This type of spatial memory updating has two significant implications, at least. First, as emphasized previously, it indicates a constant updating process of memory when faced with real-time sensory inputs. Second, it may indicate the "revising" of causal perception, albeit implicitly. That is, the initial location, the trajectory, and the final location are reorganized in a more consistent causal framework of perception in this case. Thus, it may share implications with several other studies concerning causality perception. For examples, on top of Wu et al. (2009) that is described in section Extending the "postdiction" Concept to the Memory and the Sensory Consequences of Voluntary Movements, Choi and Scholl (2006) demonstrated that visual events can determine whether a collision is perceived in an ambiguous situation even when those events occur after the moment of "impact" of the putative collision has already passed. Thus, the findings overall indicate a vigorous automatic tendency of updating shortterm memory to be consistent with on-line perceptual inputs, even at this simplest and lowest sensory level. This immediately raises a related question as to whether this type of postdictive reconstruction occurs only in positional information, or whether it may occur in any other visual attributes, such as shape or color? The logical expectation, especially from the "generalized flash lag" observation (section TMS-induced Scotoma, and Backward Filling-in), would be the latter because there is nothing intrinsically special about position in this case (i.e., dynamic reconstruction). Albeit inconclusive, we do have some evidence consistent with this expectation as described in the next section.

## **PURSUIT MISLOCALIZATION, AND EFFECTS OF THE SPATIAL CONTEXT**

Pursuit eye movement on a smoothly moving object leads to a mislocalization of the target that is briefly presented nearby during the pursuit (Mitrani and Dimitrov, 1982). To be more specific, the direction of mislocalization is in the direction of the pursuit movement (**Figure 8IA**). What if there is an obstacle (a continuously present static object) in the trajectory of the mislocalization (**Figure 8IB**)? It would be inconsistent if the brain has a spatial representation in which it has to carry the location of the flashed target along the translational trajectory.  This was the motivation of the experiments (Noguchi et al., 2007). Directly extending the implications of the previous study (with the Duncker illusion, in the previous section), one may hypothesize that the visual system pursues a more consistent interpretation of spatio-temporal events, modifying the natural tendency of the pursuit-caused spatial bias. **Figure 8IC** illustrates one variable, which is the position of an obstacle relative to that of a flashed target, and **Figure 8IIA** shows the results where the positional errors are plotted against the relative positions. Essentially, the mislocalization was "stopped" by the obstacle, but only if it is within the trajectory of the mislocalization. Likewise, when the obstacle was indeed in the trajectory of the mislocalization but only partially covering the length of the flashed target (**Figure 8III**), the perceived mislocalization is consistent with it in terms of the shape and the position of the mislocalized target in the spatial representation (**Figure 8III**).

More intriguing was when the obstacle had a different color (e.g., red) from that of the flashed target (green). As shown in **Figure 8IV**, a color mixture resulted. Note that while the color perceived was a mixture, that the mixed hue itself was never presented to the retina, which should be considered very convincing evidence for integration of signals within a temporal window. Note that the differently-colored obstacle needed to be located in the direction of the mislocalization (**Figure 8IVA**), not elsewhere (B). This effectively eliminates the possibility of any local aftereffect.

A related observation was made in the flash lag circumstance, where a red target was flashed exactly on top of a green object, for instance. This would yield an yellow percept due to color mixture normally, but when the green object underwent a smooth motion (either rotational or translational), the red flash was mislocalized and at the same time seen qualitatively very close to the original saturated red (Nijhawan, 1997). Therefore, in this case, color decomposition instead of color mixture (of the retinal inputs) occurred. What is common between these two cases, the smooth pursuit mislocalization and the flash lag, is that the color perceived was seemingly consistent with the perceptual localization, as opposed to the retinal.

In the study of pursuit-driven mislocalization, we also manipulated the timing of the obstacle with regard to that of the target. The results (**Figure 8V**) suggested that the reorganization of the shape and the color were maximal when the obstacle was presented in the "post" period (i.e., having the same

**FIGURE 8 | Saccade mislocalization, and effects of spatial context (adopted from Noguchi et al., 2007). (I)** The main experiment. **(A)** The basic effect of the pursuit mislocalization. The black arrow indicates the direction of both the target's (black) movement and smooth pursuit eye movement, while the white arrow indicates the mislocalization effect. **(B)** The main experimental configuration where a static "obstacle" was present in the trajectory of mislocalization throughout the trial. **(C)** Four different locations of the obstacle, as the main variable. **(II)** Results. Position errors (deg.) are plotted for the spatial conditions of the obstacle. The solid and dotted rectangles indicate the location of the wall in each condition. As can be seen, the position errors were the largest in the low condition (with no significant reduction), then smaller in the far, the middle, and the near conditions in this order. This was exactly what should be expected from the topographical "spatial representation" idea. **(III)** Manipulations to partially occlude the trajectory zone **(A)**,

onset as the flash, but lasting longer after the flash offset), relative to the "pre," "during" or "pre and during" periods. This suggests that the "carrying over" mechanism for the localization of the flashed target operates beyond the duration of the flashed target itself, and that the presence of the obstacle interferes with it in the critical time zone. Nonetheless, the resulting phenomenological results **(B)**, and more quantitative results plotted as length **(C)** and position **(D)** of the perceived target. **(IV)** Color mixture. The two stimulus configurations/ sequences employed **(A,B)**, and the results in the CIE xy color space **(C,D)** were shown. As can be seen in **(C)**, the colors were mixed into a subjective yellow. As can be seen in **(D)**, the color mixture effect was much larger in the "right wall" condition (**A**, where the obstacle was located right in the middle of the trajectory) than the "left wall" (**B**, where the obstacle was behind it). **(V)** Effect of timing. We compared four different timing conditions: (a) Pre, (b) During (the flash target presentation), (c) Post (during + after), and (d) Pre + Dur. In the partial occlusion ("a hole") variation **(A)**, the effect of blocking the mislocalization was largest in the Post condition **(B)**. In the color mixture variation **(C)**, the mixture effect was maximum also in the Post condition **(D,E)**. (Reproduced from Noguchi et al., 2007, Figures 1, 2, 3, 6 and 7, with permission from ARVO.)

consistent features (i.e., positions, shapes and colors) are perceptually "backward-referred" to the moment of the flashed target backward-referred because it is phenomenologically not the case that the original positions/colors/shapes are perceived first, and then re-perceived as modified. Rather, all of those "reconstructed" features are perceptually given as a one-shot, immediate percept from its onset of appearance. The similarity to the flash lag (especially the "flash initiated" case) should be obvious.

Thus, the postdictive reconstruction occurs in not only the position, but rather in various visual attributes including, the shape and color (and even the temporal order). Together with the generalized flash lag effect (section Flash-lag Effect, its Variations, and Object Updating) and the memory updating results with the Dunker illusion (section Spatial Memory Updating with Perception), in terms of postdictive processing the position is not special. Rather, all the concurrent visual feature information is dynamically and iteratively processed to reach a consistent scene interpretation at the given moment.

## **NEURAL AND COMPUTATIONAL CONSIDERATIONS**

Here, we would like to reconsider the possible mechanisms (section Underlying Neural Mechanisms?), but this time with more explicit references to specific neural mechanisms, with additional computational thoughts especially in the extended time range.

As mentioned in section Underlying Neural Mechanisms?, varying speeds of neural signal conductance even within the same pathway (say, from the retina to the V1 via the LGN) are well established (e.g., "Parvo" vs. "Magno" pathways; Livingstone and Hubel, 1988), providing the basis of the "catch up" idea (**Figure 6I**).

More recent advances in neuroscience implicate reentrant signaling as the predominant form of communication between brain areas, and this idea may help us to understand the neural correlates of visual awareness, in situations such as backward masking (Di Lillo et al., 2000). To be more specific, they identified two masking processes both of which are based on reentrant signaling. One is an early process that is affected by physical factors such as adapting to luminance, and the other is a later process that is the masking by object substitution. Iterative reentrant processing, when formalized in a computational model, provides a more comprehensible account of all forms of visual masking than do the long-held feedforward views based on inhibitory contour interactions. Along this line, V. Lamme and his colleagues revealed that the EEG derivatives that are typically associated with reentrant processing were absent in the masked, as opposed to non-masked, condition (Fahrentfort et al., 2007; although there is a notable objection, e.g., Põder et al., 2013). A study employing TMS with the metacontrast paradigm suggests that a prior visual stimulus can influence subsequent perception at the early stages of visual encoding via feedback projections (Ro et al., 2003). In the context of "blind sight," there is substantial evidence in favor of the theory that unconscious visuo-motor transformations, as in the blindsight, are executed in an entirely feedforward processing cycle, while visual awareness is critically dependent on feedback connections to the primary visual cortex (Lamme, 2001).

These findings make reentrant signaling as a good candidate for the postdictive phenomena described thus far in this paper (**Figure 6II**), for a variety of reasons. First, the reentrant feedback is appealing intuitively in the sense that an earlier (in both the temporal sense and the visual information processing hierarchy) visual representation is "revised" by the feedback from a higher level. Second, the distinction between the implicit vs. the explicit processes may nicely map onto the feedforward/feedback distinction (as shown in the case of blind sight above). Last but not the least, such reentrant signaling may in principle occur from very short-ranges (such as different layers of the visual cortex, or neighboring visual areas such as V1 and V2) to very long-ranges (such as occipito-frontal and occipito-temporal connections). This last point is especially significant in the current paper, which aims to find a common thread in various postdictive phenomena, across very different temporal and neural scales.

Finally, the idea of two major, dissociable visual streams has been presented. Whereas Mishkin et al. (1983) characterized the ventral and the dorsal pathways "what" vs. "where," Goodale and Milner later modified as "cognition" vs. action with new patient data. This provided the basis for the "different pathways" idea (**Figure 6III**).

From a more computational viewpoint, at least some of the postdictive phenomena may be understood in the Bayesian framework, where the conditional probability indicates signal-tonoise ratio in the visual input while the prior probability may be encoded in the prior internal state of the relevant brain region. Indeed, a similar attempt to account for the rabbit and some other postdictive effects in the Bayesian framework has been made elegantly (Goldreich and Tong, 2013). It is also consistent with the general implications from the TMS studies (reviewed in section TMS-induced Scotoma, and Backward Filling-in) in which a conscious percept reflects both the retinal input (as a likelihood) and the internal neural state (as a prior). More specifically, some additional (potentially arbitrary) assumptions may be necessary to be consistent with the findings. The occurrance of the scotoma itself is due to a local disruption of topographic representation of the retinal input (i.e., a local blockage of the likelihood). There is evidence that the TMS locally suppresses the retinotopic mapping of the visual field on the surface of the visual cortex (Kamitani and Shimojo, 1999) so this assumption is reasonable. Then, the backward filling-in may simply reflect the brain's tendency to rely heavily on the prior (whichever information internally available at the critical moment) when the likelihood is locally not available or very noisy. The Bayesian may provide an overarching framework to more explicitly formalize the postdictive phenomena across the wide range of time scale (from sensation, to perception to cognition).

The idea concerning "compensation of a neural delay by extrapolation" in the flash lag (Nijhawan, 1994) may also be considered in this framework, where expectation or prediction (or a "set" in a higher cognitive term) is implemented in the internal state (as suggested in Berkes et al. (2011) and de Lange et al. (2013), for example).

As for the big picture, more complex brains have more reentrant connections, thus enabling Bayesian-like complex decisions, postdictive reconstructions, and possibly "awareness."

## **HINDSIGHT BIAS, AND COGNITIVE CONSISTENCY**

As mentioned above, there is a rich source of evidence of cognitive reorganization for consistency, information compression, and ease of recall. In the social science literature, a similar effect is known as "hindsight bias." Hindsight bias is the tendency to retrospectively think of outcomes as being more foreseeable than they actually were. It is a robust judgment bias and is difficult to correct (or "debias"). It has been demonstrated in historical events as well. For example, people retrospectively overestimated how well they could predict the restoration of US-China relations during the period of Nixon's surprise visit to China, as opposed to their actual predictions during the visit. So this is a cognitive postdiction phenomena in a large time scale, where people tend to implicitly "revise" their memory on prediction in the past under the influence of the outcome. (The study on athelete's "sixth sense" which will be described in the next sub-section is also in the same format).

Hindsight bias may explain the cognitive gap between those who are accused vs. those who accuse them in a medical law suit or after a more large-scale disaster such as a nuclear plant accident, because the accusers accuse the accuses always based on their retrospective, thus postdictive, estimation of how much prediction was possible on the disastrous outcome, only after it occurred. The author and his colleagues became interested in a situation in which one who was informed regarding a problem situation tended to overestimate how much an uninformed could perform a perceptual task. In the experiments, we used a visual paradigm in which performers decided whether blurred photos contained humans, while the image was progressively made sharper (**Figure 9I**; Wu et al., 2012). Evaluators, who saw the photos unblurred (visually primed) or verbally primed thus knew the correct answer (a human present/absent), estimated the proportion of participants who would guess whether a human was present at a given degree of defocus. The evaluators exhibited visual hindsight bias, i.e., an overestimation of judgment performance by the uninformed participants (the data not shown; Wu et al., 2012), but only with a visual priming, not with a verbal priming. It can be again considered a form of cognitive postdictive bias because the known answer (presence or absence of a human) substantially affects the estimation of the task difficulty *before* knowing the correct answer (although in this case the estimation was on some others' performance, not the informed own). The data qualitatively and structurally matched earlier data on judgments of historical events surprisingly closely. Using eye tracking, we further showed that a higher correlation between the gaze patterns of performers and evaluators (shared attention; as indicated in the heat map in **Figure 9IIa**) is associated with lower hindsight bias in the stimuli with humans (**Figure 9IIb**). This association was validated by a causal method for debiasing: showing the gaze patterns of the performers to the evaluators as they viewed the stimuli progressively reduced the extent of hindsight bias, as indicated in two different measures of performance change (**Figure 9III**).

The study suggests that task difficulty/performance is often reconstructed retrospectively. The exact neural mechanism underlying such long-term cognitive hindsight bias would be different from that which underlies perceptual backward phenomena on the microscopic time scale. Nonetheless, the similarity in the results between these types of visual and the historical tasks indicate, at a functional level, that they may reflect a general intrinsic tendency of the brain to learn from experiences but exclusively in the cognitive format of "cause and effect" such that it can be used for adaptive predictions in the future.

## **AN ATHLETE'S "SIXTH SENSE"?**

For a further investigation of this type of postdiction, i.e., the re-construction of events into a cause-effect format in a more controlled way, and how such an automatic tendency overcomes the natural tendency to be consistent with one's own past decisions, we decided to examine athletes' "sixth sense" as to how well they predict they would do in the next game/match. Athletes in various sports, including top professionals and amateurs, often claim that they can tell whether they will be a hero or not in the next game/match, but is that a real prediction based on some implicit self-assessment of one's physiological and mental conditions, or simply a postdictive construction (which can occur when the question is raised only after the game or match)? We asked over 100 college and high school athletes in a variety of sports [volleyball, soccer, basketball, and Kendo (Japanese fencing)] to fill out a questionnaire in the morning before an actual game or match later in the day (Kadota et al., 2009). The question of our interest was embedded in other ordinary questions about their mental and physical conditions, their teamwork, etc., asking "How do you think you will perform today?" (Prediction). We then repeated a similar set of questions, including another question of our interest, "How did you think you would perform this morning?" (Postdictively-reconstructed prediction).

Virtually the same question was repeated within the same day within subjects, thus it should have been easy for the participants to notice their own inconsistency. Nonetheless, more than a half of the athletes who participated changed their prediction in the postdictively reconstructed case. Moreover, those who lost tended to make their changed predictions more negative, whereas those who won tended to make them more positive. The tendency of interaction was highly significant (*p* < 0.005). On the other hand, neither the predictions before the game, nor answers to other questions (such as mental and physical conditions), nor physiological measures (such as body temperature, hear rate, and blood pressure) did accurately predicted the performance, according to a path analysis performed later. The overall pattern of the results went against the natural tendency to be consistent when answering the postdictive question with the memory of the predictive, strongly indicating a robust tendency at an automatic and implicit level, of postdictive reconstruction to be consistent with the actual outcome. Such automatic and implicit characteristics thus hold generally, from the sensory to the more cognitive levels.

## **REAL-WORLD IMPLICATIONS**

These studies described above have obvious social-scientific implications because the hindsight bias can be a cause of various sorts of conflict in employer-employee relationship, sports, medial lawsuits, and even international affairs. It may even cast a doubt on some "scientific" studies in other fields. For example, millions of dollars of federal science budget have been spent in China, Japan and various European countries to explore the possibility of "predicting" massive earthquakes from certain "signs." An intuitive part of the motivation behind this came from anecdotal reports of observations such as abnormal animal behavior or natural phenomena (such as unusual shapes of clouds or an extra bright sunset, etc.) as a possible precursor to the disaster. The fundamental problem with these reports, needless to say,

just had to do this task, whereas the evaluators had to evaluate "proportion of performers said human (present)" with a visual, or a verbal priming. **(II)** A comparison of eye movement patterns and task performance. (a) The top raw shows an example of "low correlation" between the performer's and the evaluator's gaze patterns as heat maps, with the stimulus and original (clear) photo image. The bottom raw shows an example of "high correlation" stimulus. (b) Median hindsight biases plotted for each conditions (stimuli with/without

is that those episodes were collected only after the earthquake with no exception, making them highly susceptible to postdictive biases. Formalistically, the conditional probability of such a large earthquake to occur, given such an "unnatural" sign reported in a *post-hoc* fashion, should be compared with a conditional probability calculated via daily (prior) observations; that is, given a predesignated unnatural sign in one morning, what was the chance that a major earthquake would occur later on that day (or a predefined short time period). The latter type of data would be very difficult practically to collect (because it would require enormous amount of time and resources), and perhaps may never exist.

Represents statistical significance between xxx (*p* < xx). **(III)** How much debiasing effects were obtained are shown either with (left) or without (right) gaze pattern information of the performers. Two different quantitative measures (-RMSE and linear bias) of bias produced similar results. Black bars denote stimuli with humans, whereas gray bars denote stimuli without. "∗" Represents statistical significance from zero (*p* < 0.05) (reproduced from Wu et al., 2012, Figures 1, 3 and 4, with permission from Assoc. Psychol Sci.)

What did we learn thus far in this review? First, there are various cases in the perceptual domain in which a conscious percept is based on some integration process in a limited temporal time window (of approximately 100–200 ms), within which a stimulus presented later can seemingly affect causally how the subsequent stimulus is perceived. Second, conscious perception can thus be equated to a sort of "ultra-short-term" (iconic) memory, except that against the classical concept of a passive, faithfully duplicated but fainting copy of the original input, this process should be considered to be a very dynamic reconstruction from a sequence of sensory inputs. Third, there are several prototypical mechanisms conceivable, such as the "catch up," the "reentry," the "different pathway," and the "memory revision" models, each of which has reasonable behavioral/neural evidence behind it. Fourth, the structurally similar postdictive reconstruction seems to occur as well on a much larger temporal scale, in the domain of retrospective causality attribution and the postdictive reconstruction of a prediction, which may characterize complex brains.

Regarding the last remark, we have used the term "reconstruction" repeatedly, but it is not meant to imply the repeated experience of the conscious percept itself. Instead, the reconstruction process may be postulated in the following way. In the first implicit stage, there may be a faithful representation of a physical event sequence at earlier implicit levels of information processing. It is only at the later levels, a downstream of the information processing or along a different pathway, where a conscious percept is constructed (for the first time) such that it is more consistent with a context including the subsequent stimuli and a causal framework of cognition.

This last point should be taken seriously, as it implies both the presence of an implicit, automatic predictive process, as well as a reconstructive, postdictive process for conscious perception.

## **LIBET'S CLAIMS, AND THE "FREE WILL" ENDANGERED?**

Benjamin Libet made several important observations and claims which are highly relevant to the central thesis of the current paper, i.e., postdiction (Libet, 2004).

The first of these involves his simple observations with a train of electric pulses to stimulate the somatosensory cortex of the human patients. He observed that a sensation generated by a weak electric pulse (just above the threshold) can be suppressed "backwards" by a train of pulses applied with a 200–500 ms delay. If the initial stimulus is repeated within a several-second interval however, a cutaneous sensation is rather facilitated by the same subsequent train pulses with the same 200–500 ms delay. The relevance of the observations is obvious because these are considered to be another example of postdiction, but this is more related to the TMS example above (section TMS-induced Scotoma, and Backward Filling-in) because in both cases, a direct neural intervention causally affects the percept of a stimulus presented earlier (although the former case is in vision, while this is in the cutaneous modality).

Second, in the same setup with direct current stimulation, he claimed that some implicit neural process precedes conscious perception, yet the onset of the conscious percept is perceptually "referred backwards" to the stimulus onset. He also pointed out that the first peak of the evoked potential recorded from the somatosensory cortex is a good candidate for the time marker, to which the backward referral occurs (**Figure 10I**).

Along this line, Nishida and Johnston (2002) recently reexamined Moutoussis and Zeki's observation (1997) of the asynchrony of color and motion percepts, arguing that the perceived timing of a sensory event should be strictly distinguished from the objective, physical timing of its neural correlates. To be more specific, they argue that even if the critical neural process of a visual attribute (say, color) is faster than another attribute (motion), it does not necessarily require that the former (color) appears earlier than the latter (motion) in the perceived sequential order. It is because the perceived sequence is the content of the percept in

**FIGURE 10 | Benjamin Libet's findings on postdictive process, and backward referral. (I)** Time marker for the backward referral. The first peak of the evoked electric response from the primary somatosensory cortex is quick, temporarily locked to the stimulus onset, and present even when the stimulus is below the sensory threshold. Thus, it could be a good candidate of the time marker, to which the backward referral of the sensation caused by the sustained cortical activity occur. (Modified from Libet, 2004.) **(II)** Libet's functional account of the backward referral in the real world. The figure illustrates time sequences of external and mental events in 500 ms or so. When a driver hit the break because (s)he saw a small boy running into the road ahead of his/her car, his/her conscious report of the event sequence would be exactly in this order (as illustrated in red in the top raw). However, what actually happened with regard to the implicit and explicit levels of his/her mind would be different. It was rather likely that his implicit sensory-motor pathway had triggered the brake immediately (within 150 ms or so; as indicated by the gray dashed arrow), even before he was consciously aware of the presence and the content of the sudden object, i.e. the boy (as indicated at the top right). According to Libet, this scenario is well supported by a variety of laboratory evidence indicating presence of implicit and fast sensory-motor pathways. Thus, the backward referral process put the sequences of events into concise, cognitive frameworks such as causality and "intention of action." (Modified from Libet, 2004.)

the Mind Time (in **Figure 6**), whereas the neural event sequence is in the Brain time. This critical distinction logically allows a room for Libet-type backward referral, and resolves its seemingly paradoxical (or even "anti-scientific" to some) appearance. By the same token, it effectively eliminates a "homunculus," a mysterious Brain-Mind enigma who is sitting at the "brain center" to judge whether event A (color) or B (motion) occurs first. The same may apply to other postdictive phenomena, especially in the sensory-perceptual domain within 100 or 200 ms.

Libet's third claim concerns action. His findings on "preparatory potentials" suggest that there is specific neural activity that precedes and causally determines the execution of an action, in the order of several hundreds of millisecond. He also developed his own unique psychophysical paradigm in which a participant evaluated the timing of the onset of a conscious intention toward an action preceding its execution. Overall, he argued that the neural activity precedes and causes both the intention and the execution of action.

Why do we need such a complex process as backward referral? Moreover, how could we integrate his three claims into a general framework? Libet offers a functional account. He uses a real world example. The **Figure 10II** illustrates time sequences of external and mental events occurring within approximately 500 ms or so. When a driver hits the breaks because he sees a small boy running into the road ahead of his/her car, his conscious report of the event sequence would be precisely in this order (as labeled in red). However, what actually happened with regard to the implicit and explicit levels of his/her mind would be different. It was rather likely that his implicit sensory-motor pathway had triggered the brake immediately, even before he was consciously aware of the sudden appearance of the boy (as indicated at the bottom as External time line). This is akin to the other realworld example that we used earlier (section Underlying Neural Mechanisms?) of the 100 m sprinters who occasionally report their starting movements even before their conscious awareness of the sound.

According to Libet, this scenario is well supported by a variety of evidence indicating the presence of implicit and fast sensorymotor pathways. Thus, the backward referral process puts the sequences of events into concise, cognitive frameworks such as causality and "intention of action."

Libet's claims generally injected some controversy into theories of the philosophy of mind and neuro-philosophy because it may (or not) endanger what is termed "free will," which is to some the critical basis of legal responsibility in a democratic social system. Apparently, Libet himself suffered from this problem to put substantial efforts to rescue "freedom" from the implications of his own findings, relying on a concept of "vetoeing" of own intention (Libet, 2004), but it did not seem to be very successful. A different insight to resolve this difficulty actually comes by integrating his claims above, i.e., the implicit neural correlates preceding a conscious percept, and the backward referral of its perceived timing. Note especially that the backward referral may be considered an implicit, automatic (stimulus-driven) process of causal attribution. (Thus, causal attribution may not be always a higher level, cognitive process).

Finally, a remark on terminology may be necessary here to avoid a confusion. Throughout the current article, the term "postdictive phenomenon" is used strictly in the operational sense, as repeatedly mentioned above. However, the term "postdiction" sometimes refers to the "reentry" model or the Libet-type backward referral as the underlying mechanisms. One may want to make a clear distinction between these two usages.

The next section will be devoted to expounding the details of this idea of the (generalized) backward referral. Although it may seem to substantially exceed the specific scope of this paper, the author feels that this is necessary for a full understanding of the broad impacts of the findings discussed here.

## **"SENSE OF AGENCY" AS POSTDICTIVE ATTRIBUTION AND AN AUTHENTIC ILLUSION**

Based on the review and the discussion thus far, we have at least three lines of reasoning with which to believe in the compatibility of neuroscientific determinism and the spontaneity/volition of the human action. We will now examine them one after one.

## 1. *The feeling of free choice may live in the postdictive process, not in the predictive process.*

The overwhelming majority of studies on perception, choice decision making and action have focused on the neural mechanisms that precedes and causally determines an action. However, there is a good possibility that psychological/neural processes after the decision may significantly contribute to determining whether a completed decision is felt as forced or more spontaneous/voluntary. Cognitive dissonance (Festinger, 1957), causal attribution (Heider, 1958), and choice justification (Staw, 1976) are some of the keywords in the social psychology literature which are potentially related. To state this simply, the sense of agency (or a feeling of free choice in a given situation) may well play out as a postdictive construct. This may be structurally similarly to the case of conscious perception, as in that case as well, a percept can be confirmed as "conscious" only when it is consolidated and reviewed (typically in a response to a question on the event). The challenging task for neuroscientists to account for the neural mechanism underlying the feeling of agency and "freedom" (and likely visual awareness as well) may not be accomplished until they shift their attention from the predictive process to the postdictive process.

2. *The feeling of free choice is a matter of content in perception/cognition. It should be distinguished strictly from the deterministic nature of the neural correlates.* For example, a content of "red" color perception is possible even though the neurons or the neuronal activity underlying that perception itself is in no physical sense colored red. When a part of somatosensory cortex is activated, the pain is not felt there, but rather felt at the "referred" body part. Likewise, the feeling of free choice as a content of perception/cognition can be conceivable as a result of strictly deterministic neuro-physiological sequence (in the Brain Time). This is analogous to the failure of one-toone mapping in the temporal domain between the perceived sequence of two events and the underlying and corresponding neural events (section Underlying Neural Mechanisms? and Libet's Claims, and the "free will" Endangered?).

As we noted, the perceived timing of an event should be considered separately from the physical timing of its neural correlates, particularly on the microscopic time scale (Nishida and Johnston, 2002). Thus, what is termed the "first-order isomorphism" may not hold between the perceived sequence and the physiological sequences of their neural correlates.

Köhler's psychophysical isomorphism assumed that an organized structure of percept (such as relative sizes) has a direct counterpart in a common structure (relative sizes) of the dynamic neural field in the brain (Köhler, 1940). He used figural aftereffect as an example in the space domain. His claim has been criticized as being "too literally isomorphic," and is thus sometimes called the "first-order isomorphism." At present, neuroscientists do not believe that the neural correlates of "a figure A being perceived as larger than another figure B" should be "the neural circuit encoding A being spatially more extending than that encoding B." Indeed, there are notable exceptions in which a larger stimulus naturally activate a larger cortical area (Murray et al., 2006; Schwarzkopf et al., 2011), but it is very limited to the early visual cortices where a strict retinotopic mapping is maintained.

Because the skepticism on the first-order isomorphism is already a commonsense notion in the field, it is rather puzzling that the majority of scientists and philosophers still believe in such a first-order (direct) isomorphism in the time domain, between the temporal sequence of neural correlates and the time/sequence perception as the contents, especially on the microscopic scale.

Similarly, a cognitive content (a feeling of agency, spontaneity or volition) can be considered separately from its neural correlates of it. To be more specific, a neural process may causally determine that a given action is felt voluntary or not (as the cognitive content), whereas that neural process remains to be entirely deterministic. This inevitably argues for involvement of postdictive and possibly semantic functions carried by the neural mechanisms subserving the higher-order perceptual experiences, with transformations of reality and illusions being typical for this symbolic level. Note also that being stochastic is categorically different from being voluntary; hence, the author would not endorse to some attempts to rely on the stochastic/undeterministic properties of neural dynamics to save free will and consciousness from determinism.

3. *A feeling of free choice is very much like a perceptual illusion, in that it will not be eliminated by objective knowledge*.

Not all types of non-veridical perception are considered perceptual illusions in the "authentic" sense of psychophysics. For example, various sensory and cognitive hallucinations in the schizophrenia should not be considered perceptual illusions. Other than the fact that a percept is non-veridical with regard to the pertinent physical properties, a perceptual illusion should satisfy the following criteria, traditionally.

Just as with perceptual illusions, the feeling of "agency" or "free choice" is unlikely to be "exorcised" by scientific knowledge of the underlying neural mechanisms (although actually no empirical data are available). This is similar to color perception in that the subjective color experiences (as some want to call "qualia") would not disappear (as everyone's intuition tells) when color perception is fully *explained out* in neurophysiological terms, starting from photoreceptors, retinal ganglion cells, the LGN, through to the primary visual cortex, etc. And this is true even though color perception is also in a sense an "authentic illusion" because colors do not exist in the world, they are rather created by interactions between the physical stimuli and the brain. Likewise, the feeling of agency/free choice can be regarded as one type of robust, healthy and authentic illusion, for most of which not many people are concerned about the degree of compatibility to scientific determinism.

One may consider this view just as a variation of the "free will as a cognitive illusion" view proposed by Daniel Wegner and his colleagues (Wegner and Wheatley, 1999; Wegner, 2002). According to their view, people can experience conscious will quite independent of any actual causal connection between their thoughts and actions. The impression that a thought has caused an action rests on a causal inference.

Thus at a very crude level, the postdictive construction view shares a lot with Wegner's view of free will as a sort of cognitive illusion. Yet, there are several distinctive differences that would be noteworthy. Wegner's view has an obvious implication that free will is "an illusion, therefore wrong" with regard to the "true" physical causation. For instance, They make an analogy of the free will to a magic, in that there are real, and "disguised" causal relationship. The experience of conscious will in their view is merely an illusion produced by the perception of an apparent causal sequence. Apparent mental causation is generated by an interpretive process that is fundamentally separate from the mechanistic process of real causation.

Whereas we agreed that the free will (together with the sense of agency) is a mental construction, we take a somewhat different view. The free will reflects a normal function of the very general processing principle in the brain, i.e., postdictive construction employing the re-entry, the backward referral and possibly other mechanisms, which then leads to a normal experience of the "sense of agency." In the very same sense as most of the geometric illusions qualify, it should rather be considered an authentic, or valid illusion based on mostly automatic, implicit processes.

Another deviation of our view from Wegner's "illusion" view is related to the three criteria they proposed for the interpretive process to experience free will. Those are (1) priority, (2) consistency, and (3) exclusivity. Among them we would like to impose a substantial constraint on the first criterion, i.e. the priority. As obvious from the detailed examination of various postdictive phenomena in the current article, starting from very sensory to highly cognitive levels, the priority may only be a distinctive feature of *the output* (i.e., the percept) of the processing, *not the physical condition* for it. As a matter of fact, all the three properties above, including the consistency and the exclusivity, may be, at least in some cases, results of postdictive reconstruction.

Whereas the two views are consistent in various aspects, this single contrast (priority vs. postdiction) may highlight the stark distinction.

## **SUMMARY AND GENERAL DISCUSSION**

This paper reviewed "postdictive" perceptual phenomena known, in which a stimulus presented later seems to causally affect percept of another stimulus presented earlier. Starting from some classical examples such as backward masking and apparent motion, the list included the cutaneous rabbit effect and the flash lag effect. Some new studies such as the TMS-triggered scotoma and the pursuit mislocalization suggest that various visual attributes are reorganized in a postdictive fashion to be consistent with each other, or to be consistent in a causality framework.

We then extended our discussion into several directions. First, in terms of underlying mechanisms, four prototypical models have been considered: the "catch up," the "reentry," the "different pathway," and the "memory revision" models. Whereas they are meant to account for the "postdictive" phenomena but only in the operational sense above, the mechanism itself does not have to be postdictive in any sense (perhaps with the exception of the "reentry" model, and the "backward referral" idea by Benjamin Libet).

Second, by extending the list of postdictive phenomena to memory, sensory-motor and higher-level cognition (e.g., "hindsight"), one may note that such postdictive reconstruction may be a general principle of neural computation, ranged from milliseconds to months of time scale, from local neuronal interactions to long-range connectivity, in the complex brain. The operational definition of the "postdictive phenomenon" can be applicable to such sensory/cognitive effects across a wide range of time scale, even though the underlying neural implementations may vary across the variety of phenomena.

This notion of generic postdiction has a good affinity with the Bayesian framework, as well as the notion that perceptual awareness is in fact a very brief (possibly iconic) memory. As obvious in the case of a flicker perception previously mentioned (section Underlying Neural Mechanisms?), it is hard to draw a line between conscious perception and memory. And this is where a postdictive process operates on the preceding implicit process to yield a conscious visual percept.

Finally, this structurally the same mechanism may apply to body movements and its attribution to "free will." The "sense of agency" which is the basis of "free will" may be considered a sort of "authentic illusion" which may hardly evaporate merely by reductionistic neural account for it.

Closer examinations of the postdictive phenomena may provide an entirely new and insightful framework to understand perception, cognition, memory and action. Moreover, it may add a new angle in the discussion of implicit vs. explicit mental processes, determinism vs. free will, etc.

## **ACKNOWLEDGMENTS**

The author has been supported by NIH, NSF, HFSP, JST.ERATO, JST.CREST, and Tamagawa-Caltech gCOE (MEXT). He also thanks many colleagues including Kaoru Amano, Jaeseung Jeong, Roman Weber, Yong Jun Lin, Robert Tilford, the editors of this special issue, and the two reviewers for their valuable comments.

## **REFERENCES**

Interplay between Conscious and Unconscious Perceptual Streams." *Curr. Biol.* 19, 2003–2007. doi: 10.1016/j.cub.2009.10.017

Wegner, D. M. (2002). The Illusion of Conscious Will. Cambridge, MA: MIT Press.

**Conflict of Interest Statement:** The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

*Received: 20 June 2013; accepted: 20 February 2014; published online: 31 March 2014. Citation: Shimojo S (2014) Postdiction: its implications on visual awareness, hindsight, and sense of agency. Front. Psychol. 5:196. doi: 10.3389/fpsyg.2014.00196*

*This article was submitted to Consciousness Research, a section of the journal Frontiers in Psychology.*

*Copyright © 2014 Shimojo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.*

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**6. Repair principles and techniques**

The ideal method of flexor tendon repair should allow a healing response precisely at the tendon ends but not between the tendon and its surroundings, creates a repair site with minimal bulk and low friction, and places enough force across the repair to promote motion and remodelling [14].

two-strand techniques. The choice of core suture can be made independent of the choice of epitendinous repair. There is little evidence to recommend one suture material over another. Steel and fibrewire have been shown to be stronger than nylon, Prolene and braided polyester,

Flexor Tendon Injuries

29

http://dx.doi.org/10.5772/intechopen.73392

The surgeon must not only be aware of how to repair a lacerated flexor tendon but must also have an understanding of the postoperative rehabilitation regimen before consenting a patient for surgery. Failure to comply with rehabilitation may result in poor patient outcomes despite meticulous repair technique. Unfortunately, the best rehabilitation regimen remains to be elucidated. This is further convoluted by a paucity of well-designed randomised control trials with a Cochrane Collaboration analysis [37] being withdrawn in 2010 for being out of date and the most recent systematic review concluding that there is weak evidence supporting both early active motion protocols and combination protocols [38]. Therefore, it is imperative that the surgeon be aware of both current rehabilitation regimens as well as future directions. Current postoperative protocols for patients with flexor tendon injuries are immobilisation, early passive mobilisation and early active mobilisation [39] (**Figure 1**).

Immobilisation may seem counterintuitive considering the plethora of studies showing the benefits of early mobilisation on the repair strength, tenocyte healing and formation of adhesions [14, 40–44]. However, there are certain situations in which immobilisation is preferable.

• Are unable to adhere to early mobilisation protocols such as children and those with cognitive

• Have injuries to other structures that could potentially be damaged by early mobilisation

O'Connell et al. followed 78 children (under the age of 16) for 24 months and found no benefits in early mobilisation protocols in children when compared to immobilisation [45]. However, immobilisation for more than four weeks resulted in functional deterioration of the repaired tendon [45]. Kato et al. found it difficult to encourage early active motion protocols in children aged less than six and found immobilisation for three to four weeks did not increase the inci-

For the non-compliant adult patient, the protocol of Cifaldi, Collins and Schwarze may be used [39, 47]. It involves three to four weeks of immobilisation in a forearm-based dorsal splint or cast (20° wrist flexion, metacarpophalangeal (MP) joints in 50° flexion and the interphalangeal (IP) joints in full extension) followed by a weaning program (it may also be used in children) [47]. Weaning involves modifying the splint so that the wrist is in neutral and instructing the patient to remove the splint every hour and passively flexing

with no significant difference between the latter three [36].

**7.1. Immobilisation**

deficits.

These include patients who [39]:

such as fractures, nerves and vessels.

dence of tendon rupture or decrease function [46].

• Are unwilling to adhere to strict early mobilisation protocols.

**7. Postoperative rehabilitation following flexor tendon repair**

The characteristics of an ideal tendon repair were described by Strickland [31] and confirmed by a large body of research data [14]. These are:

Strength of the repair immediately post operatively is reliant on the suture and is therefore entirely responsible for the stability in early motion stress. Ideally, the suture material used should have high tensile strength, be inextensible, cause no tissue reaction and be easy to handle and knot [31]. Flexor tendon repairs consist of two parts. The core sutures and the epitendinous sutures.

Core sutures provide strength to the tendon repair. A 3/0 or 4/0 non-absorbable braided or monofilament suture are optimal for use as core suture [32]. The number of core sutures in the repair and the size of the suture is proportional to the strength of the repair. However, increasing the number of suture strands within the repair leads to increased bulk of the repair. Another factor in determining strength of the tendon repair is the grip of the core sutures. Increasing the grip of the core suture prevents the suture from pulling out of the tendon after repair [32].

The epitendinous sutures ensure smoothness of gliding and also increases the tensile strength of the repair. A locked running suture also reduces the rate of gap formation [32].

Large gaps in the tendon repair prevents healing with Gelberman et al. demonstrating that 3 mm is the maximum permissible gap to allow tendon healing [33].

Other factors include minimal handling to reduce adhesions and to avoid vascular interference to the repaired tendon [33]. Tendon lacerations less than 60% of the tendon diameter should not be repaired [34].

There are many techniques available for repairing the tendon and these have been described in detail elsewhere [35]. Four-strand techniques are generally recognised to be superior to two-strand techniques. The choice of core suture can be made independent of the choice of epitendinous repair. There is little evidence to recommend one suture material over another. Steel and fibrewire have been shown to be stronger than nylon, Prolene and braided polyester, with no significant difference between the latter three [36].


**Efficiency in Kinesiology: Innovative Approaches in Enhancing Motor Skills for Athletic Performance**

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For citation purposes, cite each article independently as indicated on the article page online and as indicated below:

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**5. Surface modification techniques**

#### **5.1. Sol-gel**

The sol-gel method has been widely used to deposit calcium phosphate onto dense or po‐ rous metallic materials. There are two routes for a sol-gel reaction, namely inorganic and or‐ ganic, using reagents consisting of a colloidal suspension solution of inorganic or organic precursors. The sol-gel technique transforms a liquid (sol) into a solid phase (gel) and re‐ quires drying and heat treatment stages. The advantages of the sol-gel method include: (i) it is cost-effective, (ii) it is easy to control the final chemical composition and thickness of the coating, (iii) the coating is readily anchored on the substrate, and it is usually homogenous with a good surface finish, and (iv) it can be used for coating implants or substrates that have complex surfaces or large surface areas.

Wen *et al.* [22] reported that a sol-gel method for HA and titania (TiO2) coatings exhibited excellent bioactivity after immersion in simulated body fluid (SBF) that mimics human body fluid of a similar ion concentration and pH value to human blood plasma. In addition to en‐ hancing titanium bioactivity, HA-titania coating is expected to increase the bonding strength and corrosion resistance. The surface morphology and microstructure of HA and titania coating before and after being immersed in SBF are presented in Figure 1 (a)-(d). It can be seen that the coating is dense, uniform and without cracks. Wen *et al.* also reported that after soaking in SBF, HA granules grow gradually.

**Figure 1.** SEM micrographs of the surface morphology of HA/TiO2 films after soaking in SBF for (a) 0 day, (b) 1 day, (c) 8 days, and (d) 15 days

#### **5.2. Electrodeposition of materials**

bone apatite and collagen production [15-16]. It is suggested that altering the nanostruc‐ tured surface morphology influences the apatite inducing ability and improves osteoblast

Calcium phosphate is a synthetic ceramic that has been proven to support bone apposition and to enhance the osteoconduction of the bone. Calcium phosphate ceramics for bone tis‐ sue applications include tricalcium phosphate (TCP), octocalcium phosphate (OCP), hydrox‐ yapatite (Ca10(PO4)6(OH)2, HA), and biphasic calcium phosphate (BCP) [18]. These ceramics accelerate the healing process and have been widely used in conjunction with metallic mate‐ rial as a bioactive coating material. The ratio of Ca/P in calcium phosphate should resemble the biological apatite mineral of bone (*i*.*e*., 1.50-1.69). Calcium phosphate has the natural fa‐

Hydroxyapatite demonstrates the best bioactivity amongst all the forms of calcium phos‐ phate. Hydroxyapatite (HA) exhibits functionality in promoting osteoblast adhesion, migra‐ tion, differentiation and proliferation; all of which are essential for bone regeneration. HA also has the ability to bond directly onto bone. The bioactivity of HA has made this ceramic the favourite for implant applications. HA nanoparticles may also induce cancer cell apopto‐ sis [19]. The crystalline form of HA exhibits biointegration and prevents formation of ad‐ verse fibrous tissue. It is a more desirable coating than amorphous HA due to its ability to provide a better substrate for a different cell line [20]. Amorphous HA tends to dissolve in human fluid more easily and leads to loosening of the implant. Nanocrystalline HA is more favourable than microcrystalline HA because of its structural similarity with apatite [21].

The sol-gel method has been widely used to deposit calcium phosphate onto dense or po‐ rous metallic materials. There are two routes for a sol-gel reaction, namely inorganic and or‐ ganic, using reagents consisting of a colloidal suspension solution of inorganic or organic precursors. The sol-gel technique transforms a liquid (sol) into a solid phase (gel) and re‐ quires drying and heat treatment stages. The advantages of the sol-gel method include: (i) it is cost-effective, (ii) it is easy to control the final chemical composition and thickness of the coating, (iii) the coating is readily anchored on the substrate, and it is usually homogenous with a good surface finish, and (iv) it can be used for coating implants or substrates that

Wen *et al.* [22] reported that a sol-gel method for HA and titania (TiO2) coatings exhibited excellent bioactivity after immersion in simulated body fluid (SBF) that mimics human body

adhesion and differentiation [17].

26 Titanium Alloys - Advances in Properties Control

**4.1. Calcium phosphate coatings**

cility to bond directly to bone.

**4.2. Nano-hydroxyapatite coatings**

**5. Surface modification techniques**

have complex surfaces or large surface areas.

**5.1. Sol-gel**

Electrodeposition is a coating method applied to the fabrication of computer chips and mag‐ netic data storage. Recently, that has been rising interest in electrochemical deposition for tissue engineering applications due to its ability to coat complex 3D components.

Lopez-Heredia *et al.* [23] coated calcium phosphate onto porous titanium using the electro‐ deposition method. In the process, Ti, platinum mesh, and supersaturated calcium phos‐ phate solution were used as the cathode, electrode and electrolyte, respectively. The ratio of Ca/P in the calcium phosphate coating was 1.65 and the coating thickness was 25 µm. The calcium phosphate coating was homogenous and covered the entire Ti surface. Moreover, they reported that the coating presented good adhesion to the underlying substrate. The electrodeposition of CaP showed that calcium phosphate enhances the adherence of cells.

**5.4. Thermal spray**

bone or dental applications.

stock particle size and velocity.

the same as the starting materials.

**5.5. Physical vapor deposition**

must be controlled to produce a high quality coating.

The thermal spray technique is a well-established and versatile technique that can be ap‐ plied for a wide variety of coating materials, *i*.*e*., metallic, non-metallic, ceramic, and poly‐ meric. Thermal spray coated medical implants, such as orthopaedic and dental prostheses, have been commercially used. Thermal spray offers several advantages, such as the ability to coat low and high melting materials, a high deposition rate, and flexibility in coating 3D shape components. It is also cost effective [28]. Despite these advantages, some problems have been revealed after long term implantations using thermal spray coatings, such as de‐ lamination, resorption, biodegradation of the thick coating and mechanical instability [29]. Thus, improving the adhesion strength of thermal sprayed coatings is a major concern for

Sputtered Hydroxyapatite Nanocoatings on Novel Titanium Alloys for Biomedical Applications

http://dx.doi.org/10.5772/54263

29

There are several types of thermal spraying; for example, plasma spray, flame spray, and cold spray [29]. Plasma spray is commonly applied to produce thick coatings for metallic corrosion protection. It is also flexible, due to its ability to coat different substrates. During plasma spraying, the precursor is atomised and injected into plasma jet, then accelerated to‐ wards the substrate with the aid of an inert carrier gas [30]. There are many parameters that

Flame spray uses a combustion flame to melt the solid precursor. There is, additionally, an‐ other type of flame spray termed as high velocity oxygen fuel (HVOF). This technology is favourable due to its high spray velocity and the formation of a strong bond coating [30-32]. The thermal spray technique has been widely employed for HA coatings. The surface morphology of HA coatings obtained with various parameters of stand-off distance (SOD) and power are presented in Figure 2 (a)-(d). Sun *et al.* [28] reported that when the spray power increased, the crystallinity of HA decreased and the amorphous phase became more obvious. The effect of SOD indicated an inverse correlation with deposition efficien‐ cy. Several parameters that influence the deposition of HA are SOD, spray power, feed‐

Cold spray is a new member of the thermal spray family. This technique uses small particles of 1-50 µm. A supersonic jet of compressed gas is used to accelerate the particles. The ad‐ vantage of using this technique is the ability to produce dense coatings and maintain the material chemistry and phase composition of the feedstock. Noppakun *et al.* [33] have ap‐ plied cold spray technique to deposit HA-Ag/poly-esther-ether-ketone on glass slides. This study reported that cold spray was able to retain and elicit a coating functionality that was

Physical vapor deposition (PVD) is a deposition method where materials are evaporated or sputtered, transferred and deposited onto the substrate surface. This physical process in‐ cludes thermal evaporation or plasma-induced ion bombardment onto the sputtering target. A condensation or reaction of the coating materials then takes place on the substrate surface to form coatings. Variants of the PVD process include evaporation, ion plating, pulsed laser dep‐

Adamek *et al.* [24] succeeded in producing an HA coating on porous Ti6Al4V using electro‐ deposition. The intermediate layer between the bone and metallic implant was rough and porous. Large pores and nanolamellae were present within the HA layer. The flexibility of the electrodeposition technique for coating solid and porous metallic implants has acquired increasing interest due to this ability to enhance the bioactivity of bone implant materials.

#### **5.3. Biomimetic creation of surfaces**

There are two major steps involved in the biomimetic technique. The first step is to conduct a pre-treatment of the implant material surface to create a layer functional group that can induce formation of an effective apatite layer. Several studies have revealed that an apatite layer has not been formed on materials without any treatment prior to immersion [25]. Pre‐ liminary treatment includes, for example, hydrothermal, sol-gel, alkali heat treatment and micro-arc. The second step is to immerse the biomaterials into a simulated body fluid (SBF). In this step, the bone apatite layer is formed on the biomaterial's surface. The high apatite forming ability of titanium arises from the formation of a hydrated titanate surface layer during chemical treatment. The advantages of the biomimetic process include (i) flexibility in the control of the chemical composition and thickness of the coating, (ii) the formation of relatively homogenous bioactive bonelike apatite coatings, (iii) a lower processing tempera‐ ture, and (iv) the ability to coat 3D geometries.

Wang *et al.* [25] used a modified biomimetic approach to improve the biocompatibility of porous titanium alloy scaffolds. In their experiment, porous Ti10Nb10Zr underwent an alka‐ li heat treatment prior to soaking in SBF. Two NaOH concentrations of 5 M and 0.5 M were used, and the samples were soaked for 1 week. The surface morphologies of porous TiNbZr after alkali soaking and heat treatment revealed a nanofiber layer, that consisted of sodium titanate. Parameters that influenced the morphology and thickness of the sodium titanate were reaction temperature and NaOH concentration.

Calcium phosphate was successfully deposited on the surface of the porous TiNbZr. The calcium phosphate layer was uniform and homogenously spread onto the surface. Anoth‐ er biomimetic study, conducted by Habibovic *et al.* [26], indicated that a thick and homo‐ genenous crystalline hyroxyapatite coating was deposited on all pores and resembled bone minerals.

An evaporation-based biomimetic coating was introduced by Duan *et al*. [27]. In their study, a supersaturated calcium phosphate was prepared by mixing NaCl, CaCl2, HCl, NH4H2PO4, tri(hydroxymethyl)aminomethane (Tris), and distilled water, which they termed the acceler‐ ated calcification solution (ACS). Calcium phosphate crystallites formed on the surface on dipping the samples into the ACS. The main component in the coating was octa-calciumphosphate (OCP) and apatite was observed after soaking in SBF. The advantages of this method include (i) no surface etching is required, (ii) high supersaturations of the coating chemistry can be achieved, and (iii) tight control of the solutions is achieved [27].

#### **5.4. Thermal spray**

they reported that the coating presented good adhesion to the underlying substrate. The electrodeposition of CaP showed that calcium phosphate enhances the adherence of cells.

Adamek *et al.* [24] succeeded in producing an HA coating on porous Ti6Al4V using electro‐ deposition. The intermediate layer between the bone and metallic implant was rough and porous. Large pores and nanolamellae were present within the HA layer. The flexibility of the electrodeposition technique for coating solid and porous metallic implants has acquired increasing interest due to this ability to enhance the bioactivity of bone implant materials.

There are two major steps involved in the biomimetic technique. The first step is to conduct a pre-treatment of the implant material surface to create a layer functional group that can induce formation of an effective apatite layer. Several studies have revealed that an apatite layer has not been formed on materials without any treatment prior to immersion [25]. Pre‐ liminary treatment includes, for example, hydrothermal, sol-gel, alkali heat treatment and micro-arc. The second step is to immerse the biomaterials into a simulated body fluid (SBF). In this step, the bone apatite layer is formed on the biomaterial's surface. The high apatite forming ability of titanium arises from the formation of a hydrated titanate surface layer during chemical treatment. The advantages of the biomimetic process include (i) flexibility in the control of the chemical composition and thickness of the coating, (ii) the formation of relatively homogenous bioactive bonelike apatite coatings, (iii) a lower processing tempera‐

Wang *et al.* [25] used a modified biomimetic approach to improve the biocompatibility of porous titanium alloy scaffolds. In their experiment, porous Ti10Nb10Zr underwent an alka‐ li heat treatment prior to soaking in SBF. Two NaOH concentrations of 5 M and 0.5 M were used, and the samples were soaked for 1 week. The surface morphologies of porous TiNbZr after alkali soaking and heat treatment revealed a nanofiber layer, that consisted of sodium titanate. Parameters that influenced the morphology and thickness of the sodium titanate

Calcium phosphate was successfully deposited on the surface of the porous TiNbZr. The calcium phosphate layer was uniform and homogenously spread onto the surface. Anoth‐ er biomimetic study, conducted by Habibovic *et al.* [26], indicated that a thick and homo‐ genenous crystalline hyroxyapatite coating was deposited on all pores and resembled

An evaporation-based biomimetic coating was introduced by Duan *et al*. [27]. In their study, a supersaturated calcium phosphate was prepared by mixing NaCl, CaCl2, HCl, NH4H2PO4, tri(hydroxymethyl)aminomethane (Tris), and distilled water, which they termed the acceler‐ ated calcification solution (ACS). Calcium phosphate crystallites formed on the surface on dipping the samples into the ACS. The main component in the coating was octa-calciumphosphate (OCP) and apatite was observed after soaking in SBF. The advantages of this method include (i) no surface etching is required, (ii) high supersaturations of the coating

chemistry can be achieved, and (iii) tight control of the solutions is achieved [27].

**5.3. Biomimetic creation of surfaces**

28 Titanium Alloys - Advances in Properties Control

ture, and (iv) the ability to coat 3D geometries.

were reaction temperature and NaOH concentration.

bone minerals.

The thermal spray technique is a well-established and versatile technique that can be ap‐ plied for a wide variety of coating materials, *i*.*e*., metallic, non-metallic, ceramic, and poly‐ meric. Thermal spray coated medical implants, such as orthopaedic and dental prostheses, have been commercially used. Thermal spray offers several advantages, such as the ability to coat low and high melting materials, a high deposition rate, and flexibility in coating 3D shape components. It is also cost effective [28]. Despite these advantages, some problems have been revealed after long term implantations using thermal spray coatings, such as de‐ lamination, resorption, biodegradation of the thick coating and mechanical instability [29]. Thus, improving the adhesion strength of thermal sprayed coatings is a major concern for bone or dental applications.

There are several types of thermal spraying; for example, plasma spray, flame spray, and cold spray [29]. Plasma spray is commonly applied to produce thick coatings for metallic corrosion protection. It is also flexible, due to its ability to coat different substrates. During plasma spraying, the precursor is atomised and injected into plasma jet, then accelerated to‐ wards the substrate with the aid of an inert carrier gas [30]. There are many parameters that must be controlled to produce a high quality coating.

Flame spray uses a combustion flame to melt the solid precursor. There is, additionally, an‐ other type of flame spray termed as high velocity oxygen fuel (HVOF). This technology is favourable due to its high spray velocity and the formation of a strong bond coating [30-32].

The thermal spray technique has been widely employed for HA coatings. The surface morphology of HA coatings obtained with various parameters of stand-off distance (SOD) and power are presented in Figure 2 (a)-(d). Sun *et al.* [28] reported that when the spray power increased, the crystallinity of HA decreased and the amorphous phase became more obvious. The effect of SOD indicated an inverse correlation with deposition efficien‐ cy. Several parameters that influence the deposition of HA are SOD, spray power, feed‐ stock particle size and velocity.

Cold spray is a new member of the thermal spray family. This technique uses small particles of 1-50 µm. A supersonic jet of compressed gas is used to accelerate the particles. The ad‐ vantage of using this technique is the ability to produce dense coatings and maintain the material chemistry and phase composition of the feedstock. Noppakun *et al.* [33] have ap‐ plied cold spray technique to deposit HA-Ag/poly-esther-ether-ketone on glass slides. This study reported that cold spray was able to retain and elicit a coating functionality that was the same as the starting materials.

#### **5.5. Physical vapor deposition**

Physical vapor deposition (PVD) is a deposition method where materials are evaporated or sputtered, transferred and deposited onto the substrate surface. This physical process in‐ cludes thermal evaporation or plasma-induced ion bombardment onto the sputtering target. A condensation or reaction of the coating materials then takes place on the substrate surface to form coatings. Variants of the PVD process include evaporation, ion plating, pulsed laser dep‐ osition and sputtering. The beneficial features of PVD are high coating density, high bio-adhe‐ sion strength, formation of multi-component layers, and low substrate temperature [34].

sectors. There are several sputtering methods, such as DC glow discharge, radio frequency

Sputtered Hydroxyapatite Nanocoatings on Novel Titanium Alloys for Biomedical Applications

http://dx.doi.org/10.5772/54263

31

The simplest model for sputtering is the diode plasma, which consists of a pair of planar electrodes, an anode and a cathode, inside a vacuum system [37]. The sputtering target is mounted on the cathode. Application of the appropriate potential difference between the cathode and anode will ionize argon gas and create a plasma discharge. The argon ions will then be attracted and accelerated toward the sputtering target. Such ion bombard‐ ment on the target will displace some of the target atoms. This results in electron emis‐ sion that will subsequently collide with gas atoms to form more ions that sustain the discharge [37]. Ion beam sputtering has disadvantages, such as a high capital investment cost (approximately one million dollars per machine), low deposition rates and a relative‐ ly small capacity per chamber batch [38]. Another type of sputtering employs radio fre‐

Magnetron sputtering is one option to overcome the problems such as delamination and low bond strength that may arise with plasma spray methods. Magnetron sputtering ena‐ bles lower pressures to be used, because a magnetic field allows trapping of the secondary electrons near the target. This induces more collisions with neutral gases and increases plas‐ ma ionisation. Figure 3 is a diagram of the magnetron sputtering mechanism. RF magnetron sputtering is an improved ion-sputtering method. It has also been noted that sputtered films

possess higher adhesion to the substrate compared to the evaporation method.

(RF), ion beam sputtering (IBS), and reactive sputtering [36].

**Figure 3.** Schematic diagram of the sputtering mechanism

quency (RF) diodes that operate at high frequency.

**Figure 2.** Surface morphology of HA coatings obtained by thermal spray method (a) 27.5 kW at 80 mm SOD, (b) 27.5 kW at 160 mm SOD, (c) 42 kW at 80 mm SOD, and (d) 42 kW at 160 mm SOD

Evaporation involves the thermal phase change from solid to vapor under vacuum condi‐ tions, in which evaporated atoms of a solid precursor placed in an open crucible can travel directly and condense onto the surface of a substrate [35]. A vacuum environment is used to minimize contamination [36]. Han *et al.* [37] have created an HA coating using electron beam evaporation and then incorporated silver by immersion into AgNO3 solution. One ad‐ vantage of this method is an improved bond strength between the coating and substrate. The ratio of Ca/P in the HA coating was 1.62 with a bond strength of 64.8 MPa, which was significantly higher than a plasma sprayed bond strength of 5.3 MPa [37].

Sputtering involves a process of ejecting neutral atoms from a target surface using energetic particle bombardment. The energetic particles used in the sputtering process are argon ions, which can be easily accelerated towards the cathode by means of an applied electric poten‐ tial, hence bombarding the target, and ejecting neutral atoms from the target. These ejected atoms are then transferred and condense to the substrate to form a coating. Sputtering has been used in many applications such as the semiconductor, photovoltaic and automotive sectors. There are several sputtering methods, such as DC glow discharge, radio frequency (RF), ion beam sputtering (IBS), and reactive sputtering [36].

**Figure 3.** Schematic diagram of the sputtering mechanism

osition and sputtering. The beneficial features of PVD are high coating density, high bio-adhe‐ sion strength, formation of multi-component layers, and low substrate temperature [34].

30 Titanium Alloys - Advances in Properties Control

**Figure 2.** Surface morphology of HA coatings obtained by thermal spray method (a) 27.5 kW at 80 mm SOD, (b) 27.5

Evaporation involves the thermal phase change from solid to vapor under vacuum condi‐ tions, in which evaporated atoms of a solid precursor placed in an open crucible can travel directly and condense onto the surface of a substrate [35]. A vacuum environment is used to minimize contamination [36]. Han *et al.* [37] have created an HA coating using electron beam evaporation and then incorporated silver by immersion into AgNO3 solution. One ad‐ vantage of this method is an improved bond strength between the coating and substrate. The ratio of Ca/P in the HA coating was 1.62 with a bond strength of 64.8 MPa, which was

Sputtering involves a process of ejecting neutral atoms from a target surface using energetic particle bombardment. The energetic particles used in the sputtering process are argon ions, which can be easily accelerated towards the cathode by means of an applied electric poten‐ tial, hence bombarding the target, and ejecting neutral atoms from the target. These ejected atoms are then transferred and condense to the substrate to form a coating. Sputtering has been used in many applications such as the semiconductor, photovoltaic and automotive

kW at 160 mm SOD, (c) 42 kW at 80 mm SOD, and (d) 42 kW at 160 mm SOD

significantly higher than a plasma sprayed bond strength of 5.3 MPa [37].

The simplest model for sputtering is the diode plasma, which consists of a pair of planar electrodes, an anode and a cathode, inside a vacuum system [37]. The sputtering target is mounted on the cathode. Application of the appropriate potential difference between the cathode and anode will ionize argon gas and create a plasma discharge. The argon ions will then be attracted and accelerated toward the sputtering target. Such ion bombard‐ ment on the target will displace some of the target atoms. This results in electron emis‐ sion that will subsequently collide with gas atoms to form more ions that sustain the discharge [37]. Ion beam sputtering has disadvantages, such as a high capital investment cost (approximately one million dollars per machine), low deposition rates and a relative‐ ly small capacity per chamber batch [38]. Another type of sputtering employs radio fre‐ quency (RF) diodes that operate at high frequency.

Magnetron sputtering is one option to overcome the problems such as delamination and low bond strength that may arise with plasma spray methods. Magnetron sputtering ena‐ bles lower pressures to be used, because a magnetic field allows trapping of the secondary electrons near the target. This induces more collisions with neutral gases and increases plas‐ ma ionisation. Figure 3 is a diagram of the magnetron sputtering mechanism. RF magnetron sputtering is an improved ion-sputtering method. It has also been noted that sputtered films possess higher adhesion to the substrate compared to the evaporation method.

A summary of the characteristics of the various coating techniques for calcium phosphate is presented in Table 2. Each technique has its own benefits and drawbacks. However, sputter‐ ing is a promising method due to its ability to produce dense and thin coatings, as well as provide good bond strength [39-41].

was higher than coatings without a sublayer. Nieh *et al.* [48] used titanium as a pre-coat on

Sputtered Hydroxyapatite Nanocoatings on Novel Titanium Alloys for Biomedical Applications

http://dx.doi.org/10.5772/54263

33

Layered materials have previously been demonstrated to improve bonding between dissim‐ ilar materials. According to Ding [45], the top layer provides an excellent interaction with the surrounding tissue and promotes bone healing. A functionally graded coating (FGC) is an alternative method to enhance coating adhesion strength. Ozeki *et al.* [49] prepared an FGC of HA/Ti onto a metallic substrate. The coating thickness was 1 µm and consisted of 5 layers. The configuration of FGC was designed so that the HA was more dense near the sur‐ face, whilst the Ti was more dense near the substrate. The bonding strength using the FGC configuration was higher than using only HA, *i*.*e*., 15.2 MPa and 8 MPa for the FGC and

*Elastic properties.* Snyders *et al.* [50] manufactured HA via RF sputtering and revealed that the chemical composition influenced the elastic properties. As the Ca/P ratio decreased, the elastic modulus also decreased due to the insertion of Ca vacancies in the HA lattices.

The biological behaviour of biomaterials has been a fundamental criterion for successful candidate implant materials, along with their mechanical properties. The surface properties of a biomaterial play a significant role in the cell response. Thus, surface modification is an established strategy that has been used for biomedical applications due to its ability to en‐ hance bioactivity. High cell density enhances bone formation. The cell adhesion behaviour and proliferation are influenced by several factors, such as pore size, porosity, and surface

Thian *et al.* [45] carried out an *in vitro* test using a human osteoblast (HOB) cell model for a silicon incorporated hydroxyapatite (Si-HA) coating on titanium. The sample demon‐ strated an increase in metabolic activity compared to mono-HA coatings. Sputtered HA and Si coatings exhibited good differentiation of osteogenic cells and good biocompatibili‐ ty. It was noted that the biological response was influenced by the crystallinity of the HA coatings. Sputtered composite coatings of HA with other compounds may provide addi‐ tional advantages for implant performance. For instance, Chen *et al*. [52] incorporated sil‐ ver into HA, conducted a cytotoxic and antibacterial test, and reported that the silver had an antibacterial effect since the bacterial attachment was reduced compared to coatings

Tin and niobium were chosen as alloying elements because both metals are biocompatible and non-cytotoxic. The titanium alloy composition was designed using the molecular orbital DV-Xα method [53]. The calculation of the nominal composition of the alloys was based on

Ti6Al4V and found strong bonding between the Ti layer and the HA coating.

*5.5.2. Biological performance of sputtered hydroxyapatite coatings*

pure HA, respectively.

composition [51].

that did not contain silver.

**6. Experimental methods**

**6.1. Design and preparation of titanium alloys**

**Table 2.** Summary of various techniques for calcium phosphate coatings

#### *5.5.1. Properties of sputtered hydroxyapatite coatings*

*Coating thickness.* The HA coating thickness varies. Molagic [42] succeeded in producing HA/ZrO2 coatings with an average thickness of 3.2 µm. Hong *et al.* [43] manufactured a 500 nm thick coating of crystalline HA using magnetron sputtering. Ding [44] sputter de‐ posited HA/Ti coatings with a film thickness of 3-7 µm onto a titanium substrate. Thian *et al.* [45] succeeded in incorporating silicon in hydroxyapatite (Si-HA) using magnetron sputtering and discovered its potential use as a bio-coating. The Si-HA film thickness was up to 700 nm.

*Bond strength.* An *in vitro* and *in vivo* experiment on coatings using the sputtering technique revealed coating detachment problems. Cooley *et al.* [46] reported that HA coatings were re‐ moved after 3 weeks of implantation. A bond layer coating was suggested to overcome this weak adhesion at the interface and subsequent delamination. Ievlev *et al.* [47] measured the adhesion strength of HA coatings with a sublayer and revealed that the adhesion strength was higher than coatings without a sublayer. Nieh *et al.* [48] used titanium as a pre-coat on Ti6Al4V and found strong bonding between the Ti layer and the HA coating.

Layered materials have previously been demonstrated to improve bonding between dissim‐ ilar materials. According to Ding [45], the top layer provides an excellent interaction with the surrounding tissue and promotes bone healing. A functionally graded coating (FGC) is an alternative method to enhance coating adhesion strength. Ozeki *et al.* [49] prepared an FGC of HA/Ti onto a metallic substrate. The coating thickness was 1 µm and consisted of 5 layers. The configuration of FGC was designed so that the HA was more dense near the sur‐ face, whilst the Ti was more dense near the substrate. The bonding strength using the FGC configuration was higher than using only HA, *i*.*e*., 15.2 MPa and 8 MPa for the FGC and pure HA, respectively.

*Elastic properties.* Snyders *et al.* [50] manufactured HA via RF sputtering and revealed that the chemical composition influenced the elastic properties. As the Ca/P ratio decreased, the elastic modulus also decreased due to the insertion of Ca vacancies in the HA lattices.

#### *5.5.2. Biological performance of sputtered hydroxyapatite coatings*

The biological behaviour of biomaterials has been a fundamental criterion for successful candidate implant materials, along with their mechanical properties. The surface properties of a biomaterial play a significant role in the cell response. Thus, surface modification is an established strategy that has been used for biomedical applications due to its ability to en‐ hance bioactivity. High cell density enhances bone formation. The cell adhesion behaviour and proliferation are influenced by several factors, such as pore size, porosity, and surface composition [51].

Thian *et al.* [45] carried out an *in vitro* test using a human osteoblast (HOB) cell model for a silicon incorporated hydroxyapatite (Si-HA) coating on titanium. The sample demon‐ strated an increase in metabolic activity compared to mono-HA coatings. Sputtered HA and Si coatings exhibited good differentiation of osteogenic cells and good biocompatibili‐ ty. It was noted that the biological response was influenced by the crystallinity of the HA coatings. Sputtered composite coatings of HA with other compounds may provide addi‐ tional advantages for implant performance. For instance, Chen *et al*. [52] incorporated sil‐ ver into HA, conducted a cytotoxic and antibacterial test, and reported that the silver had an antibacterial effect since the bacterial attachment was reduced compared to coatings that did not contain silver.