Publications by authors named "Karsten Specht"

117 Publications

"Mickey Mousing" in the Brain: Motion-Sound Synesthesia and the Subcortical Substrate of Audio-Visual Integration.

Front Hum Neurosci 2021 15;15:605166. Epub 2021 Feb 15.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Motion-sound synesthesia is characterized by illusory auditory sensations linked to the pattern and rhythms of motion (dubbed "Mickey Mousing" as in cinema) of visually experienced but soundless object, like an optical flow array, a ball bouncing or a horse galloping. In an MRI study with a group of three synesthetes and a group of eighteen control participants, we found structural changes in the brains of synesthetes in the subcortical multisensory areas of the superior and inferior colliculi. In addition, functional magnetic resonance imaging data showed activity in motion-sensitive regions, as well as temporal and occipital areas, and the cerebellum. However, the synesthetes had a higher activation within the left and right cuneus, with stronger activations when viewing optical flow stimuli. There was also a general difference in connectivity of the colliculi with the above mentioned regions between the two groups. These findings implicate low-level mechanisms within the human neuroaxis as a substrate for local connectivity and cross activity between perceptual processes that are "distant" in terms of cortical topography. The present findings underline the importance of considering the role of subcortical systems and their connectivity to multimodal regions of the cortex and they strengthen a parsimonious account of synesthesia, at the least of the visual-auditory type.
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http://dx.doi.org/10.3389/fnhum.2021.605166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917298PMC
February 2021

Reduced grey- and white matter volumes due to unilateral hearing loss following treatment for vestibular schwannoma.

Heliyon 2020 Dec 17;6(12):e05658. Epub 2020 Dec 17.

Department of Biological and Medical Psychology, University of Bergen, PB 7807, 5020 Bergen, Norway.

Objective: Previous studies of the consequences of unilateral hearing loss (UHL) on the functional-structural organization of the brain has included subjects with various degrees of UHL. We suggest that the consequences of a total loss of hearing in one ear might differ from those seen in subjects with residual hearing in the affected ear. Thus, the main aim of the present study was to compare the structural properties of auditory and non-auditory brain regions in persons with complete UHL to those of normal hearing controls. We hypothesize that the consequences of complete UHL following treatment for vestibular schwannoma will differ between ipsi- and contralateral structures, as well as between right- and left side deafness.

Design: A 3T Siemens Prisma MR-scanner was used. Anatomical images were acquired using a high-resolution T1-weighted sequence. Grey- and white matter volumes were assessed using voxel-based morphometry.

Study Sample: Twenty-two patients with left- or right-side unilateral hearing loss. Fifty normal hearing controls.

Results: Reductions in grey- and white matter volumes were seen in cortical and sub-cortical regions, mainly in the right hemisphere including the auditory cortex, lingual gyrus, cuneus, middle temporal gyrus, occipital fusiform gyrus, middle cingulate gyrus and the superior temporal gyrus. Patients displayed reduced grey- and white matter volumes in cerebellar exterior structures ipsilateral to the tumor side.

Conclusion: When compared to controls, right side hearing loss yields more widespread reduction of grey matter volume than left side hearing loss. The findings of reduced grey- and white matter volumes in auditory and non-auditory brain regions could be related to problems with speech perception in adverse listening conditions, increased listening effort and reduced quality of life reported by persons with unilateral hearing loss despite normal hearing in the unaffected ear.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754525PMC
December 2020

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Psychophysiology 2020 Oct 10. Epub 2020 Oct 10.

Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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http://dx.doi.org/10.1111/psyp.13688DOI Listing
October 2020

Glutamatergic modulation of auditory cortex connectivity with attentional brain networks in unpredictable perceptual environment.

Sci Rep 2020 09 14;10(1):15059. Epub 2020 Sep 14.

Department of Biological and Medical Biology, University of Bergen, Bergen, Norway.

In a stable environment the brain can minimize processing required for sensory input by forming a predictive model of the surrounding world and suppressing neural response to predicted stimuli. Unpredicted stimuli lead to a prediction error signal propagation through the perceptual network, and resulting adjustment to the predictive model. The inter-regional plasticity which enables the model-building and model-adjustment is hypothesized to be mediated via glutamatergic receptors. While pharmacological challenge studies with glutamate receptor ligands have demonstrated impact on prediction-error indices, it is not clear how inter-individual differences in the glutamate system affect the prediction-error processing in non-medicated state. In the present study we examined 20 healthy young subjects with resting-state proton MRS spectroscopy to characterize glutamate + glutamine (rs-Glx) levels in their Heschl's gyrus (HG), and related this to HG functional connectivity during a roving auditory oddball protocol. No rs-Glx effects were found within the frontotemporal prediction-error network. Larger rs-Glx signal was related to stronger connectivity between HG and bilateral inferior parietal lobule during unpredictable auditory stimulation. We also found effects of rs-Glx on the coherence of default mode network and frontoparietal network during unpredictable auditory stimulation. Our results demonstrate the importance of Glx in modulating long-range connections and wider networks in the brain during perceptual inference.
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http://dx.doi.org/10.1038/s41598-020-72044-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490710PMC
September 2020

A multimodal study of the effects of tDCS on dorsolateral prefrontal and temporo-parietal areas during dichotic listening.

Eur J Neurosci 2021 Jan 25;53(2):449-459. Epub 2020 Aug 25.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

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.
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http://dx.doi.org/10.1111/ejn.14932DOI Listing
January 2021

Correction to: Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG): study protocol for a randomized controlled trial.

Trials 2020 Apr 6;21(1):317. Epub 2020 Apr 6.

Faculty of Psychology, University of Bergen, Box 7800, NO-5020, Bergen, Norway.

Following the publication of our article [1], we have become aware of one error in the exclusion criteria, inconsistencies in Figure 1 and Figure 2, and a typo in the reference list.
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http://dx.doi.org/10.1186/s13063-020-04239-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132867PMC
April 2020

Current Challenges in Translational and Clinical fMRI and Future Directions.

Authors:
Karsten Specht

Front Psychiatry 2019 8;10:924. Epub 2020 Jan 8.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Translational neuroscience is an important field that brings together clinical praxis with neuroscience methods. In this review article, the focus will be on functional neuroimaging (fMRI) and its applicability in clinical fMRI studies. In the light of the "replication crisis," three aspects will be critically discussed: First, the fMRI signal itself, second, current fMRI praxis, and, third, the next generation of analysis strategies. Current attempts such as resting-state fMRI, meta-analyses, and machine learning will be discussed with their advantages and potential pitfalls and disadvantages. One major concern is that the fMRI signal shows substantial within- and between-subject variability, which affects the reliability of both task-related, but in particularly resting-state fMRI studies. Furthermore, the lack of standardized acquisition and analysis methods hinders the further development of clinical relevant approaches. However, meta-analyses and machine-learning approaches may help to overcome current shortcomings in the methods by identifying new, and yet hidden relationships, and may help to build new models on disorder mechanisms. Furthermore, better control of parameters that may have an influence on the fMRI signal and that can easily be controlled for, like blood pressure, heart rate, diet, time of day, might improve reliability substantially.
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http://dx.doi.org/10.3389/fpsyt.2019.00924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960120PMC
January 2020

Dynamic up- and down-regulation of the default (DMN) and extrinsic (EMN) mode networks during alternating task-on and task-off periods.

PLoS One 2019 19;14(9):e0218358. Epub 2019 Sep 19.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218358PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752853PMC
March 2020

Music therapy for children with autism: investigating social behaviour through music.

Lancet Child Adolesc Health 2019 11 4;3(11):759-761. Epub 2019 Sep 4.

Department of Psychology, University of Vienna, Vienna, Austria; GAMUT-The Grieg Academy Music Therapy Research Centre, NORCE Norwegian Research Centre, 5838 Bergen, Norway. Electronic address:

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http://dx.doi.org/10.1016/S2352-4642(19)30265-2DOI Listing
November 2019

Subjective judgments of rhythmic complexity in Parkinson's disease: Higher baseline, preserved relative ability, and modulated by tempo.

PLoS One 2019 3;14(9):e0221752. Epub 2019 Sep 3.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Previous research has demonstrated that people with Parkinson's disease (PD) have difficulties with the perceptual discrimination of rhythms, relative to healthy controls. It is not however clear if this applies only to simpler rhythms (a so called "beat-based" deficit), or if it is a more generalized deficit that also applies to more complex rhythms. Further insight into how people with PD process and perceive rhythm can refine our understanding of the well known problems of temporal processing in the disease. In this study, we wanted to move beyond simple/complex-dichotomy in previous studies, and further investigate the effect of tempo on the perception of musical rhythms. To this end, we constructed ten musical rhythms with a varied degree of complexity across three different tempi. Nineteen people with PD and 19 healthy controls part-took in an internet based listening survey and rated 10 different musical rhythms for complexity and likeability. In what we believe is the first study to do so, we asked for the participants subjective ratings of individual rhythms and not their capacity to directly compare or discriminate between them. We found an overall between-group difference in complexity judgments that was modulated by tempo, but not level of complexity. People with PD rated all rhythms as more complex across tempi, with significant group differences in complexity ratings at 120 and 150bpm, but not at 90bpm. Our analysis found a uniform elevated baseline for complexity judgments in the PD-group, and a strong association between the two groups' rank-ordering the rhythms for complexity. This indicates a preserved ability to discriminate between relative levels of complexity. Finally, the two groups did not significantly differ in their subjective scoring of likeability, demonstrating a dissimilarity between judgment of complexity and judgment of likeability between the two groups. This indicates different cognitive operations for the two types of judgment, and we speculate that Parkinson's disease affects judgment of complexity but not judgment of likeability.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221752PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719828PMC
March 2020

Compensatory task-specific hypersensitivity in bilateral planum temporale and right superior temporal gyrus during auditory rhythm and omission processing in Parkinson's disease.

Sci Rep 2019 09 2;9(1):12623. Epub 2019 Sep 2.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Persons with Parkinson's disease have general timing deficits and have difficulties in rhythm discrimination tasks. The basal ganglia, a crucial part of Parkinson's disease pathology, is believed to play an important role in rhythm and beat processing, with a possible modulation of basal ganglia activity by level of rhythmic complexity. As dysfunction in basal ganglia impacts function in other brain areas in Parkinson's disease during temporal processing, investigating the neuronal basis for rhythm processing is important as it could shed light on the nature of basal ganglia dysfunction and compensatory mechanisms. We constructed an auditory beat-omission fMRI paradigm with two levels of rhythm complexity, to investigate if and where persons with Parkinson's disease showed abnormal activation during rhythm and omission processing, and whether such activations were modulated by the level of rhythmic complexity. We found no effect of complexity, but found crucial group differences. For the processing of normal rhythm presentations, the Parkinson-group showed higher bilateral planum temporal activity, an area previously associated with the processing of complex patterns. For the omissions, the Parkinson-group showed higher activity in an area in the right superior temporal gyrus previously associated with detection of auditory omissions. We believe this shows a pattern of "hypersensitive" activity, indicative of task-specific, compensatory mechanisms in the processing of temporal auditory information in persons with Parkinson's disease.
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http://dx.doi.org/10.1038/s41598-019-48791-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718659PMC
September 2019

An fMRI-study on single-sided deafness: Spectral-temporal properties and side of stimulation modulates hemispheric dominance.

Neuroimage Clin 2019 6;24:101969. Epub 2019 Aug 6.

Department of Biological and Medical Psychology, University of Bergen, PB 7807, 5020 Bergen, Norway; Department of Education, UiT/The Arctic University of Norway, Tromsø, Norway. Electronic address:

Objective: Our main aim was to investigate the blood oxygenation level dependent (BOLD) response to monaural and binaural speech- and non-speech stimuli as measured with fMRI in subjects with single-sided deafness and in normal hearing controls. We hypothesised that the response to monaural stimulation in both normal hearing subjects and persons with single-sided deafness would vary with the complexity and nature of the stimuli and the side of stimulation.

Design: Patients with left- and right single-sided deafness and controls with normal hearing receiving either binaural or monaural stimuli were tested using speech and non-speech auditory stimuli in an event-related fMRI experiment.

Study Sample: Twenty-two patients with single-sided deafness after treatment for vestibular schwannoma and 50 normal hearing controls.

Results: Normal hearing persons receiving right side monaural stimuli activate bilateral temporal regions. Activation following left side monaural stimulation is more right lateralized. Persons with single-sided deafness respond similarly to controls to monaural stimulation. Persons with right side single-sided deafness show activation of frontal cortical regions not seen in persons with left side single-sided deafness following speech stimuli. This is possibly related to increased effort and more frequently reported problems with communication. Right side single-sided deafness is related to increased activation of areas usually related to processing of degraded input, including the thalamus.

Conclusion: Hemispheric dominance following monaural auditory stimulation is modulated by the spectral-temporal properties of the stimuli and by which ear is stimulated. Differences between patients with right- and left side deafness suggests that right side deafness is related to increased activation of areas involved in processing of degraded input.
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http://dx.doi.org/10.1016/j.nicl.2019.101969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706639PMC
September 2020

Neuroplastic Effects in Patients With Traumatic Brain Injury After Music-Supported Therapy.

Front Hum Neurosci 2019 25;13:177. Epub 2019 Jun 25.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Damage to the orbitofrontal cortex (OFC) often occurs following a traumatic brain injury (TBI) and can lead to complex behavioral changes, including difficulty with attention and concentration. We investigated the effects of musical training on patients with behavioral and cognitive deficits following a mild traumatic brain injury (mTBI) and found significant functional neuro-plastic changes in the OFC's networks. The results from neuropsychological tests revealed an improved cognitive performance. Moreover, six out of seven participants in this group returned to work post intervention and reported improved well-being and social behavior. In this study, we explore the functional changes in OFC following music-supported intervention in reference to connecting networks that may be responsible for enhanced social interaction. Furthermore, we discuss the factor of dopamine release during playing as an element providing a possible impact on the results. The intervention consisted of playing piano, two sessions per week in 8 weeks, 30 min each time, with an instructor. Additional playing was required with a minimum of 15 min per day at home. Mean time playing piano in reference to participant's report was 3 h per week during the intervention period. Three groups participated, one mTBI group ( = 7), two control groups consisting of healthy participants, one with music training ( = 11), and one baseline group without music training ( = 12). Participants in the clinical group had received standardized cognitive rehabilitation treatment during hospitalization without recovering from their impairments. The intervention took place 2 years post injury. All participants were assessed with neuropsychological tests and with both task and resting-state functional magnetic resonance imaging (fMRI) pre-post intervention. The results demonstrated a significant improvement of neuropsychological tests in the clinical group, consistent with fMRI results in which there were functional changes in the orbitofrontal networks (OFC). These changes were concordantly seen both in a simple task fMRI but also in resting-state fMRI, which was analyzed with dynamic causal modeling (DCM). We hypothesized that playing piano, as designed in the training protocol, may provide a positive increase in both well-being and social interaction. We suggest that the novelty of the intervention may have clinical relevance for patients with behavioral problems following a TBI.
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http://dx.doi.org/10.3389/fnhum.2019.00177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604902PMC
June 2019

Reduced grey matter volume in frontal and temporal areas in depression: contributions from voxel-based morphometry study.

Acta Neuropsychiatr 2019 Oct;31(5):252-257

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Objective: The aim of the current study was to examine whether and to what extent mood disorders, comprising major depression and bipolar disorder, are accompanied by structural changes in the brain as measured using voxel-based morphometry (VBM).

Methods: We performed a VBM study using a 3Т MRI system (GE Discovery 750w) in patients with mood disorders (n=50), namely, 39 with major depression and 11 with bipolar disorder compared to 42 age-, sex- and education-matched healthy controls.

Results: Our results show that depression was associated with significant decreases in grey matter (GM) volume of the regions located within the medial frontal and anterior cingulate cortex on the left side and middle frontal gyrus, medial orbital gyrus, inferior frontal gyrus (triangular and orbital parts) and middle temporal gyrus (extending to the superior temporal gyrus) on the right side. When the patient group was separated into bipolar disorder and major depression, the reductions remained significant only for patients with major depressive disorder.

Conclusions: Using VBM the present study was able to replicate decreases in GM volume restricted to frontal and temporal regions in patients with mood disorders, mainly major depression, compared with healthy controls.
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http://dx.doi.org/10.1017/neu.2019.20DOI Listing
October 2019

Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG): study protocol for a randomized controlled trial.

Trials 2019 Mar 18;20(1):174. Epub 2019 Mar 18.

Faculty of Psychology, University of Bergen, Box 7800, NO-5020, Bergen, Norway.

Background: Generalised anxiety disorder (GAD) is a frequent and severe anxiety disorder among older adults. GAD increases the risk of developing other disorders such as depression and coronary heart disease. Older adults with GAD exhibit a poorer response to cognitive behaviour therapy (CBT) compared to younger patients with GAD. The normal age-related cognitive decline can be a contributor to reduced treatment efficacy. One strategy for improving treatment efficacy is to combine CBT with adjunctive interventions targeted at improving cognitive functions. Physical exercise is a viable intervention in this regard. Increased levels of brain-derived neurotrophic factor may mediate improvement in cognitive function. The present study aims to investigate the proposed effects and mechanisms related to concomitant physical exercise.

Methods: The sample comprises 70 participants aged 60-75 years, who have GAD. Exclusion criteria comprise substance abuse and unstable medication; inability to participate in physical exercise; and conditions which precludes GAD as primary diagnosis. The interventions are individual treatment in the outpatient clinic at the local psychiatric hospital, with two experimental arms: (1) CBT + physical exercise and (2) CBT + telephone calls. The primary outcome measure is symptom reduction on the Penn State Worry Questionnaire. Other measures include questionnaires, clinical interviews, physiological, biological and neuropsychological tests. A subset of 40 participants will undergo magnetic resonance imaging (MRI). After inclusion, participants undergo baseline testing, and are subsequently randomized to a treatment condition. Participants attend five sessions of the add-on treatment in the pre-treatment phase, and move on to interim testing. After interim testing, participants attend 10 sessions of CBT in parallel with continued add-on treatment. Participants are tested post-intervention within 2 weeks of completing treatment, with follow-up testing 6 and 12 months later.

Discussion: This study aims to develop better treatment for GAD in older adults. Enhancing treatment response will be valuable from both individual and societal perspectives, especially taking the aging of the general population into account.

Trial Registration: ClinicalTrials.gov, NCT02690441 . Registered on 24 February 2016.
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http://dx.doi.org/10.1186/s13063-019-3268-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423789PMC
March 2019

Current Practice and New Developments in the Use of In Vivo Magnetic Resonance Spectroscopy for the Assessment of Key Metabolites Implicated in the Pathophysiology of Schizophrenia.

Curr Top Med Chem 2018 ;18(21):1908-1924

Department of Radiology, Haukeland University Hospital, Bergen, Norway.

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 done with in vivo spectroscopy. While the applications of MRS are numerous, this review has been confined to the use of single voxel spectroscopy in the assessment of five key metabolites and their roles in schizophrenia: N-acetylaspartate (NAA), glutamate (Glu) and glutamine (Gln), γ-aminobutyric acid (GABA) and glutathione (GSH). This article will briefly cover the roles they play in schizophrenia, review current methods being used in their assessment and highlight new approaches that may potentially overcome some of the limitations current methods pose.
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http://dx.doi.org/10.2174/1568026619666181130103559DOI Listing
March 2019

Language lateralisation measured across linguistic and national boundaries.

Cortex 2019 02 3;111:134-147. Epub 2018 Nov 3.

Institute of Psychology, University of Lausanne, Switzerland.

The visual half-field technique has been shown to be a reliable and valid neuropsychological measurement of language lateralisation, typically showing higher accuracy and faster correct responses for linguistic stimuli presented in the right visual field (RVF) than left visual field (LVF). The RVF advantage corresponds to the well-known dominance of the left hemisphere (LH) in processing language(s). However, clinical and experimental neuroscientists around the globe use different variations of the visual half-field paradigm, making direct comparisons difficult. The current study used a word/non-word visual half-field paradigm with translingual stimuli. In total, 496 participants from seven European countries were investigated: Belgium (64), England (49), Germany (85), Italy (34), The Netherlands (87), Norway (51), and Switzerland (126), covering six international languages (Dutch, English, French, German, Italian, Norwegian). All language groups revealed a significant RVF/LH advantage in accuracy and reaction times that accounted for up to 26.1% of the total variance in performance. We found some variation in the degree of the RVF/LH advantage across language groups, accounting for a maximum of 3.7% of the total variance in performance. The RVF/LH advantage did not differ between subsamples speaking English, French or German as first or second languages or between monolingual and early/late bi/multilinguals. The findings suggest that the translingual lexical decision task (TLDT) is a simple but reliable measurement of language lateralisation that can be applied clinically and experimentally across linguistic and national boundaries.
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http://dx.doi.org/10.1016/j.cortex.2018.10.020DOI Listing
February 2019

Abnormal phasic activity in saliency network, motor areas, and basal ganglia in Parkinson's disease during rhythm perception.

Hum Brain Mapp 2019 02 29;40(3):916-927. Epub 2018 Oct 29.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Behavioral studies indicate that persons with Parkinson's disease have complexity dependent problems with the discrimination of auditory rhythms. Furthermore, neuroimaging studies show that rhythm processing activates many brain areas that overlap with areas affected by Parkinson's disease (PD). This study sought to investigate the neural correlates of rhythm processing in PD and healthy controls, with a particular focus on rhythmic complexity. We further aimed to investigate differences in brain activation during initial phases of rhythm processing. Functional magnetic resonance imaging was used to scan 15 persons with Parkinson's disease and 15 healthy controls while they listened to musical rhythms with two different levels of complexity. Rhythmic complexity had no significant effect on brain activations, but patients and controls showed differences in areas related to temporal auditory processing, notably bilateral planum temporale and inferior parietal lobule. We found indications of a particular sequential or phasic activation pattern of brain activity, where activity in caudate nucleus in the basal ganglia was time-displaced by activation in the saliency network-comprised of anterior cingulate cortex and bilateral anterior insula-and cortical and subcortical motor areas, during the initial phases of listening to rhythms. We relate our findings to core PD pathology, and discuss the overall, rhythm processing related hyperactivity in PD as a possible dysfunction in specific basal ganglia mechanisms, and the phasic activation pattern in PD as a reflection of a lack of preparatory activation of task-relevant brain networks for rhythm processing in PD.
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http://dx.doi.org/10.1002/hbm.24421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587836PMC
February 2019

Altered Resting State Effective Connectivity of Anterior Insula in Depression.

Front Psychiatry 2018 15;9:83. Epub 2018 Mar 15.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Depression has been associated with changes in both functional and effective connectivity of large scale brain networks, including the default mode network, executive network, and salience network. However, studies of effective connectivity by means of spectral dynamic causal modeling (spDCM) are still rare and the interaction between the different resting state networks has not been investigated in detail. Thus, we aimed at exploring differences in effective connectivity among eight right hemisphere brain areas-anterior insula, inferior frontal gyrus, middle frontal gyrus (MFG), frontal eye field, anterior cingulate cortex, superior parietal lobe, amygdala, and hippocampus, between a group of healthy controls ( = 20) and medicated depressed patients ( = 20). We found that patients not only had significantly reduced strength of the connection from the anterior insula to the MFG (i.e., dorsolateral prefrontal cortex) but also a significant connection between the amygdala and the anterior insula. Moreover, depression severity correlated with connectivity of the hippocampal node. In conclusion, the results from this resting state spDCM study support and enrich previous data on the role of the right anterior insula in the pathophysiology of depression. Furthermore, our findings add to the growing evidence of an association between depression severity and disturbances of the hippocampal function in terms of impaired connectivity with other brain regions.
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http://dx.doi.org/10.3389/fpsyt.2018.00083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862800PMC
March 2018

Sex- and sex hormone-related variations in energy-metabolic frontal brain asymmetries: A magnetic resonance spectroscopy study.

Neuroimage 2018 05 31;172:817-825. Epub 2018 Jan 31.

Department of Biological and Medical Psychology, University of Bergen, Norway; Department of Education, The Arctic University of Norway, Tromsø, Norway.

Creatine is a key regulator of brain energy homeostasis, and well-balanced creatine metabolism is central in healthy brain functioning. Still, the variability of brain creatine metabolism is largely unattended in magnetic resonance spectroscopy (MRS) research. In the human brain, marginal sex differences in creatine levels have been found in the prefrontal cortex. It is however not known to what degree these sex differences are stable or change with varying gonadal hormone levels. The current study therefore investigated creatine in the prefrontal cortex across the menstrual cycle. In addition, we explored cerebral asymmetries. Creatine, Choline (Cho), N-acetylaspartate (NAA), Myo inositol (mI), and glutamate + glutamine (Glx) were assessed three times in 15 women and 14 men using MRS. Women were tested in cycle phases of varying hormone levels (menstrual, follicular, and luteal phase). Prefrontal creatine was found to change across the menstrual cycle, in a hemisphere-specific manner. Women in the follicular phase showed increased left prefrontal creatine accompanied with reduced right prefrontal creatine, while this asymmetry was not present in the luteal phase. In men, the creatine levels remained stable across three testing sessions. In general, both men and women were found to have higher creatine levels in the left as compared to the right prefrontal cortex. Exploratory analyses of other metabolites showed similar asymmetries in NAA, Cho, and mI, while Cho also showed a menstrual cycle effect. This is the first time that sex hormone-related changes in creatine metabolism have been demonstrated in the human brain. These findings may have important methodological implications for MRS research, as it supports previous concerns against uncritical usage of creatine as a reference measure for other metabolites, assumed to be invariant across individuals and conditions.
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http://dx.doi.org/10.1016/j.neuroimage.2018.01.043DOI Listing
May 2018

Effects of music production on cortical plasticity within cognitive rehabilitation of patients with mild traumatic brain injury.

Brain Inj 2018 1;32(5):634-643. Epub 2018 Feb 1.

a Department of Biological and Medical Psychology , University of Bergen , Bergen , Norway.

Objective: We explored the effects of playing the piano on patients with cognitive impairment after mild traumatic brain injury (mTBI) and, addressed the question if this approach would stimulate neural networks in re-routing neural connections and link up cortical circuits that had been functional inhibited due to disruption of brain tissue. Functional neuroimaging scans (fMRI) and neuropsychological tests were performed pre-post intervention.

Method: Three groups participated, one mTBI group (n = 7), two groups of healthy participants, one with music training (n = 11), one baseline group without music (n = 12). The music groups participated in 8 weeks music-supported intervention.

Results: The patient group revealed training-related neuroplasticity in the orbitofrontal cortex. fMRI results fit well with outcome from neuropsychological tests with significant enhancement of cognitive performance in the music groups. Ninety per cent of mTBI group returned to work post intervention.

Conclusion: Here, for the first time, we demonstrated behavioural improvements and functional brain changes after 8 weeks of playing piano on patients with mTBI having attention, memory and social interaction problems. We present evidence for a causal relationship between musical training and reorganisation of neural networks promoting enhanced cognitive performance. These results add a novel music-supported intervention within rehabilitation of patients with cognitive deficits following mTBI.
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http://dx.doi.org/10.1080/02699052.2018.1431842DOI Listing
May 2019

The functional and structural asymmetries of the superior temporal sulcus.

Scand J Psychol 2018 Feb;59(1):74-82

Department of Behavioural Sciences, Oslo, and Akershus University College of Applied Sciences, Oslo, Norway.

The superior temporal sulcus (STS) is an anatomical structure that increasingly interests researchers. This structure appears to receive multisensory input and is involved in several perceptual and cognitive core functions, such as speech perception, audiovisual integration, (biological) motion processing and theory of mind capacities. In addition, the superior temporal sulcus is not only one of the longest sulci of the brain, but it also shows marked functional and structural asymmetries, some of which have only been found in humans. To explore the functional-structural relationships of these asymmetries in more detail, this study combines functional and structural magnetic resonance imaging. Using a speech perception task, an audiovisual integration task, and a theory of mind task, this study again demonstrated an involvement of the STS in these processes, with an expected strong leftward asymmetry for the speech perception task. Furthermore, this study confirmed the earlier described, human-specific asymmetries, namely that the left STS is longer than the right STS and that the right STS is deeper than the left STS. However, this study did not find any relationship between these structural asymmetries and the detected brain activations or their functional asymmetries. This can, on the other hand, give further support to the notion that the structural asymmetry of the STS is not directly related to the functional asymmetry of the speech perception and the language system as a whole, but that it may have other causes and functions.
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http://dx.doi.org/10.1111/sjop.12410DOI Listing
February 2018

Arterial spin labelling shows functional depression of non-lesion tissue in chronic Wernicke's aphasia.

Cortex 2017 07 10;92:249-260. Epub 2016 Nov 10.

Department of Psychological Medicine, Kings College London, UK.

Behavioural impairment post-stroke is a consequence of structural damage and altered functional network dynamics. Hypoperfusion of intact neural tissue is frequently observed in acute stroke, indicating reduced functional capacity of regions outside the lesion. However, cerebral blood flow (CBF) is rarely investigated in chronic stroke. This study investigated CBF in individuals with chronic Wernicke's aphasia (WA) and examined the relationship between lesion, CBF and neuropsychological impairment. Arterial spin labelling CBF imaging and structural MRIs were collected in 12 individuals with chronic WA and 13 age-matched control participants. Joint independent component analysis (jICA) investigated the relationship between structural lesion and hypoperfusion. Partial correlations explored the relationship between lesion, hypoperfusion and language measures. Joint ICA revealed significant differences between the control and WA groups reflecting a large area of structural lesion in the left posterior hemisphere and an associated area of hypoperfusion extending into grey matter surrounding the lesion. Small regions of remote cortical hypoperfusion were observed, ipsilateral and contralateral to the lesion. Significant correlations were observed between the neuropsychological measures (naming, repetition, reading and semantic association) and the jICA component of interest in the WA group. Additional ROI analyses found a relationship between perfusion surrounding the core lesion and the same neuropsychological measures. This study found that core language impairments in chronic WA are associated with a combination of structural lesion and abnormal perfusion in non-lesioned tissue. This indicates that post-stroke impairments are due to a wider disruption of neural function than observable on structural T1w MRI.
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http://dx.doi.org/10.1016/j.cortex.2016.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480775PMC
July 2017

Listening to Rhythmic Music Reduces Connectivity within the Basal Ganglia and the Reward System.

Front Neurosci 2017 28;11:153. Epub 2017 Mar 28.

Department of Biological and Medical Psychology, University of BergenBergen, Norway; Department of Clinical Engineering, Haukeland University HospitalBergen, Norway.

Music can trigger emotional responses in a more direct way than any other stimulus. In particular, music-evoked pleasure involves brain networks that are part of the reward system. Furthermore, rhythmic music stimulates the basal ganglia and may trigger involuntary movements to the beat. In the present study, we created a continuously playing rhythmic, dance floor-like composition where the ambient noise from the MR scanner was incorporated as an additional instrument of rhythm. By treating this continuous stimulation paradigm as a variant of resting-state, the data was analyzed with stochastic dynamic causal modeling (sDCM), which was used for exploring functional dependencies and interactions between core areas of auditory perception, rhythm processing, and reward processing. The sDCM model was a fully connected model with the following areas: auditory cortex, putamen/pallidum, and ventral striatum/nucleus accumbens of both hemispheres. The resulting estimated parameters were compared to ordinary resting-state data, without an additional continuous stimulation. Besides reduced connectivity within the basal ganglia, the results indicated a reduced functional connectivity of the reward system, namely the right ventral striatum/nucleus accumbens from and to the basal ganglia and auditory network while listening to rhythmic music. In addition, the right ventral striatum/nucleus accumbens demonstrated also a change in its hemodynamic parameter, reflecting an increased level of activation. These converging results may indicate that the dopaminergic reward system reduces its functional connectivity and relinquishing its constraints on other areas when we listen to rhythmic music.
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http://dx.doi.org/10.3389/fnins.2017.00153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368249PMC
March 2017

Reading in dyslexia across literacy development: A longitudinal study of effective connectivity.

Neuroimage 2017 01 26;144(Pt A):92-100. Epub 2016 Sep 26.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway; Department of Clinical Engineering, Haukeland University Hospital, Bergen, Norway. Electronic address:

Dyslexia is a literacy disorder affecting the efficient acquisition of reading and writing skills. The disorder is neurobiological in origin. Due to its developmental nature, longitudinal studies of dyslexia are of essence. They are, however, relatively scarce. The present study took a longitudinal approach to cortical connectivity of brain imaging data in reading tasks in children with dyslexia and children with typical reading development. The participants were followed with repeated measurements through Pre-literacy (6 years old), Emergent Literacy (8 years old) and Literacy (12 years old) stages, using Dynamic Causal Modelling (DCM) when analysing functional magnetic resonance imaging (fMRI) data. Even though there are a few longitudinal studies on effective connectivity in typical reading, to our knowledge, no studies have previously investigated these issues in relation to dyslexia. We set up a model of a brain reading network involving five cortical regions (inferior frontal gyrus, precentral gyrus, superior temporal gyrus, inferior parietal lobule, and occipito-temporal cortex). Using DCM, connectivity measures were calculated for each connection in the model. These measures were further analysed using factorial ANOVA. The results showed that the difference between groups centred on connections going to and from the inferior frontal gyrus (two connections) and the occipito-temporal cortex (three connections). For all five connections, the typical group showed stable or decreasing connectivity measures. The dyslexia group, on the other hand, showed a marked up-regulation (occipito-temporal connections) or down-regulation (inferior frontal gyrus connections) from 6 years to 8 years, followed by normalization from 8 years to 12 years. We interpret this as a delay in the dyslexia group in developing into the Pre-literacy and Emergent literacy stages. This delay could possibly be detrimental to literacy development. By age 12, there was no statistically significant difference in connectivity between the groups, but differences in literacy skills were still present, and were in fact larger than when measured at younger ages.
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http://dx.doi.org/10.1016/j.neuroimage.2016.09.060DOI Listing
January 2017

Effects of Facial Symmetry and Gaze Direction on Perception of Social Attributes: A Study in Experimental Art History.

Front Hum Neurosci 2016 13;10:452. Epub 2016 Sep 13.

Department of Psychology, University of Oslo Oslo, Norway.

This article explores the possibility of testing hypotheses about art production in the past by collecting data in the present. We call this enterprise "experimental art history". Why did medieval artists prefer to paint Christ with his face directed towards the beholder, while profane faces were noticeably more often painted in different degrees of profile? Is a preference for frontal faces motivated by deeper evolutionary and biological considerations? Head and gaze direction is a significant factor for detecting the intentions of others, and accurate detection of gaze direction depends on strong contrast between a dark iris and a bright sclera, a combination that is only found in humans among the primates. One uniquely human capacity is language acquisition, where the detection of shared or joint attention, for example through detection of gaze direction, contributes significantly to the ease of acquisition. The perceived face and gaze direction is also related to fundamental emotional reactions such as fear, aggression, empathy and sympathy. The fast-track modulator model presents a related fast and unconscious subcortical route that involves many central brain areas. Activity in this pathway mediates the affective valence of the stimulus. In particular, different sub-regions of the amygdala show specific activation as response to gaze direction, head orientation and the valence of facial expression. We present three experiments on the effects of face orientation and gaze direction on the judgments of social attributes. We observed that frontal faces with direct gaze were more highly associated with positive adjectives. Does this help to associate positive values to the Holy Face in a Western context? The formal result indicates that the Holy Face is perceived more positively than profiles with both direct and averted gaze. Two control studies, using a Brazilian and a Dutch database of photographs, showed a similar but weaker effect with a larger contrast between the gaze directions for profiles. Our findings indicate that many factors affect the impression of a face, and that eye contact in combination with face direction reinforce the general impression of portraits, rather than determine it.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020052PMC
http://dx.doi.org/10.3389/fnhum.2016.00452DOI Listing
September 2016

Functional-structural reorganisation of the neuronal network for auditory perception in subjects with unilateral hearing loss: Review of neuroimaging studies.

Hear Res 2016 Feb 19;332:73-79. Epub 2015 Dec 19.

Department of Biological and Medical Psychology, University of Bergen, PB 7807, 5020 Bergen, Norway; Department of Clinical Engineering, Haukeland University Hospital, PB 1400, 5021 Bergen, Norway. Electronic address:

Objective: This paper aims to provide a review of studies using neuroimaging to measure functional-structural reorganisation of the neuronal network for auditory perception after unilateral hearing loss.

Design: A literature search was performed in PubMed. Search criterions were peer reviewed original research papers in English completed by the 11th of March 2015.

Study Sample: Twelve studies were found to use neuroimaging in subjects with unilateral hearing loss. An additional five papers not identified by the literature search were provided by a reviewer. Thus, a total of 17 studies were included in the review.

Results: Four different neuroimaging methods were used in these studies: Functional magnetic resonance imaging (fMRI) (n = 11), diffusion tensor imaging (DTI) (n = 4), T1/T2 volumetric images (n = 2), magnetic resonance spectroscopy (MRS) (n = 1). One study utilized two imaging methods (fMRI and T1 volumetric images).

Conclusion: Neuroimaging techniques could provide valuable information regarding the effects of unilateral hearing loss on both auditory and non-auditory performance. fMRI-studies showing a bilateral BOLD-response in patients with unilateral hearing loss have not yet been followed by DTI studies confirming their microstructural correlates. In addition, the review shows that an auditory modality-specific deficit could affect multi-modal brain regions and their connections.
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http://dx.doi.org/10.1016/j.heares.2015.11.015DOI Listing
February 2016

On the existence of a generalized non-specific task-dependent network.

Front Hum Neurosci 2015 6;9:430. Epub 2015 Aug 6.

Department of Biological and Medical Psychology, University of Bergen Bergen, Norway ; Department of Clinical Engineering, Haukeland University Hospital, Bergen Norway.

In this paper we suggest the existence of a generalized task-related cortical network that is up-regulated whenever the task to be performed requires the allocation of generalized non-specific cognitive resources, independent of the specifics of the task to be performed. We have labeled this general purpose network, the extrinsic mode network (EMN) as complementary to the default mode network (DMN), such that the EMN is down-regulated during periods of task-absence, when the DMN is up-regulated, and vice versa. We conceptualize the EMN as a cortical network for extrinsic neuronal activity, similar to the DMN as being a cortical network for intrinsic neuronal activity. The EMN has essentially a fronto-temporo-parietal spatial distribution, including the inferior and middle frontal gyri, inferior parietal lobule, supplementary motor area, inferior temporal gyrus. We hypothesize that this network is always active regardless of the cognitive task being performed. We further suggest that failure of network up- and down-regulation dynamics may provide neuronal underpinnings for cognitive impairments seen in many mental disorders, such as, e.g., schizophrenia. We start by describing a common observation in functional imaging, the close overlap in fronto-parietal activations in healthy individuals to tasks that denote very different cognitive processes. We now suggest that this is because the brain utilizes the EMN network as a generalized response to tasks that exceeds a cognitive demand threshold and/or requires the processing of novel information. We further discuss how the EMN is related to the DMN, and how a network for extrinsic activity is related to a network for intrinsic activity. Finally, we discuss whether the EMN and DMN networks interact in a common single brain system, rather than being two separate and independent brain systems.
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http://dx.doi.org/10.3389/fnhum.2015.00430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526816PMC
August 2015

Resting-state glutamatergic neurotransmission is related to the peak latency of the auditory mismatch negativity (MMN) for duration deviants: An (1)H-MRS-EEG study.

Psychophysiology 2015 Sep 27;52(9):1131-9. Epub 2015 Apr 27.

Institute of Psychology, University of Tartu, Tartu, Estonia.

Mismatch negativity (MMN), an ERP elicited by a deviant stimulus in a train of standard stimuli, has been suggested to be associated to glutamatergic neurotransmission, mediated by glutamatergic NMDA receptors. In this study, we examined the relationship between interindividual variation of (1)H-MRS-measured glutamate+glutamine (Glx) in the superior temporal gyrus and MMN for duration and frequency deviants in 19 healthy young adults (9 male). We found a significant relationship between the peak latency of the duration-MMN peak and creatine-scaled Glx (p = .0003, η(2)  = .43), with increased Glx level being associated to earlier peak of the duration-MMN (r = -.63). In contrast, the amplitude of the duration-MMN was not related to Glx. There was no significant relationship between Glx and the frequency-MMN. The present study is the first to demonstrate that interindividual variation in the glutamatergic neurotransmission affects the MMN response in healthy individuals.
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http://dx.doi.org/10.1111/psyp.12445DOI Listing
September 2015