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The third opium war may have already started, not only due to illicit opioid trafficking from the Golden Crescent and Golden Triangle on the international front but also through indiscriminate opioid prescription and opioid diversion at home. Opioid use disorder (OUD), among unintentional injuries, has become one of the top 4 causes of death in the United States (U.S.). An OUD is defined as a problematic pattern of opioid use resulting in clinically significant impairment or distress, consisting of 2 or more of 11 problems within 1 year, as described by the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Observation of aberrant behaviors of OUD is also helpful for overworked clinicians. For the prevention of OUD, the Opioid Risk Tool and the Current Opioid Misuse Measure are appropriate screening tests before and during opioid administration, respectively. Treatment of OUD consists of 3 opioid-based U.S. Food and Drug Administration-approved medications, including methadone, buprenorphine, and naltrexone, and non-opioid-based symptomatic medications for reducing opioid withdrawal syndromes, such as α2 agonists, β-blockers, antidiarrheals, antiemetics, non-steroidal anti-inflammatory drugs, and benzodiazepines. There are at least 6 recommendable guidelines and essential terms related to OUD. Opioid stewardship programs are now critical to promoting appropriate use of opioid medications, improving patient outcomes, and reducing misuse of opioids, influenced by the successful implementation of antimicrobial stewardship programs. Despite the lack of previous motivation, now is the critical time for trying to reduce the risk of OUD.

This study examined the re/familialization and de-familialization effects of family policy types (in-cash or in-kind), and analyzed differences in the effects in terms of stratification. The family...

Not all movements require the motor cortex for execution. Intriguingly, dependence on motor cortex of a given movement is not fixed, but instead can dynamically change over the course of long-term learning. For instance, rodent forelimb movements that initially require motor cortex can become independent of the motor cortex after an extended period of training. However, it remains unclear whether long-term neural changes rendering the motor cortex dispensable are a simple function of the training length. To address this issue, we trained mice (both male and female) to perform two distinct forelimb movements, forward versus downward reaches with a joystick, concomitantly over several weeks, and then compared the involvement of the motor cortex between the two movements. Most mice achieved different levels of motor performance between the two movements after long-term training. Of the two movements, the one that achieved higher trial-to-trial consistency (i.e., consistent-direction movement) was significantly less affected by inactivation of motor cortex than the other (i.e., variable-direction movement). Two-photon calcium imaging of motor cortical neurons revealed that the consistent-direction movement activates fewer neurons, producing weaker and less consistent population activity than the variable-direction movement. Together, the motor cortex was less engaged and less necessary for learned movements that achieved higher levels of consistency. Thus, the long-term reorganization of neural circuits that frees the motor cortex from the learned movement is not a mere function of training length. Rather, this reorganization tracks the level of motor performance that the animal achieves during training. SIGNIFICANCE STATEMENT Long-term training of a movement reshapes motor circuits, disengaging motor cortex potentially for automatized execution of the learned movement. Acquiring new motor skills often involves learning of multiple movements (e.g., forehand and backhand strokes when learning tennis), but different movements do not always improve at the same time nor reach the same level of proficiency. Here we showed that the involvement of motor cortex after long-term training differs between similar yet distinct movements that reached different levels of expertise. Motor cortex was less engaged and less necessary for the more proficient movement. Thus, disengagement of motor cortex is not a simple function of training time, but instead tracks the level of expertise of a learned movement.

The posterior parietal cortex (PPC) performs many functions, including decision-making and movement control. It remains unknown which input and output pathways of PPC support different functions. We addressed this issue in mice, focusing on PPC neurons projecting to the dorsal striatum (PPC-STR) and the posterior secondary motor cortex (PPC-pM2). Projection-specific, retrograde labeling showed that PPC-STR and PPC-pM2 represent largely distinct subpopulations, with PPC-STR receiving stronger inputs from association areas and PPC-pM2 receiving stronger sensorimotor inputs. Two-photon calcium imaging during decision-making revealed that the PPC-STR population encodes history-dependent choice bias more strongly than PPC-pM2 or general PPC populations. Furthermore, optogenetic inactivation of PPC-STR neurons or their terminals in STR decreased history-dependent bias, while inactivation of PPC-pM2 neurons altered movement kinematics. Therefore, PPC biases action selection through its STR projection, while controlling movements through PPC-pM2 neurons. PPC may support multiple functions through parallel subpopulations, each with distinct input-output connectivity.

A marine bacterium, Olleya aquimaris DAU311, was isolated from Goraebul beach in the Republic of Korea. This strain had β-glucosidase activity on Luria–Bertani esculin plates. The β-glucosidase, oabgl84, was isolated, cloned, and sequenced, based on fosmid library. The gene encoded novel β-glucosidase and consisted of an open reading frame of 2304 bp, which encodes 768 amino acids. The deduced amino acid sequence had 99% identity to Olleya sp. VCSM12, 84% identity to Olleya marilimosa, and 78% similarity to Lacinutrix sp. Hel_I_90. OaBGL84 belongs to the glycoside hydrolase family 3, and it was visualized using SDS-PAGE, approximately 84 kDa. The optimal temperature and pH of OaBGL84 were analyzed as 40 °C and 6.0, respectively, using pNPG as substrate. The Km and Vmax values for OaBGL84 were 1.35 mM and 25.3 μM/s, respectively. Furthermore, OaBGL84 activity was completely inhibited by Cu2+ and Hg2+ ions. OaBGL84 demonstrated extraordinary stability until 50% (v/v) benzene, n-hexane, or toluene. These results indicate that OaBGL84 is useful candidate to degrade cellulose or soy isoflavone in the organic solvents for various biotechnological applications.

본 연구에서는 azoxystrobin을 대상으로 작물재배 토양중 azoxystrobin의 잔류소실 및 상추로의 전이량을 파악하고자 하였다. 포장시험은 광주(GLT)와 용인(YLT)의 시설 재배지 두 곳에서 실시하였다. Azoxystrobin을 토양 중 서로 다른 두 농도로 처리한 후, 토양과 상추를 채취하였다. 토양과 상추 중 평균 회수율 범위는 86.9113.6%이었고, 변이계수는 0.14.6%였다. Azoxystrobin의 초기 토양농도는 시험포장 1에서 9.20, 11.00mg kg-1이었으며 농약처리 43일 후에 1.36, 2.70 mg kg-1로 감소하였고, 시험포장 2에서는 초기 토양농도가 1.06, 2.23 mg kg-1이었고 농약처리 36일 후에 0.20, 0.67 mg kg-1으로 감소하였다. 시험포장 1에서의 토양 중 반감기는 저농도와 고농도 처리구에서 19.4, 23.3일이었으며, 시험포장 2에서는 11.5, 17.8일 이었다. 상추 중 azoxystrobin 잔류량은 GLT과 YLT 두 포장에서 0.02 미만으로, 검출되지 않았다.

본 연구에서는 tricyclazole을 대상으로 작물재배 토양 중에 잔류된 tricyclazole의 잔류 소실 및 엇갈이 배추로의 전이량을 구명하고자 하였다. Tricyclazole은 농작물 재배 시 사용하지 않았으나 경작지 토양에서 다수 검출되는 성분 중 하나이다. 포장시험은 광주(시험포장 1)와 용인(시험포장 2)의 시설재배지 두곳에서 실시하였다. Tricyclazole을 토양 중 서로 다른 두 농도로 처리한 후, 토양과 엇갈이 배추를 채취하였다. 토양과 엇갈이 배추 중 평균 회수율 범위는 83.5-92.1%이었고, 변이계수는 1.3-6.8%였다. Tricyclazole의 초기 토양 농도는 시험포장 1에서 4.25, 8.97 mg kg-1이었으며 농약 처리 43일 후에 2.48, 4.26mg kg-1로 감소하였고, 시험포장 2에서는 초기 토양 농도가 0.88, 2.02 mg kg-1이었고 농약 처리 36일 후에 0.43, 0.98 mg kg-1으로 감소하였다. 시험포장 1에서의 토양 중 반감기는 저농도와 고농도 처리구에서 39.6, 28.1일 이었으며, 시험포장 2에서는 27.9, 17.2일 이었다. 엇갈이배추로 전이된 tricyclazole 잔류량은 시험포장 1과 2에서 초기 토양잔류농도 대비 각각 4.03-18.26%, 8.26-38.05% 범위였다.

The relationship between the brain and the environment is flexible, forming the foundation for our ability to learn. Here we review the current state of our understanding of the modifications in the sensorimotor pathway related to sensorimotor learning. We divide the process into three hierarchical levels with distinct goals: (1) sensory perceptual learning, (2) sensorimotor associative learning, and (3) motor skill learning. Perceptual learning optimizes the representations of important sensory stimuli. Associative learning and the initial phase of motor skill learning are ensured by feedback-based mechanisms that permit trial-and-error learning. The later phase of motor skill learning may primarily involve feedback-independent mechanisms operating under the classic Hebbian rule. With these changes under distinct constraints and mechanisms, sensorimotor learning establishes dedicated circuitry for the reproduction of stereotyped neural activity patterns and behavior.

Long-term training of motor skills reorganizes motor circuits to bypass primary motor cortex., Motor learning involves reorganization of the primary motor cortex (M1). However, it remains unclear how the involvement of M1 in movement control changes during long-term learning. To address this, we trained mice in a forelimb-based motor task over months and performed optogenetic inactivation and two-photon calcium imaging in M1 during the long-term training. We found that M1 inactivation impaired the forelimb movements in the early and middle stages, but not in the late stage, indicating that the movements that initially required M1 became independent of M1. As previously shown, M1 population activity became more consistent across trials from the early to middle stage while task performance rapidly improved. However, from the middle to late stage, M1 population activity became again variable despite consistent expert behaviors. This later decline in activity consistency suggests dissociation between M1 and movements. These findings suggest that long-term motor learning can disengage M1 from movement control.

The Electronic Data Interchange (EDI) medical procedure code is the code used for health insurance claims in Korea. We mapped Korean EDI codes to SNOMED CT to explore the global interoperability of health insurance claims data. We developed rules for mapping based on the mapping guideline provided by SNOMED CT International. The first and second authors mapped 726 EDI codes used to claim reimbursement in five specialty areas to SNOMED CT. Eight subject matter experts reviewed the mapping results. Out of 726 procedure codes, 82.5% were exactly or partially mapped to SNOMED CT. An EDI code was mapped to an average of 2.04 SNOMED CT concepts. Twenty-one attributes were identified in the EDI codes mapped to SNOMED CT concepts. We identified strategies to improve the EDI code in this study. They include introducing hierarchical structures, adding inclusion and exclusion criteria for procedure codes, and improving EDI code labels.

Strain AP01 was isolated for the biological cypermethrin degradation from soil and sediment in Busan. This strain was identified on the basis of phylogenetic analysis of the 16s rDNA sequence and assigned as Bacillus amyloliquefaciens AP01. AP01 could degrade about 45% of cypermethrin in the mineral medium at 30 o C and 180 rpm for 5 days. Furthermore when 2% glucose was added in the medium, the degradation rate of cypermethrin by strain AP01 was increased upto about 60%. Therefore, AP01 may serve as a promising strain in the bioremediation of soil polluted with cypermethrin.

Background Ultrasonography (US) has recently proved to be useful in diagnostic dermatology. It is convenient to use, completely safe, and provides valuable information. Objective This study was performed to compare the diagnostic accuracy of US with that of clinical diagnosis in patients with benign subcutaneous lesions. Methods We retrospectively examined data for 100 patients with benign subcutaneous lesions who were diagnosed with US and either biopsy or surgery at Seoul National University Boramae Hospital between January 2010 and May 2013. Results Ultrasonography significantly increased the diagnostic yield of benign subcuta-neous lesions (after physical examination [PE], 52.0%; after US, 82.0%; P

Trienzyme extraction coupled with microplate assay (Lactobacillus casei subsp. rhamnosus) was vali- dated and applied for the determination of folate (vitamin B9) in Korean ancestral rite foods. Foods included five Guk (Tang), eleven Sookchaes, eight Jeoks, nine Jeons, six Jjims, and twenty desserts. Folate was detected in all samples: Guk (Tang) 4.62∼18.84, Sookchae 6.13∼48.40, Jeok 5.49∼49.50, Jeon 6.96∼30.77, Jjim 10.34∼38.88, and desserts 3.33∼49.55 μg/100 g. The lowest folate content was observed in Sikhye (3.33 μg/100 g), whereas the highest was observed in Songhwa-dasik (49.55 μg/100 g). Folate analyses of certified reference materials, BCR-121 (whole meal flour) and BCR-487 (pig liver), showed good recoveries of 90.0% (0.45 mg/kg) and 92.4% (12.3 mg/kg), respectively. The recoveries (96.0 to 106.2%) obtained by analyzing eight spiked samples with different matrices also showed good accuracy. Both repeatability and reproducibility were less than 5%, indicating good precision. The quality control chart (n>30) obtained by running commercial folate fortified-wheat flour once a week for about 10 months showed that all assays were under control. All validation method and analytical quality control results showed that folate contents in Korean ancestral rite foods produced by microplate assay were reliable enough to be used for the construction of a national folate database.

Background: The results from recent brain-machine interface (BMI) studies suggest that it may be more efficient to use simple arbitrary relationships between individual neuron activity and BMI movements than the complex relationship observed between neuron activity and natural movements. This idea is based on the assumption that individual neurons can be conditioned independently regardless of their natural movement association. Results: We tested this assumption in the parietal reach region (PRR), an important candidate area for BMIs in which neurons encode the target location for reaching movements. Monkeys could learn to elicit arbitrarily assigned activity patterns, but the seemingly arbitrary patterns always belonged to the response set for natural reaching movements. Moreover, neurons that are free from conditioning showed correlated responses with the conditioned neurons as if they encoded common reach targets. Thus, learning was accomplished by finding reach targets (intrinsic variable of PRR neurons) for which the natural response of reach planning could approximate the arbitrary patterns. Conclusions: Our results suggest that animals learn to volitionally control single-neuron activity in PRR by preferentially exploring and exploiting their natural movement repertoire. Thus, for optimal performance, BMIs utilizing neural signals in PRR should harness, not disregard, the activity patterns in the natural sensorimotor repertoire.

This paper critically examines the Seoul city government’s attempts at the policy transfer of creative cities programmes, both as a policy borrower and as a policy lender, by using the emergent ‘policy mobilities’ approach. Seoul’s way of actualising the idea of creative cities places more emphasis on local-serving administration, tourism and physical cultural infrastructure. The original creative city programmes have been transformed, ideologically and materially, by Seoul into a process of downsizing government organisations and workforce and limiting the use of public space. Seoul’s attempt to be a policy lender is not a product of other foreign cities’ policy transfer from Seoul, but the result of the city government’s promotional practices. Its final outcome, thus bears relatively little relationship or similarity to the original policies, encountering unexpected administrative and operational problems, such as increasing debt and resistance from civil groups.

The spiking activity in the parietal reach region (PRR) represents the spatial goal of an impending reach when the reach is directed toward or away from a visual object. The local field potentials (LFPs) in this region also represent the reach goal when the reach is directed to a visual object. Thus PRR is a candidate area for reading out a patient's intended reach goals for neural prosthetic applications. For natural behaviors, reach goals are not always based on the location of a visual object, e.g., playing the piano following sheet music or moving following verbal directions. So far it has not been directly tested whether and how PRR represents reach goals in such cognitive, nonlocational conditions, and knowing the encoding properties in various task conditions would help in designing a reach goal decoder for prosthetic applications. To address this issue, we examined the macaque PRR under two reach conditions: reach goal determined by the stimulus location (direct) or shape (symbolic). For the same goal, the spiking activity near reach onset was indistinguishable between the two tasks, and thus a reach goal decoder trained with spiking activity in one task performed perfectly in the other. In contrast, the LFP activity at 20–40 Hz showed small but significantly enhanced reach goal tuning in the symbolic task, but its spatial preference remained the same. Consequently, a decoder trained with LFP activity performed worse in the other task than in the same task. These results suggest that LFP decoders in PRR should take into account the task context (e.g., locational vs. nonlocational) to be accurate, while spike decoders can robustly provide reach goal information regardless of the task context in various prosthetic applications.

Adaptive control of reaching depends on internal models that associate states in which the limb experienced a force perturbation with motor commands that can compensate for it. Limb state can be sensed via both vision and proprioception. However, adaptation of reaching in novel dynamics results in generalization in the intrinsic coordinates of the limb, suggesting that the proprioceptive states in which the limb was perturbed dominate representation of limb state. To test this hypothesis, we considered a task where position of the hand during a reach was correlated with patterns of force perturbation. This correlation could be sensed via vision, proprioception, or both. As predicted, when the correlations could be sensed only via proprioception, learning was significantly better as compared to when the correlations could only be sensed through vision. We found that learning with visual correlations resulted in subjects who could verbally describe the patterns of perturbations but this awareness was never observed in subjects who learned the task with only proprioceptive correlations. We manipulated the relative values of the visual and proprioceptive parameters and found that the probability of becoming aware strongly depended on the correlations that subjects could visually observe. In all conditions, aware subjects demonstrated a small but significant advantage in their ability to adapt their motor commands. Proprioceptive correlations produced an internal model that strongly influenced reaching performance yet did not lead to awareness. Visual correlations strongly increased the probability of becoming aware, yet had a much smaller but still significant effect on reaching performance. Therefore, practice resulted in acquisition of both implicit and explicit internal models.

Introduction Among non-ablative devices for wrinkle reduction and skin laxity, long pulsed 1064 nm Nd:YAG laser (LPND) has considerable effectiveness. It can penetrate to deep dermis due to its longer wavelength. This study assesses the efficacy and safety of LPND applying new parameters for skin rejuvenation in Korean subjects. Methods A prospective randomized split-faced study was done (n = 20). Half of the face was treated with three passes of LPND at a spot size of 12 mm, 20–24 J/cm 2 fluence, 12 ms width, and frequency of 2 Hz, for three sessions, every four weeks. Outcomes were measured by wrinkle evaluation of blinded investigators, subjects’ self-assessment, objective measurements of elasticity, and skin biopsy. Results Four weeks after the final treatment sessions, the average wrinkle grades of the treated side were reduced by 45.1%. Skin elasticity was significantly increased. The increment of collagen and elastic fiber in papillary dermis was confirmed histologically. No adverse reaction was reported. Pain on the treated side was mild without needing anesthesia. Discussion The authors studied new parameters for LPND for improvement of wrinkles and skin laxity with fewer treatment sessions without serious complications. Histologic findings corresponded to clinical improvement. Conclusion New parameters of LPND can achieve wrinkle improvement with few side effects.

Coordinated eye movements are crucial for precision control of our hands. A commonly believed neural mechanism underlying eye–hand coordination is interaction between the neural networks controlling each effector, exchanging, and matching information, such as movement target location and onset time. Alternatively, eye–hand coordination may result simply from common inputs to independent eye and hand control pathways. Thus far, it remains unknown whether and where either of these two possible mechanisms exists. A candidate location for the former mechanism, interpathway communication, includes the posterior parietal cortex (PPC) where distinct effector-specific areas reside. If the PPC were within the network for eye–hand coordination, perturbing it would affect both eye and hand movements that are concurrently planned. In contrast, if eye–hand coordination arises solely from common inputs, perturbing one effector pathway, e.g., the parietal reach region (PRR), would not affect the other effector. To test these hypotheses, we inactivated part of PRR in the macaque, located in the medial bank of the intraparietal sulcus encompassing the medial intraparietal area and area 5V. When each effector moved alone, PRR inactivation shortened reach but not saccade amplitudes, compatible with the known reach-selective activity of PRR. However, when both effectors moved concurrently, PRR inactivation shortened both reach and saccade amplitudes, and decoupled their reaction times. Therefore, consistent with the interpathway communication hypothesis, we propose that the planning of concurrent eye and hand movements causes the spatial information in PRR to influence the otherwise independent eye control pathways, and that their temporal coupling requires an intact PRR.

Optic ataxia is a high-order deficit in reaching to visual goals that occurs with posterior parietal cortex (PPC) lesions. It is a component of Balint’s syndrome that also includes attentional and gaze disorders. Aspects of optic ataxia are misreaching in the contralesional visual field, difficulty preshaping the hand for grasping, and an inability to correct reaches online. Recent research in nonhuman primates (NHPs) suggests that many aspects of Balint’s syndrome and optic ataxia are a result of damage to specific functional modules for reaching, saccades, grasp, attention, and state estimation. The deficits from large lesions in humans are probably composite effects from damage to combinations of these functional modules. Interactions between these modules, either within posterior parietal cortex or downstream within frontal cortex, may account for more complex behaviors such as hand-eye coordination and reach-to-grasp.

Dear Editor: Acral lentiginous melanoma (ALM) is the most common type of cutaneous melanoma in Asians. Traditionally, ALM is believed to have a poor prognosis because of its aggressive behavior and a short radial growth phase, compared with that of lentigo maligna melanoma1. We describe a case of recurrent ALM in situ around the primary site during 8 years. A 56-year-old female patient presented with a black macule having an irregular border and color variegation on the left heel, which started 8 years ago (Fig. 1A). Dermoscopic examination showed a parallel ridge pattern and irregular pigmentation. She had undergone excisional biopsy (3-mm margin), which revealed only a few scattered atypical melanocytes along the basal layer. She had returned after 2 years (Fig. 1B) and then after 4 years (Fig. 1C) because of newly appearing brown patches around the first location. Serial punch biopsies revealed mild melanocytic hyperplasia without marked cytologic atypia again. The results made a pathologist hesitant to diagnose ALM in situ instead of "atypical melanocytic proliferation." At that time, the patient didn't want additional surgery; we recommended regular follow-up considering the possibility of atypical melanocytic proliferation. Most recently, she presented with further enlarged, multiple pigmented patches (Fig. 1D). She was treated with wide excision (1-cm margin) and split-thickness skin graft under the consideration of malignant melanoma. Bland lentiginous proliferation of atypical melanocytes confined to the epidermis prompted the final diagnosis of ALM in situ (Fig. 1E). Immunohistochemically, atypical melanocytes were stained positively for Melan-A, HMB-45, and anti-S-100 (Fig. 1F). Fig. 1 Acral lentiginous melanoma in situ. Clinical and histopathological feature. (A) Initial presentation 8 years ago. (B) Second presentation 6 years ago. (C) Third presentation 4 years ago. (D) Last presentation. Left, gross picture of the lesion; center, ... ALM was believed to have an aggressive biological behavior. However, in Asians, the specific population was reported inconsistent with the classical concept. After Nogita et al.2 described atypical melanosis of the foot, acral melanocytic lesions have been described with histopathologically subtle melanocytic proliferation, despite clinically malignant melanoma3. These lesions did not show invasive behavior over a decade; though some of them reappeared around the primary site even after the surgical excision. There has been debate about the nature of these lesions; however, they are now considered as the precursor of ALM that fulfills both the clinical and dermoscopic criteria4. The most notable feature of our case was the recurrent melanocytic lesions appearing around the primary site in the absence of invasion during 8 years. Takata et al.5 suggested that acral and mucosal melanomas could originate from field melanocytes detected in normallooking skin extending over the obvious lesion. These field cells harbor mutations of the KIT gene and amplifications of cyclin D1 or cyclin-dependent kinase 4 gene. Although our case initially showed only bland melanocytic proliferation without marked atypia or invasion, local melanoma could reappear from the residual field cells. Therefore, we recommend that the clinician should consider these lesions as ALM in situ and treat with early complete excision. Also, it is better to perform an excisional biopsy for a review of the entire lesion in the suspicious acral melanocytic lesions. Finally, regular follow-up for several years is important for the detection of reappearing melanoma around the primary site, even after the surgical excision.

Objective. Local field potentials (LFPs) that carry information about the subject's motor intention have the potential to serve as a complement or alternative to spike signals for brain–machine interfaces (BMIs). The goal of this study is to assess the utility of LFPs for BMIs by characterizing the largely unknown information coding properties of multichannel LFPs. Approach. Two monkeys were implanted, each with a 16-channel electrode array, in the parietal reach region where both LFPs and spikes are known to encode the subject's intended reach target. We examined how multichannel LFPs recorded during a reach task jointly carry reach target information, and compared the LFP performance to simultaneously recorded multichannel spikes. Main Results. LFPs yielded a higher number of channels that were informative about reach targets than spikes. Single channel LFPs provided more accurate target information than single channel spikes. However, LFPs showed significantly larger signal and noise correlations across channels than spikes. Reach target decoders performed worse when using multichannel LFPs than multichannel spikes. The underperformance of multichannel LFPs was mostly due to their larger noise correlation because noise de-correlated multichannel LFPs produced a decoding accuracy comparable to multichannel spikes. Despite the high noise correlation, decoders using LFPs in addition to spikes outperformed decoders using only spikes. Significance. These results demonstrate that multichannel LFPs could effectively complement spikes for BMI applications by yielding more informative channels. The utility of multichannel LFPs may be further augmented if their high noise correlation can be taken into account by decoders.

Basal ganglia dysfunction causes profound movement disorders, often attributed to imbalance between direct and indirect pathway activity in the sensorimotor basal ganglia. In the classical view, the direct pathway facilitates movements, whereas the indirect pathway inhibits movements. However, the recent finding of co-activation of the two pathways during movement challenges this view. Reconciling the new finding with the body of evidence supporting the classical view, this perspective proposes that the direct pathway computes the expected benefits of motor plans entering the basal ganglia, while the indirect pathway computes their expected costs. Thus, basal ganglia output combining the two pathway signals in a subtraction manner weighs benefits against costs, and endorses the plan with the best prospective outcome via feedback projections to the cortex. The cost-benefit model, while retaining the antagonistic roles of the two pathways for movements, requires co-activation of the two pathways during movement as both benefit and cost are computed for every movement. The cost-benefit model, though simple, accounts for a number of confounding results, and generates new focus for future research with testable predictions.

SummaryLesions in human posterior parietal cortex can cause optic ataxia (OA), in which reaches but not saccades to visual objects are impaired, suggesting separate visuomotor pathways for the two effectors. In monkeys, one potentially crucial area for reach control is the parietal reach region (PRR), in which neurons respond preferentially during reach planning as compared to saccade planning. However, direct causal evidence linking the monkey PRR to the deficits observed in OA is missing. We thus inactivated part of the macaque PRR, in the medial wall of the intraparietal sulcus, and produced the hallmarks of OA, misreaching for peripheral targets but unimpaired saccades. Furthermore, reach errors were larger for the targets preferred by the neural population local to the injection site. These results demonstrate that PRR is causally involved in reach-specific visuomotor pathways, and reach goal disruption in PRR can be a neural basis of OA.

The source of human infection with intestinal flukes was surveyed in estuarine fishes, including the dotted gizzard shad, common sea bass, common blackish goby, redlip mullet, black sea bream, and oyster collected from Muan-gun, Jeollanam-do, Korea during August and September 2007. Collected fishes and oysters were artificially digested in pepsin-HCl solution and examined under a stereomicroscope. In 36 shads (Konosirus punctatus) and 20 basses (Lateolabrax japonicus) examined, Heterophyopsis continua metacercariae were found in 58.3% and 100%, and their average numbers were 12.0 and 6.3 per infected fish, respectively. In 34 gobies (Acanthogobius flavimanus) examined, metacercariae of H. continua were detected in 79.4%, Stictodora lari in 97.1%, and Acanthotrema felis in 92.1%, and their average numbers were 45.8, 189.3, and 235.3 per infected fish, respectively. In 37 redlip mullets (Chelon haematocheilus), Heterophyes nocens metacercariae were found in 56.8%, Pygidiopsis summa in 94.6%, and Stictodora fuscata in 45.9%, and the average metacercarial densities were 17.4, 31.3, and 35.1 per infected fish, respectively. In 30 black sea breams (Acanthopagrus schlegeli) and 45 oysters (Crassostrea gigas) examined, no metacercariae were detected. From the above results, it has been confirmed that the dotted gizzard shad, common sea bass, common blackish goby, and redlip mullet from Muan-gun, Jeollanam-do, Korea are infected with the metacercariae of heterophyid flukes.

Local field potentials (LFPs) have shown diverse relations to the spikes across different brain areas and stimulus features, suggesting that LFP-spike relationships are highly specific to the underlying connectivity of a local network. If so, the LFP-spike relationship may vary even within one brain area under the same task condition if neurons have heterogeneous connectivity with the active input sources during the task. Here, we tested this hypothesis in the parietal reach region (PRR), which includes two distinct classes of motor goal planning neurons with different connectivity to the visual input, i.e., visuomotor neurons receive stronger visual input than motor neurons. We predicted that the visual stimulation would render both the spike response and the LFP-spike relationship different between the two neuronal subpopulations. Thus we examined how visual stimulations affect spikes, LFPs, and LFP-spike relationships in PRR by comparing their planning (delay) period activity between two conditions: with or without a visual stimulus at the reach target. Neurons were classified as visuomotor if the visual stimulation increased their firing rate, or as motor otherwise. We found that the visual stimulation increased LFP power in gamma bands >40 Hz for both classes. Moreover, confirming our prediction, the correlation between the LFP gamma power and the firing rate became higher for the visuomotor than motor neurons in the presence of visual stimulation. We conclude that LFPs vary with the stimulation condition and that the LFP-spike relationship depends on a given neuron's connectivity to the dominant input sources in a particular stimulation condition.

This study demonstrates that the spiking and local field potential (LFP) activity in the parietal reach region (PRR) of the macaque monkey can be jointly used to control the location of the computer cursor when the correct target location must be inferred symbolically, e.g., leftward arrow for the leftward target, etc. The average correct target acquisition rate during this brain machine control task without actual movements was 86% for the six discrete target locations when using spikes and LFPs from 16 electrodes. This performance was significantly better than using spikes or LFPs alone. These results, together with our previous findings, suggest that a single decoder based on both spikes and LFPs in PRR can robustly provide the subjects' motor intent under varying contexts for neural prosthetic applications.

The cognitive neural prosthetic (CNP) is a very versatile method for assisting paralyzed patients and patients with amputations. The CNP records the cognitive state of the subject, rather than signals strictly related to motor execution or sensation. We review a number of high-level cortical signals and their application for CNPs, including intention, motor imagery, decision making, forward estimation, executive function, attention, learning, and multi-effector movement planning. CNPs are defined by the cognitive function they extract, not the cortical region from which the signals are recorded. However, some cortical areas may be better than others for particular applications. Signals can also be extracted in parallel from multiple cortical areas using multiple implants, which in many circumstances can increase the range of applications of CNPs. The CNP approach relies on scientific understanding of the neural processes involved in cognition, and many of the decoding algorithms it uses also have parallels to underlying neural circuit functions.

The precise control of movement execution onset is essential for safe and autonomous cortical motor prosthetics. A recent study from the parietal reach region (PRR) suggested that the local field potentials (LFPs) in this area might be useful for decoding execution time information because of the striking difference in the LFP spectrum between the plan and execution states (Scherberger et al., 2005). More specifically, the LFP power in the 0–10 Hz band sharply rises while the power in the 20–40 Hz band falls as the state transitions from plan to execution. However, a change of visual stimulus immediately preceded reach onset, raising the possibility that the observed spectral change reflected the visual event instead of the reach onset. Here, we tested this possibility and found that the LFP spectrum change was still time locked to the movement onset in the absence of a visual event in self-paced reaches. Furthermore, we successfully trained the macaque subjects to use the LFP spectrum change as a “go” signal in a closed-loop brain-control task in which the animals only modulated the LFP and did not execute a reach. The execution onset was signaled by the change in the LFP spectrum while the target position of the cursor was controlled by the spike firing rates recorded from the same site. The results corroborate that the LFP spectrum change in PRR is a robust indicator for the movement onset and can be used for control of execution onset in a cortical prosthesis.

Any passive rigid inertial object that we hold in our hand, e.g., a tennis racquet, imposes a field of forces on the arm that depends on limb position, velocity, and acceleration. A fundamental characteristic of this field is that the forces due to acceleration and velocity are linearly separable in the intrinsic coordinates of the limb. In order to learn such dynamics with a collection of basis elements, a control system would generalize correctly and therefore perform optimally if the basis elements that were sensitive to limb velocity were not sensitive to acceleration, and vice versa. However, in the mammalian nervous system proprioceptive sensors like muscle spindles encode a nonlinear combination of all components of limb state, with sensitivity to velocity dominating sensitivity to acceleration. Therefore, limb state in the space of proprioception is not linearly separable despite the fact that this separation is a desirable property of control systems that form models of inertial objects. In building internal models of limb dynamics, does the brain use a representation that is optimal for control of inertial objects, or a representation that is closely tied to how peripheral sensors measure limb state? Here we show that in humans, patterns of generalization of reaching movements in acceleration-dependent fields are strongly inconsistent with basis elements that are optimized for control of inertial objects. Unlike a robot controller that models the dynamics of the natural world and represents velocity and acceleration independently, internal models of dynamics that people learn appear to be rooted in the properties of proprioception, nonlinearly responding to the pattern of muscle activation and representing velocity more strongly than acceleration.

Studies of reaching suggest that humans adapt to novel arm dynamics by building internal models that transform planned sensory states of the limb, e.g., desired limb position and its derivatives, into motor commands, e.g., joint torques. Earlier work modeled this computation via a population of basis elements and used system identification techniques to estimate the tuning properties of the bases from the patterns of generalization. Here we hypothesized that the neural representation of planned sensory states in the internal model might resemble the signals from the peripheral sensors. These sensors normally encode the limb's actual sensory state in which movement errors occurred. We developed a set of equations based on properties of muscle spindles that estimated spindle discharge as a function of the limb's state during reaching and drawing of circles. We then implemented a simulation of a two-link arm that learned to move in various force fields using these spindle-like bases. The system produced a pattern of adaptation and generalization that accounted for a wide range of previously reported behavioral results. In particular, the bases showed gain-field interactions between encoding of limb position and velocity, very similar to the gain fields inferred from behavioral studies. The poor sensitivity of the bases to limb acceleration predicted behavioral results that were confirmed by experiment. We suggest that the internal model of limb dynamics is computed by the brain with neurons that encode the state of the limb in a manner similar to that expected of muscle spindle afferents.

Combination of plasma and wet etching was done in developing a new silicon depth-probe type microelectrode array. The plasma etch uses low temperature oxide (LTO) mask instead of thick photoresist mask, and enables the thickness of the probe shank to be defined more freely and in wider range. The entire probe shaping process was performed only at low temperature, and is CMOS compatible. A probe with 30 /spl mu/m shank thickness was successfully used in recording from rat's somatosensory cortex. A four-channel simultaneous neural recording shows signal-to-noise ratio performance comparable with that obtained using conventional microprobes.

The incidence of early gastric cancer (EGC) has increased to >50% in Korea owing to a higher detection rate caused by rapid advances in diagnostic instrumentation. EGC with distant metastasis has been rarely reported. Here, we report the case of a 76-year-old woman in whom general EGC was initially diagnosed by endoscopy and endoscopic ultrasonography. She subsequently underwent endoscopic submucosal dissection (ESD). Histological examination of the ESD specimen revealed that neoplastic cells were located predominantly in the submucosal layer and submucosal lymphatic channels. Metastatic cancer cells were also found in the pleural effusion. After conducting all analyses, including immunohistochemical staining, we concluded that the patient had primary EGC with pleural metastasis.