Functional network interactions in patients with schizophrenia with persistent auditory verbal hallucinations: A multimodal MRI fusion approach using three-way pICA.

Over the last decade, there have been an increasing number of functional magnetic resonance imaging (fMRI) studies examining brain activity in schizophrenia (SZ) patients with persistent auditory verbal hallucinations (AVH) using either task-based or resting-state fMRI (rs-fMRI) paradigms. Such data have been conventionally collected and analyzed as distinct modalities, disregarding putative crossmodal interactions. Recently, it has become possible to incorporate two or more modalities in one comprehensive analysis to uncover hidden patterns of neural dysfunction not sufficiently captured by separate analysis. A novel multivariate fusion approach to multimodal data analysis, i.e., parallel independent component analysis (pICA), has been previously shown to be a powerful tool in this regard. We utilized three-way pICA to study covarying components among fractional amplitude of low-frequency fluctuations (fALFF) for rs-MRI and task-based activation computed from an alertness and a working memory (WM) paradigm of 15 SZ patients with AVH, 16 non-hallucinating SZ patients (nAVH), and 19 healthy controls (HC). The strongest connected triplet (false discovery rate (FDR)-corrected pairwise correlations) comprised a frontostriatal/temporal network (fALFF), a temporal/sensorimotor network (alertness task), and a frontoparietal network (WM task). Frontoparietal and frontostriatal/temporal network strength significantly differed between AVH patients and HC. Phenomenological features such as omnipotence and malevolence of AVH were associated with temporal/sensorimotor and frontoparietal network strength. The transmodal data confirm a complex interplay of neural systems subserving attentional processes and cognitive control interacting with speech and language processing networks. In addition, the data emphasize the importance of sensorimotor regions modulating specific symptom dimensions of AVH.

Peripartum effects of synthetic oxytocin: The good, the bad, and the unknown.

The first clinical applications of oxytocin (OT) were in obstetrics as a hormone to start and speed up labor and to control postpartum hemorrhage. Discoveries in the 1960s and 1970s revealed that the effects of OT are not limited to its peripheral actions around birth and milk ejection. Indeed, OT also acts as a neuromodulator in the brain affecting fear memory, social attachment, and other forms of social behaviors. The peripheral and central effects of OT have been separately subject to extensive scrutiny. However, the effects of peripheral OT-particularly in the form of administration of synthetic OT (synOT) around birth-on the central nervous system are surprisingly understudied. Here, we provide a narrative review of the current evidence, suggest putative mechanisms of synOT action, and provide new directions and hypotheses for future studies to bridge the gaps between neuroscience, obstetrics, and psychiatry.

A neurodevelopmental signature of parkinsonism in schizophrenia.

While sensorimotor abnormalities in schizophrenia (SZ) are of increasing scientific interest, little is known about structural changes and their developmental origins that may underlie parkinsonism. This multimodal magnetic resonance imaging (MRI) study examined healthy controls (HC, n = 20) and SZ patients with (SZ-P, n = 38) and without (SZ-nonP, n = 35) parkinsonism, as defined by Simpson-Angus Scale total scores of ≥4 or ≤1, respectively. Using the Computational Anatomy Toolbox (CAT12), voxel- and surface-based morphometry were applied to investigate cortical and subcortical gray matter volume (GMV) and three cortical surface markers of distinct neurodevelopmental origin: cortical thickness (CTh), complexity of cortical folding (CCF) and sulcus depth. In a subgroup of patients (29 SZ-nonP, 25 SZ-P), resting-state fMRI data were also analyzed using a regions-of-interest approach based on fractional amplitude of low frequency fluctuations (fALFF). SZ-P patients showed increased CCF in the left supplementary motor cortex (SMC) and decreased left postcentral sulcus (PCS) depth compared to SZ-nonP patients (p < 0.05, FWE-corrected at cluster level). In SMC, CCF was associated negatively with activity, which also differed significantly between the patient groups and between patients and HC. In regression models, severity of parkinsonism was associated negatively with left middle frontal CCF and left anterior cingulate CTh. These data provide novel insights into altered trajectories of cortical development in SZ patients with parkinsonism. These cortical surface changes involve the sensorimotor system, suggesting abnormal neurodevelopmental processes tightly coupled with cortical activity and subcortical morphology that convey increased risk for sensorimotor abnormalities in SZ.

Right parietotemporal activity predicts sense of agency under uncertain delays of sensory outcomes.

Sense of agency is the experience of control over one's own action and its consequent outcomes. The perceived time between a motor action and its consequent sensory outcomes (e.g., a flash of light) is shorter for a voluntary than involuntary action, a phenomenon known as intentional binding, which has been used extensively as an implicit measure of sense of agency. We developed a novel task in which participants had to respond whether a flash appeared immediately or with a delay relative to their voluntary action. We found that under high, but not low, uncertainty about the perceived time between voluntary finger movement and a subsequent flash of light, a prediction signal was generated in the right inferior parietal lobule prior to motor action. This prediction signal was linked to the emergence of a sudden insight solution (colloquially referred to as "Aha!" moment) in the right superior temporal gyrus prior to response. Single-trial event-related potential analysis revealed a reliable correlation between amplitudes of premotor and preresponse activities. The results suggest the existence of a predictive mechanism under high uncertainty about the timing of the sensory consequences of a voluntary motor action. The results are in line with the optimal cue integration theory of sense of agency, which states that both predictive and postdictive agency cues are crucial for the formation of sense of agency and the weight of each type of cue (predictive or postdictive) depends on their availability and reliability.NEW & NOTEWORTHY According to the optimal cue integration theory, the formation of sense of agency relies on both predictive and postdictive agency cues and how they are weighted based on their availability and reliability. Using a novel paradigm, we show for the first time a possible existence of a prediction signal prior to voluntary movement, which appears when postdictive agency cues (i.e., the judgment of the time between voluntary movement and a subsequent flash) are not reliable.

Neurological Soft Signs Predict Auditory Verbal Hallucinations in Patients With Schizophrenia.

Neurological soft signs (NSS) are well documented in individuals with schizophrenia (SZ), yet so far, the relationship between NSS and specific symptom expression is unclear. We studied 76 SZ patients using magnetic resonance imaging (MRI) to determine associations between NSS, positive symptoms, gray matter volume (GMV), and neural activity at rest. SZ patients were hypothesis-driven stratified according to the presence or absence of auditory verbal hallucinations (AVH; n = 34 without vs 42 with AVH) according to the Brief Psychiatric Rating Scale. Structural MRI data were analyzed using voxel-based morphometry, whereas intrinsic neural activity was investigated using regional homogeneity (ReHo) measures. Using ANCOVA, AVH patients showed significantly higher NSS in motor and integrative functions (IF) compared with non-hallucinating (nAVH) patients. Partial correlation revealed that NSS IF were positively associated with AVH symptom severity in AVH patients. Such associations were not confirmed for delusions. In region-of-interest ANCOVAs comprising the left middle and superior temporal gyri, right paracentral lobule, and right inferior parietal lobule (IPL) structure and function, significant differences between AVH and nAVH subgroups were not detected. In a binary logistic regression model, IF scores and right IPL ReHo were significant predictors of AVH. These data suggest significant interrelationships between sensorimotor integration abilities, brain structure and function, and AVH symptom expression.

Moving forward: distinct sensorimotor abnormalities predict clinical outcome after 6 months in patients with schizophrenia.

Despite substantial efforts in the last decades, objective measures that can predict clinical outcome in patients with schizophrenia (SZ) after an acute psychotic episode are still lacking. Here, we introduced a comprehensive assessment of sensorimotor function to predict mid-term clinical outcome following an acute psychotic episode. This naturalistic follow-up of 43 patients with DSM-IV-TR diagnosis of SZ examined sensorimotor abnormalities (i.e. Neurological Soft Signs (NSS), parkinsonism, akathisia, catatonia and acute dyskinesia), psychopathology, cognition and psychosocial functioning using well-established instruments. A collection of statistical methods was used to examine the relationship between sensorimotor domain, psychopathology, cognition and psychosocial functioning. We also tested the clinical feasibility of this relationship when predicting clinical outcome after an acute psychotic episode. Longitudinal data were collected on 43 individuals after a follow-up period of >6 months. At follow-up, patients showed significantly reduced general symptom severity, as well as decreased levels of NSS, parkinsonism and catatonia. Further, NSS scores at baseline predicted PANSS negative scores and cognitive functioning at baseline. Finally, NSS scores at baseline predicted symptom change (reduction of PANSS positive and negative scores) at follow-up. In conclusion, our results suggest that NSS are significant predictors of poor clinical outcome in SZ at baseline and >6 months after an acute psychotic episode. These findings propose sensorimotor domain as state biomarker of SZ and support its predictive power with respect to treatment outcome.

Functional Decoupling of Language and Self-Reference Networks in Patients with Persistent Auditory Verbal Hallucinations.

BACKGROUND: Accumulating neuroimaging evidence suggests that abnormal intrinsic neural activity could underlie auditory verbal hallucinations (AVH) in patients with schizophrenia. However, little is known about the functional interplay between distinct intrinsic neural networks and their association with AVH. METHODS: We investigated functional network connectivity (FNC) of distinct resting-state networks as well as the relationship between FNC strength and AVH symptom severity. Resting-state functional MRI data at 3 T were obtained for 14 healthy controls and 10 patients with schizophrenia presenting with persistent AVH. The data were analyzed using a spatial group independent component analysis, followed by constrained maximal lag correlations to determine FNC within and between groups. RESULTS: Four components of interest, comprising language, attention, executive control networks, as well as the default-mode network (DMN), were selected for subsequent FNC analyses. Patients with persistent AVH showed lower FNC between the language network and the DMN (p < 0.05, corrected for false discovery rate). FNC strength, however, was not significantly related to symptom severity, as measured by the Psychotic Symptom Rating Scale. CONCLUSION: These findings suggest that disrupted FNC between a speech-related system and a network subserving self-referential processing is associated with AVH. The data are consistent with a model of disrupted self-attribution of speech generation and perception.

A Neural Signature of Parkinsonism in Patients With Schizophrenia Spectrum Disorders: A Multimodal MRI Study Using Parallel ICA.

Motor abnormalities in schizophrenia spectrum disorders (SSD) have increasingly attracted scientific interest in the past years. However, the neural mechanisms underlying parkinsonism in SSD are unclear. The present multimodal magnetic resonance imaging (MRI) study examined SSD patients with and without parkinsonism, as defined by a Simpson and Angus Scale (SAS) total score of ≥4 (SAS group, n = 22) or <4 (non-SAS group, n = 22). Parallel independent component analysis (p-ICA) was used to examine the covarying components among gray matter volume maps computed from structural MRI (sMRI) and fractional amplitude of low-frequency fluctuations (fALFF) maps computed from resting-state functional MRI (rs-fMRI) patient data. We found a significant correlation (P = .020, false discovery rate [FDR] corrected) between an sMRI component and an rs-fMRI component, which also significantly differed between the SAS and non-SAS group (P = .042, z = -2.04). The rs-fMRI component comprised the cortical sensorimotor network, and the sMRI component included predominantly a frontothalamic/cerebellar network. Across the patient sample, correlations adjusted for the Positive and Negative Syndrome Scale (PANSS) total scores showed a significant relationship between tremor score and loadings of the cortical sensorimotor network, as well as between glabella-salivation score, frontothalamic/cerebellar and cortical sensorimotor network loadings. These data provide novel insights into neural mechanisms of parkinsonism in SSD. Aberrant bottom-up modulation of cortical motor regions may account for these specific motor symptoms, at least in patients with SSD.

Multimodal Magnetic Resonance Imaging Data Fusion Reveals Distinct Patterns of Abnormal Brain Structure and Function in Catatonia.

Catatonia is a nosologically unspecific syndrome, which subsumes a plethora of mostly complex affective, motor, and behavioral phenomena. Although catatonia frequently occurs in schizophrenia spectrum disorders (SSD), specific patterns of abnormal brain structure and function underlying catatonia are unclear at present. Here, we used a multivariate data fusion technique for multimodal magnetic resonance imaging (MRI) data to investigate patterns of aberrant intrinsic neural activity (INA) and gray matter volume (GMV) in SSD patients with and without catatonia. Resting-state functional MRI and structural MRI data were collected from 87 right-handed SSD patients. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). A multivariate analysis approach was used to examine co-altered patterns of INA and GMV. Following a categorical approach, we found predominantly frontothalamic and corticostriatal abnormalities in SSD patients with catatonia (NCRS total score ≥ 3; n = 24) when compared to SSD patients without catatonia (NCRS total score = 0; n = 22) matched for age, gender, education, and medication. Corticostriatal network was associated with NCRS affective scores. Following a dimensional approach, 33 SSD patients with catatonia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were identified. NCRS behavioral scores were associated with a joint structural and functional system that predominantly included cerebellar and prefrontal/cortical motor regions. NCRS affective scores were associated with frontoparietal INA. This study provides novel neuromechanistic insights into catatonia in SSD suggesting co-altered structure/function-interactions in neural systems subserving coordinated visuospatial functions and motor behavior.

Patterns of co-altered brain structure and function underlying neurological soft signs in schizophrenia spectrum disorders.

Neurological soft signs (NSS) comprise a broad range of subtle neurological deficits and are considered to represent external markers of sensorimotor dysfunction frequently found in mental disorders of presumed neurodevelopmental origin. Although NSS frequently occur in schizophrenia spectrum disorders (SSD), specific patterns of co-altered brain structure and function underlying NSS in SSD have not been investigated so far. It is unclear whether gray matter volume (GMV) alterations or aberrant brain activity or a combination of both, are associated with NSS in SSD. Here, 37 right-handed SSD patients and 37 matched healthy controls underwent motor assessment and magnetic resonance imaging (MRI) at 3 T. NSS were examined on the Heidelberg NSS scale. We used a multivariate data fusion technique for multimodal MRI data-multiset canonical correlation and joint independent component analysis (mCCA + jICA)-to investigate co-altered patterns of GMV and intrinsic neural fluctuations (INF) in SSD patients exhibiting NSS. The mCCA + jICA model indicated two joint group-discriminating components (temporoparietal/cortical sensorimotor and frontocerebellar/frontoparietal networks) and one modality-specific group-discriminating component (p < .05, FDR corrected). NSS motor score was associated with joint frontocerebellar/frontoparietal networks in SSD patients. This study highlights complex neural pathomechanisms underlying NSS in SSD suggesting aberrant structure and function, predominantly in cortical and cerebellar systems that critically subserve sensorimotor dynamics and psychomotor organization.

Structure/function interrelationships in patients with schizophrenia who have persistent auditory verbal hallucinations: A multimodal MRI study using parallel ICA.

There is accumulating neuroimaging evidence for both structural and functional abnormalities in schizophrenia patients with persistent auditory verbal hallucinations (AVH). So far, the direct interrelationships between altered structural and functional changes underlying AVH are unknown. Recently, it has become possible to reveal hidden patterns of neural dysfunction not sufficiently captured by separate analysis of these two modalities. A data-driven fusion method called parallel independent component analysis (p-ICA) is able to identify maximally independent components of each imaging modality as well as the link between them. In the present study, we utilized p-ICA to study covarying components among gray matter volume maps computed from structural MRI (sMRI) and fractional amplitude of low-frequency fluctuations (fALFF) maps computed from resting-state functional MRI (rs-fMRI) data of 15 schizophrenia patients with AVH, 16 non-hallucinating schizophrenia patients (nAVH), and 19 healthy controls (HC). We found a significant correlation (r = 0.548, n = 50, p < .001) between a sMRI component and a rs-fMRI component, which was significantly different between the AVH and non AVH group (nAVH). The rs-fMRI component comprised temporal cortex and cortical midline regions, the sMRI component included predominantly fronto-temporo-parietal regions. Distinct clinical features, as measured by the Psychotic Symptoms Rating Scale (PSYRATS), were associated with two different modality specific rs-fMRI components. There was a significant correlation between a predominantly parietal resting-state network and the physical dimension of PSYRATS and the posterior cingulate/temporal cortex network and the emotional dimension of PSYRATS. These data suggest AVH-specific interrelationships between intrinsic network activity and GMV, together with modality-specific associations with distinct symptom dimensions of AVH.

Perception of facial expressions of emotion in migraine.

Both lower-level perceptual changes and especially higher-level cognitive alterations in individuals with migraine are poorly understood. Here, we behaviorally and electrophysiologically investigated the perception of emotional facial expressions in migraine. Young female individuals with migraine and healthy controls watching neutral faces gradually shifting to either happy, fearful, or angry expressions were asked to classify the facial expressions as quickly and accurately as possible by pressing a corresponding button, and to keep looking at the face until the last frame disappeared. Migraine individuals, compared to healthy controls, had a reduced habituation in the N170 time interval towards a gradually emerging emotional expression. The early P1, the early posterior negativity (EPN), and the late positive potential (LPP) amplitudes were not statistically different between groups and among expressions. The mean reaction time for recognizing an expression did not differ between groups and it was not at a cost of more incorrect responses. Interestingly, the amplitude of the early posterior negativity correlated negatively with the time interval since the last attack. It is concluded that young female individuals with migraine, compared to healthy controls, do not show a biased emotional facial processing toward positive or negative expressions.

Effect of different professions' clothing on children's height perception.

Height is a biological factor that can affect how others perceive and behave toward an individual. Height is a biological factor that can affect how others perceive and behave toward an individual. Clothing, as a non-biological factor, can affect these perceptions of height. In this study weClothing, as a non-biological factor, can affect these perceptions of height. In this study we investigated the effect of different professions' clothing on children's perceptions of height. One investigated the effect of different professions' clothing on children's perceptions of height. One hundred and eighty primary school students participated in this study and estimated the height of an actor in the clothing of four different professions which differed in terms of prestige. The results of study showed that the difference between the perceived and actual height was larger when participants estimated the height of socially esteemed professions. Also there was no difference between girls' and boys' estimation of different professions' height. The implications of these findings are discussed.

Effect of different professions’ clothing on children’s height perception

Height is a biological factor that can affect how others perceive and behave toward an individual. Clothing, as a non-biological factor, can affect these perceptions of height. In this study we investigated the effect of different professions’ clothing on children’s perceptions of height. One hundred and eighty primary school students participated in this study and estimated the height of an actor in the clothing of four different professions which differed in terms of prestige. The results of study showed that the difference between the perceived and actual height was larger when participants estimated the height of socially esteemed professions. Also there was no difference between girls’ and boys’ estimation of different professions’ height. The implications of these findings are discussed (AU)

La talla de un individuo como factor biológico, tiene diferentes efectos sobre cómo otros perciben y se comportan con dicho individuo. La indumentaria como factor no biológico puede alterar las percepciones de la talla. En este estudio, investigamos el efecto de la indumentaria de diferentes profesiones sobre la estimación de la talla percibida por los niños. Participaron en el estudio 180 niños de primaria, quienes estimaron la talla de un actor vestido con la indumentaria correspondiente a cuatro profesiones diferentes. Los resultados mostraron que la diferencia entre la talla real y la percibida era mayor cuando los participantes estimaban la talla de profesiones socialmente valoradas. No hubo diferencias de sexo en la estimación de las tallas de diferentes profesiones (AU)

Surgical treatment of myelomeningocele: year 2000 hospitalization, outcome, and cost analysis in the US.

OBJECTIVE: To review cases of surgical repair for myelomeningocele (MMC) using a large inpatient database from the year 2000. MATERIALS AND METHODS: The Nationwide Inpatient Sample (NIS) database with 7.45 million patient admissions for 2000 was retrospectively studied for the first 5 procedure diagnosis of MMC repair (ICD-9 CM procedure code 0352) and ages of less than 1 year. Eighty-eight patient stays were identified. Patient demographic data, length of stay, immediate disposition at the time of discharge, hospital information, and total cost for the hospitalization were determined. CONCLUSION: Myelomeningocele repair is mostly performed in large teaching institutions in small numbers. The majority gets to go home at discharge. It is surprising to note that only 35% also required VP shunt placement during the same hospitalization.

Predictive factors for dural tear and cerebrospinal fluid leakage in patients undergoing lumbar surgery.

OBJECT: A dural tear resulting in a cerebrospinal fluid (CSF) leak is a well-known risk of lumbar spinal procedures. The authors hypothesized that the incidence of CSF leakage is higher in cases involving repeated operations and those in which the surgeon performing the surgery is less experienced; however, they postulated that the overall outcome of the patient would not be adversely affected by a dural tear. METHODS: An institutional review board-approved protocol at Louisiana State University Health Sciences Center, Shreveport, was initiated in August 2003 to allow prospective comparison of data obtained in patients in whom a CSF leak occurred (Group A) and those in whom no CSF leak occurred (Group B) during lumbar surgery. Basic demographic information, descriptive findings regarding the tear, history of other surgeries, hospital length of stay (LOS), and immediate disposition at the time of discharge were compared between the two groups. Seventy-seven patients were eligible for this study. One patient refused to participate. In 12 (15.8%) of 76 patients CSF leakage developed. In three patients the presence of a tear was questioned, and the patients were clinically treated as if a tear were present. The patients in Group A were older than those in Group B (59.8 +/- 16.9 and 49.4 +/- 13.6 years of age, respectively; p = 0.02, Fisher exact test). In terms of those with a history of surgery, there was no significant difference between patients with and patients without a CSF leak (three [25%] of 12 patients [Group A] compared with 28 [43.8%] of 64 patients [Group B]; p = 0.34, two-sample t-test). In the 12 patients with dural tears, nine (75%) were caused by a resident-in-training, and the Kerrison punch was the instrument most often being used at the time (55%). This is significantly greater than 50% at the 5% level (p = 0.044, binomial test). The authors were able to repair the tear primarily with suture in all but one patient, whose tear was along the nerve root sleeve. In all cases fibrin glue and a muscle/fat graft were used to cover the tear, and all patients were assigned to bed rest from 24 to 48 hours after the operation. In Group A one patient required rehabilitation at discharge. The LOS in Group A was greater than that in Group B (median 5 days compared with 3 days), but no additional complication was noted. CONCLUSIONS: The incidence of CSF leakage was 16% in 76 patients, and there were no other complications. Older patient age and higher level of the surgeon's training were factors contributing to the incidence, but the history of surgery was not.

Control of refractory status epilepticus precipitated by anticonvulsant withdrawal using left vagal nerve stimulation: a case report.

OBJECTIVE: To describe a case of left vagal nerve stimulation (VNS) resulting in immediate cessation of status epilepticus (SE) with good neurological outcome. CASE DESCRIPTION: A 30-year-old man with medically intractable seizures including episodes of SE was successfully treated using left VNS. After requiring discontinuation of phenytoin, valproic acid, carbamazepine, and topiramate because of severe allergic reactions resembling Stevens-Johnson syndrome, the patient required pentobarbital coma along with phenobarbital, tiagabine, and levetiracetam for seizure frequency reduction. He underwent left vagal nerve stimulator placement after nearly 9 days of barbiturate-induced coma, with stimulation initiated in the operating room. On the following day, electroencephalography revealed resolution of previously observed periodic lateral epileptiform discharges and the patient was free of seizures. Prestimulation seizure frequency was recorded at 59 times a day, with some seizures enduring 45 minutes despite barbiturate coma. Poststimulation, the patient has been free of seizures for 19 days and is presently taking only levetiracetam and phenobarbital, from which he continues to be successfully weaned without seizures. He is awake, alert, and can recall events leading up to his seizures, with good long-term memory and residual left upper extremity and lower extremity weakness. CONCLUSION: This case illustrates the role of left vagal stimulation in the treatment of SE and otherwise medically intractable seizures caused by allergic reactions. To our knowledge, this is the first case in the world literature for adults reporting cessation of SE after VNS. Another case with a similar improvement has been reported in the pediatric population.

Nonmalignant pediatric brain tumors.

Brain tumors are the most common solid neoplasms in the pediatric population. Each year in the United States, approximately 1500 to 2000 children are affected by one of these tumors. About 50% of pediatric brain tumors are malignant. Nonmalignant pediatric brain tumors comprise an eclectic group of pathologic entities that have fascinating clinical features. Many of these tumors demonstrate a favorable prognosis. In this report, we review the epidemiology, histopathology, genetics, clinical presentation, neuroimaging, and treatment of the common nonmalignant pediatric brain tumors, including low grade astrocytomas (such as cerebellar astrocytoma and optic pathway glioma), subependymal giant cell astrocytomas, central neurocytomas, dysembryoplastic neuroepithelial tumor, choroid plexus papilloma, and craniopharyngioma. Advances in the therapeutic management of patients with these tumors have considerably improved their prognosis.