Kenneth Hugdahl

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Verified

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• PhD
• Professor Emeritus at University of Bergen

Previous studies have shown atypical language asymmetry in male participants with high schizotypy traits, but in female participants the pattern is less clear. Such sex differences could suggest a role of sex hormones, especially since hemispheric asymmetries have been shown to change across the menstrual cycle. By modulating attention in a consona...

The present functional magnetic resonance imaging (fMRI) study investigated neural correlates of switching between task-processing and periods of rest in a conventional ON-OFF block-design in patients with auditory verbal hallucinations (AVHs) and healthy controls. It has been proposed that auditory hallucinations are a failure of top-down control...

The perception of a voice in the absence of an external auditory source – an auditory verbal hallucination – is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorpor...

Variability between individual transients in an MRS acquisition presents a challenge for reliable quantification, particularly in functional scenarios where discrete subsets of the available transients may be compared. The current study aims to develop and validate a model for removing unwanted variance from GABA-edited MRS data, whilst preserving...

Background Auditory verbal hallucinations, which frequently involve negative emotions, are reliable symptoms of schizophrenia. Brain asymmetries have also been linked to the condition, but the relevance of asymmetries within the amygdala, which coordinates all emotional signals, to the content of and response to auditory verbal hallucinations has n...

In this personal recollection, I review the beginning of functional magnetic resonance imaging (fMRI) research in Norway, i.e., at the University of Bergen and the Haukeland University Hospital in Bergen. Research with fMRI had already started in Bergen in 1993, and the small group of researchers involved were the first to take up this new method f...

J-difference-edited MRS is widely used to study GABA in the human brain. Editing for low-concentration target molecules (such as GABA) typically exhibits lower signal-to-noise ratio (SNR) than conventional non-edited MRS, varying with acquisition region, volume and duration. Moreover, spectral lineshape may be influenced by age-, pathology-, or bra...

Although schizophrenia (SZ) represents a complex multiform psychiatric disorder, one of its most striking symptoms are auditory verbal hallucinations (AVH). While the neurophysiological origin of this pervasive symptom has been extensively studied, there is so far no consensus conclusion on the neural correlates of the vulnerability to hallucinate....

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 seque...

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...

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...

A recurring issue in functional neuroimaging is how to link task-driven hemodynamic BOLD-fMRI responses to underlying neurochemistry at the synaptic level. Glutamate and GABA, the major excitatory and inhibitory neurotransmitters respectively, are typically measured with MR spectroscopy (MRS) sequences in a resting state, in the absence of a task....

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...

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 a...

We used a 10-question self-report questionnaire, Mini Voice Questionnaire (MVQ), for mapping the phenomenology of auditory verbal hallucinations (AVH). The MVQ contains questions related to daily AVH frequency and duration, the events preceding AVH episode onset and offset, the very first AVH episode, emotional content, coping strategies, if the vo...

Functional magnetic resonance spectroscopy (fMRS) of GABA at 3T poses additional challenges compared to functional MRS of other metabolites due to the difficulties of measuring GABA levels; GABA is present in the brain at relatively low concentrations and its signal is overlapped by higher concentration metabolites. Using 7T fMRS, GABA levels have...

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 assu...

Although alterations of the default mode network (DMN) in schizophrenia (SZ) have been largely investigated, less research has been carried out on DMN alterations in different sub-phenotypes of this disorder. The aim of this pilot study was to compare DMN features among SZ patients with and without auditory verbal hallucinations (AVH). Three groups...

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 network...

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 restin...

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 o...

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 Alzhe...

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 a...

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 multis...

Objectives Negative emotional valence of auditory verbal hallucinations (AVHs) in schizophrenia can be a source of distress and is considered a strong predictor of illness severity. Previous studies have found glutamate to mediate AVH severity in frontal and temporal brain regions, however, they do not specifically address emotional valence of AVH....

Everyday cognitive functioning is characterized by constant alternations between different modes of information processing, driven by 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 the Default Mod...

Olfactory hallucinations referring to olfactory perceptions in the absence of chemical stimuli, occur in non-clinical and clinical populations. Few studies have investigated their prevalence in the general population and little is known about factors triggering and maintaining them such as substance use, severe life events, and mood. We analyzed se...

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 act...

Hallucinatory experiences can occur in both clinical and nonclinical groups. However, in previous studies of the general population, investigations of the cognitive mechanisms underlying hallucinatory experiences have yielded inconsistent results. We ran a large-scale preregistered multisite study, in which general-population participants ( N = 1,3...

Background Few studies have investigated hallucinations that occur at the onset/offset of sleep (called hypnagogic/hypnopompic hallucinations; HHHs), despite the fact that their prevalence in the general population is reported to be higher than the prevalence of daytime hallucinations. We utilized data from an epidemiological study to explore the p...

Background: Most studies investigating antipsychotic effectiveness report either total psychopathology or symptom cluster findings. Studies focusing on a separate symptom, such as hallucinations, a hallmark symptom in schizophrenia, are scarce.Therefore, the current study aims to compare the antihallucinatory effectiveness of 3 pharmacologically d...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The blood oxygen level dependent (BOLD) effect that provides the contrast in functional magnetic resonance imaging (fMRI) has been demonstrated to affect the linewidth of spectral peaks as measured with magnetic resonance spectroscopy (MRS) and through this, may be used as an indirect measure of cerebral blood flow related to neural activity. By ac...

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)...

Introduction: Successful inhibition of distracting emotions is important for preserving well-being and daily functioning. There is conflicting evidence regarding the impact of healthy aging on emotional inhibition, and possible age-related alterations in the neuronal underpinnings of emotional interference processing are unexplored. Methods: Thi...

The relation between auditory verbal hallucinations (AVH) and white matter has been studied, but results are still inconsistent. This inconsistency may be related to having only a single time-point of AVH assessment in many studies, not capturing that AVH severity fluctuates over time. In the current study, AVH fluctuations were captured by utilizi...

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...

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 menta...

Background: Amisulpride, aripiprazole, and olanzapine are first-line atypical antipsychotics that have not previously been compared head-to-head in a pragmatic trial. We aimed to compare the efficacy and safety of these agents in a controlled trial. Methods: This pragmatic, rater-blind, randomised controlled trial was done in three academic cent...

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 phenomenol...

The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including post-traumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed fin...

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...

Background Schizophrenia (SZ) and bipolar disorders (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (D...

Hallucinatory experiences (HEs) can occur in both clinical and non-clinical groups. However, previous studies of the general population that have investigated cognitive mechanisms underlying HEs have yielded inconsistent results. In this study, we ran a large-scale preregistered multi-site study, in which general population participants (N = 1394,...

Background Auditory hallucinations have been linked to aberrant functioning of the left superior temporal gyrus (STG) and are associated with impaired cognitive control regulated by areas in the prefrontal cortex. However, the mechanisms behind these dysfunctions are still unclear. Methods The current study combined resting state connectivity fMRI...

Background Transcranial direct current stimulation (tDCS) is a brain stimulation method which is growing in popularity in both research and clinical settings, especially as a treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia. However, the underlying neural mechanisms of this tDCS treatment are poorly understood. Curre...

Background Auditory verbal hallucinations (AVH), the sense of “hearing voices” in the absence of a corresponding auditory source, are a major symptom in schizophrenia. Hemodynamic and electrophysiology studies have shown aberrant activation in fronto-temporal speech and language areas (Curcic-Blake et al., 2017 for review) – indicating neurobiologi...

Background There is a wealth of evidence showing aberrant functional connectivity (FC) in schizophrenia but with considerable variability in findings across studies. Dynamic FC is an extension of traditional static FC, in that such analyses allow for explorations of temporal changes in connectivity. Thereby they also provide more detailed informati...

The arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conf...

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...

There is a wealth of evidence showing aberrant functional connectivity (FC) in schizophrenia but with considerable variability in findings across studies. Dynamic FC is an extension of traditional static FC, in that such analyses allow for explorations of temporal changes in connectivity. Thereby they also provide more detailed information on conne...

Auditory verbal hallucinations, or "hearing voices", is a remarkable state of the mind, occurring in psychiatric and neurological patients, and in a significant minority of the general population. An unexplained characteristic of this phenomenon is that it transiently fluctuates, with coming and going of episodes with time. We monitored neural acti...

We here report on the relationship between default and extrinsic mode networks across alternating brief periods of rest and active task processing. We used three different visual tasks: mental rotation, working memory and mental arithmetic in a classic fMRI ON-OFF block design where task (ON) blocks alternated with equal periods of rest (OFF) block...

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 co...

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....

The arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conf...

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 (...

Listening difficulties (LiD), also known as auditory processing disorders, are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD. Previous studies have focused on testing using multiple sequential dichotic digits that carry a substantial memory load and e...

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 (...

Background: Auditory verbal hallucinations (AVH) are the most frequent symptom in early-onset psychosis (EOP) and a risk factor for increased suicide attempts in adolescents. Increased knowledge of AVH characteristics can lead to better prediction of risk and precision of diagnosis and help identify individuals with AVH who need care. As 98% of Nor...

Background: Schizophrenia (SZ) and bipolar disorders (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (...

Background Auditory Hallucinations (AH) are prevalent in many psychopathologies as well as in a minority of the healthy general population. The literature suggests that people with AH present a signal detection bias, that is, in conditions of uncertainty, they tend to perceive signals that are not actually there– or false perceptions. For example,...

Over the last three decades there has been an accumulation of Magnetic Resonance Imaging (MRI) studies reporting that aberrant functional networks may underlie cognitive deficits and other symptoms across a range of psychiatric diagnoses. The use of pharmacological MRI and 1H-Magnetic Resonance Spectroscopy (1H-MRS) has allowed researchers to inves...

Background: Auditory verbal hallucinations (AVH) are the most frequent symptom in early-onset psychosis (EOP) and a risk factor for increased suicide attempts in adolescents. Increased knowledge of AVH characteristics can lead to better prediction of risk and precision of diagnosis and help identify individuals with AVH who need care. As 98% of No...

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...

Epidemiological studies have repeatedly shown that a significant minority of the general population have experienced hallucinations, however, a potential effect of age on the prevalence of hallucinations in the general population has never been previously examined in a specific study. The aim of the present study was thus to examine the effects of...

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 of...

A number of studies investigating the biological effects of transcranial direct current stimulation (tDCS) using magnetic resonance spectroscopy (MRS) have found that it may affect local levels of γ-aminobutyric acid (GABA), glutamate and glutamine (commonly measured together as “Glx” in spectroscopy), and N-acetyl aspartate (NAA), however, these e...

Background Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinat...

The past decades have seen an explosion of research into the psychological, cognitive, neural, biological, and technical mechanisms of voice perception. These mechanisms refer to the general ability to extract information from voices expressed by other living beings or by technical systems. Voice perception research is now a lively area of research...

Cognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and is, therefore, a treatment target in itself. Yet, literature on efficacy of different pharmaco-therapeutic options is inconsistent. This quantitative review provides an overview of studies that investigated potential cognitive enhancers in schiz...

Magnetic Resonance Spectroscopy (MRS) has become a valuable tool for investigating the biochemical bases of both normal processes in the healthy brain and elucidating the pathophysiology of neuropsychiatric disorders. As a rapidly advancing field, new developments in pulse sequence design have seen new possibilities arise in terms of what can be do...

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 u...

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...

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...

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 t...

Background Understanding what happens at first onset of auditory verbal hallucinations (AVHs) is important at both a clinical and theoretical level. Previous studies have focused on age with regard to first onset of AVHs. In the current epidemiological study, we investigated the role of adverse life events (e.g. accidents, divorce, bullying, unempl...

Background Recent Magnetic Resonance Imaging (MRI) studies on schizophrenia suggest that auditory verbal hallucinations (AVH) might be caused by alterations in connectivity of frontal and temporoparietal language-related areas.3 as well as in connectivity of the default mode network (DMN).1 Therefore, diffusion tensor imaging (DTI) of white matter...

Background Auditory verbal hallucinations are a major symptom in schizophrenia but also affect patients with other diagnoses and healthy people without any pathology. This applies also to delusions and hallucinations of other sensory modalities. Since most questionnaires that assess hallucinations focus on one particular disorder, the Questionnaire...

Background Cognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and should therefore be one of the main treatment targets. Pharmacological enhancement of cognition has been a main field of research in the last decades, investigating almost all neurotransmitter systems and reporting positive as well as...

Background The gamma-aminobutyric acid (GABA)-glutamate hypothesis of schizophrenia suggests a neurotransmitter imbalance – reduced GABA and increased glutamate - which causes disruption of the modulation between inhibitory GABAergic interneurons and excitatory glutamatergic neurons. In the left superior temporal gyrus (STG) both hyperactivation an...

Background We used transcranial direct current stimulation (tDCS) in a non-clinical population to simulate a model of tDCS-treatment for auditory verbal hallucinations (AVH) in schizophrenia. In tDCS, a low current is induced via two electrodes attached to the scalp. The anode and cathode typically up- and downregulate neuronal activity, respective...

Background A challenge in current research on auditory hallucinations (AHs) is that the assessment of symptom dimensions largely depends on structured interview scales, such as the PANSS, PSYRATS etc. In order to collect more ecologically valid data, we developed a smartphone app that can be used by patients to report on their experience in real-ti...