Lower cerebello-cortical functional connectivity in veterans with reactive aggression symptoms: A pilot study

A significant number of veterans experience irritability and aggression symptoms as a result of being exposed to extremely stressful and life-threatening situations. In addition to the well-established involvement of the brain's cortico-subcortical circuit in aggression-related behaviours, a role of the deep cerebellar nuclei (DCN) in reactive aggression has been suggested. In the present study, seed-based resting-state functional connectivity between the DCN and cortico-subcortical areas was explored in veterans with and without reactive aggression symptoms. Nineteen male veterans with reactive aggression symptoms and twenty-two control veterans without reactive aggression symptoms underwent 3T resting-state functional MRI scans. Region-of-interest (ROI) analyses that included the amygdala, hypothalamus and periaqueductal grey as ROIs did not yield significant group-related differences in resting-state functional connectivity with the DCN. However, exploratory whole-brain analysis showed that veterans with reactive aggression symptoms exhibited lower functional connectivity between the DCN and the orbitofrontal cortex compared to control veterans. Our findings provide preliminary evidence for the possible involvement of a cerebello-prefrontal pathway in reactive aggression in male veterans

Celio (\u2705), Orkand (\u2707) Named Up and Coming Leaders

BackgroundAlthough auditory verbal hallucinations (AVH) are a core symptom of schizophrenia, they also occur in non-psychotic individuals, in the absence of other psychotic, affective, cognitive and negative symptoms. AVH have been hypothesized to result from deviant integration of inferior frontal, parahippocampal and superior temporal brain areas. However, a direct link between dysfunctional connectivity and AVH has not yet been established. To determine whether hallucinations are indeed related to aberrant connectivity, AVH should be studied in isolation, for example in non-psychotic individuals with AVH.MethodResting-state connectivity was investigated in 25 non-psychotic subjects with AVH and 25 matched control subjects using seed regression analysis with the (1) left and (2) right inferior frontal, (3) left and (4) right superior temporal and (5) left parahippocampal areas as the seed regions. To correct for cardiorespiratory (CR) pulsatility rhythms in the functional magnetic resonance imaging (fMRI) data, heartbeat and respiration were monitored during scanning and the fMRI data were corrected for these rhythms using the image-based method for retrospective correction of physiological motion effects RETROICOR.ResultsIn comparison with the control group, non-psychotic individuals with AVH showed increased connectivity between the left and the right superior temporal regions and also between the left parahippocampal region and the left inferior frontal gyrus. Moreover, this group did not show a negative correlation between the left superior temporal region and the right inferior frontal region, as was observed in the healthy control group.ConclusionsAberrant connectivity of frontal, parahippocampal and superior temporal brain areas can be specifically related to the predisposition to hallucinate in the auditory domain.</jats:sec

Oscillatory Cortical Network Involved in Auditory Verbal Hallucinations in Schizophrenia

Auditory verbal hallucinations (AVH), a prominent symptom of schizophrenia, are often highly distressing for patients. Better understanding of the pathogenesis of hallucinations could increase therapeutic options. Magnetoencephalography (MEG) provides direct measures of neuronal activity and has an excellent temporal resolution, offering a unique opportunity to study AVH pathophysiology.Twelve patients (10 paranoid schizophrenia, 2 psychosis not otherwise specified) indicated the presence of AVH by button-press while lying in a MEG scanner. As a control condition, patients performed a self-paced button-press task. AVH-state and non-AVH state were contrasted in a region-of-interest (ROI) approach. In addition, the two seconds before AVH onset were contrasted with the two seconds after AVH onset to elucidate a possible triggering mechanism.AVH correlated with a decrease in beta-band power in the left temporal cortex. A decrease in alpha-band power was observed in the right inferior frontal gyrus. AVH onset was related to a decrease in theta-band power in the right hippocampus.These results suggest that AVH are triggered by a short aberration in the theta band in a memory-related structure, followed by activity in language areas accompanying the experience of AVH itself

Auditory verbal hallucinations and the brain

Auditory verbal hallucinations (AVH), or perceptions of speech when there is no actual auditory stimulation, are a core symptom of schizophrenia. These voices can be highly distressing, often severely affect quality of life, and increase risk for suicide. Although AVH are prevalent in schizophrenia and several other psychiatric and neurologic disorders, they are not inevitably associated with disease. A minority of people in the general population also experiences AVH without a need for care. These non-clinical individuals provide the opportunity to study AVH without several confounds associated with schizophrenia, such as antipsychotic medication use and other symptoms related to the illness. In this thesis, the pathophysiological mechanism underlying AVH was investigated in schizophrenia patients and a non-clinical population. In the “state” studies, brain activity during AVH episodes was contrasted with brain activity during non-AVH episodes. This approach can inform us about the neural activity associated with AVH. In the “trait” studies, brain activity was compared between individuals with and without AVH. This approach provides information about neural mechanisms predisposing individuals to experience AVH. Furthermore, the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of AVH was studied. A review of electroencephalography (EEG) and magnetoencephalography (MEG) studies revealed that the left superior temporal cortex is consistently reported to be involved in this symptom. Moreover, the review showed evidence that a failure in corollary discharge, i.e. a neural signal originating in frontal speech areas that indicates to sensory areas that forthcoming thought is self-generated, may underlie the experience of auditory hallucinations. In the first state study of this thesis, it was found that activity observed in the left inferior frontal gyrus and Heschl’s gyrus during AVH in schizophrenia patients as measured with fMRI may be related to stimulus detection and motor activity. Several other areas were suggested to be more specifically involved in the genesis of AVH, including the thalamus and parahippocampal gyrus. These latter structures may provide important targets for neuromodulation to alleviate AVH symptoms. In the second state study, it was found that AVH in schizophrenia patients were related to activity in auditory and language areas. AVH onset corresponded with a decrease in theta-band power in the right hippocampus, suggesting that AVH onset may be triggered by memory processes. The first trait study revealed that individuals with non-clinical AVH exhibited increased psychophysiological measures of effortful attention, suggesting that attention to auditory channels may be related to the predisposition to hallucinate in this population. The second trait study showed that non-psychotic individuals with AVH exhibited increased functional connectivity from auditory and default mode areas during the resting state compared to controls. Finally, a repetitive transcranial magnetic stimulation (rTMS) study revealed that the effect of rTMS observed in some studies may be reliant on a placebo effect. In sum, these findings highlight the importance of attention and auditory processes as well as the involvement of language and memory structures in the genesis of AVH. In addition, these results question the efficacy of rTMS as a treatment tool for AVH

The effect of rTMS on auditory hallucinations: Clues from an EEG-rTMS study

AbstractObjectiveRepetitive transcranial magnetic stimulation (rTMS) to the temporoparietal region has been proposed as a therapeutic option for auditory verbal hallucinations (AVH). However, most large randomized controlled trials failed to demonstrate a superior effect of rTMS treatment as compared to sham. Previous studies applied daily rTMS sessions for one or more weeks to summate its effects. However, the effect of a single rTMS treatment on AVH-severity has never been studied, making it unclear if there is an initial effect that could be increased by repeated treatment.MethodsIn three separate sessions, twenty-four patients with a psychotic disorder received 1-Hz rTMS to the left temporoparietal cortex, its right-sided homologue or a centro-occipital control site. Severity of AVH was assessed before and after each rTMS session and resting-state EEGs were recorded to investigate the neuronal effects of rTMS.ResultsStimulation of the temporoparietal cortices was not more effective in reducing AVH-severity than control-site stimulation. In addition, EEG-related power and connectivity measures were not affected differently across stimulation sites and changes in neuronal activity did not correlate with changes in AVH-severity.ConclusionsThese results may suggest a placebo effect of a single session of 1-Hz rTMS treatment on AVH-severity

Five year follow-up of non-psychotic adults with frequent auditory verbal hallucinations : are they still healthy?

BACKGROUND: Previously, we described 103 adults (mean age 41 years) who experienced frequent, auditory verbal hallucinations (AVH), in the absence of a need for mental healthcare. Importantly, these adults were largely past the peak incidence age for psychosis (15-35 years). It is unclear if these older individuals with AVH are still at increased risk for psychosis or other psychopathology. To address this question, we conducted a 5-year follow-up of previously included individuals (103 with AVH, 60 controls). METHOD: Eighty-one adults with AVH (78.6%) and forty-nine controls (81.7%) could be contacted and were willing to participate. Participants were screened for psychosis and a need for mental healthcare at follow-up using the Comprehensive Assessment of Symptoms and History interview (CASH). Need for mental healthcare was defined as a clinical diagnosis as identified using the CASH and/or treatment by a mental healthcare specialist. Phenomenology of AVH was assessed with the PSYRATS Auditory Hallucinations Rating Scale. RESULTS: Five individuals with AVH (6.2%) had developed psychosis and 32 (39.5%) had developed a need for mental healthcare. Voice-related distress at baseline significantly predicted need for mental healthcare. AVH persisted in most individuals (86.4%), without significant changes in phenomenology. None of the controls had developed psychotic symptoms, and need for mental healthcare (n = 6, 12.2%) was significantly lower in this group. CONCLUSIONS: These findings suggest that frequent AVH in non-psychotic adults past the peak incidence age for psychosis constitute a rather static symptom and that individuals with AVH may be best viewed as situated on a need for care continuum

Five year follow-up of non-psychotic adults with frequent auditory verbal hallucinations : are they still healthy?

BACKGROUND: Previously, we described 103 adults (mean age 41 years) who experienced frequent, auditory verbal hallucinations (AVH), in the absence of a need for mental healthcare. Importantly, these adults were largely past the peak incidence age for psychosis (15-35 years). It is unclear if these older individuals with AVH are still at increased risk for psychosis or other psychopathology. To address this question, we conducted a 5-year follow-up of previously included individuals (103 with AVH, 60 controls). METHOD: Eighty-one adults with AVH (78.6%) and forty-nine controls (81.7%) could be contacted and were willing to participate. Participants were screened for psychosis and a need for mental healthcare at follow-up using the Comprehensive Assessment of Symptoms and History interview (CASH). Need for mental healthcare was defined as a clinical diagnosis as identified using the CASH and/or treatment by a mental healthcare specialist. Phenomenology of AVH was assessed with the PSYRATS Auditory Hallucinations Rating Scale. RESULTS: Five individuals with AVH (6.2%) had developed psychosis and 32 (39.5%) had developed a need for mental healthcare. Voice-related distress at baseline significantly predicted need for mental healthcare. AVH persisted in most individuals (86.4%), without significant changes in phenomenology. None of the controls had developed psychotic symptoms, and need for mental healthcare (n = 6, 12.2%) was significantly lower in this group. CONCLUSIONS: These findings suggest that frequent AVH in non-psychotic adults past the peak incidence age for psychosis constitute a rather static symptom and that individuals with AVH may be best viewed as situated on a need for care continuum

Childhood trauma and auditory verbal hallucinations

Background. Hallucinations have consistently been associated with traumatic experiences during childhood. This association appears strongest between physical and sexual abuse and auditory verbal hallucinations (AVH). It remains unclear whether traumatic experiences mainly colour the content of AVH or whether childhood trauma triggers the vulnerability to experience hallucinations in general. In order to investigate the association between hallucinations, childhood trauma and the emotional content of hallucinations, experienced trauma and phenomenology of AVH were investigated in non-psychotic individuals and in patients with a psychotic disorder who hear voices. Method. A total of 127 non-psychotic individuals with frequent AVH, 124 healthy controls and 100 psychotic patients with AVH were assessed for childhood trauma. Prevalence of childhood trauma was compared between groups and the relation between characteristics of voices, especially emotional valence of content, and childhood trauma was investigated. Results. Both non-psychotic individuals with AVH and patients with a psychotic disorder and AVH experienced more sexual and emotional abuse compared with the healthy controls. No difference in the prevalence of traumatic experiences could be observed between the two groups experiencing AVH. In addition, no type of childhood trauma could distinguish between positive or negative emotional valence of the voices and associated distress. No correlations were found between sexual abuse and emotional abuse and other AVH characteristics. Conclusions. These results suggest that sexual and emotional trauma during childhood render a person more vulnerable to experience AVH in general, which can be either positive voices without associated distress or negative voices as part of a psychotic disorde

Opportunities and methodological challenges in EEG and MEG resting state functional brain network research

Electroencephalogram (EEG) and magnetoencephalogram (MEG) recordings during resting state are increasingly used to study functional connectivity and network topology. Moreover, the number of different analysis approaches is expanding along with the rising interest in this research area. The comparison between studies can therefore be challenging and discussion is needed to underscore methodological opportunities and pitfalls in functional connectivity and network studies. In this overview we discuss methodological considerations throughout the analysis pipeline of recording and analyzing resting state EEG and MEG data, with a focus on functional connectivity and network analysis. We summarize current common practices with their advantages and disadvantages; provide practical tips, and suggestions for future research. Finally, we discuss how methodological choices in resting state research can affect the construction of functional networks. When taking advantage of current best practices and avoid the most obvious pitfalls, functional connectivity and network studies can be improved and enable a more accurate interpretation and comparison between studies