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.

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.

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.

Reproducibility of brain activation during auditory verbal hallucinations.

Previous studies investigated fMRI-guided repetitive Transcranial Magnetic Stimulation (rTMS) as an alternative treatment for auditory verbal hallucinations (AVH). This tailor-made treatment focuses at directing the rTMS coil to the location where hallucinatory activation is maximal, as identified with fMRI scans of individual patients. For the effective use of such treatment it is important to determine whether brain activation during AVH can be reliably detected using fMRI. Thirty-three psychotic patients indicated the presence of AVH during two subsequent scans. Reproducibility was measured by calculating 1) the distance between local maxima of significantly activated clusters and 2) percentage overlap of activation patterns over the two scans. These measurements were obtained both in single subjects and on group-level in five regions of interest (ROIs). ROIs consisted of the areas that were most frequently activated during AVH. Scans were considered reproducible if the distance between local maxima was smaller than 2 cm, as rTMS-treatment may target an area of approximately 2-4 cm. The median distance between local maxima was smaller than 2 cm for all ROIs on single-subject level, as well as on group-level. In addition, on single-subject level median percentage overlap varied between 14 and 38% for the different ROIs. On group-level, this was substantially higher with percentages overlap varying between 34 and 98%. Based on these results, AVH-scans may be considered sufficiently reproducible to be suitable for fMRI-guided rTMS treatment.

Aberrant resting-state connectivity in non-psychotic individuals with auditory hallucinations.

BACKGROUND: Although 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. METHOD: Resting-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. RESULTS: In 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. CONCLUSIONS: Aberrant connectivity of frontal, parahippocampal and superior temporal brain areas can be specifically related to the predisposition to hallucinate in the auditory domain.

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 disorder.