Automated Planning with Multivariate Shape Descriptors for Fibular Transfer in Mandibular Reconstruction

Objective: This paper introduces methods to automate preoperative planning of fibular segmentation and placement for mandibular reconstruction with fibular flaps. Methods: Preoperative virtual planning for this type of surgery has been performed by manual adjustment of many parameters, or based upon a single feature of the reconstruction. We propose a novel planning procedure formulated as a non-convex minimization problem of an objective function using the multilateral shape descriptors. Results: A retrospective study was designed and 120 reconstruction plans were reproduced using computed tomography images with oral surgeons. The proposed automated planning model was quantitatively compared with both the existing model and the surgeons’ plans. Conclusion: The results show that the developed framework attains stable automated planning that agrees with the surgeons’ decisions. Significance: This method addresses trade-off problems between symmetric reconstruction and restoration of the native contour of the mandible

Neural circuit mechanisms for transforming learned olfactory valences into wind-oriented movement

How memories are used by the brain to guide future action is poorly understood. In olfactory associative learning in Drosophila, multiple compartments of the mushroom body act in parallel to assign a valence to a stimulus. Here, we show that appetitive memories stored in different compartments induce different levels of upwind locomotion. Using a photoactivation screen of a new collection of split-GAL4 drivers and EM connectomics, we identified a cluster of neurons postsynaptic to the mushroom body output neurons (MBONs) that can trigger robust upwind steering. These UpWind Neurons (UpWiNs) integrate inhibitory and excitatory synaptic inputs from MBONs of appetitive and aversive memory compartments, respectively. After formation of appetitive memory, UpWiNs acquire enhanced response to reward-predicting odors as the response of the inhibitory presynaptic MBON undergoes depression. Blocking UpWiNs impaired appetitive memory and reduced upwind locomotion during retrieval. Photoactivation of UpWiNs also increased the chance of returning to a location where activation was terminated, suggesting an additional role in olfactory navigation. Thus, our results provide insight into how learned abstract valences are gradually transformed into concrete memory-driven actions through divergent and convergent networks, a neuronal architecture that is commonly found in the vertebrate and invertebrate brains

Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila

Dopaminergic neurons with distinct projection patterns and physiological properties compose memory subsystems in a brain. However, it is poorly understood whether or how they interact during complex learning. Here, we identify a feedforward circuit formed between dopamine subsystems and show that it is essential for second-order conditioning, an ethologically important form of higher-order associative learning. The Drosophila mushroom body comprises a series of dopaminergic compartments, each of which exhibits distinct memory dynamics. We find that a slow and stable memory compartment can serve as an effective 'teacher' by instructing other faster and transient memory compartments via a single key interneuron, which we identify by connectome analysis and neurotransmitter prediction. This excitatory interneuron acquires enhanced response to reward-predicting odor after first-order conditioning and, upon activation, evokes dopamine release in the 'student' compartments. These hierarchical connections between dopamine subsystems explain distinct properties of first- and second-order memory long known by behavioral psychologists

Relationship between White Matter Lesions and Progression of Cognitive Decline in Alzheimer's Disease

Background: This study examined the relationship between baseline white matter lesions (WMLs) and the progression of cognitive decline in patients with late-onset Alzheimer's disease (AD). Methods: Fifty-six patients with AD were included in the study (23 men, 33 women; mean age, 77.8 years). All subjects were treated with acetylcholinesterase inhibitors and followed up for approximately 1 year. The Mini-Mental State Examination (MMSE) score was assessed at least twice to evaluate the progressive cognitive impairment. All subjects underwent brain MRI at baseline and were divided into WMLs(-), mild WMLs(+), and moderate WMLs(+) groups based on WML severity. Changes in MMSE scores between baseline and follow-up were analyzed using the Wilcoxon signed-rank test. Results: MMSE scores at baseline did not differ significantly among the three groups (p = 0.1658), whereas MMSE scores at the follow-up evaluation were significantly lower in the moderate WMLs(+) group than in the WMLs(-) group (p = 0.0257). The mean MMSE scores remained above baseline values during the approximately 1-year follow-up in the WMLs(-) group, whereas they were decreased in the mild and moderate WMLs(+) groups. Moreover, the frequency of improvement in patients from the WMLs(-) group tended to be higher than that in patients from the WMLs(+) groups. Conclusion: Baseline WMLs may be associated with the heterogeneous progression of cognitive decline in patients with AD

Heterosynaptic Plasticity Underlies Aversive Olfactory Learning in Drosophila

Summary Although associative learning has been localized to specific brain areas in many animals, identifying the underlying synaptic processes in vivo has been difficult. Here, we provide the first demonstration of long-term synaptic plasticity at the output site of the Drosophila mushroom body. Pairing an odor with activation of specific dopamine neurons induces both learning and odor-specific synaptic depression. The plasticity induction strictly depends on the temporal order of the two stimuli, replicating the logical requirement for associative learning. Furthermore, we reveal that dopamine action is confined to and distinct across different anatomical compartments of the mushroom body lobes. Finally, we find that overlap between sparse representations of different odors defines both stimulus specificity of the plasticity and generalizability of associative memories across odors. Thus, the plasticity we find here not only manifests important features of associative learning but also provides general insights into how a sparse sensory code is read out

インスリン様成長因子-1(IGF-1)は実験的クロロキン誘発縁取り空胞ミオパチーの筋線維における空胞の過剰形成を抑制する（英語）

Objective: We investigated the effect of insulin-like growth factor-1 (IGF-1) on the histological (e.g., rimmed vacuoles and muscle fiber atrophy) and molecular properties of the denervated muscles of chloroquine-treated rats. Methods: The left hind-legs of adult male Wistar rats were denervated by ligation of the sciatic nerve.The rats with and without chloroquine treatment were given saline or IGF-1 intraperitoneally at a daily dose of either 2 or 8 mg/kg for 8 days. Results: In the denervated soleus muscles from chloroquine-treated rats, the number of rimmed vacuoles was significantly reduced in response to either low- or high-dose IGF-1. IGF-1 administration did not affect the muscle fiber atrophy. Although proteasome and ubiquitin immunostaining, and the mRNA levels of muscle-specific ubiquitin ligases and autophagy-related genes were significantly increased in denervated muscles from both rats, those levels did not change in response to either low or high-doses of IGF-1. Conclusion: IGF-1 suppressed rimmemd vacuolar formation in muscle fibers in an animal model of chloroquine-induced myopathy.　　目的：脱神経処理したクロロキン投与ラット筋の病理所見および筋崩壊に関与する分子に対するIGF-1の影響を検討した。 　方法：予め左側の坐骨神経を結紮（脱神経）したラットにクロロキン、または生理的食塩水（生食水）を各々投与した（各20匹）。そのうち両ラットの各10匹に連日IGF（2 mg/kg、8 mg/kg、各5匹）を投与し、残りの各10匹にIGF-1の代わりに同量の生食水を8日間、腹腔内に注射した。 　結果：クロロキン投与ラットの脱神経したヒラメ筋でのみ多数の縁取り空胞（rimmed vacuole）を認め、少量および大量のIGF-1投与によりrimmed vacuoleを有する筋線維数は有意に減少した。IGF-1は筋線維の萎縮には効果はなかった。プロテアソームおよびユビキチンの免疫染色、筋特異的ユビキチンリガーゼおよびオートファジー関連遺伝子のmRNAレベルはクロロキン投与および非投与（生食水投与）の脱神経筋で有意に増加したが、少量および大量のIGF-1投与ではいずれも有意な変化はなかった。 　結論：IGF-1は、クロロキン誘発ミオパチーの動物モデルの筋萎縮は抑制しないが、筋線維内のrimmed vacuoleの形成を抑制する

Statistical Analysis of Interactive Surgical Planning Using Shape Descriptors in Mandibular Reconstruction with Fibular Segments.

This study was performed to quantitatively analyze medical knowledge of, and experience with, decision-making in preoperative virtual planning of mandibular reconstruction. Three shape descriptors were designed to evaluate local differences between reconstructed mandibles and patients' original mandibles. We targeted an asymmetrical, wide range of cutting areas including the mandibular sidepiece, and defined a unique three-dimensional coordinate system for each mandibular image. The generalized algorithms for computing the shape descriptors were integrated into interactive planning software, where the user can refine the preoperative plan using the spatial map of the local shape distance as a visual guide. A retrospective study was conducted with two oral surgeons and two dental technicians using the developed software. The obtained 120 reconstruction plans show that the participants preferred a moderate shape distance rather than optimization to the smallest. We observed that a visually plausible shape could be obtained when considering specific anatomical features (e.g., mental foramen. mandibular midline). The proposed descriptors can be used to multilaterally evaluate reconstruction plans and systematically learn surgical procedures

Automated Planning With Multivariate Shape Descriptors for Fibular Transfer in Mandibular Reconstruction

Objective: This paper introduces methods to automate preoperative planning of fibular segmentation and placement for mandibular reconstruction with fibular flaps. Methods: Preoperative virtual planning for this type of surgery has been performed by manual adjustment of many parameters, or based upon a single feature of the reconstruction. We propose a novel planning procedure formulated as a non-convex minimization problem of an objective function using the multilateral shape descriptors. Results: A retrospective study was designed and 120 reconstruction plans were reproduced using computed tomography images with oral surgeons. The proposed automated planning model was quantitatively compared with both the existing model and the surgeons’ plans. Conclusion: The results show that the developed framework attains stable automated planning that agrees with the surgeons’ decisions. Significance: This method addresses trade-off problems between symmetric reconstruction and restoration of the native contour of the mandible