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The protein of gastric cancer tissues was extracted through RIPA Buffer (Aidlab) with protease and phosphatase inhibitor cocktails (Roche). BCA protein assay (KeyGen biotech) was used to quantify protein concentration. The protein (30 μg) was separated in 10% Tris Glycine SDS gels and transferred to polyvinylidene difluoride membranes (Millipore). The membranes were blocked with 5% milk in TBST for 60 minutes at room temperature, then incubated with primary antibodies overnight at 4°C. After incubating with secondary antibodies (ZhongShan Golden Bridge Biotechnology Co., Ltd), the membranes were tested with Super Signal West Femto Masimun sensitivity substrate (Thermo Scientific).
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99.94
In IHC, staining percentage scores (0-5 points) multiplied staining intense scores (0-5 points) to get IHC scores (0-25 points). Staining percentage scores were defined as 0 point (0%-5%), 1 point (6%-25%), 2 points (26%-50%), 3 points (51%-75%), 4 points (76%-95%) and 5 points (96%-100%). Staining intense scores were defined as 0 point (negative), 1 point (weak), 2 points (weak to moderate), 3 points (moderate), 4 points (moderate to strong) and 5 points (strong). With the use of X-tile software (Version 3.6.1, Yale University), the optimal cut-points for IHC were analyzed and calculated as 12 points of CD54, 0 point of Lgr5, 0 point of CD133, 0 point of Oct4, 6 points of EpCAM and 8 points of Sox2 in primary lesions. The cut-points of these markers in metastatic LNs were the same with primary lesions, except Lgr5 (5 points) and Oct4 (1 point). Regarding qPCR, the cut-points of the expression folds of GC tissues to corresponding adjacent normal gastric tissues were also analyzed and calculated through X-tile. The cut-points were 1.5 folds of CD54, 1.3 folds of Lgr5, 2.5 folds of CD133, 0.6 folds of Oct4, 7 folds of EpCAM and 0.2 folds of Sox2. According to the cut-points in IHC and qPCR, the patients were further divided into low expression groups (≤cut-points) and high expression groups (>cut-points).
study
100.0
Statistical analyses were mainly conducted by SPSS software (Version 22, IBM). Chi-square test and rank sum test (Mann-Whitney U test) were used to analyze the unordered categorical variable and ranked data, respectively. Student's t-test was used to analyze the continuous data, if homogeneity of variance and normal distribution. Otherwise, rank sum test was used. Logistic regression was applied in multivariate correlation analysis. Kaplan-Meier and life-table methods were used to calculate the cumulative survival rates. Log-rank test and Cox's proportional hazard regression model were conducted for univariate and multivariate survival analyses, respectively. Prism 5 for Windows (Version 5.01, GraphPad Software) was used to draft the figure of Kaplan-Meier curve. Nomograms and calibration curves were performed through R for Windows (Version 3.2.0, R Foundation for Statistical Computing) with the package of Regression Modeling Strategies (rms), in which the variables were selected according to the model by Akaike information criterion in a stepwise algorithm. Comparison between the nomogram and TNM stage was performed with the package of Harrell Miscellaneous (Hmisc) and was evaluated by C-index meaning that the larger C-index, the more accurate was the prognostic prediction. Two-sided p value less than 0.05 was considered as statistical significance.
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100.0
Regular physical activity (PA) among adults has an enormous number of health benefits , but very low participation rates (e.g., ). Consequently, PA promotion initiatives are of high importance to public health. Regular walking is one of the most preferred PAs and thus a key target for intervention . One correlate of regular walking that has seen considerable attention in public health is dog ownership. Specifically, dog owners report more walking during leisure-time than non-owners [4–6]. While this is an interesting descriptive finding, its direct application to PA promotion is less practical, as dog ownership is an enormous responsibility with cost implications. Still, approximately 30% of the population in developed countries own dogs , and it is estimated that half of all dog owners do not walk their dogs regularly . While dog walking is merely one of many types of PAs that dog owners could potentially enact, it seems a logical way to engender both human and canine health benefits simultaneously among this large potential target population [8, 9]. Understanding the correlates of walking would thus help identify key intervention targets to promote owners to walk their dogs more.
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A recent review of 31 studies on the correlates of walking among dog owners found that an attachment to the dog in the form of responsibility/obligation/support and environmental access to suitable walking areas with dog supportive features (e.g., off-leash exercise) were reliable factors . More recently, Richards et al. have shown that social cognitive theory constructs of dog outcome expectations, social support and measures of the walking environment were key predictors of regular walking. Other studies have also shown some evidence that the theory of planned behavior can predict regular dog walking [12, 13]. Still, the Westgarth et al. review noted that only a handful of the studies used a theoretical framework to explain walking and this is a noteworthy limitation.
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99.9
An additional potential limitation to prior work is the positioning of intention as the proximal determinant of walking behavior. Indeed, even Westgarth and colleagues suggested that all correlates of dog walking should affect behavior through intention. This positioning makes the assumption that once a dog owner has positive intentions to walk, it will be sufficient to enact the behavior. Still, there is only modest support for the relationship between intention and behavior in general PA research . Interestingly, the relationship between intention and behavior also shows that almost all discordance occurs from those who intend but fail to perform the behavior, and not from those with low intentions who enact the behavior . The sizeable proportion of intenders who subsequently fail to follow-through and enact behavior has prompted the term ‘intention-behavior gap’, because approaches that feature intention as the proximal determinant of behavior have limited theoretical explanation for this finding . It seems a worthy line of inquiry to examine the intention-behavior gap in dog owners’ dog walking behavior and this has not been formally explored at present.
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99.9
Several models have attempted to understand the translation of intention into behavior, also known as action control . One of the most frequently applied of these in the PA domain is the multi-process action control framework (M-PAC; [16–19]). In this framework, intention (i.e., intend/do not intend) and behavior are divided into quadrants, which creates four possible profiles, but only three of substantive value: non-intenders who are subsequently not active; successful intenders who are subsequently active, and unsuccessful intenders who failed to enact their positive intentions. By contrast, the fourth profile of disinclined actors, who despite lack of intention are subsequently active, is hypothesized as empty because intention is viewed as a necessary but insufficient process to achieve PA within M-PAC [16, 17].
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The intention-behavior profiles in M-PAC have similarities to the stages of change in the transtheoretical model as intention-behavior hybrid constructs, but M-PAC profiles are not stages, as someone can move from non-intender to successful intender without ever falling into the “unsuccessful intender” profile. M-PAC suggests that intenders may be predicted by motivational processes of instrumental attitude/outcome expectations (utility of the behavior), affective judgments (enjoyment of the behavior) and perceived control (ability and opportunity to perform the behavior) which supports the tenets of most intention-based theories . In M-PAC, however, affective judgments and opportunity are also considered predictors during the intention-formation to action control process, where higher values are considered necessary for successful translation of intentions into behavior than for intention formation. Furthermore, action control is thought to be dependent on regulation behaviors (e.g., planning, self-monitoring), as people begin to use volitional tactics to help translate positive intentions into action. Regulation behaviors are conceptually similar to action/coping planning in the health action process approach or the behavioral processes of change in the transtheoretical model .
review
99.56
Continuance of action control is thought to also add reflexive processes such as automaticity/habit (i.e., behavior performed from stimulus–response bonds) and identity (self-categorisation) as one begins to perform the behavior more regularly. Specifically, as a behavior has become more routine, Rhodes and de Bruijn suggest that intention-driven behavior is executed partially from environmental cues , selective processing of information congruent with one’s self-categorization and the dissonance that arises from any discrepancy between self-categorization and behavior . To date, M-PAC has not been applied to understand dog walking behavior but it may show utility, given the likelihood of the intention-behavior gap. Furthermore, the regulatory and reflexive processes in M-PAC offer constructs that have not yet been examined within this domain. As much of this walking behavior has the potential to be ritualized and routine, habit also seems like a worthy concept in this domain. Further, as dog-owner attachment constructs have prior validation with owner dog walking , an exploration of dog-walking identity in action control may be important.
review
89.0
Thus, the purpose of this paper was to apply the M-PAC framework in a sample of dog owners to understand the translation of daily walking intention and behavior. It was hypothesized that participants would group into three (i.e., non-intenders, unsuccessful intenders, successful intenders) of the four possible intention-behavior profiles based on prior research in general physical activity contexts . It was further hypothesized that affective judgments (enjoyment of owner dog walking), opportunity (availability of time and environment to walk), regulation behaviors (detailed plans to dog walk) and reflexive processes of habit (learned responses to walking cues) and identity (personal standards of dog walking behavior) would explain successful, compared to unsuccessful, intenders based on prior research with this model .
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The details of the sample and the recruitment methods have been reported elsewhere , although this present study does not contain any of the same measures used from this prior report or address similar research questions. Eligibility to participate was delimited to English-speaking adults, 18+ years of age, who lived in Greater Victoria, Canada, and owned at least one healthy dog between one to seven years of age. Owners of young dogs under one year of age and senior dogs were excluded due to the larger variability in health status and physical ability to walk regularly . Following ethical approval, participants were given details of the study and asked for their informed consent online before proceeding to answer the questionnaire. The survey was published online for public access via Fluid Surveys between December 2013 and January 2014. The published link to the survey was shared primarily on various Facebook pages that were involved in canine rescue/rehoming, pet-related services, dog training services, etc. within the Greater Victoria, Canada region. The online survey link was also published on several websites (e.g., researcher’s laboratory website, graduate student society) and disseminated via the graduate student society’s weekly electronic mailing list. Pamphlets containing the study details, online survey link, and researcher’s contact information were also used in reaching out to more people in-person at dog parks; physical posters containing the same information were put up on notice boards located within recreation centres, university campus, libraries, and selected veterinary clinics that agreed to allow recruitment materials to be displayed. Due to the anonymity of the survey, specific technical settings were created to reduce the chances of multiple responses from the same respondent; access to the survey was limited to one time per computer. For every completed response that matched the eligibility criteria, one dollar in Canadian currency was donated to a local dog rescue of the respondent’s choice.
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Owner Dog Walking Behavior was measured using an adapted version of the Godin Leisure-Time Exercise Questionnaire that has been applied in prior related research [13, 29, 30]. Participants were asked to recall their average weekly walking with their dog during their free time over the past week. The questions were phrased to focus on their walking and not the physical activity of their dog during an outing (e.g., off leash running time). The measure contained three open-ended questions asking for the average frequency at 20+ minutes duration of mild (i.e., minimal effort, no perspiration, a casual walk), moderate (i.e., not exhausting, light perspiration, a good brisk pace) and strenuous (i.e., heart beats rapidly, sweating, as fast as you could walk) walking during the past week. The 20+ minutes duration was modified from the original 15+ min Godin Leisure-Time Questionnaire to correspond with the American College of Sports Medicine’s recommendation of 20+ minutes of strenuous physical activity for public health and to match the minimum walking recommendations for canine health . Commensurate with recommended physical activity guidelines for adults , we retained and aggregated the moderate and strenuous intensity categories (20+ min bouts) for analyses.
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100.0
We measured human outcome expectations based on the following two items from prior research : 1) Regular dog walking would help me to maintain or lose weight; 2) Regular dog walking would allow me to get to know my neighbourhood (α = 0.69) and measured canine-based outcome expectations with the item: Regular dog walking would help keep my dog healthy. The items began with the phrase “Assuming you walked with your dog daily, how likely or unlikely is it that each of the following would occur?” and were scored from 1 (very unlikely) to 5 (very likely).
study
99.9
Affective Judgments were measured using the intrinsic regulation scale from the Behavioral Regulations in Exercise Scale-2 , adapted for daily dog walking (α = 0.92). Example items included “I walk my dog because it is fun” and “I find dog walking a pleasurable activity”.
study
99.7
Perceived control over dog walking in the form of capability and opportunity were measured with items from Rhodes and colleagues [36, 37]. The items were: I am physically able to walk my dog regularly if I wanted to (capability) and I have the opportunity to walk my dog regularly if I wanted to (opportunity), scored from 1 (strongly disagree) to 5 (strongly agree).
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99.7
Behavioral regulation was measured using three items adapted from Sniehotta and colleagues for daily dog walking. The measures were scored from strongly disagree (1) to strongly agree (5). The reliability of these three items had a Cronbach’s α. = 0.76. Examples of these items included “I made detailed plans regarding what to do if something interfered with my plans to engage in dog walking over the past week” and “I made plans concerning “when”, “where”, “what” and “how” I was going to engage in regular dog walking over the past week”.
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99.9
Habit/Automaticity was measured with the self-reported automaticity subscale . The measure was scored on a five-point scale from strongly disagree (1) to strongly agree (5) and reliability was satisfactory (α = 0.93). Example items included “I engage in dog walking without consciously thinking about it” and “I engage in dog walking automatically”.
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Identity was measured using the three-item exercise role identity subscale adapted for dog walking. Example items included “I consider myself someone who is physically active with my dog” and “When I describe myself to others, I usually include being physically active with my dog”. The measure was scored on a five-point scale from strongly disagree (1) to strongly agree (5) and reliability was satisfactory (α = 0.87).
study
99.9
Our M-PAC measures were defined as daily dog walking because this target corresponds well to a mix of both human (i.e., 7 x 20+ min = 140+ min MVPA) and canine (at least daily walking 20+ for all healthy breeds of adult dogs) walking recommendations [9, 41]. Similarly, the creation of the action control framework of intention-behavior profiles was built to correspond with this definition. This allows for a scale correspondent prediction model as both the M-PAC predictors and the action control outcome variable are defined with the same target value of daily dog walking. Using this criterion, intention/behavior scores were dichotomized as below daily walking (<7 days per week) and daily walking (7 days per week). The categorization provided four possible quadrants of: a) non-intenders (low intention, low walking), b) non-intenders who were walking their dogs daily (low intention, high walking), c) unsuccessful intenders (high intention, low walking), and d) successful intenders (high intention, high walking) who were walking at least 140 min per week. To define our minimum cell size needed among these four possible action control categories, we used basic one-way analysis of variance power estimation. Considering a small medium effect size (f = .25), an alpha of .05, and a power of .80, 45 participants were needed in a particular intention-behavior profile to be included in the analyses . Based on prior research , we expected that participants classified as non-intenders who were walking their dogs daily would not be a large enough group to be included in subsequent analyses but we expected all other groups to be above this n = 45 criterion.
study
100.0
Before conducting the multivariate prediction of the action control framework, we examined potential demographic (age, gender, income, occupational status, education), home environment (presence of a back yard), and dog (breed size) characteristics as covariates using analysis of variance and chi-square analyses. Significant covariates (p < 0.05) were carried forward to the main analyses. For the main analyses, prediction of action control category membership used discriminant function analysis. Associations with a significant discriminant function used r = 0.20 as the minimum recommended effect size for the social sciences based on recent recommendations . For predictors that had a meaningful correlation with the discriminant function, follow-up univariate F-tests and Tukey post-hoc difference tests were conducted similar to prior work with the action control framework . Significance was set at p < 0.05, but effect sizes were used to aid in the interpretation of the inferential statistics results. Specifically, we used d = 0.30 as the minimum recommended effect size because the estimate is between Ferguson’s d = 0.41 and Cohen’s d = 0.20 recommendations. Our a priori power analysis of this prediction equation suggested that we required a sample size of N = 166, considering our estimated small effect size, p-level (0.05), an estimated power of 0.80, and the seven M-PAC predictors with an estimated two additional covariates.
study
100.0
The advantage of the action control framework approach is that researchers can gain insight into intention translation at a particular value. Typically, this value is correspondent with public health guidelines so it has strong applied relevance . Daily dog walking shares this strong applied relevance because it represents a criterion that is meaningful to both human (i.e., 140+ min of walking) and canine (at least daily walking 20+ min) physical activity recommendations [9, 41]. However, given the dichotomization procedure for walking that is used in the creation of the action control framework, it is possible that some of the participants will be classified as unsuccessful intenders from a very minor lapse in walking behavior that isn’t particularly meaningful and this may confound the prediction results and the relevance of the findings. For example, walking six days per week when intending to walk daily represents only a 14% intention-behavior gap. To address the possibility that a minor deviation in behavior is accounting for our findings, we conducted three sensitivity analyses. First, we computed descriptives for the MVPA walking frequency variable among unsuccessful intenders in order to ascertain a basic understanding of the distribution of this group. The group mean and standard deviation should be at five or less bouts of walking in order to show that the dichotomization is meaningful in terms of deviation from daily walking intentions. Second, we recoded those who report six days or more of walking as “successful intenders” and examined whether the proportional shift was significant compared to the original seven day coding. Finally, we re-ran the discriminant function analyses to examine whether any of the findings changed as a result of this recode. The results should not change unless the findings are sensitive to this minor recode. All data are available from the second author.
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A total of 228 respondents began the online survey, but only 227 completed the M-PAC items (see Table 1). The mean age of respondents was 43.11 (SD 12.37) years, 88.4% were females, 98.5% were Caucasians, 53.3% were currently employed full-time, 54.2% had four-year college education and above, and 36.5% reported annual household incomes above $100,000. The sample was comparable to census data, with the exception of the inequitable gender response . All participants responded that their dogs were healthy and thus capable of daily walking.Table 1Sample demographicsCharacteristicsDog Owner Demographic Profile Age in Years (SD)43.11 (12.37) % Female88.4 % Caucasian98.5 % 4 year college and above54.2 % Income $100 k and above36.5 % Full-time Employed53.3 % Retired11.0 % Presence of a Yard92.2Health Profile % Smoker7.1Self-Reported Health: % Poor2.4 % Fair9.9 % Good36.8 % Very Good37.7 % Excellent13.2 Mean BMI (SD)25.59 (5.04)Dog Profile % Healthy Dogs100 % Female50.2 % Small27.3 % Medium34.8 % Large35.7 % Giant2.2
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The intention-behavior profiles of the action control framework yielded the following distributions: a) non-intenders (26%; n = 59), b) non-intenders who did walk daily (1%; n = 2), c) unsuccessful intenders (33%; n = 75), and d) successful intenders (40%; n = 91). Given the small and severely unequal sample size of the non-intenders who walked daily, it was dropped from subsequent analyses as it did not meet power analyses requirements. Overall, the intention-behavior gap (unsuccessful intenders n = 73/total intenders n = 164) was 45%.
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Our preliminary covariate analyses showed that participant demographics (age, gender, income, occupational status, education) and the presence of a residential back yard space were not associated with these action control categories (all p > 0.25). Dog breed size, however, was significantly different across the action control framework [χ 2 (4) = 13.18; p < .01), with small breeds more likely to be present in the non-intender and unsuccessful intender categories and larger breed dogs more likely to be present in the successful intender category. Thus, dog breed size was carried forward to the main analyses. The main discriminant analysis identified one discriminant function that significantly distinguished among the three groups [χ 2 (18) = 75.31, p < 0.01; canonical r = 0.49]. Affective judgements (r = 0.33), automaticity (r = 0.38), behavioral regulation (r = 0.33) identity (r = 0.22) and dog breed size (r = 0.28) had meaningful correlations with the discriminant function (see Table 2). Follow-up tests showed that affective judgments, automaticity, and behavioral regulation differentiated non-intenders, unsuccessful intenders, and successful intenders with consecutively larger values in each predictor variable (d > 0.30). Identity and dog breed size, however, discriminated between unsuccessful and successful intenders (d > 0.30), but not between non-intenders and unsuccessful intenders.Table 2Prediction of daily dog walking intention-behavior profiles using multi-process action control variables and dog sizeIntention-Behavior ProfilesCorrelation with Discriminant FunctionUnivariate Follow-Up F2,218 Post HocsNon-intenders(n = 59)Unsuccessful Intenders(n = 75)Successful Intenders(n = 91)Dog Breed Size2.05 (0.87)1.89 (0.86)2.34 (0.77).286.33*NI,UI < SIOutcome Expectations (Human)3.98 (0.77)3.92 (0.83)4.28 (0.78).14NANAOutcome Expectation (Canine)4.60 (0.52)4.65 (0.47)4.81 (0.40).07NANAAffective Judgements4.10 (0.82)4.35 (0.59)4.69 (0.41).3318.43*NI < UI < SIPerceived Capability4.48 (0.98)4.73 (0.52)4.76 (0.61)-.03NANAPerceived Opportunity4.27 (0.84)4.54 (0.61)4.62 (0.67).03NANABehavioral Regulation2.73 (0.93)3.04 (0.93)3.42 (0.92).3310.27*NI < UI < SIAutomaticity3.00 (1.02)3.63 (1.09)3.96 (0.98).3815.65*NI < UI < SIIdentity3.33 (1.01)3.49 (0.85)4.07 (0.63).2217.53*NI,UI < SINote: * = p < 0.01. NI = non-intenders, UI = unsuccessful intenders, SI = successful intenders. NA = not applicable. Post hoc tests interpreted as p < 0.05 and d > 0.30 based on the recommended minimum effect size for social science data (Ferguson ; Cohen )
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Note: * = p < 0.01. NI = non-intenders, UI = unsuccessful intenders, SI = successful intenders. NA = not applicable. Post hoc tests interpreted as p < 0.05 and d > 0.30 based on the recommended minimum effect size for social science data (Ferguson ; Cohen )
other
98.7
The unsuccessful intenders group reported a mean of 2.97 bouts of walking with a standard deviation of 2.36. This is a sizeable deviation from their reporting of intended daily walking, suggesting meaningful intention-behavior discordance in this group. Recoding of the participants who reported six walks as “successful intenders” however, did shift 12 participants (16%) out of the unsuccessful intenders category and this was a significant change to the proportions [Cochran’s Q (1) = 12.00; p < 0.01]. Results from the discriminant function analysis with this new categorization were almost identical to the original action control classification [χ 2 (18) = 88.16, p < 0.01; canonical r = 0.49] with the same overall findings and no deviations in the results by p-value or effect size classifications. Thus, the results were not sensitive to minor deviations in intention and behavior.
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This study was the first to examine the intention-behavior gap in daily walking behavior among dog owners and predict this gap using the M-PAC framework designed for this purpose [16, 17]. We hypothesized that three of four possible intention-behavior profiles would emerge (i.e., non-intenders, unsuccessful intenders, successful intenders), commensurate with prior research in general PA . This hypothesis was supported. Only two participants in the sample were classified as having low intentions and engaged in daily dog walking. By contrast, 73% of the sample was comprised of intenders, yet 45% of these intenders were not walking congruent with their intentions and most of these participants walked <50% below what they intended.
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The finding has both theoretical and applied implications. From a theoretical perspective, the results demonstrate that intention formation is a necessary process but it may be insufficient for walking enactment among many dog owners. Thus, frameworks that propose intention as the bridge to behavior, which comprise many of our most popular health behavior models and contemporary models for dog walking , may not be as useful as models that separate intention translation from intention formation . From an applied perspective, these results also help explain that some dog owners have yet to form daily walking intentions, while even more participants intend to walk their dog daily but fail to follow-through. Thus, dog walking promotion may benefit from both intention formation and action control interventions, depending on the readiness of the population.
study
99.9
In light of this aim, the second purpose of the study was to predict these intention-behavior profiles using the M-PAC framework. The findings support almost all of the tenets of that model. M-PAC suggests that instrumental outcome expectations about walking may not be as important to action control because they do not reflect the experience of the action itself. Perceptions of capability are also generalized to the act (i.e., am I physically able to walk or not) and not specific to each action but could be important to dog owners given the additional demands of controlling dog behavior. Congruent with theory, outcome expectations and perceived capability to walk did not contribute to the intention-behavior profiles while controlling for other M-PAC variables. Thus, educational/informational campaigns based on the benefits of walking and interventions to improve one’s ability to walk are not recommended as standalone interventions for closing the intention-behavior gap, even though these constructs have been shown to be general correlates of owner dog walking .
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By contrast, affective judgements did contribute to the discriminant function, predicting all three intention-behavior profiles. While affective judgments have been shown to predict owner intentions to dog walk in prior research , this finding supports the approach taken in M-PAC , where higher affect is also needed to enact a behavior than form the intention. From a theoretical perspective, the importance of affective over instrumental outcome expectations during action control supports hedonic theories of behavior. The practical aspect of this finding suggests that consideration of pleasure in walking interventions may facilitate closing the intention-behavior gap. M-PAC constructs are considered the consequence of individual, social, and environmental/policy factors . For affective judgments, this could involve several factors that require future research, such as pleasant walking conditions (e.g., environmental design and dog-friendly amenities), social aspects of walking (e.g., walks with friends/ other dog owners), and dog-related variables that could affect the walking experience (e.g., level of training and responsiveness, dog’s sociability towards other dogs and people, owner enjoyment related to bonding with their dog).
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100.0
The hallmark of most action control models, including M-PAC, is the premise that volitional self-regulation tactics are needed to tie good intentions to behavior . In support of this hypothesis, behavioral regulation correlated with the discriminant function and predicted all three intention-behavior profiles. The inclusion of behavioral regulation variables in understanding general PA has had considerable support but this is the first study in dog owners to apply this variable to our knowledge. The results suggest that having dog owners make action (when, where, how, and with whom) and coping (details about how to overcome potential set-backs) plans and subsequently track these plans (e.g., with mobile phone apps, diaries) may be very useful to close the intention-behavior gap.
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100.0
The reflexive M-PAC constructs of habit/automaticity and identity also contributed to the discriminant function. Habit predicted all three intention-behavior profiles while identity was considerably higher for successful intenders compared to unsuccessful intenders. These are new constructs to the dog owner and walking correlates literature, and represents potentially important considerations for future intervention. Both constructs are considered for the maintenance of action control, as performance experience with the behavior is necessary for their formation. From a theoretical standpoint, habits are thought to be formed from consistent repetitions of action and exposure to similar cues , which highlight the importance of environmental and social context. Preliminary research suggest that the key to habit formation is consistency of practice . Dog owners with a regular walk routine may thus be more likely to acquire automaticity over time and facilitate action control partially independent of motivation. Given the long period of owning a dog, this may be a critical factor to behavior maintenance over time.
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100.0
Our measure of dog walking identity in this study may overlap with prior research on dog support/obligation (e.g., [12, 13, 49]). Identity is a self-categorization of oneself into a particular role and a sense of obligation and responsibility for one’s dog would seemingly be a part of a dog walking identity. Our findings with identity and action control support this prior work. Qualitative interviews with dog owners highlight how dog walking is a duty or a role described with similarities to parenting children . Further, Brown and Rhodes found that a sense of dog responsibility/obligation was able to predict walking behavior independent of walking intention, which is similar to the results of the current study. In M-PAC, identity is expected to impact action control via selective processing of information, thus shielding from other intentions (i.e., staying on course) and by imposing dissonance (i.e., negative affect) when behavior is not congruent with the identity . It seems worthy to explore whether dog walking identity can be modified, presumably through pre-set rank-ordering (e.g., priority lists, I will walk the dog before I do household chores), commitment affirmations (realizations and statements about the value of dog walking to companionship), and social activations (purposeful statements about dog walking when describing one’s self to others) .
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100.0
The only variable discrepant with our hypotheses was perceived opportunity, which did not contribute to the discriminant function with a meaningful effect size. Our assessment of this construct used Williams and Rhodes’ suggestion to include a motivational qualifier in the assessment (i.e., if I wanted to), which may have explained the null result as opportunity was circumscribed from motivation. Westgarth and colleagues point out that opportunities to dog walk is not a consistent correlate within the dog walking literature, and it may also not be a critical predictor of action control.
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100.0
Interestingly, dog breed size also predicted action control independent of the M-PAC variables. Those owners with larger dogs were more likely to enact their walking intentions compared to those with smaller dogs, yet dog size did not distinguish between non-intenders and unsuccessful intenders. The finding is interesting and may highlight how the dog influences walking independent of initial owner-related walking motivations, although assessment with a stronger design (i.e., longitudinal, experimental) is needed to advance this conjecture. Large dogs have higher energy expenditure needs than smaller dogs so this finding may represent the dog’s influence on action control. Regular dog walking has been characterised as a unique physical activity due to the symbiotic inter-dependency between the canine and owner and dog characteristics have been correlated with regular walking . This is the first study to examine action control of dog walking, but future research into the role the dog plays in facilitating or inhibiting owner intentions seems warranted.
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100.0
Despite the novel findings of this study, the results need to be considered within the context of its limitations and these prompt areas for future research. First, the survey was cross-sectional, making interpretations limited to the assumption that past walking is a good predictor of future dog walking. Second, the assessment of walking is subject to self-report bias. It would stand to reason that an objective assessment of walking would be ideal and a more stringent test of the M-PAC model. Third, the outcome expectation, perceived capability, and perceived opportunity items had limited items that might be compromising the reliability and validity of these constructs. Replication with measures employing multi-item measures with test-retest validation, frames other than daily walking (e.g., 5 times per week) and more dog-related and environmental characteristics is warranted. Finally, the sampling frame was limited to those who visit dog-related social media, posters, and advertisements around Victoria, Canada, and included mainly affluent middle-aged non-Hispanic white women. Recent research suggests that the effects of dog ownership on walking may not extend across racial/ethnic groups , so a broader sampling approach is needed in future research in order to examine whether these findings replicate to other regions and participants with different socio-demographic profiles.
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99.94
Overall, the findings demonstrate that dog walkers show an intention-behavior profile similar to general physical activity research, with almost half of those intending to engage in daily walks falling short of this criterion. Using the M-PAC framework, differences between successful and unsuccessful intenders were associated with affective judgments about walking, behavioral regulation tactics, habit, and identity. Addressing these should be the focus of interventions aimed at improving dog walking.
study
99.94
Patients with massive and submassive pulmonary embolism (PE) have an increased risk of cardiovascular collapse and death.1 Standard anticoagulation alone is inadequate for patients with massive (high-risk) PE.2 Early reperfusion therapy with fibrinolysis, surgical embolectomy, or catheter-based ‘pharmacomechanical’ therapy is recommended.3–5 For patients with submassive (intermediate-risk) PE, routine reperfusion is not advised. However, a subset of submassive PE patients who have increased cardiac troponin and imaging evidence of right heart dysfunction may benefit from reperfusion.5,6 While the data are most extensive for systemic fibrinolysis,6–8 clinicians are often hesitant to administer fibrinolytic therapy, even in the highest-risk PE patients, because of the concern of major bleeding, especially intracranial hemorrhage (ICH).
review
99.9
The frequency of major bleeding complications in the setting of fibrinolysis for PE is thought to be related, in part, to the dose of fibrinolytic agent. In 1990, the Food and Drug Administration approved full-dose peripheral venous administration of tissue-plasminogen activator (t-PA) 100 mg over 2 hours for PE. Half-dose fibrinolytic therapy may offer a reduced risk of ICH.9,10 Pharmacomechanical catheter-directed fibrinolytic therapy utilizes lower doses of fibrinolytic drug than systemic therapy, and the pharmacological effect is concentrated in the area of greatest thrombotic burden. One of the most extensively studied pharmacomechanical catheter-based techniques is ultrasound-facilitated, catheter-directed, low-dose fibrinolytic therapy, which we evaluated in SEATTLE II for treatment of massive and submassive PE.
study
69.1
SEATTLE II enrolled 150 patients and showed a prompt reduction in the right ventricular (RV)-to-left ventricular (LV) diameter ratio, pulmonary artery systolic pressure, and pulmonary angiographic obstruction at 48 hours without any ICH.11 In this exploratory analysis, we evaluate patients who suffered major bleeding events during and after ultrasound-facilitated, catheter-directed, low-dose fibrinolysis to identify risk factors for bleeding.
study
99.94
SEATTLE II has been reported in detail.11 From June 2012 to February 2013, 150 patients were enrolled at 22 sites across the US. Eligible patients were required to have proximal PE (filling defect in at least one main or lobar pulmonary artery), be at least 18 years old, a PE symptom duration of 14 days or fewer, and an RV/LV diameter ratio of at least 0.9 on a contrast-enhanced chest computed tomogram (CT). We included patients with massive (defined as syncope, systemic arterial hypotension, cardiogenic shock, or resuscitated cardiac arrest) or submassive (defined as a normotensive patient with PE and evidence of RV dysfunction) PE. Major exclusion criteria were stroke or transient ischemic attack, head trauma, or other active intracranial or intraspinal disease within 12 months; major surgery within 7 days; recent active bleeding from a major organ; hematocrit less than 30%; and systolic blood pressure less than 80 mmHg despite vasopressor or inotropic support.
study
99.94
The EkoSonic® Endovascular System (EKOS, a BTG International Group company, Bothell, WA, USA) procedure was performed by an experienced operator from Interventional Cardiology, Interventional Radiology, Vascular Surgery, or Cardiothoracic Surgery. Venous access was obtained, most often with ultrasound guidance, via common femoral or internal jugular venipuncture.
other
99.9
The fixed-dose regimen of t-PA was 24 mg for both unilateral and bilateral PE. A continuous catheter-directed pulmonary artery infusion of t-PA (Genentech, San Francisco, CA, USA) was started at 1 mg/hour for 24 hours for unilateral PE. For patients with bilateral PE, two drug delivery devices were placed, and a continuous infusion of t-PA was started at 1 mg/hour per catheter for 12 hours. No adjunctive interventional techniques to assist thrombus removal or dissolution were permitted. During the procedure, intravenous unfractionated heparin was continued at intermediate intensity with a goal activated partial thromboplastin time (aPTT) of 40–60 seconds. After removal of the catheters, the access site was manually compressed for a minimum of 5 minutes. Fifteen minutes after achieving hemostasis, full therapeutic anticoagulation was reinitiated.
clinical case
98.4
The primary safety outcome was major bleeding within 72 hours of initiation of the procedure. Bleeding events were classified by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) bleeding criteria.12 Major bleeding was defined as either GUSTO moderate or GUSTO severe/life-threatening bleeding events. All monitoring for major bleeding within 72 hours was performed during the hospitalization. All bleeding complications were adjudicated by a designated independent Study Safety Monitor.
other
99.25
Comparisons between those with and without major bleeding were performed by t-test for continuous data and by Fisher’s exact test for binary data. Categorical data comparisons with greater than 2×2 dimensions were performed by the Freeman-Halton exact test. Univariate analyses were performed for various baseline and treatment characteristics to assess their relationship with major bleeding status. Co-morbid conditions that could complicate the use of fibrinolytic therapy and had a univariate p<0.10 were included in the multivariate logistic regression model as potential predictors for bleeding. These included recent major surgery, cerebrovascular disease, recent gastrointestinal or genitourinary bleeding, and recent trauma. Aside from the multivariate logistic regression analyses, no adjustments for multiple comparisons were made. All analyses were performed using SAS® software version 9.2 (SAS Institute, Cary, NC, USA).
study
100.0
Data from 149 patients are included in this analysis (Table 1) because one patient died from massive PE before completion of the procedure. Fifteen patients (10%) developed 17 major bleeding complications, defined as GUSTO severe/life-threatening and moderate bleeding events (Table 2). None suffered ICH. GUSTO mild bleeding was observed in 20% of patients. GUSTO mild bleeding was observed in 15 (14%) patients with submassive PE and six (25%) of those with massive PE (p=0.21).
study
99.94
Of the 15 patients with major bleeding, four (26.6%) developed access site-related bleeding (Figure 1). Three patients (20%) developed thoraco-abdominal wall hematomas, while two (13.3%) suffered nasopharyngeal bleeding. One patient developed major bleeding from the site of hysterectomy and required blood transfusion.
clinical case
98.8
The dose of t-PA administered in both groups was identical, with a median dose of 24 mg (Table 3). The median duration of fibrinolytic therapy in both groups was 12 hours. The mean aPTT was similar in both groups (40.8 ± 18.5 seconds for major bleeding vs 38.5 ± 26.8 seconds for no major bleeding; p=0.8).
study
99.94
Most patients in the study (87%) received two devices for delivery of fibrinolytic therapy and hence required more than one site of vascular access (Table 4). However, there was no difference in the number of devices used between those who developed major bleeding and those who did not. The majority of devices (238/278; 86%) were inserted via femoral venipuncture. Of these, 177 (74%) were inserted via the right femoral vein. All patients with major bleeding had femoral vein access for device delivery, compared to 84% in the group without major bleeding (p=0.04).
study
99.94
The use of ultrasound guidance for obtaining venous access to deliver therapy was common (73%). There was no difference in the utilization of ultrasound guidance between the two groups; however, multiple venous access attempts were more frequent in the major bleeding group (27.6% vs 3.6%; p<0.001).
study
99.94
The overall rate of IVC filter insertion in the study was 16%. The frequency of IVC filter placement was 40% in the major bleeding group compared with 13% in the group without major bleeding (p=0.02), and 83% of these filters were placed because of discontinuation of anticoagulation due to major bleeding. IVC filter insertion was performed in 7.4% of patients at the end of an ultrasound-facilitated, catheter-directed, low-dose fibrinolytic procedure through the same sheath and in 8.7% of patients at a later point during the hospitalization as a separate procedure.
study
99.94
A patient-level multivariate logistic regression analysis was performed to explore potential predictors of major bleeding (Table 6). The variables (univariate p<0.10) predicting patients with and without major bleeding were massive versus submassive PE, immobility within 30 days of PE, presence of co-morbid conditions, multiple venous access attempts, use of an adjunctive IVC filter, and baseline serum creatinine level. Only massive PE (adjusted odds ratio 3.6, 95% confidence interval 1.01–12.9; p=0.049) and multiple venous access attempts (adjusted odds ratio 10.09, 95% confidence interval 1.98–51.46; p=0.005) were independently associated with increased risk of major bleeding.
study
99.94
In SEATTLE II, major bleeding occurred in 10% of patients undergoing ultrasound-facilitated, catheter-directed, low-dose fibrinolysis. Nearly a quarter of these major bleeds were associated with vascular access, including one GUSTO severe/life-threatening bleed. No patient suffered ICH, and there were no fatal bleeds. Factors most strongly associated with an increased risk of bleeding were the presence of massive PE and multiple attempts at obtaining venous access. All patients with major bleeding had femoral access for placement of the ultrasound-facilitated, catheter-directed, low-dose fibrinolysis. Major bleeding was associated with a longer length of hospital stay and more frequent insertion of IVC filters.
study
96.06
Clinical trial and registry data demonstrate that the ‘real world’ use of fibrinolytic agents in PE patients is associated with a high major bleeding and ICH risk. In the International Cooperative Pulmonary Embolism Registry (ICOPER),13 the rate of major bleeding was 21.7% and that of ICH 3.0%, while Fiumara et al.14 reported a 19.2% and 5.0% frequency, respectively. Previous studies have shown an association between bleeding complications and factors such as older age,15 female sex,16,17 high or low BMI,15 underlying malignancy, and several other co-morbid conditions.3,18 In our study, none of these factors significantly influenced the rate of major bleeding. This may have been because of the relatively small number of major bleeding events in this analysis.
study
99.94
We identified multiple access attempts as an area where procedural safety could be improved. Use of ultrasound guidance in obtaining vascular access is becoming widely accepted.19 Ultrasound guidance may increase the accuracy of venous access and potentially reduce bleeding complications by minimizing the chance of inadvertent arterial puncture. Routine use of this technique in patients being considered for catheter-directed fibrinolysis may reduce the number of failed venous access attempts. While we found no difference in major bleeding between patients in which venous access was guided by ultrasound and those in which it was not, the relatively small number of major bleeding events may have limited our ability to detect a difference. Other potential strategies to reduce major bleeding complications are to use upper extremity veins (e.g. cephalic) that are not adjacent to an artery and to utilize micro-puncture access needles.
study
98.9
We observed that all patients with major bleeding had femoral access for placement of the ultrasound-facilitated, catheter-directed, low-dose fibrinolysis compared with 84% of those without major bleeding. Femoral access attempts are associated with an increased risk of unintended femoral artery or side branch puncture. Alternative access sites, such as the internal jugular vein, may reduce the risk of major bleeding in patients undergoing ultrasound-facilitated, catheter-directed, low-dose fibrinolysis.
study
70.0
The lack of a comparator group in SEATTLE II precludes any conclusions regarding the relative safety of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis compared with systemic fibrinolysis versus anticoagulation alone. The number of patients enrolled in the study was relatively small and may have limited the power of our multivariate analysis to identify significant predictors of bleeding.
study
97.44
Massive PE, multiple venous access attempts, and femoral vein access are risk factors for major bleeding associated with ultrasound-facilitated, catheter-directed, low-dose fibrinolysis. These findings point toward continuous quality improvement by focusing on decreasing the morbidity of venipuncture when undertaking catheter-directed thrombolysis.
other
99.9
The location and pattern of interconnections between neocortical areas processing visual information in the eutherian carnivore, domestic cat, are illustrated in Figures 1A,B. As in other mammals studied so far: (1) “lower-order” visuotopically organized cortical areas, some of which receive their principal or a substantial, direct thalamic input from the dorsal lateral geniculate nuclei (LGNd), send numerous “feedforward” associational projections to the “higher-order” visual areas; (2) beyond the primary visual cortices, information about pattern/form vs. motion is processed along two largely parallel “quasi-hierarchical” feedforward streams; and (3) higher-order areas send numerous associational “recurrent” or “feedback” projections back to lower-order areas (cat: Rosenquist, 1985; Dreher, 1986; Salin and Bullier, 1995; Scannell et al., 1995; Dreher et al., 1996; macaque monkey: Van Essen and Maunsell, 1983; Felleman and Van Essen, 1991; Bullier, 2004; Nassi and Callaway, 2009; Gilbert and Li, 2013; Markov and Kennedy, 2013; rat: Sanderson et al., 1991; Coogan and Burkhalter, 1993; Johnson and Burkhalter, 1996; mouse: Wang and Burkhalter, 2007; Wang et al., 2012).
study
99.94
(A) The dorsolateral view of cat’s left cerebral hemisphere with approximate location of electrode penetrations in area 19. Upward arrow indicates approximate position of the Horsley-Clarke anterior-posterior zero coordinates. Dark gray area indicates the location of the foot of the cooling probe which covered most of areas 20a and 20b. Lighter gray indicates the spread of cooling in the vicinity of cooling foot. (B) A block diagram of the cat’s visual system with simplified neuronal circuitry of retino-geniculo-cortical pathways, pattern/form and motion processing cortico-cortical hierarchies. Note that many cortical areas including area 19 and postero-temporal visual (PTV) cortex are directly interconnected via horizontal cortico-cortical feedforward and feedback connections (after Rosenquist, 1985; Dreher, 1986; Salin and Bullier, 1995; Scannell et al., 1995; Dreher et al., 1996). (C) The location of receptive field (RF) centers of 28 area 19 neurons tested for the effects of cooling of PTV. Note the location of RF centers of 11 area 17 neurons examined for velocity-tuning in the previous series of experiments (Huang et al., 2007). (D) Outlines of RFs of area 19 neurons of two cats included in the present study. The effects of cooling PTV were tested only in some cells. The bottom right insert plots area 19 cells’ average RF areas at azimuths around 5° and 20°. (E) Frequency distribution of eye dominance classes of area 19 cells recorded in the present study (solid lines) and the cooling sample (red dotted lines). Area 17 data are shown in green.
study
100.0
The direct connections between visual areas are reciprocal but not strictly hierarchically sequential. In particular: (1) primary visual cortices (striate cortices, areas 17, areas V1) at the very bottom of the postulated hierarchies, send direct feedforward projections not only to areas at the immediate next level of putative hierarchies but also to areas higher-up; and (2) areas at the intermediate levels of the putative hierarchy send their direct feedforward and feedback projections not only to their immediate hierarchical neighbors but also to hierarchically more remote areas, including the primary visual cortices (Dreher, 1986; Felleman and Van Essen, 1991; Markov and Kennedy, 2013; Markov et al., 2014).
study
99.25
The cat’s postero-temporal ventral (PTV) cortex encompasses cytoarchitectonic areas 20a and 20b (Tusa and Palmer, 1980). PTV constitutes a distinct part of pattern/form information processing stream (Campbell, 1978; Lomber et al., 1996a, b) and is the presumed homolog of primate infero-temporal cortex (Payne, 1993). Although PTV and primary visual cortices are interconnected only indirectly (Figure 1B, Rosenquist, 1985; Dreher, 1986; Dreher et al., 1996; Burke et al., 1998; Batardiere et al., 1998), reversible inactivation of PTV affects the responses and a number of receptive field (RF) characteristics, of a substantial proportion of neurons in the part of V1 corresponding visuotopically to PTV (Bardy et al., 2006, 2009; Huang et al., 2007).
study
99.94
Cytoarchitectonic area 19 (peristriate cortex, presumed homolog of V3 of primates—Payne, 1993; Rosa and Manger, 2005) and cytoarchitectonic area 21a (presumed homolog of V4 of primates—Payne, 1993), like PTV, constitute distinct parts of the pattern/form information processing cortical stream (area 19: Sprague et al., 1977; Khayat et al., 2000; reviews Orban, 1984; Dreher, 1986; Dreher et al., 1996; area 21a: Dreher, 1986; Mizobe et al., 1988; Wimborne and Henry, 1992; Dreher et al., 1993; Lomber et al., 2001; Villeneuve et al., 2009). Both areas 19 and 21a have substantial direct interconnections with the primary visual and PTV cortices, and are likely therefore to play important roles in shaping the exchange of information between PTV and V1 (Figure 1B, for reviews, see Rosenquist, 1985; Dreher, 1986; Dreher et al., 1996; Batardiere et al., 1998). Indeed, reversible inactivation of entire area 21a and part of area 19, results in substantial changes in the magnitude of responses and many RF properties of large subsets of neurons in the visuotopically corresponding part of V1 (Wang et al., 2000).
review
89.44
A substantial amount of data has been accumulated concerning the role of feedback from the higher-order visual areas on the responses of V1 neurons (for review see Gilbert and Li, 2013). However, very little is known about the role of feedback from the higher-order visual areas on the responses of neurons in the intermediate areas and putative role played by those areas in shaping the exchange of information between the higher-order areas and V1. Thus, in the present study, we examined the effects of reversible inactivation by transient cooling to 10°C of ipsilateral PTV cortex, on the responses of neurons located in the intermediate part of pattern/form information processing stream—area 19. In a substantial proportion of these cells, PTV inactivation affected the magnitude of responses to optimal and peri-optimal visual stimuli and/or induced upward changes in velocity preferences and direction selectivity indices (DSIs), that is, the properties which are thought to be determined by the properties of their dorsal thalamic and/or feedforward cortical inputs.
study
99.94
Animal preparation and recording procedures followed the guidelines of the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes and were approved by the Animal Care Ethics Committee of The University of Sydney. The effects of PTV cooling on background activity and responses of area 19 cells were tested in four adult female cats (Felis catus) weighing 2.5–3.4 kg. Animals were initially anesthetized with a gaseous mixture of 2.5%–5% of halothane in N2O/O2 (67%/33%). Throughout subsequent surgery, halothane level in the mixture was reduced to 1%–2%, while throughout the single-neuron recording sessions and between the intervals, halothane level was kept within 0.4%–0.8%. A tracheotomy was performed in order to reliably maintain artificial ventilation. Right cephalic vein was cannulated to allow continuous slow infusion of nutrients and paralyzing agent gallamine triethiodide injected at a rate of 10 mg/kg/h. Gallamine triethiodide-block resistant, residual eye movements were largely eliminated by bilateral cervical sympathectomy (see Rodieck et al., 1967). Opportunistic infections, brain swelling and excessive mucous secretion were controlled by daily injections of respectively the antibiotic amoxycillin trihydrate (75 mg, i.m.), dexamethasone phosphate (4 mg, i.m.) and atropine sulfate (0.3 mg, i.m.). Body temperature (37.5°C), heart rate (180–220 beats/min), alveolar CO2 level (3.5%–4%) and electroencephalogram (δ waves 0.5–4 Hz) were continuously monitored and maintained at appropriate levels. Phenylephrine hydrochloride (0.1%) was applied to each eye to block accommodation and to retract nictitating membranes. Pupils were dilated by daily applications of a couple of drops of atropine sulfate (1%). Neutral-power, air-permeable plastic contact lenses (radius 8.5 mm) were fitted to protect the corneas from drying. Artificial pupils (3 mm in diameter) and corrective lenses were placed in front of the eyes. Refractive power of corrective lenses necessary to focus the eyes on a tangent screen located 57 cm in front of the cat was determined by slit/streak retinoscopy (range: +0.5 to +3.0 diopters). In order to monitor the residual eye movements, positions of optic discs and areae centrales (Bishop et al., 1962) were, back-projected, at least twice daily, onto the tangent screen using a fiber-optic light source (Pettigrew et al., 1979).
study
98.44
Following an injection of 10 ml of D-mannitol (25%; i.v.), separate craniotomies were performed over the left ventral posterior suprasylvian region (Horsley-Clarke or HC coordinates: P3–P8 mm, lateral 15–20 mm) and left area 19 (HC coordinates: A2–P8 mm, lateral 2–12 mm). Between cooling sessions, silver foot temperature was maintained at 36°C.
clinical case
97.94
A craniotomy in stereotaxic coordinates was positioned according to the visuotopic map of area 19 (Tusa et al., 1979). A plastic cylinder around it was glued with dental acrylic forming a well. Then a small opening was made in the dura mater where stainless steel microelectrodes (impedance 7–12 MΩ; FHC, Bowdoinham, ME, USA) were positioned vertically above the recording site. The well was filled with 4% agar in physiological saline then sealed with warm liquid wax (melting point ~40°C). Using a hydraulic micromanipulator (David Kopf’s Instruments Tujunga, CA, USA) the electrode was advanced slowly (20–60 μm/min) along the medial suprasylvian sulcus (MS in Figure 1A).
study
99.44
A Peltier device attached to a specially designed silver probe was used to reversibly inactivate areas 20a and 20b (Tusa and Palmer, 1980) by cooling the probe to ~10°C, and subsequently rewarming it back to 36°C (Figure 1A). The foot of the probe covered almost all of areas 20a and 20b located on the dorso-lateral surface of cerebral hemisphere and the part of posterior suprasylvian area behind posterior suprasylvian gyrus (Figure 1A). The probe and the opening were sealed with vacuum grease, which also acted as a thermal insulator. At the end of each experiment, cooling probe’s location was checked by careful inspection of indentation marks left by the probe on the dura over PTV. We related these marks to the location of areas 20a and 20b (Tusa and Palmer, 1980) and PS area (Updyke, 1986). In several control experiments, we monitored the temperature and neuronal activity of the cortex under and around the cooling probe using a pair of micro-thermo-couples (25 μm thick wires) glued to the recording electrode. Monitoring was conducted before, during and after rewarming PTV cortex at various (0–11 min) time intervals and at various depths below the cortical surface.
study
100.0
The computer-controlled screen monitor located 57 cm in front of the cat’s eyes was usually set at a luminance of 15 cd/m2 against a background of 1 cd/m2. The stimuli—elongated light bars were set at cell’s RF center. The extracellular action potentials from single neurons were recorded, conventionally amplified and monitored both visually and acoustically (via a loud speaker). To exclude multiunit data, special attention was paid to the shape and magnitude of the action potentials. Only identified single unit potentials triggered standard pulses which were then fed into a microcomputer for data collection.
study
99.94
After single-neuron data collection, the probe and underlying PTV were cooled (within 2 min) to 10°C and kept at this temperature throughout the period (15–18 min) of repeated data collection. Subsequently, the probe and underlying PTV was rapidly (~2 min) rewarmed back to 36°C. Then at set times (10, 30, 45 and if necessary 60 min) after rewarming PTV covering probe to 36°C, the same tests were repeated again.
study
99.5
Quantitative assessment of RF properties was based on the analysis of responses to stimuli presented via the dominant eye. To prevent cell habituation (or adaptation), a delay of 800 ms was introduced when the stimulus velocity exceeded 6.6°/s. In all runs in which the stimulus velocity did not exceed 33°/s, the bin width was 22 ms. In runs in which the stimulus velocity was higher, the bin width was 6 ms. Thus, the same number of spikes per bin at velocities ≥46.2°/s (bin width 6 ms) and at velocities ≤33°/s (bin width 22 ms) do not indicate the same or similar number of spikes/s. Optimally oriented visual stimuli were usually traveling at its preferred velocity across the RF in the direction orthogonal to its optimum orientation. Peri-stimulus time histograms (PSTHs) were constructed from a sum of 5 or 10 repeats for each test condition. A Gaussian weighted average over five neighboring bins of PSTHs were then applied to smooth the responses. Peak response rates and mean background activity were determined at each condition, tuning curves as well as widths at half-height (WHH, see Figure 3Aii) were calculated.
study
100.0
(A) Peri-stimulus time histograms (PSTHs) of spike-responses of a class 2 complex area 19 cell, to optimally oriented bar moving at different velocities across it’s RF. Upper row—before cooling, middle row—during cooling and lower row—after rewarming. Note, the absence of background spike-activity in all conditions. (B) Effects of cooling on peak magnitudes (spikes/s) of visually evoked responses of an area 19 neuron whose responses are illustrated in (A). (C) Effects of cooling on visually evoked background spike-activities of area 19 neurons. Note that only in two cells (*) there was significant reduction. (D) The peak magnitudes of visually evoked responses before cooling PTV vs. those during cooling (i). (ii) Cells tested for velocity-tuning. (iii) Cells tested for orientation-tuning. A-pr and A-npr refer to responses of cell in Figure 3A at preferred and non-preferred directions respectively. Note that the same cell is represented twice. (iv) Responses after rewarming PTV—all but one cell exhibited significant recovery. # In (i, ii and iv) denote responses indicated by # in (B).
study
100.0
(Ai) PSTHs of spike-responses of an area 19 complex, class 2 cell, illustrating the influence of cooling of PTV on peak spike-responses to moving stimuli of two different orientations. Note that during PTV inactivation the cell exhibited substantial decrease in its peak responses to stimuli moving along the axis of one orientation (20°–200°) and a substantial increase in its peak responses to stimuli of another orientation (60°–240°). Stimulus size: 10° × 0.6°. (Aii) Effects of PTV cooling on orientation-tuning property of the same cell shown in (Ai). Note during cooling, there was a 40° shift in optimal orientation but only in the non-preferred direction of movements. The shift was accompanied by an increase in orientation-tuning width at half-height (WHH). Thirty minutes after PTV was rewarmed, the responses and optimal orientation recovered to the pre-cooling levels. (B) Optimal orientations prior to cooling vs. those during cooling(i—preferred direction, ii—non-preferred direction) or after rewarming of PTV (iii—preferred direction, iv—non-preferred direction). In the insert frequency histogram within (Bi), cells exhibiting large (≥20°) shifts in optimal orientation during inactivation of PTV are represented. Note that the numbers indicate the number of data points that overlap. (C) The widths of orientation-tuning curves at half-height calculated from the control condition vs. those during PTV cooling (i) and control condition vs. those after PTV rewarming (ii) * in (Ci) and (Cii) indicate a cell whose responses are illustrated in (Ai) and (Aii). A-pr and A-npr refer to responses of cell in panel (A) at preferred and non-preferred directions respectively. Note the same cell is represented twice. The responses in non-preferred direction is indicated by * -npr.
study
100.0
The DSI was calculated according to: [(Rp − Rnp)/Rp] × 100% where Rp and Rnp are the peak discharge rates (in spikes/s) to optimally oriented stimuli moving in respectively preferred and anti-preferred directions along the axis perpendicular to the cell’s preferred orientation.
study
99.6
Statistical comparisons of the background spike-activity and magnitude of spike-responses between two sets of data were made using non-parametric tests. Using Mann-Whitney U test, for each cell, comparisons were made between successive control runs, control vs. PTV cooled runs, control vs. PTV rewarmed runs and PTV cooled vs. PTV rewarmed runs (Siegel, 1956). For comparisons of activities of groups of cells, we used Wilcoxon pair-matched signed-rank (referred to as Wilcoxon test; Siegel, 1956). In all comparisons a P value of the difference between two sets of data was ≤0.05 at the two-tailed criterion was considered to be significant. The ±values in the text are the standard deviations. In the Figures, bars indicate the standard error of the mean (SEM).
study
100.0
Experiments were terminated by deeply anesthetizing the animals with sodium pentobarbitone (Nembutal). Animals were perfused transcardially with Hartmann’s solution (1.2 L at 36°C), followed by 1 L of 4% paraformaldehyde in phosphate buffer (0.2 M at pH 7.4). In order to reconstruct the recording sites, brains were sectioned coronally at 50 μm, and stained with cresyl violet.
study
99.94
The centers of the RFs (classical RFs − CRFs) of all 66 area, 19 cells studied were located within the contralateral visual hemifield in the region 0° − 32° from the vertical meridian and 2° − 15° from the horizontal meridian. The CRFs of all but two of 28 area 19 neurons examined for the effects of PTV inactivation were located within the part of the visual field represented in areas 20a and 20b (Figure 1C based on Tusa and Palmer, 1980). Our electrode penetrations proceeded along the middle suprasylvian sulcus and our sample is strongly biased toward particular cellular layers. Indeed, all but a couple of area 19 cells were recorded from the middle layers 3 and 4. Consistent with previous studies (see Tusa et al., 1979; Dreher et al., 1980; Duysens et al., 1982b; Rapaport et al., 1982; Dreher, 1986; Mulligan and Sherk, 1993), the RFs located more peripherally tended to be larger (Figure 1D). As indicated in Figure 1E, the majority of cells (85.5%; 66/77) were binocular and could be activated by appropriate stimuli presented via either eye (see Duysens et al., 1982a; Rapaport et al., 1982; Dreher, 1986; Pettigrew and Dreher, 1987; Tanaka et al., 1987; Guillemot et al., 1993; Tardif et al., 1997; Bergeron et al., 1998). About half of binocular cells (53%; 35/66) responded more strongly to stimuli presented via the contralateral eye (class 2 vs. class 4 cells—Figure 1E) with only a few cells (9/66; 13.5%) responding equally well to stimuli presented via either eye (class 3 cells). Note that the eye dominance distribution of area 19 cells tested for the effects of PTV inactivation was similar to that of the entire sample (Figure 1E).
study
100.0
The majority of neurons (64.3%; 18/28) examined for the effects of PTV cooling were classified as complex cells: they had spatially overlapping on and off discharge regions to optimally oriented stationary flashing light bars and/or spatially overlapping discharge regions to moving optimally oriented bars darker and brighter than the background. Simple cells, characterized by spatially non-overlapping on and off discharge regions, and/or spatially non-overlapping discharge regions to moving optimally oriented bars darker and brighter than the background, constituted about a third (32.1%; 9/28) of the sample. We were unable to classify one cell (1/28; 3.5%) on the basis of the above criteria.
study
100.0
It is worth noting that in the first study of RF properties of area 19 neurons of anesthetized cat (Hubel and Wiesel, 1965), no simple cells were reported (see also Guillemot et al., 1993). On the other hand, the proportions of simple or simple-like (see S cells, Sh cells and A cells of Henry, 1977) cells defined on the basis of existence of spatially distinct on (light bar) and/or off (dark bar) discharge regions are quite similar (25%—Dreher, 1986; Pettigrew and Dreher, 1987; to 31%—Duysens et al., 1982b) to that reported here. However, the reported proportions of simple-like cells defined on the basis of modulation ratio of the responses to moving luminance-modulated sinusoidal achromatic gratings (Skottun et al., 1991) with one exception (27%—Tanaka et al., 1987) were much lower (~10%—Tardif et al., 1997; Bergeron et al., 1998; Mimeault et al., 2002).
study
99.94
In the majority of neurons (78.5%; 22/28), the background (“spontaneous”) activity was <1 spike/s (Figures 2A,C). Before PTV inactivation, the mean background activities of simple and complex cells were almost identical (mean: 0.78 spikes/s vs. 0.72 spikes/s; see Table 1). There was some reduction in the background activities of both simple (mean: 0.48 spikes/s) and complex (mean: 0.44 spikes/s) cells during PTV inactivation. However, only in a couple of cells (2/28; 7%—1 simple, 1 complex), the background activities during PTV inactivation were significantly lower than those before inactivation (Figure 2C). The mean background activities after rewarming PTV were lower but not significantly different from those before cooling (Table 1).
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100.0
The mean peak-firing rate of 28 area 19 neurons before PTV inactivation at 63.55 spikes/s was almost identical to that (63.3 spikes/s) during PTV cooling. However, in a quarter of cells (7/28; 4 complex; 3 simple), inactivation resulted in significant reduction (Figures 2Di, 3Ai,ii), or a complete cessation (Figures 2A,B) of responses to stimuli. In another quarter of the sample (7/28; Figure 2Di) the reductions in magnitude of responses were not significant. The last group included two cells (both complex—one binocular class 4, the other monocular class 5) whose RFs were located at the very periphery of the part of the contralateral hemifield represented in areas 20a and 20b (Figure 1C).
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On the other hand, in almost a third of the sample (28.5%; 8/28 cells, all but one complex), inactivation of PTV resulted in increases in the magnitude of spike-responses to the optimized stimuli (Figures 2Di, 4A,B) and the increases were significant in ~10% (3/28, all complex) of the sample (Figure 2Di). In 2/19 cells in which effects of cooling on velocity preferences were tested, inactivation resulted in a clear enhancement of responses to stimuli moving at higher velocities (see Figure 2Dii, Preferred velocities). For a subset of cells tested for orientation-tuning, their peak responses are shown in Figure 2Diii. Note that only in one of those cells, there was a significant increase in peak firing rate during cooling (Figure 2Diii—A-npr).
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(A) Effects of PTV cooling on PSTHs of spike-responses of a class 2 complex area 19 cell to optimally oriented bar moving at different velocities. The stimulus was presented via the dominant (contralateral) eye. Stimulus size: 5° × 1°. (B) Velocity-tuning of peak spike-responses of the same cell whose responses are shown in (A). Note in (A,B) there is a substantial increase in the magnitude of responses during inactivation of PTV, especially for movement from left to right. (C) Preferred velocities of area 19 cells before inactivation vs. those during PTV inactivation (i) and control vs. rewarming (ii). In most cases, during cooling, inactivation resulted in upward shifts in preferred velocities. Note that the numbers indicate the number of data points that overlap. (Di) The direction selectivity indices (DSIs) of area 19 cells at stimulus velocities optimal before inactivation. In a large proportion of cells, inactivation resulted in large (≥20%) changes in their DSIs. Also in five cells (*) inactivation resulted in reversal of preferred directions of movements. # Denotes the response indicated by # in upper panel of (B). (Dii) DSIs at stimulus velocities optimal after PTV rewarming. @ Denotes the response indicated by @ in upper panel of (B). (Ei) The DSIs of a subpopulation of area 19 cells calculated at stimulus velocities optimal during cooling. Note in a majority of cells, inactivation resulted in large increases in their DSIs. (Eii) DSIs at stimulus velocities optimal during cooling in control condition vs. those after PTV rewarming.
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In a substantial proportion of cases (6/15, 40%), cooling of PTV resulted in decreases in the magnitude of spike-responses to particular visual stimuli as well as increases in the magnitude of spike-responses to some other visual stimuli. Thus, in one cell, small significant reductions in the magnitude of spike-responses to optimally oriented moving light bar were accompanied by stimulus-direction dependant, significant increases in response to para-optimally oriented moving light bar (Figure 3Ai,ii; see effect on Orientation-tuning). Similarly, inactivation induced reductions in the magnitude of spike-responses to a light bar moving in one direction were accompanied by large and significant increases in the magnitude of spike-response to the same stimulus moving in the opposite direction (Figures 4A,B; see effect on Direction selectivity). The direction sensitive enhancement of response was even greater at higher velocities (Figures 4A,B; see effect on Direction selectivity and Preferred velocities).
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The RFs of a quarter (3/12—2 complex, 1 simple) of area 19 cells tested for length selectivity, contained clear-cut silent strongly suppressive regions along the axis of optimal orientation. In these termed end-stopped cells, stimulation of suppressive regions resulted in ≥50% reduction in the number of spikes (see hypercomplex cells of Hubel and Wiesel, 1965; see also Dreher, 1972). The proportion of end-stopped cells in our sample is at the lower end of the range reported previously (25%–38%: Hubel and Wiesel, 1965; Duysens et al., 1982b; Rapaport et al., 1982; Pettigrew and Dreher, 1987; Tanaka et al., 1987; Guillemot et al., 1993; Tardif et al., 1997; Bergeron et al., 1998; Mimeault et al., 2002). However, in the present sample, inactivation did not have a clear effect on the presence and relative strength of suppressive regions of RFs.
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In our sample all neurons exhibited clear orientation selectivity. In the majority (73.5%; 11/15), PTV cooling did not induce clear changes in the optimal orientation. In particular, in all but four cells (4/15; 26.5%), the optimal orientations during inactivation were either the same or differed by no more than 15° from their control optimal orientations (Figures 3A,Bi,Bii). Note that only in one cell, the optimal orientation after rewarming PTV differed by more than 10° from that before inactivation of PTV (Figures 3Biii,iv).
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Although in all area 19 cells, inactivation resulted in some changes in their orientation-tuning curves, substantial (≥20° change in WHH) widening (2/10 cells) or narrowing (1/10 cell) were rare (Figure 3Ci). Furthermore, in case of one of these cells, after rewarming of PTV there was still a substantial (>20°) difference in WHH of orientation-tuning with that in control run (Figure 3Cii). Overall, in cells in which inactivation caused widening of orientation-tuning curves, their mean WHH during inactivation was 55° (±34.2°) vs. 45.3° (±26.7°) before inactivation. In the case of cells in which inactivation resulted in the opposite effect, their mean WHH during cooling was 40.8° (±19.6°) vs. 47.4° (±18.7°) before inactivation.
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Consistent with numerous previous reports (Dreher et al., 1980; Duysens et al., 1982b; Rapaport et al., 1982; Dreher, 1986; Pettigrew and Dreher, 1987; see however Bergeron et al., 1998), in control condition, a large proportion (42%; 8/19) of area 19 cells preferred low (<15°/s) velocities and responded poorly to optimally oriented stimuli moving at velocities exceeding 20°/s (Figures 2A,B, 4Ci). Two of these cells with preferred velocities 6.6°/s and 13.2°/s, ceased to respond at velocities 46.2°/s and 66°/s, respectively. A majority (58%; 11/19) however, responded preferentially at velocities in the 40°–50°/s range (Figure 4Ci) and only one of them ceased to respond at the highest velocity (66°/s) tested.
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However, in over a third of the sample (37%; 7/19), inactivation of PTV caused an upward shift in their preferred velocities (Figures 4A–C; control: 21.8 ± 19.1°/s; range: 1.1°–46.2°/s vs. during PTV inactivation: 35.4 ± 19.9°/s; range: 3.3°–52.8°/s). Furthermore, in two of these cells, their high cut-off velocities also shifted upward. The RF centers of all seven cells were located over 10° from areae centrales. It is worth noting that in all but one cell, after rewarming of PTV the preferred velocity was the same as that before cooling PTV (Figure 4Cii).
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Consistent with previous reports (Duysens et al., 1982a; Rapaport et al., 1982; Pettigrew and Dreher, 1987), most area 19 cells exhibited only a weak direction selectivity in control condition (low DSI—Figures 2A, 3Ai, 4A). Inactivation of PTV resulted in substantial changes in their DSIs (Figures 4A,B,Di). Thus, when DSI was calculated for velocities preferred before cooling (see Preferred velocities), a large proportion of cells exhibited substantial (≥20%) increases (21.5%; 6/28 cells) or decreases (6/28 cells) in their DSIs (Figure 4Di). Indeed, a couple of cells started with large (>70%) DSIs became absolutely direction selective (DSI = 100%) during inactivation (Figure 4Di). However, three cells that were weakly direction selective (DSIs < 40%) became completely non-direction selective (DSI = 0%) during inactivation (Figure 4Di). In addition, in a proportion (18%; 5/28) of cells, inactivation resulted in a 180° directional shift, that is, a complete reversal of their preferred direction (Figures 4A,Di**). Note that four of these cells also exhibited DSI changes of 20% or more. Overall however, low mean DSI, characteristic of area 19 neurons before cooling (mean: 48.81 ± 25.68%; range: 11.32%–100%, n = 28) was almost identical (P = 0.57, Wilcoxon test) with that (46.34 ± 34.09%; range: 0%–100%) during inactivation. Similarly, for the complex cells, the DSIs before PTV cooling (47.12 ± 26.69%, range: 11.32%–100%; n = 18) were not significantly (P = 0.62, Wilcoxon test) different from those (50.68 ± 27.96%, range: 0%–100%) during PTV cooling. However, for the simple cells, the DSIs in the control condition (49.44 ± 25.09%, range: 29.50%–100%; n = 9) were significantly (P = 0.04, Wilcoxon test) higher than PTV cooling (31.71 ± 40.22%, range: 0%–100%). Note that after rewarming of PTV, DSIs of most cells were much closer to these before PTV cooling (Figure 4Dii).
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By contrast, when DSIs were calculated from the velocities optimal during cooling (see Preferred velocities), most cells (8/10) exhibited greater DSIs. In most of them (6/8), the increases exceeded 20% (Figures 4A,B,Ei). Not surprisingly, the mean DSI during inactivation at 69% (±28.45; range: 18.2%–100%; n = 10) was substantially higher than that (44.25 ± 35.1%; range: 9.6%–100%) before inactivation. Note however, that after rewarming of PTV, the DSIs at stimulus velocities preferred during cooling remained quite similar to those during PTV cooling (Figure 4Eii).
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In a previous series of experiments (Huang et al., 2007), we have examined the effects of inactivation of PTV cortex on velocity-tuning of a small sample of area 17 neurons. However, the data were not included in our analysis of effects of inactivation of PTV cortex (Huang et al., 2007) and are included here for comparison.
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Before inactivation, the mean background activity of simple cells at 0.23 spikes/s (±0.48; range: 0.01–1.33; n = 7) was almost identical to that (mean: 0.25 ± 0.50; range: 0.01–1.37) during inactivation. For complex cells, their control mean background activity (1.22 ± 1.98 spikes/s; range: 0.19–4.19; n = 4) was slightly higher than that (1.05 ± 1.55; range: 0.18–3.38) during cooling and substantially higher than that of simple cells (see Huang et al., 2007).
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In control condition, the mean peak-firing rate of area 17 neurons at 80.65 spikes/s (±54.45; range: 38.35–221.9; n = 11) was substantially higher than that of area 19 neurons in either control or PTV inactivation conditions (see above) but slightly lower than that (85.65 ± 60.05; range: 4.0–192.9) of area 17 neurons during inactivation of PTV (Figure 5D).
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(A) Effects of PTV cooling on PSTHs of spike-responses of a class 2 area 17 complex cell to optimally oriented light bar moving at different velocities. Stimulus size: 10° × 0.4°. Note the bin widths for PSTHs for stimulus velocities 6.6°/s, 19.8°/s and 33°/s were 22 ms while those for the velocity 46.2°/s, the bin width was 6 ms. (B) Velocity-tuning of peak spike-responses of the same cell shown in (A). Note that during PTV inactivation there is a substantial increase in the magnitude of responses as well as substantial increases in DSI especially at velocities of 6.6°/s and 19.8°/s. (C) Preferred velocities of area 17 cells before vs. those during cooling. Note also that in a couple of cells (a and b), PTV cooling resulted in upward shifts in the preferred velocities. Finally, note that the numbers indicate the number of data points that overlap. (D) Effects of PTV cooling on the magnitude of spike-responses of area 17 cells. ! In (C) and (D) denote the cell marked in lower panel of (B). (E) DSIs of area 17 cells at stimulus velocities optimal before cooling. Note in three cells, cooling PTV resulted in large (≥20%) changes in their DSIs. *Indicates cell in which inactivation of PTV resulted in complete reversal of preferred direction.
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Before inactivation, a majority (63.5%; 7/11) of area 17 neurons preferred low (<15°/s) velocities (Figure 5C). During inactivation, an upward shift in preferred velocities was observed in two cells (both were complex; Figures 5A–C). Overall however, the mean preferred velocity of area 19 neurons during inactivation at 21.85°/s (±21.65; range: 1.4°–66°/s) was virtually the same as that (19.45 ± 20.95°/s; range: 1.1°–66°/s) before inactivation.
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In one cell, PTV cooling resulted in a substantial increase in its firing rate during motion along the axis perpendicular to optimal orientation and this increase was accompanied by substantial stimulus velocity-linked changes in DSI (Figure 5E; see Figures 4A,B for area 19 neurons).
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When DSIs were calculated for preferred velocities before cooling, in most cells there were substantial (≥20%) changes (Figure 5E). In one cell, inactivation resulted not only in a big reduction in DSI but also in a 180° directional shift (Figure 5E*). Overall however, the mean DSIs of area 17 cells before (72.15 ± 31.3%; range: 17.0%–100%; n = 11) and during (68.25 ± 34.5%; range: 13.2%–100%) inactivation of PTV cortex were quite high (see Duysens et al., 1982a).
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The temperature gradient in the cat visual cortex, measured along the center of the cooling probe, is consistently ~5°–6°C/mm (see for control experiments and review Huang et al., 2007; cf. also Casanova et al., 1997). Indeed, when the temperature of the probe confined to PTV was lowered to ~10°C, the tissue within 2 mm radius from the edge of the probe was between 10°C and 20°C. At this range, the generation of neuronal action potentials (spikes) becomes unreliable (Volgushev et al., 2000). Furthermore, in control experiments we (Huang et al., 2007) have found that when the probe was cooled to ~10°C, the spike-activity have largely ceased not only in PTV directly under the probe but also in parts of the cortex in the immediate proximity (2 mm) of the probe’s edge. Overall, the spike-activity silenced region included parts of areas 20a and 20b located on the ventro-lateral aspect of cerebral hemispheres, PS area (Updyke, 1986) and parts of areas 17 (V1), 18 (V2), 19 (V3) and 21b (Figure 1A). All areas 19 and 17 neurons in which the effects of PTV inactivation have been studied had their RFs located along the visual streak. In parts of areas 18, 19 and 21b (Figure 1A) affected by the spread of cooling, the upper contralateral visual field is represented (Tusa et al., 1979; Tusa and Palmer, 1980) while area PS contains representation of the lower contralateral visual field (Updyke, 1986). Feedforward and to a lesser extent, feedback connections between visuotopically organized cortical areas, appear to be confined to their visuotopically corresponding regions (Salin and Bullier, 1995; Dreher et al., 1996; Morley et al., 1997). Consistent with this, reversible inactivation of the higher-order areas does not seem to affect responses of neurons in topographically non-corresponding parts of the lower areas (Martinez-Conde et al., 1999; Huang et al., 2007). Nevertheless, in view of the fact that there are long-range intrinsic cortico-cortical connections in cat’s areas 17 and 18 (e.g., Gilbert, 1993; Dreher et al., 2001; Chavane et al., 2011), it is remotely possible that inactivation of parts of areas 18 and 19 in which the upper contralateral visual field is represented contributes somehow to the effects observed in the present samples of areas 19 and 17 neurons.
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Virtually all extrinsic afferents, including feedback cortico-cortical inputs to the cat’s primary visual cortex use glutamate and/or asparate as neurotransmitters and are thus presumably excitatory (Pérez-Cerdá et al., 1996). Indeed, electrical stimulation of areas 18 (V2) or 19 (V3) of the cat (Bullier et al., 1988) or the latero-medial (LM presumptive V2) area of the rat (Shao and Burkhalter, 1996) or area V2 of the mouse (De Pasquale and Sherman, 2011) result in the orthodromic, monosynaptic spike discharges or mono-synaptic depolarizations of neurons in their respective ipsilateral V1.
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