When a stimulus is presented, its encoding is known to progress from low-to high-level features. How these features are decoded to produce perception is less clear, and most models assume that decoding follows the same low-to high-level hierarchy of encoding. There are also theories arguing for global precedence, reversed hierarchy, or bidirectional processing, but they are descriptive without quantitative comparison with human perception. Moreover, observers often inspect different parts of a scene sequentially to form overall perception, suggesting that perceptual decoding requires working memory, yet few models consider how working-memory properties may affect decoding hierarchy. We probed decoding hierarchy by comparing absolute judgments of single orientations and relative/ordinal judgments between two sequentially presented orientations. We found that lower-level, absolute judgments failed to account for higher-level, relative/ordinal judgments. However, when ordinal judgment was used to retrospectively decode memory representations of absolute orientations, striking aspects of absolute judgments, including the correlation and forward/backward aftereffects between two reported orientations in a trial, were explained. We propose that the brain prioritizes decoding of higher-level features because they are more behaviorally relevant, and more invariant and categorical, and thus easier to specify and maintain in noisy working memory, and that more reliable higher-level decoding constrains less reliable lower-level decoding.Bayesian prior | interreport correlation | bidirectional tilt aftereffect | efficient coding | adaptation theory V isual stimuli evoke neuronal responses (a process termed encoding), which lead to our perceptual estimation of the stimuli (decoding). Experimental studies have firmly established that encoding is hierarchical, progressing from lower-level representations of simpler and less invariant features to higher-level representations of more complex and invariant features along visual pathways (1). Researchers have also studied decoding by using models to relate neuronal responses to perceptual estimation. Most models posit, explicitly or implicitly, that decoding follows the same low-to high-level hierarchy, often in the form of what we call the absolute-to-relative assumption (2-6). For example, these models may decode V1 responses to a line into a perceived orientation of, say 51.2°(or a distribution around it). Psychophysically, this is termed an absolute judgment. To determine the relationship between two lines, the models first decode each orientation separately and the two resulting absolute orientations are then compared. For instance, the two absolute orientations may be subtracted to obtain the angle between the lines (relative orientation), or the sign of the difference may be used to determine whether the second line is clockwise or counterclockwise from the first (ordinal orientation discrimination). Absolute orientation of a single line is a simpler, less invariant, lower-...

BackgroundPersistently active PKMζ has been implicated in maintaining spinal nociceptive sensitization that underlies pain hypersensitivity. However, evidence for PKMζ in the maintenance of pain hypersensitivity comes exclusively from short-term studies in males using pharmacological agents of questionable selectivity. The present study examines the contribution of PKMζ to long-lasting allodynia associated with neuropathic, inflammatory, or referred visceral and muscle pain in males and females using pharmacological inhibition or genetic ablation.ResultsPharmacological inhibition or genetic ablation of PKMζ reduced mild formalin pain and slowly developing contralateral allodynia in nerve-injured rats, but not moderate formalin pain or ipsilateral allodynia in models of neuropathic and inflammatory pain. Pharmacological inhibition or genetic ablation of PKMζ also effectively reduced referred visceral and muscle pain in male, but not in female mice and rats.ConclusionWe show pharmacological inhibition and genetic ablation of PKMζ consistently attenuate long-lasting pain hypersensitivity. However, differential effects in models of referred versus inflammatory and neuropathic pain, and in males versus females, highlight the roles of afferent input-dependent masking and sex differences in the maintenance of pain hypersensitivity.

Purpose: To test the hypothesis that the US Food and Drug Administration approval of vismodegib in early 2012 has reduced the prevalence of orbital exenteration for locally advanced periocular basal cell carcinoma (BCC). Methods: Following institutional review board approval, the authors reviewed clinical and pathological data of patients with locally advanced periocular BCC (T4 per the eyelid carcinoma classification in the 8th edition of the AJCC Cancer Staging Manual) treated by the senior author during 2006–2018. Patients were grouped into those who were treated before February 2012 (“before vismodegib approval”) and those who presented later (“after vismodegib approval”). Results: Forty-two patients with locally advanced periocular BCC were treated during the study period, of whom 31 were men. The median age at presentation was 66 years (range, 43–90). Twenty-two patients had T4a and 20 had T4b tumors. Thirteen patients were treated before and 29 were treated after vismodegib approval. The 2 groups did not differ in age distribution (p = 0.164), sex distribution (p = 0.270), prevalence of recurrent tumor at presentation (p = 0.317), or duration of treatment with vismodegib (p = 0.605). Orbital exenteration was significantly more prevalent in patients treated before vismodegib approval than after (46% vs. 10%, p = 0.016), and vismodegib treatment was significantly more prevalent in patients treated after vismodegib approval than before (when vismodegib was given in clinical trials; 69% vs. 23%, p = 0.008). There was a trend toward more patients retaining their eyes at last follow-up in patients treated after vismodegib approval (83% vs. 54%, p = 0.066). Conclusions: The prevalence of orbital exenteration as a necessary surgical procedure in patients with a locally advanced periocular BCC has fallen since the Food and Drug Administration approval of vismodegib. Although vismodegib is not specifically approved for organ-sparing, it has changed the authors’ practice and enabled eye preservation in patients with locally advanced periocular BCC, who would otherwise require an orbital exenteration.

Application of the 8th-edition American Joint Committee on Cancer criteria for eyelid carcinoma changed the T category in 75% of patients. In general, the new 8th-edition American Joint Committee on Cancer tumor, node, metastasis (TNM) designations allow for a more objective and consistent designation of the T category.