation. This study was performed to investigate the effect of TUDCA on erythropoiesis in hematopoietic stem cells (HSCs). Since erythropoiesis of CD34(+) HSCs is divided into four phases, the total cell number, viable cell number, cell viability, cell morphology, and expressed erythroid markers in each phase were examined. The number of viable control cells and their viability did not differ from those of the TUDCA-treated cells in phase I and II. However, TUDCA increased cell viability compared to the control in phases III and IV. Cell distribution differed that the immature erythroid cell number was higher for the TUDCA-treated cells than for the control cells until phase III, but all developed into RBCs in the last. The final RBC number and viability was significantly higher in TUDCA-treated cells compared to the control cells. Taken together, we suggest that TUDCA addition to cell cultures for artificial RBC production could be used as a new protocol for improving the viability of RBCs.

Frontostriatal Connectivity Changes in Major Depressive Disorder After Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Controlled Study.

OBJECTIVE: The aim of this randomized, sham-controlled study was to investigate the therapeutic effects of underlying neurobiological changes after 2-week repetitive transcranial magnetic stimulation (rTMS) treatment using functional connectivity magnetic resonance imaging in patients with major depression. METHODS: Twenty-four patients with major depressive disorder diagnosed with DSM-IV-TR criteria were randomly assigned to the active rTMS (n = 13) or sham (n = 11) groups from January 2009 to June 2011. rTMS was given for 2 weeks at 110% of the motor threshold for 10 minutes at 10 Hz over the left dorsolateral prefrontal cortex (DLPFC). Resting state functional connectivity was evaluated before and after rTMS. The 17-item Hamilton Depression Rating Scale (HDRS) was administered, and neurocognitive tasks were performed. We examined between-group differences in functional connectivity changes from the bilateral DLPFC. RESULTS: Participants in the active rTMS group showed significant clinical improvement in HDRS scores compared to those in the sham group (P < .001). After 2-week rTMS, there were significant differences in changes in DLPFC-left caudate connectivity (corrected P < .05): the active group showed a greater reduction of connectivity strength between the DLPFC and left caudate compared to the sham group. Reduced levels of DLPFC-left caudate connectivity predicted improvement in depressive symptoms (r = 0.58, P = .001). Additionally, a positive correlation between residual depressive symptoms and connectivity strength after 2-week rTMS was found (r = 0.46, P = .023). CONCLUSIONS: High-frequency rTMS over the left DLPFC showed therapeutic effects in patients with major depression. The therapeutic effect of rTMS is related to the modulation of functional connectivity in the frontostriatal network. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01325831​.

Foraminoplastic Superior Vertebral Notch Approach with Reamers in Percutaneous Endoscopic Lumbar Discectomy : Technical Note and Clinical Outcome in Limited Indications of Percutaneous Endoscopic Lumbar Discectomy.

To describe the details of the foraminoplastic superior vertebral notch approach (FSVNA) with reamers in percutaneous endoscopic lumbar discectomy (PELD) and to demonstrate the clinical outcomes in limited indications of PELD. Retrospective data were collected from 64 patients who underwent PELD with FSVNA from August 2012 to April 2014. Inclusion criteria were high grade migrated disc, high canal compromised disc, and disc protrusion combined with foraminal stenosis. The clinical outcomes were assessed using by the visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified MacNab criteria. Complications related to the surgery were reviewed. The procedure used a unique approach, using the superior vertebral notch as the target and performing foraminoplasty with only reamers under C-arm control. The mean age of the 55 female and 32 male patients was 52.73 years. The mean F/U period was 12.2±4.2 months. Preoperative VAS (8.24±1.25) and ODI (67.8±15.4) score improved significantly at the last follow-up (VAS, 1.93±1.78; ODI, 17.14±15.7). Based on the modified MacNab criteria, excellent or good results were obtained in 95.3% of the patients. Postoperative transient dysthesia (n=2) and reoperation (n=1) due to recurred disc were reported. PELD with FSVNA could be a good method for treating lumbar disc herniation. This procedure may offer safe and efficacious results, especially in the relatively limited indications for PELD.

The antibody atliximab attenuates collagen-induced arthritis by neutralizing AIMP1, an inflammatory cytokine that enhances osteoclastogenesis.

ARS-interacting multifunctional protein 1 (AIMP1) induces production of inflammatory cytokines from immune cells. Since osteoclastogenesis is promoted by positive regulation of inflammatory cytokines, whether AIMP1 could promote osteoclastogenesis was investigated. AIMP1 induced osteoclastogenesis and acted synergistically with RANKL to promote osteoclastogenesis. Down-regulation of CD23, an AIMP1 receptor, abolished AIMP1-mediated osteoclastogenesis. Enzyme-linked immunosorbent assays showed that the AIMP1 level was significantly higher in the peripheral blood (PB) and synovial fluid of rheumatoid arthritis patients than in normal PB. A monoclonal antibody (clone 15B3AF) that blocked the cytokine activity of AIMP1 inhibited the AIMP1-mediated production of inflammatory cytokines. Clone 15B3AF inhibited the AIMP1-mediated osteoclastogenesis in vitro. We then cloned the complementary determining regions of clone 15B3AF and generated a chimeric antibody (atliximab). In a collagen-induced arthritis mouse model (CIA), atliximab administration significantly attenuated disease severity and improved various histopathological parameters. Three-dimensional micro-computed tomography scanning confirmed that atliximab enhanced the joint structures in CIA mice. Furthermore, atliximab decreased the expression of inflammatory cytokines in the serum and inflamed joints of CIA mice. Taken together, our findings suggest that AIMP1 exacerbates RA by promoting inflammation and osteoclastogenesis and that atliximab could be developed as a therapeutic antibody to target inflammatory diseases, including RA.

Tauroursodeoxycholic acid, a bile acid, promotes blood vessel repair by recruiting vasculogenic progenitor cells.

Although serum bile acid concentrations are approximately 10 µM in healthy subjects, the crosstalk between the biliary system and vascular repair has never been investigated. In this study, tauroursodeoxycholic acid (TUDCA) induced dissociation of CD34(+) hematopoietic stem cells (HSCs) from stromal cells by reducing adhesion molecule expression. TUDCA increased CD34(+) /Sca1(+) progenitors in mice peripheral blood (PB), and CD34(+) , CD31(+) , and c-kit(+) progenitors in human PB. In addition, TUDCA increased differentiation of CD34(+) HSCs into EPC lineage cells via Akt activation. EPC invasion was increased by TUDCA, which was mediated by fibroblast activating protein via Akt activation. Interestingly, TUDCA induced integration of EPCs into human aortic endothelial cells (HAECs) by increasing adhesion molecule expression. In the mouse hind limb ischemia model, TUDCA promoted blood perfusion by enhancing angiogenesis through recruitment of Flk-1(+) /CD34(+) and Sca-1(+) /c-kit(+) progenitors into damaged tissue. In GFP(+) bone marrow-transplanted hind limb ischemia, TUDCA induced recruitment of GFP(+) /c-kit(+) progenitors to the ischemic area, resulting in an increased blood perfusion ratio. Histological analysis suggested that GFP(+) progenitors mobilized from bone marrow, integrated into blood vessels, and differentiated into VEGFR(+) cells. In addition, TUDCA decreased cellular senescence by reducing levels of p53, p21, and reactive oxygen species and increased nitric oxide. Transplantation of TUDCA-primed senescent EPCs in hind limb ischemia significantly improved blood vessel regeneration, as compared with senescent EPCs. Our results suggested that TUDCA promoted neovascularization by enhancing the mobilization of stem/progenitor cells from bone marrow, their differentiation into EPCs, and their integration with preexisting endothelial cells.

Distinct functional connectivity of limbic network in the washing type obsessive-compulsive disorder.

Neurobiological models of obsessive-compulsive disorder (OCD) emphasize disturbances of the corticostriatal circuit, but it remains unclear as to how these complex network dysfunctions correspond to heterogeneous OCD phenotypes. We aimed to investigate corticostriatal functional connectivity alterations distinct to OCD characterized predominantly by contamination/washing symptoms. Functional connectivity strengths of the striatal seed regions with remaining brain regions during the resting condition and the contamination symptom provocation condition were compared among 13 OCD patients with predominant contamination/washing symptoms (CON), 13 OCD patients without these symptoms (NCON), and 18 healthy controls. The CON group showed distinctively altered functional connectivity between the ventral striatum and the insula during both the resting and symptom-provoking conditions. Also, the connectivity strength between the ventral striatum and the insula significantly correlated with contamination/washing symptom severity. As common connectivity alterations of the whole OCD subjects, corticostriatal circuits involving the orbitofrontal and temporal cortices were again confirmed. To our knowledge, this is the first study that examined specific abnormalities in functional connectivity of contamination/washing symptom dimension OCD. The findings suggest limbic network dysfunctions to play a pivotal role in contamination/washing symptoms, possibly associated with emotionally salient error awareness. Our study sample allowed us to evaluate the corticostriatal network dysfunction underlying the contamination/washing symptom dimension, which leaves other major symptom dimensions to be explored in the future.

Radicular compression by intraspinal epidural gas bubble occurred in distant two levels after lumbar microdiscectomy.

The authors report a case of symptomatic epidural gas accumulation 2 weeks after the multi-level lumbar surgery, causing postoperative recurrent radiculopathy. The accumulation of epidural gas compressing the dural sac and nerve root was demonstrated by CT and MRI at the distant two levels, L3-4 and L5-S1, where vacuum in disc space was observed preoperatively and both laminectomy and discectomy had been done. However, postoperative air was not identified at L4-5 level where only laminectomy had been done in same surgical field, which suggested the relationship between postoperative epidural gas and the manipulation of disc structure. Conservative treatment and needle aspiration was performed, but not effective to relieve patient's symptoms. The patient underwent revision surgery to remove the gaseous cyst. Her leg pain was improved after the second operation.

Disruption of orbitofronto-striatal functional connectivity underlies maladaptive persistent behaviors in alcohol-dependent patients.

OBJECTIVE: Alcohol dependence is characterized by persistent alcohol-seeking despite negative consequences. Previous studies suggest that maladaptive persistent behaviors reflect alcohol-induced brain changes that cause alterations in the cortico-striatal-limbic circuit. METHODS: Twenty one alcohol dependent patients and 24 age-matched healthy controls performed a decision-making task during functional MRI. We defined the medial orbitofrontal cortex (mOFC) as a region-of-interest and performed seed-based functional connectivity analysis. RESULTS: Healthy controls were more flexible in adapting an alternative behavioral strategy, which correlated with stronger mOFC-dorsal striatum functional connectivity. In contrast, alcohol dependent patients persisted to the first established behavioral strategy. The mOFC-dorsal striatum functional connectivity was impaired in the alcohol-dependent patients, but increased in correlation with the duration of abstinence. CONCLUSION: Our findings support that the disruption of the mOFC-striatal circuitry contribute to the maldaptive persistent behaviors in alcohol dependent patients.

ARS-interacting multi-functional protein 1 induces proliferation of human bone marrow-derived mesenchymal stem cells by accumulation of ß-catenin via fibroblast growth factor receptor 2-mediated activation of Akt.

ARS-Interacting Multi-functional Protein 1 (AIMP1) is a cytokine that is involved in the regulation of angiogenesis, immune activation, and fibroblast proliferation. In this study, fibroblast growth factor receptor 2 (FGFR2) was isolated as a binding partner of AIMP peptide (amino acids 6-46) in affinity purification using human bone marrow-derived mesenchymal stem cells (BMMSCs). AIMP1 peptide induced the proliferation of adult BMMSCs by activating Akt, inhibiting glycogen synthase kinase-3ß, and thereby increasing the level of ß-catenin. In addition, AIMP1 peptide induced the translocation of ß-catenin to the nucleus and increased the transcription of c-myc and cyclin D1 by activating the ß-catenin/T-cell factor (TCF) complex. By contrast, transfection of dominant negative TCF abolished the effect of AIMP1. The inhibition of Akt, using LY294002, abolished the accumulation and nuclear translocation of ß-catenin induced by AIMP1, leading to a decrease in c-myc and cyclin D1 expression, which decreased the proliferation of BMMSCs. An intraperitoneal injection of AIMP1 peptide into C57/BL6 mice increased the colony formation of fibroblast-like cells. Fluorescence activated cell sorting analysis showed that the colony-forming cells were CD29(+)/CD44(+)/CD90(+)/CD105(+)/CD34(-)/CD45(-), which is characteristic of MSCs. In addition, the fibroblast-like cells differentiated into adipocytes, chondrocytes, and osteocytes. Taken together, these data suggest that AIMP1 peptide promotes the proliferation of BMMSCs by activating the ß-catenin/TCF complex via FGFR2-mediated activation of Akt, which leads to an increase in MSCs in peripheral blood.

rTMS over bilateral inferior parietal cortex induces decrement of spatial sustained attention.

Sustained attention is an essential brain function that enables a subject to maintain attention level over the time of a task. In previous work, the right inferior parietal lobe (IPL) has been reported as one of the main brain regions related to sustained attention, however, the right lateralization of vigilance/sustained attention is unclear because information about the network for sustained attention is traditionally provided by neglect patients who typically have right brain damage. Here, we investigated sustained attention by applying a virtual lesion technique, transcranial magnetic stimulation (TMS), over the left and right superior parietal lobe (SPL) and IPL. We used two different types of visual sustained attention tasks: spatial (location based) and non-spatial (feature based). When the participants performed the spatial task, repetitive TMS (rTMS) over either the right or left IPL induced a significant decrement of sustained attention causing a progressive increment of errors and response time. In contrast, participants' performance was not changed by rTMS on the non-spatial task. Also, omission errors (true negative) gradually increased with time on right and left IPL rTMS conditions, while commission errors (false positive) were relatively stable. These findings suggest that the maintenance of attention, especially in tasks regarding spatial location, is not uniquely lateralized to the right IPL, but may also involve participation of the left IPL.

Neural evidence for emotional involvement in pathological alcohol craving.

AIMS: Reducing craving is a key to success in the treatment of alcohol dependence. The emotion circuit may be involved in pathological craving for alcohol. In this study, we investigated neural correlates of emotional involvement in craving in alcohol dependence. METHODS: The study included 17 detoxified alcoholic patients and 25 social drinkers. We used functional magnetic resonance imaging to examine brain activation (blood oxygen level-dependent signals) while participants reported craving and emotion in response to visually presented, alcohol-related stimuli and emotional stimuli. RESULTS: In the craving-rating paradigm, negative emotional stimuli as well as alcohol cues activated craving-related brain regions in alcoholic patients. Activations of the inferior parietal lobule and dorsolateral prefrontal cortex by negative emotional stimuli were negatively correlated with craving; meanwhile limbic activation was positively correlated with craving. For the emotion paradigm, greater limbic activation was evident by alcohol-related stimuli in the alcohol-dependent group. CONCLUSIONS: Our findings constitute neural evidence for emotional involvement in pathological craving for alcohol, underscoring the importance of emotion management in abstinent alcoholic patients for relapse prevention.

Schwann-like cells from human melanocytes and their fate in sciatic nerve injury.

We induced human melanocyte dedifferentiation to Schwann cell-like cells in vitro by a combination of forskolin, neuregulin-ß1, neurotrophin-3, platelet-derived growth factor-aa, basic fibroblast growth factor, laminin, and heparin. Cultured human melanocytes constitutively expressed neural cell and melanocyte markers but melanocyte-specific marker, including microphthalmia-associated transcription factor and tyrosinase, expression was selectively lost after induction. In the sciatic nerve injury site, the induced cells were engrafted and closely aligned to axons and P0-expressing myelin sheaths, whereas uninduced cells were not colocalized with axons and myelin sheaths and reexpressed melanocyte-specific tyrosinase activity in vivo. Human melanocytes lose their melanocyte phenotype and transdifferentiate into Schwann cells under specific induction conditions and display their Schwann cell phenotype after transplantation to injured sciatic nerve tissue.