Pancreatic Enucleation Patients Share the Same Quality of Life as the General Population at Long-Term Follow-Up: A Propensity Score-Matched Analysis.

OBJECTIVE: The aim of this study was to assess short- and long-term outcomes including quality of life (QoL) following pancreatic enucleation (PE). BACKGROUND: PE is deemed to preserve both the endocrine and the exocrine function while ensuring radicality. However, to assess whether this reflects an actual benefit perceived by patients, QoL has to be considered. METHODS: Data from all consecutive patients undergoing PE from January 2010 to December 2019 were retrospectively analyzed. Surgical outcomes were graded according to the Clavien-Dindo classification, and EORTC-C30 and the EORTC-Pan26 were administered as a cross-sectional assessment of QoL. A control group consisting of healthy individuals from the general population was obtained and matched using the propensity score matching method. RESULTS: Eighty-one patients underwent PE using the open (59.3%), laparoscopic (27.2%), or robot-assisted (13.5%) approach. Sixty-five (80.2%) patients exhibited functioning/nonfunctioning pancreatic neuroendocrine tumors at final pathology.Surgical morbidity and complications of a Clavien-Dindo grade ≥3 were 48.1% and 16.0%, respectively. In-hospital mortality was 0%. Postoperative pancreatic fistula, post-pancreatectomy hemorrhage, and delayed gastric emptying rates were 21.0%, 9.9%, and 4.9%, respectively.Patients returned the questionnaires after a median of 74.2 months from the index surgery. Postoperative new onset of diabetes mellitus (NODM) was observed in 5 subjects (7.1%), with age being an independent predictor. Seven patients (10.0%) developed postoperative exocrine insufficiency. At the analysis of QoL, all function and symptom scales were comparable between the 2 groups, except for 2 of the EORTC-Pan 26 symptom scales, ("worries for the future" and "body image", P < 0.05). CONCLUSIONS: Despite being associated with significant postoperative morbidity, PE provides excellent long-term outcomes. The risk of NODM is low and related to patient age, with QoL being comparable to the general population. Such information should drive surgeons to pursue PE whenever properly indicated.

Screening Second Victims for Emotional Distress: Assessment of the Clinimetric Properties of the WITHSTAND-PSY Questionnaire.

INTRODUCTION: Adverse events (AEs) are a leading cause of patient morbidity and mortality, greatly impacting healthcare providers' well-being (second victim (SV) phenomenon). Since it is not accurately captured by existing psychometric instruments, we developed a clinimetric instrument for assessing SVs' emotional distress before and after an AE. METHODS: Content validity and clinical utility of the WITHSTAND-PSY Questionnaire (WS-PSY-Q) were examined using cognitive interviews. Rasch analysis (n = 284) was applied for clinimetric assessment (i.e., construct, concurrent, and clinical validity, internal consistency), considering two crucial psychological facets of the SV phenomenon (1st: emotional impact of the AE, 2nd: current emotional state). RESULTS: The Rasch partial credit model was used. The 1st facet demonstrated overall acceptable clinimetric properties with the subscale anxiety meeting clinimetric threshold values (e.g., all items with ordered thresholds, Loevinger's coefficient h ≥ 0.40; Person Separation Reliability Index (PSI) = 0.7). The 2nd facet showed overall better clinimetric properties for both subscales (e.g., h ≥ 0.40, PSI = 0.82 and 0.79, respectively; receiver operating characteristic area of 0.80 and 0.86, respectively). For both datasets, item fit statistics, except those for item 19, were within the critical range (z-score < ±2.5), and meaningful differential functioning analysis was observed for only 4 (out of 24) items. Local dependency was not observed, except for two item couples in the depression subscales. CONCLUSIONS: The WS-PSY-Q is the first clinimetric tool assessing SVs' emotional distress. It should be regarded as part of the armamentarium used by clinicians to assess in-depth healthcare providers' psychological reactions in the aftermath of an AE to mitigate burnout and allostatic overload.

The prognostic role of fatigue, depression and anxiety on postoperative outcomes after pancreatectomy for pancreatic cancer. A prospective observational study (FAT-PRO study).

OBJECTIVES: This study aims to assess the prevalence of preoperative fatigue, depression and anxiety among patients undergoing pancreatic surgery for pancreatic cancer (PC), and possible relationship with postoperative outcomes. METHODS: Prospective data from 162 consecutive patients undergoing pancreatectomy for PC at a third-level referral centers for pancreatic surgery were collected. All patients preoperatively completed four questionnaires assessing depression (PHQ-9), anxiety (STAI-Y2), chronic illness fatigue (FACIT-F) and cancer therapy fatigue (FACT-G). RESULTS: Forty patients (25%) where in the first quartile for chronic illness (FACIT-F ≤34) and/or cancer therapy (FACT-G ≤78) fatigue, 26 patients (16%) met the criteria for major depression (PHQ-9 ≥10) and 34 patients (21%) had anxiety symptoms (STAI-Y2 ≥40). Cancer therapy fatigue was significantly associated with higher rates of morbidity (70% vs 49%), major morbidity (Clavien-Dindo ≥3) (28% vs 11%), post-pancreatectomy hemorrhage (18% vs 4%), pulmonary complications (20% vs 9%) and mortality (8% vs null) (all P ≤ 0.01). Major depression was associated with higher rates of post-pancreatectomy hemorrhage and readmission (23% vs 5%). Multivariable logistic regression analysis of preoperative factors confirmed diabetes (OR 2.71, 95%CI 1.01-7.20; P = 0.04), ASA score ≥3 (OR 4.12, 95%CI 1.52-11.21; P < 0.01) and cancer therapy fatigue (OR 2.95, 95%CI 1.01-8.74; P = 0.04) to be independent predictors of major morbidity. CONCLUSIONS: Higher levels of fatigue (in particular cancer therapy fatigue) strongly correlates with worse postoperative outcomes.

Prevalence of depression in a cohort of 400 patients with pancreatic neoplasm attending day hospital for major surgery: Role on depression of psychosocial functioning and clinical factors.

OBJECTIVE: (1) To determine the prevalence and type of depressive symptoms at day-hospital clinical evaluation, before undergoing major surgery in patients diagnosed with pancreatic neoplasm. (2) To analyze the association between depression and sociodemographic, clinical, and psychosocial variables. (3) To understand how coping strategies, perceived social support, and self-efficacy might affect depressive symptoms in this cohort of patients. METHODS: Secondary data analysis collected during the baseline phase of a randomized controlled trial performed at the Pancreas Institute of the University Hospital of Verona, Italy, between June 2017 and June 2018. RESULTS: 18.5% of pancreatic patients had a PHQ-9 score ≥10 (cut-off). Depressed patients were basically more often female (p = 0.07), younger (p = 0.06), and married/with a partner (p = 0.02). Depression was associated to high trait anxiety (p < 0.01), the use of anxiolytics (p < 0.01), sleep-inducing drugs (p < 0.01), and painkillers (p < 0.01). Among psychosocial variables, depressed patients showed lower perceived self-efficacy (p < 0.01) and family and friends' social support (p < 0.01) and used significantly more often dysfunctional coping strategies (p < 0.01), compared to nondepressed. A logistic multivariate model using psychosocial variables as explanatory and depression as dependent was calculated and post hoc analyses were conducted to describe the contribution of each psychosocial variable on depression. CONCLUSIONS: Our study advocates the need for screening for distress and depression in cancer surgery units and recommends to strengthen patients' adaptive coping, social support, and sense of effectiveness in facing the challenges related to the medical condition and treatment process.

Psychological distress in patients under surveillance for intraductal papillary mucinous neoplasms of the pancreas: The "Sword of Damocles" effect calls for an integrated medical and psychological approach a prospective analysis.

INTRODUCTION: Most intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can be safely surveilled. Their psychological impact is not known. The aim of this study is to obtain a psychological profile of patients under surveillance and compare the results to patients undergoing surgery. METHODS: Patients under surveillance for IPMNs evaluated between 2017 and 2019 at the pancreatic cysts clinic of The Pancreas Institute of Verona were compared to patients undergoing surgery for the same disease. Patients with high-risk stigmata were excluded in both groups. Patients were profiled with the Barratt Simplified Measure of Socio-Economic Status (BSMSS), the Brief Coping Orientation to Problems Experienced (Brief-COPE), the Perceived Stress Scale (PSS), the Symptom Checklist-90 and the Short Form Health Survey (SF-36). Age, sex, BSMSS and Brief-COPE were used to match patients with the propensity score as potential sources of bias. RESULTS: Two hundred patients were profiled. After the matching, 74 patients under surveillance were compared to 74 patients who underwent surgery. Patients under surveillance reported significantly increased scores for symptoms such as somatization (0.71 vs. 0.54, p = 0.032), depression (0.45 vs 0.31, p = 0.047) and anxiety (0.45 vs. 0.27, p = 0.002). They also reported a reduced health perception in the domain of physical role functioning (54 vs. 68, p = 0.046). CONCLUSION: Patients under surveillance for a presumed IPMN experience anxiety and stress and feel less healthy than do patients undergoing surgery. This reduction in quality of life should always be taken into account and warrants an integrated medical-psychological approach in selected cases.

Resting state networks activity in euthymic bipolar disorder.

OBJECTIVES: Bipolar disorder (BD) is a psychiatric condition causing shifts in mood, energy and activity levels severely altering the quality of life of the patients even in the euthymic phase. Although widely accepted, the neurobiological bases of the disorder in the euthymic phase remain elusive. This study aims at characterizing resting state functional activity of the BD euthymic phase in order to better understand the pathogenesis of the disease and build future neurobiological models. METHODS: Fifteen euthymic BD patients (10 females; mean age 40.2; standard deviation 13.5; range 20-61) and 27 healthy controls (HC) (21 females; mean age 37; standard deviation 10.6; range 22-60) underwent a 3T functional MRI scan at rest. Resting state activity was extracted through independent component analysis (ICA) run with automatic dimensionality estimation. RESULTS: ICA identified 22 resting state networks (RSNs). Within-network analysis revealed decreased connectivity in the visual, temporal, motor and cerebellar RSNs of BD patients vs HC. Between-network analysis showed increased connectivity between motor area and the default mode network (DMN) partially overlapping with the fronto-parietal network (FPN) in BD patients. CONCLUSION: Within-network analysis confirmed existing evidence of altered cerebellar, temporal, motor and visual networks in BD. Increased connectivity between the DMN and the motor area network suggests the presence of alterations of the fronto-parietal regions, precuneus and cingulate cortex in the euthymic condition. These findings indicate that specific connectivity alterations might persist even in the euthymic state suggesting the importance of examining both within and between-network connectivity to achieve a global understanding of the BD euthymic condition.

The emotional impact of surveillance programs for pancreatic cancer on high-risk individuals: A prospective analysis.

OBJECTIVE: Literature shows that emotional status can influence participation in screening/surveillance programs, and that screening/surveillance programs may alter the psychological well-being of subjects examined. This study aims to assess if participating in a surveillance program for pancreatic cancer early detection is associated with abnormal levels of psychological distress in high-risk individuals (HRIs), compared to the general population. METHODS: Fifty-four HRIs participating in a magnetic resonance cholangiopancreatography (MRCP)-based surveillance program completed several psychological assessment questionnaires, investigating global functioning, self-efficacy, perceived stress, coping abilities, and social support. The questionnaires were administered by a clinical psychologist after the MRCP but before the subjects were informed about the results of the scans. The HRIs were subjects with strong familiarity of pancreatic cancer and/or carriers of known genetic mutations related to cancer susceptibility. The psychological assessment was made at the time of the first examination. RESULTS: The population was characterized by an overall good psychological status. Scoring of our sample was comparable to the general population norms. The HRIs showed decent global functioning, high self-efficacy levels, low perceived stress in the last month prior to examination, efficient emotion-focused coping strategies, and an adequate social support system. The younger subjects' subpopulation only revealed higher levels of stress. CONCLUSIONS: From a psychological point of view, an MRCP-based pancreatic cancer annual surveillance seemed not to influence the HRIs' psychological well-being, unless in young people. Further studies are needed to better establish if there are any changes in distress levels over time and how emotional status influences participation in surveillance programs.

Pituitary gland shrinkage in bipolar disorder: The role of gender.

BACKGROUND: Hyperactivity of the Hypothalamic-Pituitary-Adrenal Axis (HPAA) has been consistently reported in mood disorders. However, only few studies investigated the Pituitary gland (PG) in Bipolar Disorder (BD) and the results are so far contrasting. Therefore, the aim of this study is to explore the integrity of the PG as well as the role of gender and the impact of clinical measurements on this structure in a sample of BD patients compared to healthy controls (HC). METHODS: 34 BD patients and 41 HC underwent a 1.5 T MRI scan. PG volumes were manually traced for all subjects. Psychiatric symptoms were assessed by means of the Brief Psychiatry Rating Scale, the Hamilton Depression Rating Scale and the Bech Rafaelsen Mania Rating Scale. RESULTS: We found decreased PG volumes in BD patients compared to HC (F = 24.9, p < 0.001). Interestingly, after dividing the sample by gender, a significant PG volume decrease was detected only in female BD patients compared to female HC (F = 9.1, p < 0.001), but not in male BD compared to male HC (F = -0.12, p = 0.074). No significant correlations were observed between PG volumes and clinical variables. CONCLUSIONS: Our findings suggest that BD patients have decreased PG volumes, probably due to the long-term hyperactivity of the HPAA and to the consequent strengthening of the negative feedback control towards the PG volume itself. This alteration was particularly evident in females, suggesting a role of gender in affecting PG volumes in BD. Finally, the absence of significant correlations between PG volumes and clinical variables further supports that PG disruption is a trait feature of BD, being independent of symptoms severity and duration of treatment.

Classification of first-episode psychosis: a multi-modal multi-feature approach integrating structural and diffusion imaging.

Currently, most of the classification studies of psychosis focused on chronic patients and employed single machine learning approaches. To overcome these limitations, we here compare, to our best knowledge for the first time, different classification methods of first-episode psychosis (FEP) using multi-modal imaging data exploited on several cortical and subcortical structures and white matter fiber bundles. 23 FEP patients and 23 age-, gender-, and race-matched healthy participants were included in the study. An innovative multivariate approach based on multiple kernel learning (MKL) methods was implemented on structural MRI and diffusion tensor imaging. MKL provides the best classification performances in comparison with the more widely used support vector machine, enabling the definition of a reliable automatic decisional system based on the integration of multi-modal imaging information. Our results show a discrimination accuracy greater than 90 % between healthy subjects and patients with FEP. Regions with an accuracy greater than 70 % on different imaging sources and measures were middle and superior frontal gyrus, parahippocampal gyrus, uncinate fascicles, and cingulum. This study shows that multivariate machine learning approaches integrating multi-modal and multisource imaging data can classify FEP patients with high accuracy. Interestingly, specific grey matter structures and white matter bundles reach high classification reliability when using different imaging modalities and indices, potentially outlining a prefronto-limbic network impaired in FEP with particular regard to the right hemisphere.

Preoperative Anxiety in Patients with Pancreatic Cancer: What Contributes to Anxiety Levels in Patients Waiting for Surgical Intervention.

Pancreatic cancer is one of the most lethal malignancies. Currently, the only treatment is surgical resection, which contributes to significant preoperative anxiety, reducing quality of life and worsening surgical outcomes. To date, no standard preventive or therapeutic methods have been established for preoperative anxiety in pancreatic patients. This observational study aims to identify which patients' socio-demographic, clinical and psychological characteristics contribute more to preoperative anxiety and to identify which are their preoperative concerns. Preoperative anxiety was assessed the day before surgery in 104 selected cancer patients undergoing similar pancreatic major surgery, by administering the STAI-S (State-Trait Anxiety Inventory Form) and the APAIS (Amsterdam Preoperative Anxiety and Information Scale). Our data suggest that patients with high STAI-S showed higher levels of APAIS and that major concerns were related to surgical aspects. Among psychological characteristics, depressive symptoms and trait anxiety appeared as risk factors for the development of preoperative anxiety. Findings support the utility of planning a specific psychological screening to identify patients who need more help, with the aim of offering support and preventing the development of state anxiety and surgery worries in the preoperative phase. This highlights also the importance of good communication by the surgeon on specific aspects related to the operation.

Is neuregulin 1 involved in determining cerebral volumes in schizophrenia? Preliminary results showing a decrease in superior temporal gyrus volume.

BACKGROUND/AIMS: Reduced left superior temporal gyrus (STG) volume is one of the most replicated imaging findings in schizophrenia. However, it remains unclear whether genes play any role in our understanding of such structural alteration. It has been proposed that Neuregulin 1 (NRG1) might be a promising gene involved in schizophrenia, because of its role in neurodevelopment and neuroplasticity. In this study, the association between NRG1 and STG anatomy in patients with schizophrenia was explored for the first time. METHODS: We investigated a 1-year treated prevalence cohort of patients with schizophrenia in contact with the South Verona Community-Based Mental Health Service. A blood sample was collected for DNA extraction and brain structure was assessed with an MRI scan. A total of 27 subjects with schizophrenia underwent both assessments and were included in the study. RESULTS: We investigated the association between the polymorphism SNP8NRG222662 (rs4623364) of NRG1 and volume of the STG. We found that patients homozygous for the C allele had reduced left STG gray and white matter volumes in comparison to those homozygous for the G allele (p < 0.01 and p < 0.001, respectively). CONCLUSIONS: This exploratory study suggests that NRG1 may be involved in determining STG size in schizophrenia, and may play a role in the neurogenetic basis of the language disturbances seen in this disorder. However, due to our small sample size, the results should be regarded as preliminary and replicated in a larger sample.

Bioethics in an oncological surgery unit during the COVID-19 pandemic: the Verona experience.

The spread of COVID-19 has overwhelmed medical facilities across the globe, with patients filling beds in both regular wards and in intensive care units. The repurposing of hospital facilities has resulted in a dramatic decrease in the capacity of hospitals-in terms of available beds, surgical facilities, and medical and nursing staff- to care for oncology patients. The Italian National Board of Bioethics provided precise and homogeneous guidelines for the allocation of the scarce resources available. In our experience, strictly following these general guidelines and not considering the clinical vocation of each single health care center did not allow us to resume usual activities but generated further confusion in resource allocation. To face the scarcity of available resources and guarantee our patients fair access to the health care system we created a surgical triage with four fundamental steps. We took into consideration " well defined and widely accepted clinical prognostic factors " as stated by the Italian Society of Anesthesia and Resuscitation. We were able to draw up a list of patients giving priority to those who theoretically should have a greater chance of overcoming their critical situation. The age criterion has also been used in the overall evaluation of different cure options in each case, but it has never been considered on its own or outside the other clinical parameters. Although not considered acceptable by many we had to forcefully adopt the criterion of comparison between patients to give priority to those most in need of immediate care.

Laterality effects in schizophrenia and bipolar disorder.

There are numerous reports in the literature of lateralised structural cerebral abnormalities and alterations of the corpus callosum in the major psychoses. In the light of these findings the purpose of this study was to directly compare hemispheric differences and callosal interhemispheric transmission (IT) in schizophrenia and bipolar disorder. To do that we tested schizophrenic (SCZ), bipolar disorder (BD) patients and controls in a simple manual reaction time (RT) task with lateralised visual stimuli (Poffenberger paradigm) which enables one to test both laterality effects and IT time. We found an overall slowing of responses with the right hand in schizophrenics but not in bipolar patients, who, like controls, showed no hand differences. This selective slowing down of the right hand is likely to be related to abnormalities of intrahemispheric cortico-cortical connections in the left hemisphere. In contrast, IT time was similar in SCZ and BD patients and did not differ with respect to controls. Two are the novel findings of the present study: first both SZC and BD share a normal IT of visuomotor information despite the presence of callosal abnormalities. Second, an impairment of intrahemispheric left hemispheric processing is present only in SCZ patients. This represents a potentially important clue to a further understanding of the pathogenetic differences between the two major psychoses.

PREPARE: PreoPerative Anxiety REduction. One-Year Feasibility RCT on a Brief Psychological Intervention for Pancreatic Cancer Patients Prior to Major Surgery.

INTRODUCTION: The aim of the present paper is to establish feasibility and required power of a one-session psychological intervention devoted to increasing patient's self-efficacy and awareness in dealing with anxiety symptoms before major pancreatic cancer surgery. METHODS: Parallel assignment RCT. All consenting patients listed for pancreatic major surgery during day-hospital visits (T0) between June 2017-June 2018 were assigned randomly in blocks of ten to a psychological intervention vs usual care group to be held the day before surgery (T1). The psychological intervention provided the patient the opportunity to increase self-efficacy in dealing with anxiety by talking with a psychologist about personal concerns and learning mindfulness based techniques to cope with anxiety. RESULTS: 400 patients were randomized into the experimental vs. usual care group. 49 and 65, respectively, completed baseline and post-intervention measures. The dropout rate between day-hospital (T0) and pre-surgery intervention (T1) was high (74.5%) due to several management and organization pitfalls. The main outcome, perceived self-efficacy in managing anxiety, showed a significant increase in the intervention group compared to the control group (p < 0.001), and was related to a reduction in state anxiety (p < 0.001). The intervention group perceived also lower emotional pain (p = 0.03). A power analysis was performed to define the appropriate sample size in a definitive RCT. CONCLUSION: Beneath the complexity in retaining patients along their trajectory in pancreatic surgery department, when they had the opportunity to follow a brief psychological intervention, most of them adhered, showing a significant reduction in preoperative emotional distress and less emotional pain perception after surgery. Even if results need caution because of the high attrition rate, we can infer that our psychological intervention has the potential to be proposed in surgical setting, being short, easy to learn and applicable to a wide range of patients. CLINICAL TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (identifier: NCT03408002). The full protocol is available from the last author.

The brief assessment of cognition in affective disorders: Normative data for the Italian population.

BACKGROUND: To date there are no validated tests in Italian to assess cognitive functions in Bipolar Disorder. Therefore, this study aimed to provide normative data for the Italian version of the Brief Assessment of Cognition in Affective Disorders (BAC-A), a battery targeting neuro- and affective-cognition in affective disorders. METHODS: Data were collected from 228 healthy participants (age range: 18-67; mean age: 34.68 ± 12.15 years) across eight recruiting sites. The influence of age, sex and education was measured and adjusted for using multivariate stepwise regression models. Normative values were established by means of the Equivalent Score approach. RESULTS: Most of the BAC-A subtests showed patterns of association with age (inversely associated with overall cognitive performance), education (positively associated with Verbal Memory and Fluency, Digit Sequencing and Affective Processing subtests) and sex (females performed better than males in the Affective Interference Test but worse in the Emotion Inhibition Task, Digit Sequencing and Tower of London). LIMITATIONS: The sample size was not sufficiently large for developing stratified norms, using 10-years ranges. Moreover, the participants included in the study were, on average, highly educated. CONCLUSIONS: The normative data of the BAC-A provided in this study can serve as a cognitive functioning reference for Italian-speaking participants within the age range of the study sample. This can increase the applicability of this test in both clinical and research settings. The reliability and validity of the Italian BAC-A need to be further investigated.

Increased gyrification in schizophrenia and non affective first episode of psychosis.

BACKGROUND: Prefrontal cortex gyrification has been suggested to be altered in patients with schizophrenia and first episode psychosis. Therefore, it may represent a possible trait marker for these illnesses and an indirect evidence of a disrupted underlying connectivity. The aim of this study was to add further evidence to the existing literature on the role of prefrontal gyrification in psychosis by carrying out a study on a sizeable sample of chronic patients with schizophrenia and non-affective first-episode psychosis (FEP-NA) patients. METHODS: Seventy-two patients with schizophrenia, 51 FEP-NA patients (12 who later develop schizophrenia) and 95 healthy controls (HC) underwent magnetic resonance imaging (MRI). Cortical folding was quantified using the automated gyrification index (GI). GI values were compared among groups and related to clinical variables. RESULTS: Both FEP-NA and patients with schizophrenia showed a higher mean prefrontal GI compared to HC (all p<0.05). Interestingly, no differences have been observed between the two patients groups as well as between FEP-NA patients who did and did not develop schizophrenia. CONCLUSIONS: Our results suggest the presence of a shared aberrant prefrontal GI in subjects with both schizophrenia and first-episode psychosis. These findings support the hypothesis that altered GI represents a neurodevelopmental trait marker for psychosis, which may be involved in the associated neurocognitive deficits.

Erratum to: Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness.

The original version of this article unfortunately contained a mistake. The family name of Paolo Brambilla was incorrectly spelled as Bambilla.

Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness.

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition.

Longitudinal investigation of the parietal lobe anatomy in bipolar disorder and its association with general functioning.

The parietal lobe (PL) supports cognitive domains, including attention and memory, which are impaired in bipolar disorder (BD). Although cross-sectional voxel-based morphometry studies found reduced PL grey matter (GM) in BD, none has longitudinally focused on PL anatomy in BD, relating it to patients' functioning. Thirty-eight right-handed BD patients and 42 matched healthy subjects (HS) underwent a Magnetic Resonance Imaging (MRI) scan at baseline. Seventeen BD patients and 16 matched HS underwent a follow-up MRI. PL white matter (WM) and GM volumes were measured. The trajectory of parietal volumes over time and the possible relation with the global functioning were investigated in both BD patients and HS. At baseline, BD patients showed significant reduced PL WM and GM and different WM laterality compared with HS. Furthermore, smaller PL WM volumes predicted lower global functioning in BD, but not in HS. At follow-up, although BD patients reported reduced PL WM compared with HS, no different pattern of volume changes over time was detected between groups. This study suggests the involvement of the PL in the pathophysiology of BD. In particular, PL WM reductions seem to predict an impairment in general functioning in BD and might represent a marker of functional outcome.

Common and distinct structural features of schizophrenia and bipolar disorder: The European Network on Psychosis, Affective disorders and Cognitive Trajectory (ENPACT) study.

INTRODUCTION: Although schizophrenia (SCZ) and bipolar disorder (BD) share elements of pathology, their neural underpinnings are still under investigation. Here, structural Magnetic Resonance Imaging (MRI) data collected from a large sample of BD and SCZ patients and healthy controls (HC) were analyzed in terms of gray matter volume (GMV) using both voxel based morphometry (VBM) and a region of interest (ROI) approach. METHODS: The analysis was conducted on two datasets, Dataset1 (802 subjects: 243 SCZ, 176 BD, 383 HC) and Dataset2, a homogeneous subset of Dataset1 (301 subjects: 107 HC, 85 BD and 109 SCZ). General Linear Model analyses were performed 1) at the voxel-level in the whole brain (VBM study), 2) at the regional level in the anatomical regions emerged from the VBM study (ROI study). The GMV comparison across groups was integrated with the analysis of GMV correlates of different clinical dimensions. RESULTS: The VBM results of Dataset1 showed 1) in BD compared to HC, GMV deficits in right cingulate, superior temporal and calcarine cortices, 2) in SCZ compared to HC, GMV deficits in widespread cortical and subcortical areas, 3) in SCZ compared to BD, GMV deficits in insula and thalamus (p<0.05, cluster family wise error corrected). The regions showing GMV deficits in the BD group were mostly included in the SCZ ones. The ROI analyses confirmed the VBM results at the regional level in most of the clusters from the SCZ vs. HC comparison (p<0.05, Bonferroni corrected). The VBM and ROI analyses of Dataset2 provided further evidence for the enhanced GMV deficits characterizing SCZ. Based on the clinical-neuroanatomical analyses, we cannot exclude possible confounding effects due to 1) age of onset and medication in BD patients, 2) symptoms severity in SCZ patients. CONCLUSION: Our study reported both shared and specific neuroanatomical characteristics between the two disorders, suggesting more severe and generalized GMV deficits in SCZ, with a specific role for insula and thalamus.