Risk, prevention, screening and management of carotid artery stenosis in head & neck cancer patients-An evidence based review.

Our review aims to clarify the incidence of carotid artery stenosis, risks of development, screening, management, and primary prevention strategies documented in the literature after radiation therapy for head and neck cancers. The high prevalence of carotid stenosis after radiation therapy for head and neck cancers has made surveillance and risk stratification critical. In addition to general cardiovascular risk factors such as smoking, diabetes, and dyslipidemia, risk factors for carotid artery stenosis after head and neck radiation included total plaque score, radiotherapy use and dosage, length of time after radiotherapy, and age greater than 50. Cancer subtype, namely nasopharyngeal cancer, may be correlated with increased risk as well, though contrasting results have been found. Interestingly, however, no significant relationship has been found between radiotherapy dose and stroke risk. Surgical management of post-radiation carotid stenosis is similar to that of stenosis unrelated to radiation, with carotid endarterectomy considered to be the gold standard treatment and carotid artery stenting being an acceptable, less-invasive alternative. Medical management of these patients has not been well-studied, but antiplatelet therapy, statins, and blood pressure control may be beneficial. The mainstay of screening for radiation-induced stenosis has been Doppler ultrasound, with measurement of changes in the intima-media thickness being a primary marker of disease development. A literature review was carried out using the MeSH terms "Carotid Artery Stenosis," "Head and Neck Neoplasms," and "Radiotherapy."

Is ChatGPT a trusted source of information for total hip and knee arthroplasty patients?

Aims: While internet search engines have been the primary information source for patients' questions, artificial intelligence large language models like ChatGPT are trending towards becoming the new primary source. The purpose of this study was to determine if ChatGPT can answer patient questions about total hip (THA) and knee arthroplasty (TKA) with consistent accuracy, comprehensiveness, and easy readability. Methods: We posed the 20 most Google-searched questions about THA and TKA, plus ten additional postoperative questions, to ChatGPT. Each question was asked twice to evaluate for consistency in quality. Following each response, we responded with, "Please explain so it is easier to understand," to evaluate ChatGPT's ability to reduce response reading grade level, measured as Flesch-Kincaid Grade Level (FKGL). Five resident physicians rated the 120 responses on 1 to 5 accuracy and comprehensiveness scales. Additionally, they answered a "yes" or "no" question regarding acceptability. Mean scores were calculated for each question, and responses were deemed acceptable if ≥ four raters answered "yes." Results: The mean accuracy and comprehensiveness scores were 4.26 (95% confidence interval (CI) 4.19 to 4.33) and 3.79 (95% CI 3.69 to 3.89), respectively. Out of all the responses, 59.2% (71/120; 95% CI 50.0% to 67.7%) were acceptable. ChatGPT was consistent when asked the same question twice, giving no significant difference in accuracy (t = 0.821; p = 0.415), comprehensiveness (t = 1.387; p = 0.171), acceptability (χ2 = 1.832; p = 0.176), and FKGL (t = 0.264; p = 0.793). There was a significantly lower FKGL (t = 2.204; p = 0.029) for easier responses (11.14; 95% CI 10.57 to 11.71) than original responses (12.15; 95% CI 11.45 to 12.85). Conclusion: ChatGPT answered THA and TKA patient questions with accuracy comparable to previous reports of websites, with adequate comprehensiveness, but with limited acceptability as the sole information source. ChatGPT has potential for answering patient questions about THA and TKA, but needs improvement.

Utilization of Topical Polysporin and Triamcinolone for the Treatment of Hypergranulation Tissue.

Hypergranulation is the abnormal accumulation of granulation tissue in a wound and is commonly seen in burns. It impairs wound healing and can predispose patients to infection. There is no gold standard treatment for hypergranulation tissue, but some options include surgical debridement, chemical cautery with silver nitrate, and topical steroids. Silver nitrate treatment is painful and can lead to scarring, so topical steroid use is on the rise. A retrospective review, between January 1, 2017 and August 30, 2021, at a tertiary burn center was performed to analyze outcomes of hypergranulation tissue after treatment with a topical 50/50 mixture of triamcinolone (Perrigo, Dublin, Ireland) and Polysporin (Johnson & Johnson, New Brunswick, NJ). One hundred and sixteen patients were treated with triamcinolone and Polysporin for hypergranulation tissue, although 24 did not meet inclusion criteria. Eighty-eight out of 92 patients were successfully treated until hypergranulation resolution, while 4/92(4.3%) required silver nitrate or surgery despite the topical cream to achieve resolution. In the 88 patients successfully treated until hypergranulation resolution, 99 areas of hypergranulation were treated. Forty-one of 99 (41.4%) hypergranulation areas resolved within 2 weeks. The average time to hypergranulation resolution was 27.5 ± 2.5 days. We found that a novel 50/50 mixture of triamcinolone and Polysporin topical ointment is an effective and safe treatment for hypergranulation tissue in burn wounds. Further prospective studies are needed to determine its efficacy and safety profile.

Enhanced BRAF engagement by NRAS mutants capable of promoting melanoma initiation.

A distinct profile of NRAS mutants is observed in each tumor type. It is unclear whether these profiles are determined by mutagenic events or functional differences between NRAS oncoproteins. Here, we establish functional hallmarks of NRAS mutants enriched in human melanoma. We generate eight conditional, knock-in mouse models and show that rare melanoma mutants (NRAS G12D, G13D, G13R, Q61H, and Q61P) are poor drivers of spontaneous melanoma formation, whereas common melanoma mutants (NRAS Q61R, Q61K, or Q61L) induce rapid tumor onset with high penetrance. Molecular dynamics simulations, combined with cell-based protein-protein interaction studies, reveal that melanomagenic NRAS mutants form intramolecular contacts that enhance BRAF binding affinity, BRAF-CRAF heterodimer formation, and MAPK > ERK signaling. Along with the allelic series of conditional mouse models we describe, these results establish a mechanistic basis for the enrichment of specific NRAS mutants in human melanoma.

Remote cognitive assessment in severe mental illness: a scoping review.

Many individuals living with severe mental illness, such as schizophrenia, present cognitive deficits and reasoning biases negatively impacting clinical and functional trajectories. Remote cognitive assessment presents many opportunities for advancing research and treatment but has yet to be widely used in psychiatric populations. We conducted a scoping review of remote cognitive assessment in severe mental illness to provide an overview of available measures and guide best practices. Overall, 34 studies (n = 20,813 clinical participants) were reviewed and remote measures, psychometrics, facilitators, barriers, and future directions were synthesized using a logic model. We identified 82 measures assessing cognition in severe mental illness across 11 cognitive domains and four device platforms. Remote measures were generally comparable to traditional versions, though psychometric properties were infrequently reported. Facilitators included standardized procedures and wider recruitment, whereas barriers included imprecise measure adaptations, technology inaccessibility, low patient engagement, and poor digital literacy. Our review identified several remote cognitive measures in psychiatry across all cognitive domains. However, there is a need for more rigorous validation of these measures and consideration of potentially influential factors, such as sex and gender. We provide recommendations for conducting remote cognitive assessment in psychiatry and fostering high-quality research using digital technologies.

Medial temporal lobe and basal ganglia volume trajectories in persistent negative symptoms following a first episode of psychosis.

BACKGROUND: Persistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS: concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected by structural brain changes, particularly in the medial temporal lobe (MTL) and basal ganglia. AIMS: We sought to characterize dynamic brain changes related to PNS over the course of 2 years following a first episode of psychosis. METHOD: Longitudinal volumetric trajectories within the MTL (hippocampus, parahippocampal gyrus, entorhinal cortex, perirhinal cortex) and basal ganglia (caudate, putamen, pallidum) were investigated in 98 patients with first-episode psychosis and 86 healthy controls using generalized estimating equations. RESULTS: In left hippocampus, PNS (n = 25 at baseline) showed decreased volumes over time, sPNS (n = 26) volumes remained stable, and non-PNS (n = 47) volumes increased over time to control levels. PNS-specific changes were observed in left hippocampus and left perirhinal cortex, with the greatest decline from 12 to 24 months to levels significantly below those of non-PNS and controls. Affective/non-affective diagnosis, antipsychotic medication dosage and adherence at baseline did not significantly impact these findings. Basal ganglia volume trajectories did not distinguish between PNS and sPNS. CONCLUSIONS: The current study highlights distinct structural brain trajectories in PNS that are prominent in the left MTL. Basal ganglia alterations may contribute to PNS irrespective of their etiology. Left MTL volume reductions were most evident after 1 year of treatment, highlighting the importance of targeted early interventions.

Dynamic Interplay Between Insight and Persistent Negative Symptoms in First Episode of Psychosis: A Longitudinal Study.

Persistent negative symptoms (PNS) are an important factor of first episode of psychosis (FEP) that present early on in the course of illness and have a major impact on long-term functional outcome. Lack of clinical insight is consistently associated with negative symptoms during the course of schizophrenia, yet only a few studies have explored its evolution in FEP. We sought to explore clinical insight change over a 24-month time period in relation to PNS in a large sample of FEP patients. Clinical insight was assessed in 515 FEP patients using the Scale to assess Unawareness of Mental Disorder. Data on awareness of illness, belief in response to medication, and belief in need for medication were analyzed. Patients were divided into 3 groups based on the presence of negative symptoms: idiopathic (PNS; n = 135), secondary (sPNS; n = 98), or absence (non-PNS; n = 282). Secondary PNS were those with PNS but also had clinically relevant levels of positive, depressive, or extrapyramidal symptoms. Our results revealed that insight improved during the first 2 months for all groups. Patients with PNS and sPNS displayed poorer insight across the 24-month period compared to the non-PNS group, but these 2 groups did not significantly differ. This large longitudinal study supported the strong relationship known to exist between poor insight and negative symptoms early in the course of the disorder and probes into potential factors that transcend the distinction between idiopathic and secondary negative symptoms.

Neurocognitive functions in persistent negative symptoms following a first episode of psychosis.

Negative symptoms are present at the onset of psychosis and their persistence is significantly associated with poor psychosocial functioning and lower quality of life. Persistent negative symptoms (PNS) may be idiopathic or secondary to other factors such as depression, positive symptoms, and medication side-effects. Several studies have examined neurocognitive functions in early psychosis patients with PNS relative to non-PNS, but have not systematically controlled for secondary PNS (sPNS). The latter may have a distinct neurocognitive profile that could obscure differences between PNS and non-PNS. Using a large (n = 425) sample, we examined neurocognitive functions in PNS, sPNS, and non-PNS and hypothesized that PNS would be associated with greater impairments relative to non-PNS. Following admission to an early intervention program, a neurocognitive battery was administered after at least 3 months of treatment, and symptom data collected during a subsequent 6-month period were used to classify patients as PNS, sPNS and non-PNS. At month 12, both PNS and sPNS groups had significantly lower level of functioning relative to the non-PNS group but the sPNS group experienced higher levels of depressive and positive symptoms and were on a higher dose of antipsychotics. Relative to non-PNS, PNS patients exhibited significant impairments in verbal memory and working memory, whereas sPNS patients exhibited a trend towards greater impairments in verbal memory. This study confirms that the presence of PNS or sPNS negatively influences functioning with more selective cognitive impairments found in PNS, providing evidence that these groups of patients could benefit from different personalised interventions.

Do Unremitted Psychotic Symptoms Have an Effect on the Brain? A 2-Year Follow-up Imaging Study in First-Episode Psychosis.

BACKGROUND: To examine whether the duration of unremitted psychotic symptoms after the onset of a first episode of psychosis (FEP) is associated with cortical thickness and hippocampal volume, as well as structural covariance of these measures. METHOD: Longitudinal MRI scans were obtained for 80 FEP patients shortly after entry to FEP clinic (baseline), and then 12 months and 24 months later. The proportion of time patients experienced unremitted positive symptoms for 2 interscan intervals (baseline to 12 mo, 12 mo to 24 mo) was calculated. Changes in cortical thickness and hippocampal volumes were calculated for each interscan interval and associated with duration of unremitted psychotic symptoms. Significant regions were then used in seed-based structural covariance analyses to examine the effect of unremitted psychotic symptoms on brain structural organization. Importantly, analyses controlled for antipsychotic medication. RESULTS: Cortical thinning within the left medial/orbitofrontal prefrontal cortex and superior temporal gyrus were significantly associated with the duration of unremitted psychotic symptoms during the first interscan interval (ie, baseline to 12 mo). Further, changes in cortical thickness within the left medial/orbitofrontal cortex positively covaried with changes in thickness in the left dorsal and ventrolateral prefrontal cortex during this period. No associations were observed during the second interscan interval, nor with hippocampal volumes. CONCLUSIONS: These results demonstrate that cortical thickness change can be observed shortly after an FEP, and these changes are proportionally related to the percentage of time spent with unremitted psychotic symptoms. Altered structural covariance in the prefrontal cortex suggests that unremitted psychotic symptoms may underlie reorganization in higher-order cortical regions.

Altered hippocampal centrality and dynamic anatomical covariance of intracortical microstructure in first episode psychosis.

Hippocampal circuitry has been posited to be fundamental to positive symptoms in psychosis, but its contributions to other factors important for outcome remains unclear. We hypothesized that longitudinal changes in the hippocampal circuit and concomitant changes of intracortical microstructure are altered in first episode psychosis (FEP) patients and that such changes are associated with negative symptoms and verbal memory. Longitudinal brain scans (2-4 visits over 3-15 months) were acquired for 27 FEP and 29 age- and sex-matched healthy controls. Quantitative T1 maps, sensitive to myelin content, were used to sample the microstructure of the hippocampal subfields and output circuitry (fimbria, alveus, fornix, mammillary bodies), and intracortical regions. Dynamic anatomical covariance in pair-wise regional trajectories were assessed for each subject, and graph theory was used to calculate a participation coefficient metric that quantifies the similarity/divergence between hippocampal and intracortical microstructure. The mean participation coefficient of the hippocampus was significantly reduced in FEP patients compared with controls, reflecting differences in output hippocampal regions. Importantly, lower participation coefficient of the hippocampal circuit was associated with worse negative symptoms, a relationship that was mediated by changes in verbal memory. This study provides evidence for reduced hippocampal centrality in FEP and concomitant changes in intracortical anatomy. Myelin-rich output regions of the hippocampus may be an important biological trigger in early psychosis, with cascading effects on broader cortical networks and resultant clinical profiles.

Investigating subjective cognitive complaints in psychosis: Introducing the brief scale to Investigate cognition in schizophrenia (SSTICS-Brief).

Background: Cognitive difficulties are a core deficit for people with schizophrenia and are generally assessed with neuropsychological tests. Self-report assessments are also useful in understanding difficulties from the service user's perspective. This study aims to introduce and test the shorter version of the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) to improve its acceptability and comprehensibility.Methods: In consultation with service users and clinicians, we identified items from the original 21-item SSTICS that were found difficult and these were excluded. The reduced scale was explored with Confirmatory Factor Analysis (CFA) in two independent samples in the UK and Canada. Convergent validity with symptoms and IQ was assessed and compared between the original and the reduced scale.Results: Six-hundred and seven people with schizophrenia and first-episode psychosis took part in this study. Seven items were removed to produce the SSTICS-Brief. This had good reliability and the CFA confirmed a unidimensional structure. Convergent validity with symptoms and IQ were optimal between the long and short versions.Conclusions: The SSTICS-B has better acceptability than its longer form and could be administered in less time. The resulting measure is likely to be a valuable short self-assessment of cognitive complaints for people with schizophrenia.

Impact of age-related T cell dynamics on the identification of biomarkers predictive of immunotherapy discontinuation: a prospective cohort study.

BACKGROUND: The impact of biologic aging on immune checkpoint inhibitor (ICI) toxicity and efficacy is underexplored in metastatic melanoma (MM). In peripheral blood T-lymphocytes (PBTLs), biologic aging is characterized by changes in T-cell composition and cellular senescence. Whether indicators of PBTL biologic aging vary in MM patients or can be used to predict premature ICI discontinuation (pID) is unknown. METHODS: We prospectively collected PBTLs from 117 cancer-free controls and 46 MM patients scheduled to begin pembrolizumab or nivolumab monotherapy. 74 mRNAs indicative of T-cell subsets, activation, co-stimuation/inhibition and cellular senescence were measured by Nanostring. Relationships between each mRNA and chronologic age were assessed in patients and controls. Candidate biomarkers were identified by calculating the hazard ratio (HR) for pID in patients divided into low and high groups based on log-transformed mRNA levels or the magnitude by which each mRNA measurement deviated from the control trend (Δage). Area under the curve (AUC) analyses explored the ability of each biomarker to discriminate between patients with and without pID at 6 months and 1 year. RESULTS: Fifteen mRNAs correlated with chronologic age in controls, including markers of T-cell subsets, differentiation, cytokine production and co-stimulation/inhibition. None of these mRNAs remained correlated with age in patients. Median follow-up was 94.8 (1.6-195.7) weeks and 35 of 46 patients discontinued therapy (23 progression, 7 toxicity, 5 comorbidity/patient preference). Elevated pre-therapy CD8A (HR 2.2[1.1-4.9]), CD45RB (HR 2.9[1.4-5.8]) and TNFRSF14 (HR 2.2[1.1-4.5]) levels predicted pID independent of Δage-correction. CD3ε, CD27 and FOXO1 predicted pID only after Δage-correction (HR 2.5[1.3-5.1]; 3.7[1.8-7.8]; 2.1[1.1-4.3]). AUC analysis identified Δage-CD3ε and -CD27 as candidate predictors of pID (AUC=0.73; 0.75). CONCLUSIONS: Correlations between transcriptional markers of PBTL composition and chronologic age are disrupted in MM. Correcting for normal, age-related trends in biomarker expression unveils new biomarker candidates predictive of ICI outcomes.

Association of Pre-onset Subthreshold Psychotic Symptoms With Longitudinal Outcomes During Treatment of a First Episode of Psychosis.

Importance: The clinical high-risk state in psychosis is most often characterized by subthreshold psychotic symptoms (STPS) and represents a target for psychosis prevention. However, evidence suggests that between 30% and 50% of patients with a first episode of psychosis (FEP) report no prior history of STPS, indicating that not all patients with FEP experience a previous clinical high-risk phase. As with other early characteristics of illness onset, this diversity in the early course of symptoms may offer prognostic value for subsequent clinical trajectories. Objective: To determine whether a history of pre-onset STPS is associated with differential 1-year treatment outcomes in an early intervention service for FEP. Design, Setting, and Participants: Data on 195 patients 15 to 35 years of age who were recruited between January 17, 2003, and October 17, 2013, were collected from a catchment-based specialized early intervention service for FEP. Patients who reported experiencing at least 1 STPS prior to the onset of FEP were identified as STPS present (STPSp; n = 135); those who reported no such history were identified as STPS absent (STPSa; n = 60). Statistical analysis was conducted from December 15, 2016, to February 15, 2018. Main Outcomes and Measures: Summary scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia, Hamilton Anxiety Rating Scale, Global Assessment of Functioning scores, and Social and Occupational Functioning Assessment Scale scores at baseline and after 1 year of treatment were analyzed to evaluate 1-year outcomes. Results: Individuals in the STPSp group (39 female and 96 male participants; mean [SD] age, 23.4 [4.2] years) and the STPSa group (20 female and 40 male participants; mean [SD] age, 23.9 [5.1] years) did not differ in symptom severity or functioning at baseline. Although both groups improved by 1 year of treatment, mixed analyses of covariance (controlling for duration of untreated psychosis) revealed group-by-time interactions for scores on the Scale for the Assessment of Negative Symptoms (F1,192 = 6.17; P = .01), the Global Assessment of Functioning (F1,188 = 7.54; P = .006), and the Social and Occupational Functioning Assessment Scale (F1,192 = 3.79; P = .05). Mixed analyses of covariance also revealed a group effect for scores on the Scale for the Assessment of Positive Symptoms (F1,192 = 5.31; P = .02). After controlling for multiple comparisons, all significant results indicate poorer 1-year outcomes for patients with STPSp compared with patients with STPSa. Conclusions and Relevance: A history of pre-onset STPS consistent with a prior clinical high-risk state is associated with poorer outcomes in psychotic symptoms and global functioning for patients after 1 year of treatment for FEP. The presence or absence of pre-onset STPS therefore has prognostic value for treatment outcomes, even during a later stage of psychotic illness.

The effect of second-generation antipsychotics on hippocampal volume in first episode of psychosis: longitudinal study.

BACKGROUND: Current neuroscience literature has related treatment with aripiprazole to improved memory performance and subcellular changes in the hippocampus. AIMS: To explore the volumetric changes in hippocampal grey matter in people with a first episode of psychosis (FEP) treated with second-generation antipsychotics. METHOD: Baseline and 1-year follow-up magnetic resonance images were obtained. Hippocampal volumes were estimated by using FreeSurfer and MAGeT-Brain. Subgroups included: aripiprazole (n=13), olanzapine (n=12), risperidone/paliperidone (n=24), refused-antipsychotics (n=13) and controls (n=44). RESULTS: Aripiprazole subgroup displayed significant increases in bilateral hippocampal volume compared with all other subgroups (FreeSurfer: all P's<0.012; MAGeT-Brain: all P's<0.040). CONCLUSIONS: Aripiprazole is a first-line, second-generation treatment option that may provide an added benefit of pro-hippocampal growth. The biological underpinnings of these changes should be the focus of future investigations and may be key towards achieving a better clinical outcome for more individuals. DECLARATION OF INTEREST: M.L. received financial assistance/compensation for research and educational events from Janssen-Ortho, Eli Lilly, Roche and Otsuka/Lundbeck Alliance. A.K.M. received financial assistance/compensation for research and educational activities from Pfizer, Janssen-Ortho, AstraZeneca and Bristol-Myers Squibb. R.J. received consultancy honorariums from Pfizer and Janssen-Ortho. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Age-related cortical thickness trajectories in first episode psychosis patients presenting with early persistent negative symptoms.

Recent work has clearly established that early persistent negative symptoms (ePNS) can be observed following a first episode of psychosis (FEP), and can negatively affect functional outcome. There is also evidence for cortical changes associated with ePNS. Given that a FEP often occurs during a period of ongoing complex brain development and maturation, neuroanatomical changes may have a specific age-related component. The current study examines cortical thickness (CT) and trajectories with age using longitudinal structural imaging. Structural T1 volumes were acquired at three time points for ePNS (N=21), PNS due to secondary factors (N=31), non-PNS (N=45) patients, and controls (N=48). Images were processed using the CIVET pipeline. Linear mixed models were applied to test for the main effects of (a) group, (b) time, and interactions between (c) time and group membership, and (d) age and group membership. Compared with the non-PNS and secondary PNS patient groups, the ePNS group showed cortical thinning over time in temporal regions and a thickening with age primarily in prefrontal areas. Early PNS patients also had significantly different linear and quadratic age relationships with CT compared with other groups within cingulate, prefrontal, and temporal cortices. The current study demonstrates that FEP patients with ePNS show significantly different CT trajectories with age. Increased CT may be indicative of disruptions in cortical maturation processes within higher-order brain regions. Individuals with ePNS underline a unique subgroup of FEP patients that are differentiated at the clinical level and who exhibit distinct neurobiological patterns compared with their non-PNS peers.

Investigation of white matter abnormalities in first episode psychosis patients with persistent negative symptoms.

Aberrant white matter structures in fronto-temporal regions have previously been identified in patients with schizophrenia. However, scant research has focused on white matter integrity in patients presenting with a first episode of psychosis (FEP) with persistent negative symptoms (PNS). This study aimed to explore microstructure in the neurocircuitry proposed to be involved in PNS, by using a region-of-interest approach. Secondly, the relationship between individual negative symptoms and white matter were explored. Fractional anisotropy (FA) was measured in the fornix and three other tracts bilaterally including the uncinate fasciculus, superior longitudinal fasciculus and the cingulum bundle. Twelve patients with PNS were compared to a non-PNS group (52) and a healthy control group (51). Results showed that the PNS group had significantly lower FA values in the fornix when compared to healthy controls and that the non-PNS group had significantly lower FA values in the right uncinate fasciculus compared to healthy controls. Significant correlations were observed between SANS global score for anhedonia-asociality and lower FA values in the right cingulum bundle. Our results suggest that fronto-temporal white matter might be more closely related to PNS and that this relationship may possibly be mediated by greater anhedonia in PNS patients.

Source retrieval is not properly differentiated from object retrieval in early schizophrenia: an fMRI study using virtual reality.

Source memory, the ability to identify the context in which a memory occurred, is impaired in schizophrenia and has been related to clinical symptoms such as hallucinations. The neurobiological underpinnings of this deficit are not well understood. Twenty-five patients with recent onset schizophrenia (within the first 4.5 years of treatment) and twenty-four healthy controls completed a source memory task. Participants navigated through a 3D virtual city, and had 20 encounters of an object with a person at a place. Functional magnetic resonance imaging was performed during a subsequent forced-choice recognition test. Two objects were presented and participants were asked to either identify which object was seen (new vs. old object recognition), or identify which of the two old objects was associated with either the person or the place being presented (source memory recognition). Source memory was examined by contrasting person or place with object. Both patients and controls demonstrated significant neural activity to source memory relative to object memory, though activity in controls was much more widespread. Group differences were observed in several regions, including the medial parietal and cingulate cortex, lateral frontal lobes and right superior temporal gyrus. Patients with schizophrenia did not differentiate between source and object memory in these regions. Positive correlations with hallucination proneness were observed in the left frontal and right middle temporal cortices and cerebellum. Patients with schizophrenia have a deficit in the neural circuits which facilitate source memory, which may underlie both the deficits in this domain and be related to auditory hallucinations.

Cortical thinning in temporo-parietal junction (TPJ) in non-affective first-episode of psychosis patients with persistent negative symptoms.

BACKGROUND: Negative symptoms represent an unmet therapeutic need in many patients with schizophrenia. In an extension to our previous voxel-based morphometry findings, we employed a more specific, vertex-based approach to explore cortical thinning in relation to persistent negative symptoms (PNS) in non-affective first-episode of psychosis (FEP) patients to advance our understanding of the pathophysiology of primary negative symptoms. METHODS: This study included 62 non-affective FEP patients and 60 non-clinical controls; 16 patients were identified with PNS (i.e., at least 1 primary negative symptom at moderate or greater severity sustained for at least 6 consecutive months). Using cortical thickness analyses, we explored for differences between PNS and non-PNS patients as well as between each patient group and healthy controls; cut-off threshold was set at p<0.01, corrected for multiple comparisons. RESULTS: A thinner cortex prominently in the right superior temporal gyrus extending into the temporo-parietal junction (TPJ), right parahippocampal gyrus, and left orbital frontal gyrus was identified in PNS patients vs. non-PNS patients. Compared with healthy controls, PNS patients showed a thinner cortex prominently in the right superior temporal gyrus, right parahippocampal gyrus, and right cingulate; non-PNS patients showed a thinner cortex prominently in the parahippocampal gyrus bi-laterally. CONCLUSION: Cortical thinning in the early stages of non-affective psychosis is present in the frontal and temporo-parietal regions in patients with PNS. With these brain regions strongly related to social cognitive functioning, our finding suggests a potential link between primary negative symptoms and social cognitive deficits through common brain etiologies.

Functional magnetic resonance imaging study of external source memory and its relation to cognitive insight in non-clinical subjects.

AIM: Previous research has linked cognitive insight (a measure of self-reflectiveness and self-certainty) in psychosis with neurocognitive and neuroanatomical disturbances in the fronto-hippocampal neural network. The authors' goal was to use functional magnetic resonance imaging (fMRI) to investigate the neural correlates of cognitive insight during an external source memory paradigm in non-clinical subjects. METHODS: At encoding, 24 non-clinical subjects travelled through a virtual city where they came across 20 separate people, each paired with a unique object in a distinct location. fMRI data were then acquired while participants viewed images of the city, and completed source recognition memory judgments of where and with whom objects were seen, which is known to involve prefrontal cortex. Cognitive insight was assessed with the Beck Cognitive Insight Scale. RESULTS: External source memory was associated with neural activity in a widespread network consisting of frontal cortex, including ventrolateral prefrontal cortex (VLPFC), temporal and occipital cortices. Activation in VLPFC correlated with higher self-reflectiveness and activation in midbrain correlated with lower self-certainty during source memory attributions. Neither self-reflectiveness nor self-certainty significantly correlated with source memory accuracy. CONCLUSION: By means of virtual reality and in the context of an external source memory paradigm, the study identified a preliminary functional neural basis for cognitive insight in the VLPFC in healthy people that accords with our fronto-hippocampal theoretical model as well as recent neuroimaging data in people with psychosis. The results may facilitate the understanding of the role of neural mechanisms in psychotic disorders associated with cognitive insight distortions.