Previous studies have found deficits in imaginative elaboration and social inference to be associated with agenesis of the corpus callosum (ACC; Renteria-Vasquez et al., 2022; Turk et al., 2009). In the current study, Thematic Apperception Test (TAT) responses from a neurotypical control group and a group of individuals with ACC were used to further study the capacity for imaginative elaboration and story coherence.

Topic modeling was employed utilizing Latent Diritchlet Allocation to characterize the narrative responses to the pictures used in the TAT. A measure of the difference between models (perplexity) was used to compare the topics of the responses of individual participants to the common core model derived from the responses of the control group. Story coherence was tested using sentence-to-sentence Latent Semantic Analysis.

Group differences in perplexity were statistically significant overall, and for each card individually (p < .001). There were no differences between the groups in story coherence.

TAT narratives from persons with ACC were normally coherent, but more conventional (i.e., more similar to the core text) compared to those of neurotypical controls. Individuals with ACC can make conventional social inferences about socially ambiguous stimuli, but are restricted in their imaginative elaborations, resulting in less topical variability (lower perplexity values) compared to neurotypical controls.

Previous research suggests that individuals with isolated Agenesis of the Corpus Callosum (AgCC) have cognitive and psychosocial deficiencies that include impaired recognition of the emotions of others (Symington et al., 2010) and a diminished ability to infer and describe the emotions of others (Paul et al., 2021; Turk et al., 2010). In addition, galvanic skin responses effectively discriminated between emotional images despite atypical emotion ratings (Paul et al, 2006), supporting a dissociation between cognitive and affective empathy in AgCC. Likewise, atypical patterns of visual attention to faces corresponded with impaired emotion recognition in AgCC (Bridgman et al, 2014), suggesting that atypical visual attention in AgCC negatively impacts the ability to identify others’ emotions. This study used the Multifaceted Empathy Test [MET] (Foell et al., 2018) to examine the impact of visual aesthetics (photo composition) on empathetic feelings (affective empathy) and situational emotion recognition (cognitive empathy) in persons with AgCC. Both cognitive and affective empathy scores are typically higher on MET stimuli composed according to the “Golden Spiral” (Callaway, 2022).

Results from 50 control participants recruited from Cloud Research were compared to responses from 19 participants with AgCC and normal-range FSIQ (>80). Data was gathered through an online version of the MET, which uses a series of photographs of individuals displaying an emotion, half of which adhere to the compositional technique known as “The Golden Spiral.” To measure cognitive empathy, the participants are asked to pick the correct emotion being displayed with three distractors for each item. To measure affective empathy, they are then asked on a sliding scale, “how much do you empathize with the person shown” (1 = Not at all, 7 = Very much).

Repeated measures mixed ANOVAs revealed no difference between AgCC and control groups on affective empathy, and as expected on the MET, both groups had significantly higher ratings for photos composed according to the Golden Spiral (AgCC, np2 = .071; control, np2 = .136). In contrast, the AgCC group scored significantly lower than controls overall on cognitive empathy, np2 =.065. Exploratory post-hoc found a significant group difference in cognitive empathy only on photos composed according to the Golden Spiral, np2 = .090, with the scores in the AgCC group unimpacted by composition type while the control group exhibiting significantly higher scores Golden Spiral images, np2 = .254.

Empathic deficits in AgCC were restricted to the cognitive component, while affective empathy was not impaired. Visual aesthetics of photo composition influenced affective empathy ratings in both AgCC and control groups. However, adults with AgCC had diminished ability to give cognitive labels to the emotional states of others, which was not enhanced by the formal aesthetics of stimuli. Thus the corpus callosum seems to facilitate the ability to cognitively label emotions by facilitating visual attention. It also suggests that the corpus callosum does not facilitate affective empathy, in part because it does not appear to determine whether formal aesthetics influences the processing of visual stimuli in AgCC or neurotypical controls.

Agenesis of the Corpus Callosum (AgCC) is the congenital absence of all or part of the corpus callosum. Previous research has demonstrated that isolated AgCC results in a pattern of cognitive and psychosocial deficiencies, even when FSIQ is in the normal range (FSIQ > 80; Brown & Paul, 2019). Importantly, individuals with AgCC have been shown to provide narratives containing fewer emotional words, social interactions, and mental inferences on the Thematic Apperception Test (TAT; Turk et al., 2009). Similarly, research has suggested deficits in the elaborative imagination of persons with AgCC when they are providing narrative descriptions of simple animations (Renteria-Vasquez et al., 2021). Such findings raise questions about aesthetic perception in AgCC. While previous research has demonstrated differences in aesthetic perception among other neuropsychological populations (e.g. Parkinson's Disease; Lauring et al., 2019), there is no research reported regarding aesthetic appreciations in AgCC. The present study employed the Assessment of Art Attributes (AAA; Chatterjee et al., 2010) to compare the conceptual and perceptual aspects of aesthetic perception of persons with AgCC to neurotypical control participants. Prior investigation by Bromberger and colleagues (2011) utilized the AAA to examine the aesthetic perception of persons with right hemisphere lesions, finding deviations in judgements of abstractness, symbolism, realism, and animacy– all classified as “conceptual attributes.” Based on these findings, it was predicted that individuals with AgCC would rate paintings differently than neurotypical controls on conceptual attributes, but not on perceptual attributes.

Thirteen persons with AgCC and 49 neurotypical individuals completed the AAA. After completing measures of artistic experience and colorblindness, participants rated 24 paintings on 14 attributes. Balance, color saturation, color temperature, depth, simplicity, and stroke made up the “perceptual scales,” while abstractness, animacy, emotion, objective accuracy, realism, interest, and preference made up the “conceptual scales.”

Following Bromberger and colleagues (2011), average ratings from all control participants were used to rank the 24 paintings for each scale. Spearman's rank-order correlations were then conducted between the rankings of each participant and the average of the controls for each scale. Spearman's rho coefficients were then compared between AgCC and control groups using t-tests, controlling for multiple comparisons. As hypothesized, the AgCC group had significant deviations from the average of the controls (lower rho values) on several conceptual attributes: Abstractness (p = .004, d = .11), emotion (p < .001, d = .12), and interest (p < .001, d = .18), whereas individuals with AgCC deviated on only one perceptual attribute: Simplicity (p = .003, d = .12).

While generally unremarkable in the sensory aspects, persons with AgCC demonstrated greatest differences in three important conceptual aspects of aesthetic perception. This outcome suggests that such higher-order aesthetic appreciations require interhemispheric interactivity. These results further support the hypothesis that decreased elaborative imagination is a fundamental component of AgCC.

Hemispherectomy (HE) is a surgical intervention to treat intractable epilepsy. It involves disconnecting or removing the right or left cerebral hemisphere, depending on the location of the pathological substrate or epileptogenic activity. HE impacts neural functions related to social cognition (Fournier et al., 2008). This study investigates the effects of childhood HE on social deception and sarcasm using the Thames Awareness of Social Inferences Task (TASIT; McDonald, Flanagan, & Rollins, 2010) to explore emotion identification and social inference appraisal as adults.

Fifteen adults with hemispherectomy and 16 neurotypical controls completed the TASIT. All HE patients underwent hemispherectomy (right-HE = 10) during childhood (age of surgery = 3 months to 16 years) and had FSIQ > 70 at the time of study. HE and control groups were matched for age (HE M = 25.7, SD = 5.4; control M = 27.1, SD = 10.7) and education (HE M = 14.0, SD = 1.88; control M = 13.3, SD = 1.8). FSIQ was significantly lower in the HE group than control group (HE M= 90.8, SD = 9.4; control (M = 100.4, SD = 7.1). TASIT uses videotaped vignettes to assess aspects of social perception: emotion recognition (Part 1), social inference regarding sincerity, simple sarcasm, and paradoxical sarcasm (Part 2) and social inference regarding sincerity of speech (lie vs sarcasm) in the presence of additional text or visual cues (Part 3).

For Part 1, MANCOVA (covarying FSIQ) found no group difference in emotion identification. Analysis of data from Part 2 was conducted using repeated measures ANCOVA accounting for 2 groups x 3 conditions (sincere, simple sarcasm, and paradoxical sarcasm) and revealed only a significant overall group effect, F (1, 28) = 5.72, p = .024, np2 = .170. Likewise, analysis of Part 3 using repeated measures ANCOVA accounting for 2 groups x 2 cue types (visual, text) and 2 actor intentions (lie, sarcasm) revealed only a significant overall group effect, F (1,28) = 11.35, p = .002, np2 = .288, with no interaction of group by condition.

HE patients exhibited no difficulty identifying basic emotional expressions. Performance was significantly impaired when additional social information was added to the context (i.e., detecting sarcasm or deception). HE patients begin to struggle with the complexity of new social information or how it changes the meaning of a conversation. Even simple sarcastic exchanges are difficult to interpret. When a visual or textual cue was introduced to reveal the true state of affairs, HE patients could not could integrate the information into their interpretations of the scenario. There are unique contributions of the left and right hemispheres to cognitive processes for complex social behavior, and absence of an entire hemisphere results in deficits in social language comprehension. Future research should investigate performance differences in left vs. right HE patients.

Agenesis of the corpus callosum(AgCC) is a disorder in which the connection between the two brain hemispheres is congenitally absent. Previous research has suggested that the auditory system can be affected in individuals with AgCC (Demopoulos et al., 2015). However, the nature of AgCC’s effect on musical perception skills is unclear. This study investigated the impact of AgCC on the music perception skills in high-functioining adults using a brief version of the Profile of Music Perception Skills (PROMS; Zentner, M. & Strauß, H. 2017). It was hypothesized that individuals with AgCC would have diminished music perception abilities when compared to a neurotypical control group.

Participants included 10 high-functioning adults with AgCC that had an intelligence quotation within the normal range (FSIQ>80) and 63 neurotypical controls who were recruited via Cloud Research. During the PROMS the participants were asked to listen to two different sound excerpts after which they were asked whether the second sound was the same or different from the first (correct answers= 2 points, uncertain answers= 1 point, and remaining answers not coded). The participants answered questions in four different areas of musical perception: Melody, Tuning, Accent, and Tempo.

Results indicated that there was not a significant difference between the control group and the AgCC participants on music perception skills on the overall PROMS scores F(1,72)= .365, P-value= .548. Tested individually, none of the 4 individual domains showed a significant difference: Melody F(1,72)=2.67, P-value= .107; Tuning F(1,72)= .271, P-value= .606; Accent F(1,72)= .017, P-value= .897; or Tempo F(1,72)=.106, P-value= .746.

Contrary to the hypothesis of this study, the results showed that the participants with AgCC did not perform significantly differently in the PROMS total score when compared to neurotypical controls, nor were there significant differences in any of the four of the subtests (Melody, Tuning, Accent, and Tempo). Thus these high-functioning individuals with AgCC did not have deficient music perception abilities. These findings demonstrate that although the auditory system may be affected in some individuals with AgCC, we do not see differences in musical perception skills in high-functioning individuals with AgCC.

A previous review of the syndrome of Agenesis of the Corpus Callosum (ACC) identified three primary deficits: reduced interhemispheric transfer of sensory motor information, slowed cognitive processing, and deficits in complex problem solving (Brown & Paul, 2019). Interaction of these three deficits contributes to a variety of secondary cognitive and psychosocial deficiencies across domains. Recent research has also identified a possible fourth core deficit in ACC: restricted capacity for elaborative thought and creativity (Renteria et al., 2022; Bogen & Bogen 1988). We examined the syndrome of ACC using an exploratory factor analysis of neuropsychological test data (not including data regarding interhemispheric transfer) and hypothesized it would organize into factors of (1) reduced cognitive processing speed, (2) difficulty with complex problem solving, and (3) difficulty with creative tasks.

The present study analyzed archival data from individuals with ACC (N=60) acquired from common neuropsychological instruments: D-KEFS, WAIS-III, and WRAT-2. Among the participants, 13 had partial ACC, 1 was unspecified, and the remainder had complete ACC. The participants’ ages ranged from 7 to 55 years (M = 21.55, SD = 12.36), with an education level that ranged from 2 to 19 years (M = 11.59, SD = 3.77). All participants had complete data for at least one assessment and all available data was included. Missing values (49.85%) were excluded from analysis. Factor analysis (principal factor solution with promax rotation) was conducted with 33 commonly derived summary (standard) scores. Horn’s Parallel Analysis recommended a 4-factor solution, but we elected to generate a 3-factor model that would more closely follow previous literature.

Factor one involved processing speed and was comprised primarily of D-KEFS Color Word Interference Word Reading (1.02) and Color Naming (.78), D-KEFS Trail Making Test Visual Scanning (.86) and Number Sequencing (.74), and WAIS-III Processing Speed Index (.68). The second factor included several problem solving measures [e.g. D-KEFS Sorting Test Free Sorting (.90) and Sort Recognition (.90), and WAIS-III Perceptual Organization Index (.72)], as well as several additional measures including WAIS-III Working Memory Index (.84), WRAT-2 Arithmetic (.83), and WAIS-III Verbal Comprehension Index (.80). Finally, the third factor involved several measures requiring mental flexibility and cognitive control [e.g. D-KEFS Twenty Questions Test Achievement Score (.70), D-KEFS Design Fluency Switching Condition (.56), and D-KEFS Trail Making Test Number-Letter Switching Condition (.44)], as well as a measure of single word reading [WRAT-2 Reading (.66)].

The findings support inclusion of slowed cognitive processing speed as a core feature of the neurocognitive syndrome in ACC described by Brown and Paul (2019). The second factor is partially consistent with a deficit in complex problem solving, but is not restricted to that cognitive domain. Likewise, the third factor is largely related to mental flexibility and control (one aspect of creativity), but is not restricted to that domain. Future attempts to model the neurocognitive syndrome of ACC may provide greater clarity by including a wider range of cognitive and psychosocial indices and excluding individuals with comorbid neuropathology.

Previous research suggests that individuals with isolated Agenesis of the Corpus Callosum (AgCC) have cognitive and psychosocial deficits including that of complex processing of emotions (Anderson et al., 2017) and their ability to verbally express emotional experiences (Paul et al., 2021). Additionally, research suggests individuals with AgCC show impaired recognition of the emotions of others (Symington et al., 2010), as well as diminished ability to infer and describe the emotions of others (Renteria-Vazquez et al., 2022; Turk et al., 2010). However, the nature of the empathic abilities of individuals with AgCC remains unclear in empirical research. Capacity for empathetic feelings and situational recognition in persons with AgCC were tested using the Multifaceted Empathy Test [MET] (Foell et al., 2018). We hypothesized that individuals with AgCC would have lower abilities for both cognitive and affective empathy than neurotypical controls.

Results from 50 neurotypical control participants recruited from MTurk Cloud were compared to responses from 19 AgCC participants with normal-range FSIQ (>80) drawn from the individuals with AgCC involved with the Human Brain and Cognition Lab at the Travis Research Institute. The research was completed through an online version of the MET. The MET uses a series of photographs of individuals displaying an emotion. To measure cognitive empathy, the participants are asked to pick the correct emotion being displayed with three distractors for each item. To measure affective empathy, they are then asked on a sliding scale, “how much do you empathize with the person shown” (1 = Not at all, 7 = Very much).

Results of a MANOVA showed a trend for a significant overall difference between individuals with AgCC and controls for empathic abilities F(1, 67) = 2.59, p-value = .082, with persons with AgCC showing less empathy overall. Follow-up one-way ANOVAs showed that individuals with AgCC scored significantly lower in cognitive empathy F(1, 67) = 4.63, p-value = .035, ηp2 = .065; however, affective empathy was not significantly different between groups F(1, 67) = .537, p-value = .466, ηp2 = .008.

Results suggest that adults with AgCC have a diminished ability to give cognitive labels to the emotional states of others compared to neurotypical controls. However, contrary to our hypothesis, participants with AgCC had affective responses to the pictures of the emotional states of others which were similar to neurotypical controls. Recent research has shown that individuals with AgCC have difficulty inferring and elaborating on the more complex cognitive, social, and emotional aspects of simple animations (Renteria-Vazquez et al., 2022; Turk et al., 2010). Cognitive empathy would require this form of elaborative thinking, even when affective empathy is normal. Similarly, Paul et al. (2021) described alexithymia in persons with AgCC as difficulty in expressing emotions linguistically, but found similar endorsements of emotional experience when compared to neurotypical controls. This study provides further evidence to suggest the corpus callosum facilitates the ability to cognitively label emotions but not necessarily the ability to experience emotions affectively.

Previous research has demonstrated that individuals with Agenesis of the Corpus Callosum (AgCC), the congenital absence of all or part of the corpus callosum, exhibit a pattern of cognitive and psychosocial deficits, even with a FSIQ in the normal range (FSIQ > 80; Brown & Paul, 2019). This includes a core deficit in their complex reasoning and novel problem-solving (Brown & Paul, 2019), with secondary deficits in capacity to imagine complex emotional/cognitive consequences of potential actions involving others (Young et al, 2019), deficits in emotion

perception (Symington et at., 2010, Bridgman et al 2014), and difficulty with cognitively processing emotions within the context of social interactions (Anderson et al., 2017). This constellation of deficits is likely to also impact moral reasoning. While previous research has demonstrated differences in moral reasoning among other neuropsychological populations such as those with ventromedial prefrontal damage (Moretto et al., 2010) and frontotemporal dementia (Gleichgerrcht et al., 2011), there is no research reported regarding moral judgements in AgCC. This study employed the Moral Dilemmas Scale (Greene, 2001) to compare the moral judgements of persons with AgCC to neurotypical controls. It was predicted that individuals with AgCC would be less contextually nuanced than neurotypical controls in responding to moral dilemmas.

Results consist of data derived from 57 neurotypical control participants (ages 23 to 64 years) recruited from MTurk Cloud and 19 AgCC participants (ages 23 to 77 years) with normal-range FSIQ (>80) drawn from the individuals with AgCC involved with the Human Brain and Cognition Lab at the Travis Research Institute. All participants completed an online version of the Moral Dilemmas Scale (Greene, 2001). The scale consists of 25 dilemmas, of which 11 are considered high-conflict, 7 low-conflict and 7 impersonal. Participants were instructed to read each dilemma and rate whether they found the action to be “appropriate” or not. The high-conflict dilemmas share a similar structure in which responses reflect either a utilitarian or deontological judgement.

“Approve” responses to each of the 3 categories of dilemma were separately tallied for each individual and subjected to a 2group ANOVA. Results revealed the control group produced a significantly higher rate of “appropriate” responses to high-conflict dilemmas than did the individuals with AgCC (F=8.17, p = .006, n2 =.113). However, no significant differences were found among the two groups for results on low (n2 = .013) and impersonal (n2 = .003) dilemmas alone. Furthermore, a X2 analysis of responses to each high conflict dilemma revealed a significant difference in 5 out of the 11 such that more persons with AgCC gave a deontological judgement.

Results suggested that adults with AgCC respond similarly to neurotypical controls with respect to the low conflict or

impersonal dilemmas. However, with respect to high conflict dilemmas, compared to controls they tend to respond in a more deontological than utilitarian basis - that is, based on general principles without contextual nuance. These findings are consistent with the conclusion of Renteria-Vasquez et al. (2021) that persons with AgCC have difficulty imagining the wider implications of present information.

It has been previously identified that levels of peripheral inflammatory proteins, such as cytokines, are altered in people with schizophrenia spectrum disorders (SSD).

As there is considerable inconsistency in the literature with respect to how inflammatory profiles differ between acute and chronic stages of SSD, a systematic review and network meta-analysis was performed.

Records from CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and PsycINFO were systematically searched from inception until 31 March 2022 for published studies that had measured levels of inflammatory proteins in cases of SSD and healthy controls. Pairwise and network meta-analyses were performed to determine whether there were significant differences in mean peripheral protein concentrations between acute SSD, chronic SSD, and healthy controls.

After application of the screening process, 215 articles were included for data-analysis. One group of markers were consistently elevated (p<0·05) in both acute and chronic SSD, relative to healthy controls; this group comprised interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP). A second group of markers were inconsistently altered between illness stages: IL-2 and interferon (IFN)-γ were significantly elevated (p<0·05) in acute SSD, whilst IL-4, IL-12 and IFN-γ were significantly decreased (p<0·05) in chronic SSD.

These results indicate that a baseline level of inflammatory protein alteration occurs in SSD throughout the course of illness. This was evident from the group of markers that were consistently elevated in acute and chronic SSD (e.g., IL-6), representing possible trait markers. Moreover, superimposed immune activity may occur in acute SSD, given the group of possible state markers that were increased only in acute illness (e.g., IFN-γ). Further research is required to elucidate whether these peripheral changes are reflected within the central nervous system.

None Declared

Although clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response.

Using individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice.

We conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response.

We included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223–558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine.

Clozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.

Agenesis of the corpus callosum (AgCC) is associated with a range of cognitive deficits, including mild to moderate problems in higher order executive functions evident in neuropsychological assessments. Previous research has also suggested a lack of self-awareness in persons with AgCC.

We investigated daily executive functioning and self-awareness in 36 individuals with AgCC by analyzing self-ratings on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), as well as ratings on the same instrument from close relatives. Discrepancies between self- and informant-ratings were compared to the normative sample and exploratory analyses examined possible moderating effects of participant and informant characteristics.

Significant deficiencies were found in the Behavioral Regulation and Metacognitive indices for both the self and informant results, with elevated frequency of metacognition scores in the borderline to clinical range. Informants also endorsed elevated frequency of borderline to clinically significant behavioral regulation scores. The proportion of AgCC participants whose self-ratings indicated less metacognitive impairment than informant-ratings was greater than in the normative sample. Self-ratings of behavioral regulation impairment decreased with age and informant-ratings of metacognition were higher in males than females.

These findings provide evidence that individuals with AgCC experience mild to moderate executive functioning problems in everyday behavior which are observed by others. Results also suggest a lack of self-understanding or insight into the severity of these problems in the individuals with AgCC, particularly with respect to their metacognitive functioning.

To utilise a community-based participatory approach in the design and implementation of an intervention targeting diet-related health problems on Navajo Nation.

A dual strategy approach of community needs/assets assessment and engagement of cross-sectorial partners in programme design with systematic cyclical feedback for programme modifications.

Navajo Nation, USA.

Navajo families with individuals meeting criteria for programme enrolment. Participant enrolment increased with iterative cycles.

The Navajo Fruit and Vegetable Prescription (FVRx) Programme.

A broad, community-driven and culturally relevant programme design has resulted in a programme able to maintain core programmatic principles, while also allowing for flexible adaptation to changing needs.