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A recurring issue in functional neuroimaging is how to link task‐driven haemodynamic blood oxygen level dependent functional MRI (BOLD‐fMRI) responses to underlying neurochemistry at the synaptic level. Glutamate and γ‐aminobutyric acid (GABA), the major excitatory and inhibitory neurotransmitters respectively, are typically measured with MRS sequences separately from fMRI, in the absence of a task. The present study aims to resolve this disconnect, developing acquisition and processing techniques to simultaneously assess GABA, glutamate and glutamine (Glx) and BOLD in relation to a cognitive task, at 3 T. Healthy subjects (N = 81) performed a cognitive task (Eriksen flanker), which was presented visually in a task‐OFF, task‐ON block design, with individual event onset timing jittered with respect to the MRS readout. fMRS data were acquired from the medial anterior cingulate cortex during task performance, using an adapted MEGA‐PRESS implementation incorporating unsuppressed water‐reference signals at a regular interval. These allowed for continuous assessment of BOLD activation, through T2*‐related changes in water linewidth. BOLD‐fMRI data were additionally acquired. A novel linear model was used to extract modelled metabolite spectra associated with discrete functional stimuli, building on well established processing and quantification tools. Behavioural outcomes from the flanker task, and activation patterns from the BOLD‐fMRI sequence, were as expected from the literature. BOLD response assessed through fMRS showed a significant correlation with fMRI, specific to the fMRS‐targeted region of interest; fMRS‐assessed BOLD additionally correlated with lengthening of response time in the incongruent flanker condition. While no significant task‐related changes were observed for GABA+, a significant increase in measured Glx levels (~8.8%) was found between task‐OFF and task‐ON periods. These findings verify the efficacy of our protocol and analysis pipelines for the simultaneous assessment of metabolite dynamics and BOLD. As well as establishing a robust basis for further work using these techniques, we also identify a number of clear directions for further refinement in future studies. [ABSTRACT FROM AUTHOR]

Introduction: Functional Magnetic Resonance Imaging (fMRI) block-design experiments typically include active ON-blocks with presentation of cognitive tasks which are contrasted with OFF- blocks with no tasks presented. OFF-blocks in between ON-blocks can however, also be seen as a proxy for intermittent periods of resting, inducing temporary resting-states. We still do not know if brain activity during such intermittent periods reflects the same kind of resting-state activity as that obtained during a continuous period, as is typically the case in studies of the classic Default Mode Network (DMN). The purpose of the current study was therefore to investigate both similarities and differences in brain activity between intermittent and continuous resting conditions. Methods: There were 47 healthy participants in the 3T fMRI experiment. Data for the intermittent resting-state condition were acquired from resting-periods in between active task-processing periods in a standard ON-OFF block design, with three different cognitive tasks presented during ON-blocks. Data for the continuous resting-state condition were acquired during a 5 min resting period after the task-design had been presented. Results and discussion: The results showed that activity was overall similar in the two conditions, but with some differences. These differences were within the DMN network, and for the interaction of DMN with other brain networks. DMN maps showed weak overlap between conditions in the medial prefrontal cortex (MPFC), and in particular for the intermittent compared to the continuous restingstate condition. Moreover, DMN showed strong connectivity with the salience network (SN) in the intermittent resting-state condition, particularly in the anterior insula and the supramarginal gyrus. The observed differences may reflect a "carryover" effect from task-processing to the next resting-state period, not present in the continuous resting-state condition, causing interference from the ON-blocks. Further research is needed to fully understand the extent of differences between intermittent and continuous resting-state conditions. [ABSTRACT FROM AUTHOR]

Childhood trauma (CT) has been linked to increased risk for psychosis. Moreover, CT has been linked to psychosis phenotypes such as impaired cognitive and sensory functions involved in the detection of novel sensory stimuli. Our objective was to investigate if CT was associated with changes in hippocampal and superior temporal gyrus functional activation and connectivity during a novelty detection task. Fifty-eight young adults were assigned to High-CT (n = 28) and Low-CT (n = 24) groups based on their scores on the childhood trauma questionnaire (CTQ) and underwent functional Magnetic Resonance Imaging during an auditory oddball task (AOT). Relative to the Low CT group, High CT participants showed reduced functional activation in the left hippocampus during the unpredictable tone condition of the AOT. Furthermore, in the High CT group, psychophysiological interaction analysis revealed hypoconnectivity between the hippocampus and temporal and medial regions. The present study indicates both altered hippocampal activation and hippocampal-temporal-prefrontal connectivity during novelty detection in individuals that experienced CT, similarly to that reported in psychosis risk populations. Early stressful experiences and environments may alter hippocampal function during salient events, mediating the relationship between childhood trauma and psychosis risk. [ABSTRACT FROM AUTHOR]

Background: Childhood trauma (CT) has been linked to increased risk for mental illness in adulthood. Although work in experimental animals has shown that early life stressors can affect inhibitory and excitatory neurotransmission in adult rodents, with possible excitotoxic effects on local grey matter volumes (GMV), the neurobiological mechanisms that mediate this relationship in humans remain poorly understood. Aim: To examine glutamate and gamma-aminobutyric acid (GABA) metabolite concentrations and potential excitotoxic effects on GMV, in adults who experienced CT. Methods: Fifty-six young adults (M age = 20.41) were assigned to High CT (n = 29) and Low CT (n = 27) groups (by using the CT questionnaire) and underwent magnetic resonance spectroscopy (1H-MRS) to measure temporal lobe metabolite concentrations and volumetric imaging to measure GMV. Results: Glutamate concentrations did not differ between groups; however, relative to the Low CT group, participants in the High CT group had reduced GABA concentrations in the left superior temporal gyrus (STG) voxel. Furthermore, logistic regression showed that participants with low left STG GABA concentrations and low left STG volumes were significantly more likely to be in the high CT group. Conclusions: This study provides the first evidence that both low GABA concentrations and its interaction with GMV in the left STG are associated with high levels of CT and suggest that altered inhibitory neurotransmission/metabolism may be linked to a lower GMV in the left STG in adults who experienced CT. Future studies are warranted to establish if utilizing these measures can stratify clinical high-risk and predict future clinical outcomes in high CT individuals. [ABSTRACT FROM AUTHOR]

About 95% of right-handers and 70% of left-handers have a left-hemispheric specialization for language. Dichotic listening is often used as an indirect measure of this language asymmetry. However, while it reliably produces a right-ear advantage (REA), corresponding to the left-hemispheric specialization of language, it paradoxically often fails to obtain statistical evidence of mean differences between left- and right-handers. We hypothesized that non-normality of the underlying distributions might be in part responsible for the similarities in means. Here, we compare the mean ear advantage scores, and also contrast the distributions at multiple quantiles, in two large independent samples (Ns = 1,358 and 1,042) of right-handers and left-handers. Right-handers had an increased mean REA, and a larger proportion had an REA than in the left-handers. We also found that more left-handers are represented in the left-eared end of the distribution. These data suggest that subtle shifts in the distributions of DL scores for right- and left-handers may be at least partially responsible for the unreliability of significantly reduced mean REA in left-handers. [ABSTRACT FROM AUTHOR]

Background It has been theorized that hallucinations, a common symptom of schizophrenia, are caused by failures in reality monitoring. The paracingulate sulcus (PCS) has been implicated as a brain structure supporting reality monitoring with the absence or shorter length of PCS associated with an occurrence of hallucinations in schizophrenia. The absence or shorter length of PCS has been associated with an occurrence of hallucinations. There are inconsistent findings in the literature regarding the role of the asymmetry of this structure for hallucinations. Here, we investigated the length of the PCS and cortical thickness of surrounding structures in patients with a lifetime history of auditory verbal hallucinations (AVH). Design Seventy-seven patients and twenty-eight healthy controls (HC) underwent an anatomical MRI scan. PCS length and cortical thickness were estimated using Mango brain visualization and FreeSurfer, respectively. Patients with AVH (n = 45) and patients without AVH were compared (n = 32) to the controls. Results PCS length significantly differed between HC and patient groups (F (2,102) = 3.57, P =.032) in the left but not in the right sulcus. We found significantly longer PCS between HC and AVH group but no difference between patient groups. Similarly, we found significant thinning of cortical structures including structures surrounding anterior parts of PCS between HC and patients either in general or per group, but no significant differences were observed between patient groups. Conclusions PCS length in the left hemisphere is shorter in schizophrenia patients with hallucinations as compared to HC subjects. The patient group without hallucinations was in between those 2 groups. Cortical thickness of neighboring areas of PCS is diminished in patient groups relative to the healthy comparison subjects. The role of lateralization and functional involvement of the PCS region in processes underlying hallucinations, such as reality monitoring, needs further clarification. [ABSTRACT FROM AUTHOR]

Background and Hypotheses Auditory verbal hallucinations (AVHs) is not only a common symptom in schizophrenia but also observed in individuals in the general population. Despite extensive research, AVHs are poorly understood, especially their underlying neuronal architecture. Neuroimaging methods have been used to identify brain areas and networks that are activated during hallucinations. A characteristic feature of AVHs is, however, that they fluctuate over time, with varying frequencies of starts and stops. An unanswered question is, therefore, what neuronal events co-occur with the initiation and inhibition of an AVH episode. Study Design We investigated brain activation with fMRI in 66 individuals who experienced multiple AVH-episodes while in the scanner. We extracted time-series fMRI-data and monitored changes second-by-second from 10 s before to 15 s after participants indicated the start and stop of an episode, respectively, by pressing a hand-held response-button. Study Results We found a region in the ventromedial prefrontal cortex (VMPFC) which showed a significant increase in activation initiated a few seconds before participants indicated the start of an episode, and a corresponding decrease in activation initiated a few seconds before the end of an episode. Conclusions The consistent increase and decrease in activation in this area in advance of the consciously experienced presence or absence of the "voice" imply that this region may act as a switch in turning episodes on and off. The activation is unlikely to be confounded by motor responses. The findings could have clinical implications for brain stimulation treatments, like transcranial magnetic stimulation. [ABSTRACT FROM AUTHOR]

Background: Transcranial direct current stimulation (tDCS) is used as treatment for auditory verbal hallucinations (AVH). The theory behind the treatment is that tDCS increases activity in prefrontal cognitive control areas, which are assumed to be hypoactive, and simultaneously decreases activity in temporal speech perception areas, which are assumed to be hyperactive during AVH. We tested this hypofrontal/hypertemporal reversal theory by investigating anatomical, neurotransmitter, brain activity, and network connectivity changes over the course of tDCS treatment. Methods: A double-blind, randomized controlled trial was conducted with 21 patients receiving either sham or real tDCS treatment (2 mA) twice daily for 5 days. The anode was placed over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the left temporo-parietal cortex (TPC). Multimodal neuroimaging as well as clinical and neurocognitive functioning assessment were performed before, immediately after, and three months after treatment. Results: We found a small reduction in AVH severity in the real tDCS group, but no corresponding neuroimaging changes in either DLPFCD or TPC. Limitations: The study has a small sample size. Conclusion: The results suggest that the currently leading theory behind tDCS treatment of AVH may need to be revised, if confirmed by studies with larger N. Tentative findings point to the involvement of Broca's area as a critical structure for tDCS treatment. [ABSTRACT FROM AUTHOR]

Edited MRS sequences are widely used for studying γ‐aminobutyric acid (GABA) in the human brain. Several algorithms are available for modelling these data, deriving metabolite concentration estimates through peak fitting or a linear combination of basis spectra. The present study compares seven such algorithms, using data obtained in a large multisite study. GABA‐edited (GABA+, TE = 68 ms MEGA‐PRESS) data from 222 subjects at 20 sites were processed via a standardised pipeline, before modelling with FSL‐MRS, Gannet, AMARES, QUEST, LCModel, Osprey and Tarquin, using standardised vendor‐specific basis sets (for GE, Philips and Siemens) where appropriate. After referencing metabolite estimates (to water or creatine), systematic differences in scale were observed between datasets acquired on different vendors' hardware, presenting across algorithms. Scale differences across algorithms were also observed. Using the correlation between metabolite estimates and voxel tissue fraction as a benchmark, most algorithms were found to be similarly effective in detecting differences in GABA+. An interclass correlation across all algorithms showed single‐rater consistency for GABA+ estimates of around 0.38, indicating moderate agreement. Upon inclusion of a basis set component explicitly modelling the macromolecule signal underlying the observed 3.0 ppm GABA peaks, single‐rater consistency improved to 0.44. Correlation between discrete pairs of algorithms varied, and was concerningly weak in some cases. Our findings highlight the need for consensus on appropriate modelling parameters across different algorithms, and for detailed reporting of the parameters adopted in individual studies to ensure reproducibility and meaningful comparison of outcomes between different studies. [ABSTRACT FROM AUTHOR]

Functional connectome alterations, including modular network organization, have been related to the experience of hallucinations. It remains to be determined whether individuals with hallucinations across the psychosis continuum exhibit similar alterations in modular brain network organization. This study assessed functional connectivity matrices of 465 individuals with and without hallucinations, including patients with schizophrenia and bipolar disorder, nonclinical individuals with hallucinations, and healthy controls. Modular brain network organization was examined at different scales of network resolution, including (1) global modularity measured as Qmax and Normalised Mutual Information (NMI) scores, and (2) within- and between-module connectivity. Global modular organization was not significantly altered across groups. However, alterations in within- and between-module connectivity were observed for higher-order cognitive (e.g. central-executive salience, memory, default mode), and sensory modules in patients with schizophrenia and nonclinical individuals with hallucinations relative to controls. Dissimilar patterns of altered within- and between-module connectivity were found bipolar disorder patients with hallucinations relative to controls, including the visual, default mode, and memory network, while connectivity patterns between visual, salience, and cognitive control modules were unaltered. Bipolar disorder patients without hallucinations did not show significant alterations relative to controls. This study provides evidence for alterations in the modular organization of the functional connectome in individuals prone to hallucinations, with schizophrenia patients and nonclinical individuals showing similar alterations in sensory and higher-order cognitive modules. Other higher-order cognitive modules were found to relate to hallucinations in bipolar disorder patients, suggesting differential neural mechanisms may underlie hallucinations across the psychosis continuum. [ABSTRACT FROM AUTHOR]

Everyday cognitive functioning is characterized by constant alternations between different modes of information processing, driven by constant fluctuations in environmental demands. At the neural level, this is realized through corresponding dynamic shifts in functional activation and network connectivity. A distinction is often made between resting and task processing and between task-negative and task-positive functional networks. The Default Mode Network (DMN) is classically considered as a resting state (i.e. task-negative) network, upregulated in the absence of cognitive demands. In contrast, task-positive networks have been labelled the Extrinsic Mode Network (EMN). We investigated changes in brain activation and functional network connectivity in an experimental situation of repeated alterations between levels of cognitive effort, following a block-design. Using fMRI and a classic Stroop paradigm, participants switched back and forth between periods of no effort (resting), low effort (word reading, i.e. automatic processing based on learned internal representations and rules) and high effort (color naming, i.e. cognitively controlled perceptual processing of specific features of external stimuli). Results showed an expected EMN-activation for task versus resting contrasts, and DMN-activation for rest versus task contrasts. The DMN was in addition more strongly activated during periods of low effort contrasted with high effort, suggesting a gradual up- and down-regulation of the DMN network, depending on the level of demand and the type of processing required. The often reported "anti-correlation" between DMN and EMN was strongest during periods of low effort, indicating intermittent contributions of both networks. Taken together, these results challenge the traditional view of the DMN as solely a task-negative network. Instead, both the EMN and DMN may contribute to low-effort cognitive processing. In contrast, periods of resting and high effort are dominated by the DMN and EMN, respectively. [ABSTRACT FROM AUTHOR]

Objectives: Understanding the biological changes that occur prior to onset of late-life depression (LLD) is key to its prevention. To investigate potential predictors of LLD, we assessed cognitive scores and neurodegenerative and vascular biomarkers in healthy older adults who later developed depression.Methods: Longitudinal data from the Alzheimer's Disease Neuroimaging Initiative of 241 cognitively unimpaired and non-depressed older adults aged 56-90 at baseline with at least 4 years of follow-up were included. Participants were classified based on whether they developed an incident depression (n = 96) or not (n = 145). Cognitive measures of memory, executive functioning, and language, and biomarkers proposed to be related to LLD: hippocampal volume, white matter hyperintensity volume (WMH), and cortical and cerebrospinal fluid (CSF) amyloid beta levels, were compared between the incident depression and the never-depressed groups at four time points: at baseline, the visit prior to onset, at onset, and after the onset of depression.Results: In the incident depression group, there was a mild decline in cognitive scores from baseline to the visit before depression onset compared with the never-depressed group. The cognitive differences between the groups became more marked after depression onset. Baseline cortical amyloid burden, CSF amyloid beta levels, and WMH were significant predictors of incident depression. Compared to the non-depressed group, hippocampal volume was not reduced before onset, but was reduced following depression.Conclusions: Amyloid pathology and WMH can predict future development of LLD in cognitively unimpaired individuals and may be involved in precipitating vulnerability for depression in older adults. [ABSTRACT FROM AUTHOR]

Dichotic listening along with the right-ear advantage (REA) has been a standard method of investigating auditory laterality ever since it was first introduced into neuropsychology in the early 1960s. Beginning in the 1980s, authors reported that it was possible to modulate the bottom-up driven perceptual REA by instructing subjects to selectively attend to and report only from the right or left ear. In the present study, we investigated neuronal correlates of both the bottom-up and top-down modulation of the REA through two fMRI analysis approaches: a traditional region approach and a network connectivity approach. Blood-Oxygenation-Level-Dependent (BOLD) fMRI data were acquired while subjects performed the standard forced-attention paradigm. We asked two questions, could the behavioral REA be replicated in unique brain markers, and second if the profound instruction-induced modulation of the REA found in behavioral data would correspond to a similar modulation of brain activation, both region- and network-specific modulations. The subjects were 70 healthy adult right-handers, about half men and half women. fMRI data were acquired in a 3T MR scanner, and the behavioral results replicated previous findings with a REA in the non-forced (NF) and forced-right (FR) conditions, and a tendency for a left-ear advantage (LEA) in the FL-condition. The fMRI data showed unique activations in the speech perception areas of the left temporal lobe when directly contrasted with activations in the homologous right side. However, there were no remaining unique activations when the FR- and FL-conditions were contrasted against each other, and with the NF-condition, using a conservative significance thresholding. The fMRI results are conceptualized within a network connectivity frame of reference, especially with reference to the extrinsic mode network (EMN). The EMN is a generalized task-positive network that is upregulated whenever the task demands exceed a certain threshold irrespective of the specifics and demands of the task. This could explain the similarity of activations for the FR- and FL-conditions, despite the clear differences in behavior. [ABSTRACT FROM AUTHOR]

Source monitoring refers to the ability to identify the origin of a memory, for example, whether you remember saying something or thinking about it, and confusions of these sources have been associated with the experience of auditory verbal hallucinations (AVHs). Both AVHs and source confusions are reported to originate from dysfunctional brain activations in the prefrontal cortex (PFC) and the superior temporal gyrus (STG); specifically, it is assumed that a hypoactive PFC and a hyperactive STG gives rise to AVHs and source confusions. We set out to test this assumption by trying to mimic this hypertemporal/hypofrontal model in healthy individuals with transcranial direct current stimulation (tDCS): the inhibitory cathode was placed over the left PFC and the excitatory anode over the left dorsolateral STG. Participants completed a reality monitoring task (distinguishing between external and internal memory sources) and an internal source monitoring task (distinguishing between two or more internal memory sources) in two separate experiments (offline vs. online tDCS). In the offline experiment (n = 34), both source monitoring tasks were completed after tDCS stimulation, and in the online experiment (n = 27) source monitoring tasks were completed while simultaneously being stimulated with tDCS. We found that internal source monitoring abilities were significantly enhanced during active online tDCS, while reality monitoring abilities were unaffected by stimulation in both experiments. We speculate, based on combining the present findings with previous studies, that there might be different brain areas involved in reality and internal source monitoring. While internal source monitoring seems to involve speech production areas, specifically Broca's area, as suggested in the present study, reality monitoring seems to rely more on the STG and DLPFC, as shown in other studies of the field. [ABSTRACT FROM AUTHOR]

Suggestions have been made that psychotic‐like experiences (PLEs), such as hallucinatory and delusional experiences, exist on a continuum from healthy individuals to patients with a diagnosis of schizophrenia. We used the screening questions of the Questionnaire for Psychotic Experiences (QPE), an interview that captures the presence and phenomenology of various psychotic experiences separately, to assess PLEs in Norway. Based on data from an online survey in a sample of more than 1,400 participants, we demonstrated that the QPE screening questions show satisfactory psychometric properties. Participants with mental disorders reported more frequent lifetime and current hallucinatory experiences than participants without mental disorders. Childhood experiences were rather low and ranged from 0.7% to 5.2%. We further replicated findings that young age, illegal drug use, lower level of education, and having parents with a mental disorder are associated with higher endorsement rates of PLEs. Finally, a binomial regression revealed that the mere presence of PLEs does not discriminate between individuals with and without a mental disorder. Taken together, the findings of the present study support existing models that both hallucinations and delusions exist on a structural and phenomenological continuum. Moreover, we demonstrated that the QPE screening questions can be used by themselves as a complementary tool to the full QPE interview. [ABSTRACT FROM AUTHOR]

Background: Auditory verbal hallucinations (AVH) have been linked to aberrant interhemispheric connectivity between the left and the right superior temporal gyrus (STG), labeled the interhemispheric miscommunication theory. The present study investigated if interhemispheric miscommunication is modulated at the neurochemical level by glutamate (Glu) and gamma-aminobutyric acid (GABA) concentrations in temporal and prefrontal lobe areas, as proposed by the theory. Methods: We combined resting-state fMRI connectivity with MR spectroscopy (MRS) in a sample of 81 psychosis patients, comparing patients with high hallucination severity (high-AVH) and low hallucination severity (low-AVH) groups. Glu and GABA concentrations were acquired from the left STG and the anterior cingulate cortex (ACC), an area of cognitive control that has been proposed to modulate STG functioning in AVH. Results: Functional connectivity showed significant interaction effects between AVH Group and ACC-recorded Glu and GABA metabolites. Follow-up tests showed that there was a significant positive association for Glu concentration and interhemispheric STG connectivity in the high-AVH group, while there was a significant negative association for GABA concentration and interhemispheric STG connectivity in the low-AVH group. Conclusion: The results show neurochemical modulation of STG interhemispheric connectivity, as predicted by the interhemispheric miscommunication hypothesis. Furthermore, the findings are in line with an excitatory/inhibitory imbalance model for AVH. By combining different neuroimaging modalities, the current results provide a more comprehensive insight into the neural correlates of AVH. [ABSTRACT FROM AUTHOR]

The underlying neural mechanisms of transcranial direct current stimulation (tDCS), especially beyond the primary motor cortex, remain unclear. Several studies examined tDCS effects on either functional activity, neurotransmitters or behavior but few investigated those aspects together to reveal how the brain responds to tDCS. The objective is to elucidate the underlying mechanisms of tDCS using a multimodal approach that extends from behavioral to neurotransmitter levels of explanation. Thirty‐two healthy participants performed an auditory dichotic listening task at two visits, one session with sham and one session with real tDCS (2 mA) while simultaneously undergoing functional magnetic resonance imaging (fMRI). The anode and cathode were placed over the left temporo‐parietal cortex (TPC) and dorsolateral prefrontal cortex, respectively. Before and after simultaneous dichotic listening/fMRI/tDCS, combined glutamate and glutamine (Glx) and myo‐inositol levels were assessed in the stimulated areas. While fMRI and dichotic listening showed expected functional activity and behavioral effects, neither method demonstrated differences between real and sham stimulation. Glx only showed a statistical trend towards higher levels after real tDCS in both stimulated brain areas. There were no significant correlations between behavior and Glx. Despite a reasonable sample size, electrical field strength, and replication of behavioral and functional activity results, tDCS had little to no effect on dichotic listening, Glx, and functional activity. The study emphasizes that findings about the underlying neural mechanisms of the primary motor cortex cannot simply be generalized to other brain areas. Particularly, the TPC might be less sensitive to tDCS. Moreover, the study demonstrates the general feasibility of multimodal approaches. [ABSTRACT FROM AUTHOR]

Hallucinations may arise from an imbalance between sensory and higher cognitive brain regions, reflected by alterations in functional connectivity. It is unknown whether hallucinations across the psychosis continuum exhibit similar alterations in functional connectivity, suggesting a common neural mechanism, or whether different mechanisms link to hallucinations across phenotypes. We acquired resting-state functional MRI scans of 483 participants, including 40 non-clinical individuals with hallucinations, 99 schizophrenia patients with hallucinations, 74 bipolar-I disorder patients with hallucinations, 42 bipolar-I disorder patients without hallucinations, and 228 healthy controls. The weighted connectivity matrices were compared using network-based statistics. Non-clinical individuals with hallucinations and schizophrenia patients with hallucinations exhibited increased connectivity, mainly among fronto-temporal and fronto-insula/cingulate areas compared to controls (P < 0.001 adjusted). Differential effects were observed for bipolar-I disorder patients with hallucinations versus controls, mainly characterized by decreased connectivity between fronto-temporal and fronto-striatal areas (P = 0.012 adjusted). No connectivity alterations were found between bipolar-I disorder patients without hallucinations and controls. Our results support the notion that hallucinations in non-clinical individuals and schizophrenia patients are related to altered interactions between sensory and higher-order cognitive brain regions. However, a different dysconnectivity pattern was observed for bipolar-I disorder patients with hallucinations, which implies a different neural mechanism across the psychosis continuum. [ABSTRACT FROM AUTHOR]

In this study we report on the relationship between default and extrinsic mode networks across alternating brief periods of rest and active task processing. Three different visual tasks were used in a classic fMRI ON–OFF block design where task (ON) blocks alternated with equal periods of rest (OFF) blocks: mental rotation, working memory and mental arithmetic. We showed the existence of a generalized task-positive network, labelled the extrinsic mode network (EMN) that is anti-correlated with the default mode network (DMN) as processing demands shifted from rest to active processing. We then identified two key regions of interest (ROIs) in the supplementary motor area (SMA) and precuneus/posterior cingulate cortex (PCC) regions as hubs for the extrinsic and intrinsic networks, and extracted the time-course from these ROIs. The results showed a close to perfect anti-correlation for the SMA and Precuneus/PCC time-courses for ON- and OFF-blocks. We suggest the existence of two large-scale networks, an extrinsic mode network and an intrinsic mode network, which are up- and down-regulated as environmental demands change from active to passive processing. [ABSTRACT FROM AUTHOR]

Proactive control is the ability to manipulate and maintain goal-relevant information within working memory (WM), allowing individuals to selectively attend to important information while inhibiting irrelevant distractions. Deficits in proactive control may cause multiple cognitive impairments seen in schizophrenia. However, studies of cognitive control have largely relied on visual tasks, even though the functional deficits in schizophrenia are more frequent and severe in the auditory domain (i.e., hallucinations). Hence, we developed an auditory analogue of a visual ignore/suppress paradigm. Healthy adults (N = 40) listened to a series of four letters (600-ms stimulus onset asynchrony) presented alternately to each ear, followed by a 3.2-s maintenance interval and a probe. Participants were directed either to selectively ignore (I) the to-be-presented letters at one ear, to suppress (S) letters already presented to one ear, or to remember (R) all presented letters. The critical cue was provided either before (I) or after (S) the encoding series, or simultaneously with the probe (R). The probes were encoding items presented to either the attended/not suppressed ear ("valid") or the ignored/suppressed ear ("lure"), or were not presented ("control"). Replicating prior findings during visual ignore/suppress tasks, response sensitivity and latency revealed poorer performance for lure than for control trials, particularly during the suppress condition. Shorter suppress than remember latencies suggested a behavioral advantage when discarding encoded items from WM. The paradigm-related internal consistencies and 1-week test–retest reliabilities (n = 38) were good to excellent. Our findings validate these auditory WM tasks as a reliable manipulation of proactive control and set the stage for studies with schizophrenia patients who experience auditory hallucinations. [ABSTRACT FROM AUTHOR]

Glutamate (Glu), gamma amino-butyric acid (GABA), and excitatory/inhibitory (E/I) imbalance have inconsistently been implicated in the etiology of schizophrenia. Elevated Glu levels in language regions have been suggested to mediate auditory verbal hallucinations (AVH), the same regions previously associated with neuronal hyperactivity during AVHs. It is, however, not known whether alterations in Glu levels are accompanied by corresponding GABA alterations, nor is it known if Glu levels are affected in brain regions with known neuronal hypo-activity. Using magnetic resonance spectroscopy (MRS), we measured Glx (Glu+glutamine) and GABA+ levels in the anterior cingulate cortex (ACC), left and right superior temporal gyrus (STG), and left inferior frontal gyrus (IFG), in a sample of 77 schizophrenia patients and 77 healthy controls. Two MRS-protocols were used. Results showed a marginally significant positive correlation in the left STG between Glx and AVHs, whereas a significant negative correlation was found in the ACC. In addition, high-hallucinating patients as a group showed decreased ACC and increased left STG Glx levels compared to low-hallucinating patients, with the healthy controls in between the 2 hallucinating groups. No significant differences were found for GABA+ levels. It is discussed that reduced ACC Glx levels reflect an inability of AVH patients to cognitively inhibit their "voices" through neuronal hypo-activity, which in turn originates from increased left STG Glu levels and neuronal hyperactivity. A revised E/I-imbalance model is proposed where Glu-Glu imbalance between brain regions is emphasized rather than Glu-GABA imbalance within regions, for the understanding of the underlying neurochemistry of AVHs. [ABSTRACT FROM AUTHOR]

Listening difficulties (LiD) are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD when there is no hearing loss, also known as auditory processing disorder (APD). We examined the ability of 6–13 year old (y.o.) children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT; www.dichoticlistening.com). Children were recruited as typically developing (TD; n = 39) or having LiD (n = 35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6 × 36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right [forced right (FR)] or left [forced left (FL)] ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening (DL) data [correct responses, laterality index (LI)] were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL), and ILD (0, ± 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic, and intelligibility components. Some activated areas [planum temporale (PT), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC)] were correlated with dichotic results in TD children only. Neither group, age, nor report method affected the LI of right/left recall. However, a significant interaction was found between ear, group, and ILD. Laterality indices were small and tended to increase with age, as previously reported. Children with LiD had significantly larger mean LIs than TD children for stimuli with ILDs, especially those favoring the left ear. Neural activity associated with Speech, Phonetic, and Intelligibility sentence cues did not differ significantly between groups. Significant correlations between brain activity level and BDLT were found in several frontal and temporal locations for the TD but not for the LiD group. Overall, the children with LiD had only subtle differences from TD children in the BDLT, and correspondingly minor changes in brain activation. [ABSTRACT FROM AUTHOR]

Using fMRI, Hugdahl et al. (2015) reported the existence of a general-domain cortical network during active task-processing which was non-specific to the cognitive task being processed. They labelled this network the extrinsic mode network (EMN). The EMN would be predicted to be negatively, or anti-correlated with the classic default mode network (DMN), typically observed during periods of rest, such that while the EMN should be down-regulated and the DMN up-regulated in the absence of demands for task-processing, the reverse should occur when demands change from resting to task-processing. This would require alternating periods of task-processing and resting and analyzing data continuously when demands change from active to passive periods and vice versa. We were particularly interested in how the networks interact in the critical transition points between conditions. For this purpose, we used an auditory task with multiple cognitive demands in a standard fMRI block-design. Task-present (ON) blocks were alternated with an equal number of task-absent, or rest (OFF) blocks to capture network dynamics across time and changing environmental demands. To achieve this, we specified the onset of each block, and used a finite-impulse response function (FIR) as basis function for estimation of the fMRI-BOLD response. During active (ON) blocks, the results showed an initial rapid onset of activity in the EMN network, which remained throughout the period, and faded away during the first scan of the OFF-block. During OFF blocks, activity in the DMN network showed an initial time-lag where neither the EMN nor the DMN was active, after which the DMN was up-regulated. Studying network dynamics in alternating passive and active periods may provide new insights into brain network interaction and regulation. [ABSTRACT FROM AUTHOR]

Background: Neurobiological models of stress and stress-related mental illness, including post-traumatic stress disorder, converge on the amygdala and the prefrontal cortex (PFC). While a surge of research has reported altered structural and functional connectivity between amygdala and the medial PFC following severe stress, few have addressed the underlying neurochemistry. Methods: We combined resting-state functional magnetic resonance imaging measures of amygdala connectivity with in vivo MR-spectroscopy (1H-MRS) measurements of glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control subjects. Results: Traumatized youths showed altered amygdala–anterior midcingulate cortex (aMCC) and amygdala–ventromedial prefrontal cortex (vmPFC) connectivity. Moreover, the trauma survivors exhibited reduced levels of glutamate in the vmPFC which fits with the previous findings of reduced levels of Glx (glutamate + glutamine) in the aMCC (Ousdal et al., 2017) and together suggest long-term impact of a traumatic experience on glutamatergic pathways. Importantly, local glutamatergic metabolite levels predicted the individual amygdala–aMCC and amygdala–vmPFC functional connectivity, and also mediated the observed group difference in amygdala–aMCC connectivity. Conclusions: Our findings suggest that traumatic stress may influence amygdala–prefrontal neuronal connectivity through an effect on prefrontal glutamate and its compounds. Understanding the neurochemical underpinning of altered amygdala connectivity after trauma may ultimately lead to the discovery of new pharmacological agents which can prevent or treat stress-related mental illness. [ABSTRACT FROM AUTHOR]

According to a longstanding view, sex differences in cognitive abilities such as mental rotation or verbal memory arise from sex differences in hemispheric asymmetry: males are thought to be more lateralized than females which boosts their spatial but hampers their verbal skills. This idea sparked great interest and, even though it lost support in the 1990s, it is still put forward in contemporary (popular) scientific papers and textbooks. We aimed to provide a comprehensive review that summarizes the last 40 years of research. First, we confirm previous findings that the stronger hemispheric asymmetry in males is very small but robust. Second, we conclude that stronger hemispheric asymmetry, in general, does not enhance spatial and reduce verbal performance. Crucially, we carried out a systematic literature review showing that cognitive sex differences often emerge in the absence of sex differences in hemispheric asymmetry (and vice versa), implying the two phenomena are at least partly independent of each other. At present, there is insufficient data to conclude that sex differences in hemispheric asymmetry and cognitive performance are uncorrelated. However, we can conclude that sex differences in hemispheric asymmetry are certainly not the driving force behind sex differences in cognitive functioning. [ABSTRACT FROM AUTHOR]

The field of digital mental health is rapidly expanding with digital tools being used in assessment, intervention, and supporting self-help. The application of digital mental health to hallucinations is, however, at a very early stage. This report from a working group of the International Consortium on Hallucinations Research considers particular synergies between the phenomenon of hallucinations and digital tools that are being developed. Highlighted uses include monitoring and managing intermittently occurring hallucinations in daily life; therapeutic applications of audio and video media including virtual and augmented reality; targeting verbal aspects of hallucinations; and using avatars to represent hallucinatory voices. Although there is a well-established Internet-based peer support network, digital resources for hallucinations have yet to be implemented in routine practice. Implementation may benefit from identifying how to market resources to the broad range of populations who experience hallucinations and identifying sustainable funding models. It is envisaged that digital tools will contribute to improved self-management and service provision for people experiencing hallucinations. [ABSTRACT FROM AUTHOR]

That trauma can play a significant role in the onset and maintenance of voice-hearing is one of the most striking and important developments in the recent study of psychosis. Yet the finding that trauma increases the risk for hallucination and for psychosis is quite different from the claim that trauma is necessary for either to occur. Trauma is often but not always associated with voice-hearing in populations with psychosis; voice-hearing is sometimes associated with willful training and cultivation in nonclinical populations. This article uses ethnographic data among other data to explore the possibility of multiple pathways to voice-hearing for clinical and nonclinical individuals whose voices are not due to known etiological factors such as drugs, sensory deprivation, epilepsy, and so forth. We suggest that trauma sometimes plays a major role in hallucinations, sometimes a minor role, and sometimes no role at all. Our work also finds seemingly distinct phenomenological patterns for voice-hearing, which may reflect the different salience of trauma for those who hear voices. [ABSTRACT FROM AUTHOR]

Background: Developmental cortical plasticity with reorganization of cerebral cortex, has been known to occur in young and adult animals after permanent, restricted elimination of afferent (visual or somatosensory) input. In animals, cortical representation of unaffected muscles or sensory areas has been shown to invade the neighboring cortex when this is deprived of its normal sensory input or motor functions. Some studies indicate that similar cortical plasticity may take place in adult humans. Methods: In patients with a high cervical spinal cord injury leaving the patient without any movements of the fingers, we performed fMRI studies of the cortical representation of an elbow flexor muscle before and after a surgical procedure that changed its function to a thumb flexor, thus providing the patient with a useful grip. Results: Preoperatively, the elbow flexion movement was elicited from a cortical area corresponding with the “elbow area” in healthy individuals. Despite the fact that an elbow flexor was used for the post-operative key-grip, this movement in the tetraplegic patients was elicited from a similar brain region as in healthy controls (the “hand area”). This supports our hypothesis that control of that muscle shifts from a brain region typically associated with elbow movement, to one typically associated with wrist movements. Conclusion: The findings presented here show with fMRI that the human cortex is capable of reorganizing itself spatially after a relatively acute change in the periphery. [ABSTRACT FROM AUTHOR]

We present a case of a young female with a slowly progressing visual impairment who was examined with multifocal visual evoked potentials and functional magnetic resonance imaging (fMRI) for underlying neuronal abnormality. The fMRI examination consisted of presenting black-and-white checkerboard stimuli, and her activation patterns were compared to the patterns from 4 normal-sighted subjects. The results showed clear differences in neuronal activation between the patient and the controls in the occipital and parietal lobes. Although we have shown neuronal correlates in a case of unexplained visual loss, it is still an open question as to whether this has an organic or functional cause, which should be the subject for future research. [ABSTRACT FROM AUTHOR]

Cognitive control processes play an essential role not only in controlling actions but also in guiding attentional selection processes. Interestingly, these processes are strongly affected by organizational principles of the cerebral cortex and related functional asymmetries, but the neurobiological foundations are elusive. We ask whether neurobiological mechanisms that affect functional cerebral asymmetries will also modulate effects of top-down control processes on functional cerebral asymmetries. To this end, we examined potential effects of the imprinted gene leucine-rich repeat transmembrane neuronal 1 (LRRTM1) on attentional biasing processes in a forced attention dichotic listening task in 983 healthy adult participants of Caucasian descent using the “iDichotic smartphone app.” The results show that functional cerebral asymmetries in the language domain are associated with the rs6733871 LRRTM1 polymorphism when cognitive control and top-down attentional mechanisms modulate processes in bottom-up attentional selection processes that are dependent on functional cerebral asymmetries. There is no evidence for an effect of LRRTM1 on functional cerebral asymmetries in the language domain unrelated to cognitive control processes. The results suggest that cognitive control processes are an important factor to consider when being interested in the molecular genetic basis of functional cerebral architecture. [ABSTRACT FROM AUTHOR]

As a reliable and valid measures of perceptual auditory laterality, dichotic listening has been successfully applied in studies in many countries and languages. However, languages differ in the linguistic relevance of change in initial phoneme of words (e.g., for word identification). In the present cross-language study, we examine the effect of these differences on dichotic-listening task performance to establish how characteristics of one's native language affect the perception of nonnative phonological features. We compared 33 native speakers of Norwegian, a language characterized by a clear distinction between voiced and unvoiced initial plosive consonants, with 30 native speakers of Estonian, a language that has exclusively unvoiced initial phonemes. Using a free-report dichotic-listening paradigm utilizing pairs of voiced (/ba/, /da/, /ga/) and unvoiced (/pa/, /ta/, /ka/) stop-consonant vowels as stimulus material, the Norwegian native speakers were found to be more sensitive to the voicing of the initial plosive than the Estonian group. “Voicing” explained 69% and 18% of the variance in the perceptual auditory laterality in the Norwegian and the Estonian sample, respectively. This indicates that experiential differences, likely during acquisition of the mother tongue in early development, permanently shape the sensitivity to the voicing contrast. [ABSTRACT FROM PUBLISHER]

In the present article, we present a "Levels of Explanation" (LoE) approach to auditory verbal hallucinations (AVHs) in schizophrenia. Mental phenomena can be understood at different levels of explanation, including cultural, clinical, cognitive, brain imaging, cellular, and molecular levels. Current research on AVHs is characterized by accumulation of data at all levels, but with little or no interaction of findings between levels. A second advantage with a Levels of Explanation approach is that it fosters interdisciplinarity and collaboration across traditional borders, facilitating a real breakthrough in future research. We exemplify a Levels of Explanation approach with data from 3 levels where findings at 1 level provide predictions for another level. More specifi- cally, we show how functional neuroimaging data at the brain level correspond with behavioral data at the cognitive level, and how data at these 2 levels correspond with recent findings of changes in neurotransmitter function at the cellular level. We further discuss implications for new therapeutic interventions, and the article is ended by suggestion how future research could incorporate genetic influences on AVHs at the molecular level of explanation by providing examples for animal work. [ABSTRACT FROM AUTHOR]

We present in this article a study design that combines clinical self-assessment scale, simultaneously administered with fMRI data acquisition. We have used a standard block-design with two different conditions. Each active block consisted of four text statements (items), alternating diagnostically specific (DS) blocks comprising items from von Zerssen depression scale and diagnostically neutral (DN) blocks with items from a questionnaire about general interests. All items were rated on four degree Likert scale, and patients provided responses with corresponding four buttons during the fMRI session. Our results demonstrated that in healthy controls, contrasting the two types of stimuli yielded no residual activations, e.g., the DS did not produce significantly different activations compared to the DN stimuli. Furthermore, the correlation analyses did not find a relationship between brain activations and the total score of the DS statements in this group. However, contrasting the DS stimuli to the DN stimuli in the patients produced significant residual activations in several brain regions: right pre- and postcentral gyrus (including right supramarginal gyrus), left middle frontal gyrus, triangular part of the left inferior frontal gyrus and middle temporal gyrus. The left precuneus demonstrated correlations with the patients' DS score. In the between-group comparisons, we found residual activations in the right pre- and postcentral gyrus, right supplementary motor area, medial segment of the right precentral gyrus, right superior parietal lobule, left middle frontal gyrus, left superior frontal gyrus, left occipital pole. Our results confirm the possibility of translational cross-validation of a clinical psychological test (von Zerssen's depression scale) and fMRI. At this stage, however, we can only confirm the sensitivity of the method (its ability to distinguish healthy controls from depressed patients), but we cannot conclude anything about its specificity (distinction from different psychopathology conditions). [ABSTRACT FROM AUTHOR]

In this article I have summarized some of the main trends and topics of my research career, spanning a time period of 50 years, from its start as a master student at the Department of Psychology, University of Uppsala, Sweden to seeing the end of a long career, now at the University of Bergen, Norway. This journey has, apart from having been a journey across various disciplines and topics in experimental psychology, psychophysiology and neuropsychology, functional neuroimaging and cognitive neuroscience, also been a social class journey for me personally. I describe my academic career from my arrival as a young student at the University of Uppsala, Sweden in the late 1960s to my graduation as PhD in 1977 at the age of 29 years, brief postdoc period at the University of Pennsylvania, USA, and finally professor at the University of Bergen, Norway. The article focuses on my view of the research and research findings during these years, including studies of hemispheric asymmetry, dyslexia and language, dichotic listening, fMRI, and during the last years, studies of auditory hallucinations in schizophrenia. I have collaborated with numerous people, both nationally and internationally over the years, far too many to mention in a space‐limited overview article. I apologize for this, and wish that I had time and space to mention all the fantastic colleagues and friends that I have met during my career. This article is what I recall of dates, places, encounters, etc., and any errors and misunderstandings are entirely due to my far from perfect memory, for which I also apologize. [ABSTRACT FROM AUTHOR]

Laterality for language processing can be assessed by auditory and visual tasks. Typically, a right ear/right visual half-field (VHF) advantage is observed, reflecting left-hemispheric lateralization for language. Historically, auditory tasks have shown more consistent and reliable results when compared to VHF tasks. While few studies have compared analogous tasks applied to both sensory modalities for the same participants, one such study by Voyer and Boudreau [(2003). Cross-modal correlation of auditory and visual language laterality tasks: a serendipitous finding.Brain Cogn,53(2), 393–397] found opposite laterality for visual and auditory language tasks. We adapted an experimental paradigm based on a dichotic listening and VHF approach, and applied the combined language paradigm in two separate experiments, including fMRI in the second experiment to measure brain activation in addition to behavioural data. The first experiment showed a right-ear advantage for the auditory task, but a left half-field advantage for the visual task. The second experiment, confirmed the findings, with opposite laterality effects for the visual and auditory tasks. In conclusion, we replicate the finding by Voyer and Boudreau (2003) and support their interpretation that these visual and auditory language tasks measure different cognitive processes. [ABSTRACT FROM AUTHOR]

In this invited review article, I present a translational perspective and overview of our research on auditory hallucinations in schizophrenia at the University of Bergen, Norway, with a focus on the neuronal mechanisms underlying the phenomenology of experiencing "hearing voices". An auditory verbal hallucination (i.e. hearing a voice) is defined as a sensory experience in the absence of a corresponding external sensory source that could explain the phenomenological experience. I suggest a general frame or scheme for the study of auditory verbal hallucinations, called Levels of Explanation. Using a Levels of Explanation approach, mental phenomena can be described and explained at different levels (cultural, clinical, cognitive, brainimaging, cellular and molecular). Another way of saying this is that, to advance knowledge in a research field, it is not only necessary to replicate findings, but also to show how evidence obtained with one method, and at one level of explanation, converges with evidence obtained with another method at another level. To achieve breakthroughs in our understanding of auditory verbal hallucinations, we have to advance vertically through the various levels, rather than the more common approach of staying at our favourite level and advancing horizontally (e.g., more advanced techniques and data acquisition analyses). The horizontal expansion will, however, not advance a deeper understanding of how an auditory verbal hallucination spontaneously starts and stops. Finally, I present data from the clinical, cognitive, brain-imaging, and cellular levels, where data from one level validate and support data at another level, called converging of evidence. Using a translational approach, the current status of auditory verbal hallucinations is that they implicate speech perception areas in the left temporal lobe, impairing perception of and attention to external sounds. Preliminary results also show that amygdala is implicated in the emotional «colouring» of the voices and that excitatory neurotransmitters might be involved. What we do not know is why hallucinatory episodes occur spontaneously, why they fluctuate over time, and what makes them spontaneously stop. Moreover, is voice hearing a category or dimension in its own right, independent of diagnosis, and why is the auditory modality predominantly implicated in psychotic disorders, while the visual modality dominates in, for example, neurological diseases? [ABSTRACT FROM AUTHOR]

Purpose: The reproducibility of the MEGA-PRESS (MEshcher-GArwood Point RESolved Spectroscopy) MR spectroscopy sequence for the measurement of gamma- aminobutyric acid (GABA) is addressed, focusing on optimizing the number of repetitions at two voxel locations in the human brain and associated possibilities in analysis tools.Materials and Methods: Two 20-min MEGA-PRESS acquisitions were run (echo time = 68 ms, repetition time = 1800 ms, repetitions = 328): one from a 21 mL volume in the anterior cingulate cortex (ACC) and one from a 22 mL volume in the left Broca's area in 21 healthy male volunteers (age 32 years ± 6[SD]). Subjects were scanned twice with identical protocols, 1 week apart. Data were acquired on a 3 Tesla GE Discovery 750 scanner using a 32-channel head coil. Spectroscopy data were partitioned into shorter epochs, numerically equivalent to scans of progressively increasing duration, and compared both within and between sessions. Three different analysis schemes were applied: (1) Vendor prototype preprocessor, with quantification by LCModel. (2) Pure Gannet pipeline. (3) Preprocessing with Gannet, and quantification with LCModel. The coefficient of variation (CV) were calculated as a measure of reproducibility.Results: Increasing the number of repetitions showed improvements for within- and between-session reproducibility up to around 218 repetitions. (CV ranging from 4 to 14%). Gannet combined with LCModel approach proved the best method. (CV = 4-5%). Measurements from the ACC area had higher CVs than the Broca area. (CV = 6-14% versus 4-7%).Conclusion: Measurement in the Broca area yields better reproducibility than the ACC. With appropriate acquisition times and preprocessing tools, measurements from the ACC area are also reliable.Level Of Evidence: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:421-430. [ABSTRACT FROM AUTHOR]

Background: Tourette Syndrome (TS) is a neurodevelopmental disorder with childhood-onset, with a typical decline in tic severity, as well as an increasing ability to suppress tics in late childhood and adolescence. These processes develop in parallel with general improvement of self-regulatory abilities, and performance monitoring during this age-span. Hence, changes in performance monitoring over time might provide insight into the regulation of tics in children and adolescents with TS. Method: We measured reaction time, reaction time variability, accuracy, and event-related potentials (ERP) in 17 children with TS, including 10 children with comorbid Attention-Deficit/Hyperactivity Disorder (ADHD), 24 children with ADHD, and 29 typically developing children, using a modified Eriksen Flanker task in two testing sessions administered on average 4.5 years apart. We then compared task performance, as well as ERP components across groups, and over time using regression models. Results: Task performance improved in all groups with age, and behavioral differences between children with TS and controls diminished at second assessment, while differences between controls and children with ADHD largely persisted. In terms of ERP, the early P3 developed earlier in children with TS compared with controls at the first assessment, but trajectories converged with maturation. ERP component amplitudes correlated with worst-ever tic scores. Conclusions: Merging trajectories between children with TS and controls are consistent with the development of compensatory self-regulation mechanisms during early adolescence, probably facilitating tic suppression, in contrast to children with ADHD. Correlations between ERP amplitudes and tic scores also support this notion. [ABSTRACT FROM AUTHOR]

The present pilot study investigated neuronal correlates of executive functioning in patients previously diagnosed with recurrent major depressive disorder ( MDD). The aim of the study was to examine a partially remitted and remitted MDD patient group with functional magnetic resonance imaging ( fMRI) using a cognitive activation paradigm in order to probe aspects of response inhibition, attention shift, and working memory. Twenty MDD patients and 19 healthy controls, matched for age and sex, participated in the study. A working memory n-back task with single presentations of incongruent Stroop words was used, with the instruction to either remember the color of the ink the word was written in, or the color word itself, presented two or three words back in the presentation series. MR images were acquired on a 1.5-T GE Signa HD MR scanner. In addition to MR data, response time ( RT) and response accuracy ( RA) behavioral data were recorded. The behavioral results showed longer RT and lower RA in the MDD group compared to the control group across instruction conditions and working memory load. Based on previous studies of executive function, a composite region of interest ( ROI) mask of the anterior cingulate cortex ( ACC), dorsolateral prefrontal cortex ( DLPFC), caudate, and putamen was used in statistical analysis. Significant activation was observed in controls throughout this corticostriatal network. When compared to controls, patients showed no significant difference in the level of activation in the ACC and the DLPFC. However, in the putamen and caudate, hypoactivation in the patient group was observed. It was concluded that these effects could be due to a scar effect as a result of previous episodes of MDD. [ABSTRACT FROM AUTHOR]

In this article I review the early auditory laterality and dichotic listening research from the perspective of the legacy of Phil Bryden's pioneering contributions to not only empirical work, but also on theory, critical interpretations of results, and statistical issues, with a focus on the role of attention. In doing so, I am describing how my own research was shaped and influenced by Phil Bryden and his work on auditory laterality and dichotic listening. In addition to personal recollections of my meetings and discussions with Phil that had a profound impact on my later career, I have focused the overview on Phil's early dichotic listening papers from the 1960s, to be followed by a detailed review and discussion of the seminal [Bryden, M. P., Munhall, K., & Allard, F. (1983). Attentional biases and the right-ear effect in dichotic listening.Brain and Language, 18, 236–248] paper on attentional effects on the ear advantage in dichotic listening. Finally, I review the little known fact that Phil was also a contributor to the very first functional neuroimaging study that used dichotic stimuli. [ABSTRACT FROM PUBLISHER]

Background: We examined the blood-oxygen level-dependent (BOLD) activation in brain regions that signal errors and their association with intraindividual behavioural variability and adaptation to errors in children with attention-deficit/hyperactivity disorder (ADHD). Methods: We acquired functional MRI data during a Flanker task in medication-naive children with ADHD and healthy controls aged 8-12 years and analyzed the data using independent component analysis. For components corresponding to performance monitoring networks, we compared activations across groups and conditions and correlated them with reaction times (RT). Additionally, we analyzed post-error adaptations in behaviour and motor component activations. Results: We included 25 children with ADHD and 29 controls in our analysis. Children with ADHD displayed reduced activation to errors in cingulo-opercular regions and higher RT variability, but no differences of interference control. Larger BOLD amplitude to error trials significantly predicted reduced RT variability across all participants. Neither group showed evidence of post-error response slowing; however, post-error adaptation in motor networks was significantly reduced in children with ADHD. This adaptation was inversely related to activation of the right-lateralized ventral attention network (VAN) on error trials and to task-driven connectivity between the cinguloopercular system and the VAN. Limitations: Our study was limited by the modest sample size and imperfect matching across groups. Conclusion: Our findings show a deficit in cingulo-opercular activation in children with ADHD that could relate to reduced signalling for errors. Moreover, the reduced orienting of the VAN signal may mediate deficient post-error motor adaptions. Pinpointing general performance monitoring problems to specific brain regions and operations in error processing may help to guide the targets of future treatments for ADHD. [ABSTRACT FROM AUTHOR]

Background: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder and its impact on cognitive development needs further study. Evidence from neuropsychological, neuroimaging and electrophysiological studies suggests that the decline in tic severity and the ability to suppress tics relate to the development of self-regulatory functions in late childhood and adolescence. Hence, tasks measuring performance monitoring might provide insight into the regulation of tics in children with TS. Method: Twenty-five children with TS, including 14 with comorbid Attention-deficit/ hyperactivity disorder (ADHD), 39 children with ADHD and 35 typically developing children aged 8-12 years were tested with a modified Eriksen-Flanker task during a 34-channel electroencephalography (EEG) recording. Task performance, as well as stimulus-locked and response-locked event-related potentials (ERP) were analyzed and compared across groups. Results: Participants did not differ in their behavioral performance. Children with TS showed higher amplitudes of an early P3 component of the stimulus-locked ERPs in ensemble averages and in separate trial outcomes, suggesting heightened orienting and/or attention during stimulus evaluation. In response-locked averages, children with TS had a slightly higher positive complex before the motor response, likely also reflecting a late P3. Groups did not differ in post-response components, particularly in the error-related negativity (ERN) and error-related positivity (Pe). Conclusions: These findings suggest that children with TS may employ additional attentional resources as a compensatory mechanism to maintain equal behavioral performance. [ABSTRACT FROM AUTHOR]