The representation of priors and decisions in the human parietal cortex.

Animals actively sample their environment through orienting actions such as saccadic eye movements. Saccadic targets are selected based both on sensory evidence immediately preceding the saccade, and a "salience map" or prior built-up over multiple saccades. In the primate cortex, the selection of each individual saccade depends on competition between target-selective cells that ramp up their firing rate to saccade release. However, it is less clear how a cross-saccade prior might be implemented, either in neural firing or through an activity-silent mechanism such as modification of synaptic weights on sensory inputs. Here, we present evidence from magnetoencephalography for 2 distinct processes underlying the selection of the current saccade, and the representation of the prior, in human parietal cortex. While the classic ramping decision process for each saccade was reflected in neural firing rates (measured in the event-related field), a prior built-up over multiple saccades was implemented via modulation of the gain on sensory inputs from the preferred target, as evidenced by rapid frequency tagging. A cascade of computations over time (initial representation of the prior, followed by evidence accumulation and then an integration of prior and evidence) provides a mechanism by which a salience map may be built up across saccades in parietal cortex. It also provides insight into the apparent contradiction that inactivation of parietal cortex has been shown not to affect performance on single-trials, despite the presence of clear evidence accumulation signals in this region.

Dissecting Bayes: Using influence measures to test normative use of probability density information derived from a sample.

Bayesian decision theory (BDT) is frequently used to model normative performance in perceptual, motor, and cognitive decision tasks where the possible outcomes of actions are associated with rewards or penalties. The resulting normative models specify how decision makers should encode and combine information about uncertainty and value-step by step-in order to maximize their expected reward. When prior, likelihood, and posterior are probabilities, the Bayesian computation requires only simple arithmetic operations: addition, etc. We focus on visual cognitive tasks where Bayesian computations are carried out not on probabilities but on (1) probability density functions and (2) these probability density functions are derived from samples. We break the BDT model into a series of computations and test human ability to carry out each of these computations in isolation. We test three necessary properties of normative use of pdf information derived from a sample-accuracy, additivity and influence. Influence measures allow us to assess how much weight each point in the sample is assigned in making decisions and allow us to compare normative use (weighting) of samples to actual, point by point. We find that human decision makers violate accuracy and additivity systematically but that the cost of failure in accuracy or additivity would be minor in common decision tasks. However, a comparison of measured influence for each sample point with normative influence measures demonstrates that the individual's use of sample information is markedly different from the predictions of BDT. We will show that the normative BDT model takes into account the geometric symmetries of the pdf while the human decision maker does not. An alternative model basing decisions on a single extreme sample point provided a better account for participants' data than the normative BDT model.

Temporal scaling of human scalp-recorded potentials.

Much of human behavior is governed by common processes that unfold over varying timescales. Standard event-related potential analysis assumes fixed-duration responses relative to experimental events. However, recent single-unit recordings in animals have revealed neural activity scales to span different durations during behaviors demanding flexible timing. Here, we employed a general linear modeling approach using a combination of fixed-duration and variable-duration regressors to unmix fixed-time and scaled-time components in human magneto-/electroencephalography (M/EEG) data. We use this to reveal consistent temporal scaling of human scalp-recorded potentials across four independent electroencephalogram (EEG) datasets, including interval perception, production, prediction, and value-based decision making. Between-trial variation in the temporally scaled response predicts between-trial variation in subject reaction times, demonstrating the relevance of this temporally scaled signal for temporal variation in behavior. Our results provide a general approach for studying flexibly timed behavior in the human brain.

Reward positivity affects temporal interval production in a continuous timing task.

The neural circuits of reward processing and interval timing (including the perception and production of temporal intervals) are functionally intertwined, suggesting that it might be possible for momentary reward processing to influence subsequent timing behavior. Previous animal and human studies have mainly focused on the effect of reward on interval perception, whereas its impact on interval production is less clear. In this study, we examined whether feedback, as an example of performance-contingent reward, biases interval production. We recorded EEG from 20 participants while they engaged in a continuous drumming task with different realistic tempos (1728 trials per participant). Participants received color-coded feedback after each beat about whether they were correct (on time) or incorrect (early or late). Regression-based EEG analysis was used to unmix the rapid occurrence of a feedback response called the reward positivity (RewP), which is traditionally observed in more slow-paced tasks. Using linear mixed modeling, we found that RewP amplitude predicted timing behavior for the upcoming beat. This performance-biasing effect of the RewP was interpreted as reflecting the impact of fluctuations in reward-related anterior cingulate cortex activity on timing, and the necessity of continuous paradigms to make such observations was highlighted.

Two sources of uncertainty independently modulate temporal expectancy.

The environment is shaped by two sources of temporal uncertainty: the discrete probability of whether an event will occur and-if it does-the continuous probability of when it will happen. These two types of uncertainty are fundamental to every form of anticipatory behavior including learning, decision-making, and motor planning. It remains unknown how the brain models the two uncertainty parameters and how they interact in anticipation. It is commonly assumed that the discrete probability of whether an event will occur has a fixed effect on event expectancy over time. In contrast, we first demonstrate that this pattern is highly dynamic and monotonically increases across time. Intriguingly, this behavior is independent of the continuous probability of when an event will occur. The effect of this continuous probability on anticipation is commonly proposed to be driven by the hazard rate (HR) of events. We next show that the HR fails to account for behavior and propose a model of event expectancy based on the probability density function of events. Our results hold for both vision and audition, suggesting independence of the representation of the two uncertainties from sensory input modality. These findings enrich the understanding of fundamental anticipatory processes and have provocative implications for many aspects of behavior and its neural underpinnings.

Lightness constancy in reality, in virtual reality, and on flat-panel displays.

Virtual reality (VR) displays are being used in an increasingly wide range of applications. However, previous work shows that viewers often perceive scene properties very differently in real and virtual environments and so realistic perception of virtual stimuli should always be a carefully tested conclusion, not an assumption. One important property for realistic scene perception is surface color. To evaluate how well virtual platforms support realistic perception of achromatic surface color, we assessed lightness constancy in a physical apparatus with real lights and surfaces, in a commercial VR headset, and on a traditional flat-panel display. We found that lightness constancy was good in all three environments, though significantly better in the real environment than on the flat-panel display. We also found that variability across observers was significantly greater in VR and on the flat-panel display than in the physical environment. We conclude that these discrepancies should be taken into account in applications where realistic perception is critical but also that in many cases VR can be used as a flexible alternative to flat-panel displays and a reasonable proxy for real environments.

Visual Motion and Decision-Making in Dyslexia: Reduced Accumulation of Sensory Evidence and Related Neural Dynamics.

Children with and without dyslexia differ in their behavioral responses to visual information, particularly when required to pool dynamic signals over space and time. Importantly, multiple processes contribute to behavioral responses. Here we investigated which processing stages are affected in children with dyslexia when performing visual motion processing tasks, by combining two methods that are sensitive to the dynamic processes leading to responses. We used a diffusion model which decomposes response time and accuracy into distinct cognitive constructs, and high-density EEG. Fifty children with dyslexia (24 male) and 50 typically developing children (28 male) 6-14 years of age judged the direction of motion as quickly and accurately as possible in two global motion tasks (motion coherence and direction integration), which varied in their requirements for noise exclusion. Following our preregistered analyses, we fitted hierarchical Bayesian diffusion models to the data, blinded to group membership. Unblinding revealed reduced evidence accumulation in children with dyslexia compared with typical children for both tasks. Additionally, we identified a response-locked EEG component which was maximal over centro-parietal electrodes which indicated a neural correlate of reduced drift rate in dyslexia in the motion coherence task, thereby linking brain and behavior. We suggest that children with dyslexia tend to be slower to extract sensory evidence from global motion displays, regardless of whether noise exclusion is required, thus furthering our understanding of atypical perceptual decision-making processes in dyslexia.SIGNIFICANCE STATEMENT Reduced sensitivity to visual information has been reported in dyslexia, with a lively debate about whether these differences causally contribute to reading difficulties. In this large preregistered study with a blind modeling approach, we combine state-of-the art methods in both computational modeling and EEG analysis to pinpoint the stages of processing that are atypical in children with dyslexia in two visual motion tasks that vary in their requirement for noise exclusion. We find reduced evidence accumulation in children with dyslexia across both tasks, and identify a neural marker, allowing us to link brain and behavior. We show that children with dyslexia exhibit general difficulties with extracting sensory evidence from global motion displays, not just in tasks that require noise exclusion.

The neural correlates of continuous feedback processing.

Feedback processing is commonly studied by analyzing the brain's response to discrete rather than continuous events. Such studies have led to the hypothesis that rapid phasic midbrain dopaminergic activity tracks reward prediction errors (RPEs), the effects of which are measurable at the scalp via electroencephalography (EEG). Although studies using continuous feedback are sparse, recent animal work suggests that moment-to-moment changes in reward are tracked by slowly ramping midbrain dopaminergic activity. Some have argued that these ramping signals index state values rather than RPEs. Our goal here was to develop an EEG measure of continuous feedback processing in humans, then test whether its behavior could be accounted for by the RPE hypothesis. Participants completed a stimulus-response learning task in which a continuous reward cue gradually increased or decreased over time. A regression-based unmixing approach revealed EEG activity with a topography and time course consistent with the stimulus-preceding negativity (SPN), a scalp potential previously linked to reward anticipation and tonic dopamine release. Importantly, this reward-related activity depended on outcome expectancy: as predicted by the RPE hypothesis, activity for expected reward cues was reduced compared to unexpected reward cues. These results demonstrate the possibility of using human scalp-recorded potentials to track continuous feedback processing, and test candidate hypotheses of this activity.

The bounded rationality of probability distortion.

In decision making under risk (DMR) participants' choices are based on probability values systematically different from those that are objectively correct. Similar systematic distortions are found in tasks involving relative frequency judgments (JRF). These distortions limit performance in a wide variety of tasks and an evident question is, Why do we systematically fail in our use of probability and relative frequency information? We propose a bounded log-odds model (BLO) of probability and relative frequency distortion based on three assumptions: 1) log-odds: probability and relative frequency are mapped to an internal log-odds scale, 2) boundedness: the range of representations of probability and relative frequency are bounded and the bounds change dynamically with task, and 3) variance compensation: the mapping compensates in part for uncertainty in probability and relative frequency values. We compared human performance in both DMR and JRF tasks to the predictions of the BLO model as well as 11 alternative models, each missing one or more of the underlying BLO assumptions (factorial model comparison). The BLO model and its assumptions proved to be superior to any of the alternatives. In a separate analysis, we found that BLO accounts for individual participants' data better than any previous model in the DMR literature. We also found that, subject to the boundedness limitation, participants' choice of distortion approximately maximized the mutual information between objective task-relevant values and internal values, a form of bounded rationality.

Detecting visual texture patterns in binary sequences through pattern features.

We measured human ability to detect texture patterns in a signal detection task. Observers viewed sequences of 20 blue or yellow tokens placed horizontally in a row. They attempted to discriminate sequences generated by a random generator ("a fair coin") from sequences produced by a disrupted Markov sequence (DMS) generator. The DMSs were generated in two stages: first a sequence was generated using a Markov chain with probability, pr = 0.9, that a token would be the same color as the token to its left. The Markov sequence was then disrupted by flipping each token from blue to yellow or vice versa with probability, pd-the probability of disruption. Disruption played the role of noise in signal detection terms. We can frame what observers are asked to do as detecting Markov texture patterns disrupted by noise. The experiment included three conditions differing in pd (0.1, 0.2, 0.3). Ninety-two observers participated, each in only one condition. Overall, human observers' sensitivities to texture patterns (d' values) were markedly less than those of an optimal Bayesian observer. We considered the possibility that observers based their judgments not on the entire texture sequence but on specific features of the sequences such as the length of the longest repeating subsequence. We compared human performance with that of multiple optimal Bayesian classifiers based on such features. We identify the single- and multiple-feature models that best match the performance of observers across conditions and develop a pattern feature pool model for the signal detection task considered.

Are Surgical Approaches Correlated With BREAST-Q Score Improvements After Reduction Mammoplasty? A Systematic Review.

BACKGROUND: Despite the commonly recognized benefits and drawbacks of each surgical technique for reduction mammoplasty, data on the influence of each surgical approach on patient quality of life and satisfaction remains limited. Our study aims to evaluate the association between surgical factors and BREAST-Q scores for reduction mammoplasty patients. METHODS: A literature review through August 6, 2021, was conducted using the PubMed database to select publications that used the BREAST-Q questionnaire to evaluate outcomes after reduction mammoplasty. Studies examining breast reconstruction, breast augmentation, oncoplastic reduction, or breast cancer patients were excluded. The BREAST-Q data were stratified by incision pattern and pedicle type. RESULTS: We identified 14 articles that met selection criteria. Among 1816 patients, the mean age ranged from 15.8 to 55 years, mean body mass index ranged from 22.5 to 32.4 kg/m 2 , and bilateral mean resected weight ranged from 323 to 1845.96 g. Overall complication rate was 19.9%. On average, satisfaction with breasts improved by 52.1 ± 0.9 points ( P < 0.0001), psychosocial well-being improved by 43.0 ± 1.0 points ( P < 0.0001), sexual well-being improved by 38.2 ± 1.2 points ( P < 0.0001), and physical well-being improved by 27.9 ± 0.8 points ( P < 0.0001). No significant correlations were observed when mean difference was modeled against complication rates or prevalence of superomedial pedicle use, inferior pedicle use, Wise pattern incision, or vertical pattern incision. Complication rates were not correlated with preoperative, postoperative, or mean change in BREAST-Q scores. A negative correlation was noted between the prevalence of superomedial pedicle use and postoperative physical well-being (Spearman rank correlation coefficient [SRCC], -0.66742; P < 0.05). The prevalence of Wise pattern incision was negatively correlated with postoperative sexual well-being (SRCC, -0.66233; P < 0.05) and physical well-being (SRCC, -0.69521; P < 0.05). CONCLUSIONS: Although either preoperative or postoperative BREAST-Q scores may be individually influenced by pedicle or incision type, there was no statistically significant effect of surgical approach or complication rates on the average change of these scores, and overall satisfaction and well-being scores improved. This review suggests that any of the main surgical approaches to reduction mammoplasty provide equally substantial improvements in patient-reported satisfaction and quality of life, but more robust comparative studies would strengthen this area of research.

A Systematic Review of the Impact of Patient Factors on BREAST-Q Outcomes After Reduction Mammoplasty.

BACKGROUND: As reduction mammoplasty rises in popularity, it will become increasingly important to understand the patient-reported outcome measurements associated with a successful operation. There has been a growing body of literature on BREAST-Q outcomes for patients undergoing reduction mammoplasty, but meta-analyses of patient factors and BREAST-Q Reduction Module scores are lacking. This study sought to ascertain which patient factors were associated with improvements in BREAST-Q scores compared with preoperative levels. METHODS: A literature review through August 6, 2021, was conducted using the PubMed database to select publications using the BREAST-Q questionnaire to evaluate outcomes after reduction mammoplasty. Studies examining breast reconstruction, breast augmentation, oncoplastic reduction, or breast cancer patients were excluded. BREAST-Q data were stratified by comorbidities, age, body mass index (BMI), complication rate, and resection weight. RESULTS: Among 14 articles and 1816 patients, the mean age ranged from 15.8 to 55 years, mean BMI ranged from 22.5 to 32.4 kg/m2, and bilateral mean resected weight ranged from 323 to 1845.96 g. Overall complication rate was 19.9%. On average, satisfaction with breasts improved by 52.1 ± 0.9 points (P < 0.0001), psychosocial well-being improved by 43.0 ± 1.0 points (P < 0.0001), sexual well-being improved by 38.2 ± 1.2 points (P < 0.0001), and physical well-being improved by 27.9 ± 0.8 points (P < 0.0001). The mean age was positively correlated with preoperative sexual well-being (Spearman rank correlation coefficient [SRCC]: 0.61, P < 0.05). Body mass index was negatively correlated with preoperative physical well-being (SRCC: -0.78, P < 0.01) and positively correlated with postoperative satisfaction with breasts (SRCC: 0.53, P < 0.05). The mean bilateral resected weight was significantly positively correlated with postoperative satisfaction with breasts (SRCC: 0.61, P < 0.05). No significant correlations were observed between complication rate and preoperative, postoperative, or mean change in BREAST-Q scores. CONCLUSIONS: Reduction mammoplasty improves patient satisfaction and quality of life as reflected by the BREAST-Q. Although preoperative or postoperative BREAST-Q scores may be individually influenced by age and BMI, these variables demonstrated no statistically significant effect on the average change between these scores. This literature review suggests that reduction mammoplasty delivers high satisfaction across a diverse range of patient populations, and additional prospective cohort or comparative studies gathering robust data on other patient factors would benefit this area of research.

Task-level value affects trial-level reward processing.

Despite disagreement about how anterior cingulate cortex (ACC) supports decision making, a recent hypothesis suggests that activity in this region is best understood in the context of a task or series of tasks. One important task-level variable is average reward because it is both a known driver of effortful behaviour and an important determiner of the tasks in which we choose to engage. Here we asked how average task value affects reward-related ACC activity. To answer this question, we measured a reward-related signal said to be generated in ACC called the reward positivity (RewP) while participants gambled in three tasks of differing average value. The RewP was reduced in the high-value task, an effect that was not explainable by either reward magnitude or outcome expectancy. This result suggests that ACC does not evaluate outcomes and cues in isolation, but in the context of the value of the current task.

A distributed, hierarchical and recurrent framework for reward-based choice.

Many accounts of reward-based choice argue for distinct component processes that are serial and functionally localized. In this Opinion article, we argue for an alternative viewpoint, in which choices emerge from repeated computations that are distributed across many brain regions. We emphasize how several features of neuroanatomy may support the implementation of choice, including mutual inhibition in recurrent neural networks and the hierarchical organization of timescales for information processing across the cortex. This account also suggests that certain correlates of value are emergent rather than represented explicitly in the brain.

Visual fixation patterns during economic choice reflect covert valuation processes that emerge with learning.

Visual fixations play a vital role in decision making. Recent studies have demonstrated that the longer subjects fixate an option, the more likely they are to choose it. However, the role of evaluating stimuli covertly (i.e., without fixating them), and how covert evaluations determine where to subsequently fixate, remains relatively unexplored. Here, we trained monkeys to perform a decision-making task where they made binary choices between reward-predictive stimuli which were well-learned ("overtrained"), recently learned ("novel"), or a combination of both ("mixed"). Subjects were free to saccade around the screen and make a choice (via joystick response) at any time. Subjects rarely fixated both options, yet choice behavior was better explained by assuming the values of both stimuli governed choices. The first fixation latency was fast (∼150 ms) but, surprisingly, its direction was value-driven. This suggests covert evaluation of stimulus values prior to first saccade. This was particularly evident for overtrained stimuli. For novel stimuli, first fixations became increasingly value-driven throughout a behavioral session. However, this improvement lagged behind learning of accurate economic choices, suggesting separate processes governed their learning. Finally, mixed trials revealed a strong bias toward fixating the novel stimulus first but no bias toward choosing it. Our results suggest that the primate brain contains fast covert evaluation mechanisms for guiding fixations toward highly valuable and novel information. By employing such covert mechanisms, fixation behavior becomes dissociable from the value comparison processes that drive final choice. This implies that primates use separable decision systems for value-guided fixations and value-guided choice.

Frontal circuit specialisations for decision making.

There is widespread consensus that distributed circuits across prefrontal and anterior cingulate cortex (PFC/ACC) are critical for reward-based decision making. The circuit specialisations of these areas in primates were likely shaped by their foraging niche, in which decision making is typically sequential, attention-guided and temporally extended. Here, I argue that in humans and other primates, PFC/ACC circuits are functionally specialised in two ways. First, microcircuits found across PFC/ACC are highly recurrent in nature and have synaptic properties that support persistent activity across temporally extended cognitive tasks. These properties provide the basis of a computational account of time-varying neural activity within PFC/ACC as a decision is being made. Second, the macrocircuit connections (to other brain areas) differ between distinct PFC/ACC cytoarchitectonic subregions. This variation in macrocircuit connections explains why PFC/ACC subregions make unique contributions to reward-based decision tasks and how these contributions are shaped by attention. They predict dissociable neural representations to emerge in orbitofrontal, anterior cingulate and dorsolateral prefrontal cortex during sequential attention-guided choice, as recently confirmed in neurophysiological recordings.

Regimented Phosphodiesterase Type 5 Inhibitor Use Reduces Emergency Department Visits for Recurrent Ischemic Priapism.

PURPOSE: We evaluated the real-world effectiveness of regimented phosphodiesterase type 5 inhibitor dosing on recurrent ischemic priapism outcomes using emergency department visits as a proxy for therapeutic control of the disorder. MATERIALS AND METHODS: We performed a retrospective chart review of patients with recurrent ischemic priapism who were started on regimented phosphodiesterase type 5 inhibitor therapy from May 2006 to January 2020. We compared the number of emergency department visits per month during a 6-month period before treatment, during treatment and after treatment discontinuation. We extracted and categorized priapism outcomes such as priapism frequency and duration. RESULTS: Of 216 patients identified with all cause priapism 114 were diagnosed with recurrent ischemic priapism and 42 were initiated on regimented phosphodiesterase type 5 inhibitor therapy. Treatment effectiveness was analyzed for 24 evaluable patients. Priapism etiology was idiopathic in 12 patients (50%), sickle cell disease in 11 (46%) and drug-induced in 1 (4%). The median length of regimented phosphodiesterase type 5 inhibitor use was 3 months (IQR 2-7). Treatment decreased emergency department visits per month by 4.4-fold (p <0.001), priapism duration tiers (p <0.001) and priapism frequency tiers (p <0.001). Of 24 patients 22 (92%) reported improvement in priapism outcomes, 9 of whom reported resolution of recurrent ischemic priapism episodes. A subgroup analysis of 17 patients with recurrent ischemic priapism relapse after treatment discontinuation showed a significant increase in priapism duration (p <0.001) and frequency (p <0.001) but no significant change in emergency department visits per month (p=0.91). CONCLUSIONS: Regimented phosphodiesterase type 5 inhibitor therapy was an impactful treatment in managing recurrent ischemic priapism according to objective and subjective parameters. This study provides further support for the use of regimented phosphodiesterase type 5 inhibitor dosing as a preventive strategy for recurrent ischemic priapism.

Gender Compensation Gap for Ophthalmologists in the First Year of Clinical Practice.

PURPOSE: To identify the role of gender and other factors in influencing ophthalmologists' compensation. DESIGN: Cross-sectional study. PARTICIPANTS: U.S. practicing ophthalmologists. METHODS: Between January and March 2020, an anonymous survey was sent to U.S. residency program directors and practicing ophthalmologists who recently completed residency training. Respondents who completed residency ≤ 10 years ago and responded to questions about gender, fellowship training, state of practice, and salary were included. Propensity score match (PSM) analysis was performed with age, academic residency, top residency, fellowship, state median wage, practice type, ethnicity, and number of workdays. Multivariate linear regression (MLR) analysis controlled for additional factors along with the aforementioned variables. MAIN OUTCOME MEASURES: Base starting salary with bonus (SWB) received in the first year of clinical position was the main outcome measure. A multiplier of 1.2 (20%) was added to the base salary to account for bonus. RESULTS: Of 684 respondents, 384 (56% were female, 44% were male) from 68 programs were included. Female ophthalmologists received a mean initial SWB that was $33 139.80 less than that of their male colleagues (12.5%, P = 0.00). The PSM analysis showed an SWB difference of -$27 273.89 (10.3% gap, P = 0.0015). Additionally, SWB differences were calculated with the number of workdays substituted by operating room (OR) days (-$27 793.67 [10.5% gap, P = 0.0013]) and clinic days (-$23 597.57 [8.90% gap, P = 0.0064]) in separate PSM analyses. The SWB differences between genders were significant using MLR analyses, which also controlled for work, clinic, and OR days separately (-$22 261.49, $-18 604.65, and $-16 191.26, respectively; P = 0.017, P = 0.015, P = 0.002, respectively). Gender independently predicted income in all 3 analyses (P < 0.05). Although an association between gender and the attempt to negotiate was not detected, a greater portion of men subjectively reported success in negotiation (P = 0.03). CONCLUSIONS: Female ophthalmologists earn significantly less than their male colleagues in the first year of clinical practice. Salary differences persist after controlling for demographic, educational, and practice type variables with MLR and PSM analyses. These income differences may lead to a substantial loss of accumulated earnings over an individual's career.

Correction: Approach-Induced Biases in Human Information Sampling.

[This corrects the article DOI: 10.1371/journal.pbio.2000638.].

Sapphire advanced mitigation process: wet etch to expose sub-surface damage and increase laser damage resistance and mechanical strength.

A novel, to the best of our knowledge, method of wet chemical etching of sapphire workpieces (such as optics, wafers, windows, and cones), called the sapphire advanced mitigation process (or sapphire AMP), has been developed that exposes sub-surface mechanical damage created during the optical fabrication process and significantly enhances the surface laser damage resistance ($ \gt {2{\times}}$>2×) and mechanical strength (up to $\sim{2.6{\times}}$∼2.6×). Sapphire AMP involves first treating the workpiece with a mixture of sulfuric and phosphoric acid $([{\rm H_{2}{\rm SO_{4}}}]:[{\rm H_{3}{\rm PO_{4}}}]=1:3)$([H2SO4]:[H3PO4]=1:3) at 220°C, followed with phosphoric acid at 160°C, then with sodium hydroxide base (NaOH) and surfactant at 40°C, and finally with a high-pressure deionized water spray rinse. Sapphire AMP has been demonstrated on both A- and C-plane sapphire workpieces. The mechanism of this etch process involves the reaction of the sapphire $({\rm Al_{2}}{\rm O_{3}})$(Al2O3) surface with sulfuric acid $({\rm H_{2}}{\rm SO_{4}})$(H2SO4) forming aluminum sulfate $[{{\rm Al}_2}{({{\rm SO}_4})_3}]$[Al2(SO4)3], which has low solubility. The high phosphoric acid content in the first and second steps of sapphire AMP results in the efficient conversion of ${{\rm Al}_2}{({{\rm SO}_4})_3}$Al2(SO4)3 to aluminum phosphate $({\rm AlPO_{4}})$(AlPO4), which is very soluble, greatly reducing reaction product redeposition on the workpiece surface. Sapphire AMP is shown to expose sub-surface mechanical damage on the sapphire surface created during the grinding and polishing processes, whose etched morphology has either isotropic or anisotropic evolution depending on the nature of the initial surface damage. Sapphire AMP was also designed to remove the key known surface, laser absorbing precursors (namely, foreign chemical impurities, the fracture surface layer of preexisting sub-surface damage, and reaction product or foreign species redeposition or precipitation). Static and sliding indention induced surface microfractures on sapphire are shown after sapphire AMP to have a significant decrease in the fast photoluminescence intensity (a known metric for measuring the degree of laser damaging absorbing precursors). In addition, the onset of laser damage (at 351 nm 3 ns) on sapphire AMP treated workpieces was shown to increase in fluence from $\sim{4}$∼4 to $ \gt {9}.{5}\;{{\rm J/cm}^2}$>9.5J/cm2. Finally, biaxial ball-on-ring mechanical tests on sapphire disks showed an increase in the failure stress from 340 MPa (with pre-existing 28 µm flaws) to $\sim{900}\;{\rm MPa}$∼900MPa after sapphire AMP, which is attributed to the blunting of the surface microfractures.