Hypoactivation of the language network during auditory imagery contributes to hallucinations in Schizophrenia.

Auditory verbal hallucinations (AVHs) involve perceptions, often voices, in the absence of external stimuli, and rank among the most common symptoms of schizophrenia. Metrical stress evaluation requires determination of the stronger syllable in words, and therefore requires auditory imagery, of interest for investigation of hallucinations in schizophrenia. The current functional magnetic resonance imaging study provides an updated whole-brain network analysis of a previously published study on metrical stress, which showed reduced directed connections between Broca's and Wernicke's regions of interest (ROIs) for hallucinations. Three functional brain networks were extracted, with the language network (LN) showing an earlier and shallower blood-oxygen-level dependent (BOLD) response for hallucinating patients, in the auditory imagery condition only (the reduced activation for hallucinations observed in the original ROI-based results were not specific to the imagery condition). This suggests that hypoactivation of the LN during internal auditory imagery may contribute to the propensity to hallucinate. This accords with cognitive accounts holding that an impaired balance between internal and external linguistic processes (underactivity in networks involved in internal auditory imagery and overactivity in networks involved in speech perception) contributes to our understanding of the biological underpinnings of hallucinations.

The efficacy of combining cognitive training and noninvasive brain stimulation: A transdiagnostic systematic review and meta-analysis.

Over the past decade, an increasing number of studies investigated the innovative approach of supplementing cognitive training (CT) with noninvasive brain stimulation (NIBS) to increase the effects on outcomes. In this review, we aim to summarize the evidence for this treatment combination. We identified 72 published and unpublished studies (reporting 773 effect sizes), including 2,518 participants from healthy and clinical populations indexed in PubMed, MEDLINE, APA PsycInfo, ProQuest, Web of Science, and https://ClinicalTrials.gov (last search: August 9, 2022) that compared the effects of NIBS combined with CT on cognitive, symptoms, and everyday functioning to CT alone at postintervention and/or follow-up. We performed random-effects meta-analyses with robust variance estimation and assessed risk of bias with the Cochrane ROB tool. Only four studies had low risk of bias in all domains, and many studies lacked standard controls such as keeping the outcome assessor and trainer unaware of the treatment condition. Following sensitivity analyses, only learning/memory robustly improved significantly more when CT was combined with NIBS compared to CT only (g = 0.18, 95% CI [0.07, 0.29]) at postintervention, but not in the long term. The effect was small and limited by substantial heterogeneity. The other seven cognitive outcome domains, symptoms, and everyday functioning did not benefit from adding NIBS to CT. Given the methodological limitation of prior studies, more high-quality trials that focus on the potential of combining NIBS and CT to enhance benefits in everyday functioning in the short and long term are needed to evaluate whether combining NIBS and CT is relevant for clinical practice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Hallucinations in Hearing Impairment: How Informed Are Clinicians?

BACKGROUND AND HYPOTHESIS: Patients with hearing impairment (HI) may experience hearing sounds without external sources, ranging from random meaningless noises (tinnitus) to music and other auditory hallucinations (AHs) with meaningful qualities. To ensure appropriate assessment and management, clinicians need to be aware of these phenomena. However, sensory impairment studies have shown that such clinical awareness is low. STUDY DESIGN: An online survey was conducted investigating awareness of AHs among clinicians and their opinions about these hallucinations. STUDY RESULTS: In total, 125 clinicians (68.8% audiologists; 18.4% Ear-Nose-Throat [ENT] specialists) across 10 countries participated in the survey. The majority (96.8%) was at least slightly aware of AHs in HI. About 69.6% of participants reported encountering patients with AHs less than once every 6 months in their clinic. Awareness was significantly associated with clinicians' belief that patients feel anxious about their hallucinations (ß = .018, t(118) = 2.47, P < .01), their belief that clinicians should be more aware of these hallucinations (ß =.018, t(118) = 2.60, P < .01), and with confidence of clinicians in their skills to assess them (ß = .017, t(118) = 2.63, P < .01). Clinicians felt underequipped to treat AHs (Median = 31; U = 1838; PFDRadj < .01). CONCLUSIONS: Awareness of AHs among the surveyed clinicians was high. Yet, the low frequency of encounters with hallucinating patients and their belief in music as the most commonly perceived sound suggest unreported cases. Clinicians in this study expressed a lack of confidence regarding the assessment and treatment of AHs and welcome more information.

Paracingulate Sulcus Length and Cortical Thickness in Schizophrenia Patients With and Without a Lifetime History of Auditory Hallucinations.

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.

Time varying dynamics of hallucinations in clinical and non-clinical voice-hearers.

Auditory verbal hallucinations (AVH) are frequently associated with psychotic disorders, yet also occur in non-clinical voice-hearers. AVH in this group are similar to those within clinical voice-hearers in terms of several phenomenological aspects, but non-clinical voice-hearers report to have more control over their AVH and attribute less emotional valence to them. These dissimilarities may stem from differences on the neurobiological level, as it is still under debate whether the mechanisms involved in AVH are the same in clinical and non-clinical voice-hearers. In this study, 21 clinical and 21 non-clinical voice-hearers indicated the onset and offsets of AVH during an fMRI scan. Using a method called leading eigenvector dynamics analysis (LEiDA), we examined time-varying dynamics of functional connectivity involved in AVH with a sub-second temporal resolution. We assessed differences between groups, and between hallucination and rest periods in dwell time, switching frequency, probability of occurrence, and transition probabilities of nine recurrent states of functional connectivity with a permutation ANOVA. Deviations in dwell times, switching frequencies, and switch probabilities in the hallucination period indicated more erratic dynamics during this condition regardless of their clinical status. Post-hoc analyses of the dwell times exhibited the most distinct differences between the rest and hallucination condition for the non-clinical sample, suggesting stronger differences between the two conditions in this group. Overall, these findings suggest that the neurobiological mechanisms involved in AVH are similar in clinical and non-clinical individuals.

Extended FNAME performance is preserved in subjective cognitive decline but highly affected in amnestic mild cognitive impairment.

OBJECTIVE: The cognitive characterization of Alzheimer's disease risk states, such as amnestic mild cognitive impairment (aMCI) and subjective cognitive decline (SCD), is fundamental for timely diagnosis and interventions. The Face Name Associative Memory Exam (FNAME) is sensitive to early Alzheimer's disease brain changes, and an extended version captures a fuller range of associative memory abilities. We aimed to assess group effects in the extended FNAME in older adults with SCD, aMCI, and older adult controls (CON). METHOD: Two concurrently created versions of the extended FNAME were used to test three groups of older adults (CON = 35, SCD = 37, aMCI = 31) at two sites (Mexico = 59, Netherlands = 44). Extended FNAME memory abilities were analyzed in five analyses of variance. Group and site were considered as independent variables. For the recall ability, subtest levels were entered as a within-subject variable. The remaining abilities (Face Recognition, Name Recognition, Spontaneous Name Recall, and Face-Name Matching) were analyzed in independent models. RESULTS: In all models, the main effect for group was significant with large effect sizes, driven by a worse performance of aMCI participants. No significant differences were found between SCD and CON. The main effect for site was only significant in Face Recognition. CONCLUSIONS: The worse performance of aMCI in the extended FNAME implies an impairment in associative memory abilities beyond recall. The similar performance of CON and SCD might be explained by the recruitment of SCD participants that did not spontaneously seek help for memory decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Benchmarking the effects of transcranial temporal interference stimulation (tTIS) in humans.

Deep brain stimulation (DBS) provides clinical benefits for several neurological and psychiatric conditions. By overcoming the limitations and risks of conventional DBS, transcranial temporal interference stimulation (tTIS) has the potential to offer non-invasive stimulation of deep brain regions. However, research that investigates the efficacy of tTIS is limited to animal studies or computer simulations and its capability to modulate neural oscillations in humans has not been demonstrated so far. The method of tTIS is hypothesized to elicit its effects via neural entrainment, corresponding to the supposed mechanism of action underlying transcranial alternating current stimulation (tACS), another, more established non-invasive brain stimulation technique. Physiological effects of tACS are well established for cortical brain oscillations, but not for deep brain structures. In particular, aftereffects on the power of parieto-occipital alpha oscillations have been shown repeatedly. In a first attempt to test the efficacy of tTIS in the human brain, the current study thus seeks to compare the effects of tTIS to the well-studied aftereffect of tACS in the cortex. To investigate this research question, the current study compared MEG-recorded brain activity during a simple visual change detection task in 34 healthy subjects pre- and post-tTIS. Additionally, the effects of tTIS were contrasted to conventional tACS and a control stimulation. We expected that the parieto-occipital α-power will increase after tTIS and tACS, in contrast to the control stimulation. Overall, no difference between the experimental groups (tTIS, tACS and control stimulation) were found regarding the source-projected increase in α-power. Based on the results of the study two hypothesis can be made: tTIS, tACS and the control stimulation condition don't have an effect on human brain oscillations in the α-band, or, any experimental conditions of the current study can modulate brain oscillations in the α-band. Both hypotheses emphasize the importance of further studies investigating different carrier frequencies, and the comparison to sham stimulation.

Causal connectivity from right DLPFC to IPL in schizophrenia patients: a pilot study.

Abnormal function and connectivity of the fronto-parietal network (FPN) have been documented in patients with schizophrenia, but studies are correlational. We applied repetitive transcranial magnetic stimulation (rTMS) to the dorso-lateral prefrontal cortex (DLPFC) and observed causal connectivity to the inferior parietal lobe (IPL). We hypothesized that patients with schizophrenia would have lower activation and slower reaction in the IPL following DLPFC stimulation. Thirteen patients with schizophrenia (SZ) and fourteen healthy controls subjects (HC) underwent rTMS at 10 Hz to the right DLPFC. Simultaneously, we measured brain activation in the IPL, represented as oxygenized hemoglobin (HbO) levels, using functional near-infrared spectroscopy (fNIRS). rTMS consisted of 20 trains of impulses at 10 Hz for 3 seconds, and 60 seconds waiting time. Using NIRSLab software, GLM was applied to estimate both hemodynamic response function (HRF) and its derivative. Following TMS to the DLPFC, SZ showed a smaller decrease in HbO levels in the bilateral IPL than HC (p = 0.05). Timecourse analysis revealed an immediate decrease in parietal HbO levels in HC, but not in SZ. This difference was significant (at a threshold level of p ≤ 0.05, with Bonferroni correction) for several time segments and channels in both rights and left IPL. Our findings suggest abnormal fronto-temporal connectivity in patients with schizophrenia, beyond a mere decrease or slowing of information processing. This is in line with the hypothesis of reduced fronto-parietal inhibition in schizophrenia.

Planning in amnestic mild cognitive impairment: an fMRI study.

INTRODUCTION: The memory impairment that is characteristic of amnestic mild cognitive impairment (aMCI) is often accompanied by difficulties in executive functioning, including planning. Though planning deficits in aMCI are well documented, their neural correlates are largely unknown, and have not yet been investigated with functional magnetic resonance imaging (fMRI). OBJECTIVES: The aim of this study was to: (1) identify differences in brain activity and connectivity during planning between people with aMCI and cognitively healthy older adults, and (2) find whether planning-related activity and connectivity are associated with cognitive performance and symptoms of apathy. METHODS: Twenty-five people with aMCI and 15 cognitively healthy older adults performed a visuospatial planning task (Tower of London; ToL) during fMRI. Task-related brain activation, spatial maps of task-related independent components, and seed-to-voxel functional connectivity were compared between the two groups and regressed against measures of executive functions (Trail Making Test difference score, TMT B-A; Digit Symbol Substitution Test, DSST), delayed recall (Rey Auditory Verbal Learning Test), and apathy (Apathy Evaluation Scale). RESULTS: People with aMCI scored lower on task-switching (TMT B-A), working memory (DSST), and planning (ToL). During planning, people with aMCI had less activation in the bilateral anterior calcarine sulcus/cuneus, the bilateral temporal cortices, the left precentral gyrus, the thalamus, and the right cerebellum. Across all participants, higher planning-related activity in the supplementary motor area, the retrosplenial cortex and surrounding areas, and the right temporal cortex was related to better delayed recall. There were no between-group differences in functional connectivity, nor were there any associations between connectivity and cognition. We also did not find any associations between brain activity or connectivity and apathy. CONCLUSION: Impaired planning in people with aMCI appears to be accompanied by lower activation in a diffuse cortico-thalamic network. Across all participants, higher planning-related activity in parieto-occipital, temporal, and frontal areas was related to better memory performance. The results point to the relevance of planning deficits for understanding aMCI and extend its clinical and neurobiological signature.

Interindividual variability of electric fields during transcranial temporal interference stimulation (tTIS).

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive brain stimulation technique for electrical stimulation of neurons at depth. Deep brain regions are generally small in size, making precise targeting a necessity. The variability of electric fields across individual subjects resulting from the same tTIS montages is unknown so far and may be of major concern for precise tTIS targeting. Therefore, the aim of the current study is to investigate the variability of the electric fields due to tTIS across 25 subjects. To this end, the electric fields of different electrode montages consisting of two electrode pairs with different center frequencies were simulated in order to target selected regions-of-interest (ROIs) with tTIS. Moreover, we set out to compare the electric fields of tTIS with the electric fields of conventional tACS. The latter were also based on two electrode pairs, which, however, were driven in phase at a common frequency. Our results showed that the electric field strengths inside the ROIs (left hippocampus, left motor area and thalamus) during tTIS are variable on single subject level. In addition, tTIS stimulates more focally as compared to tACS with much weaker co-stimulation of cortical areas close to the stimulation electrodes. Electric fields inside the ROI were, however, comparable for both methods. Overall, our results emphasize the potential benefits of tTIS for the stimulation of deep targets, over conventional tACS. However, they also indicate a need for individualized stimulation montages to leverage the method to its fullest potential.

Neuroanatomy of the grey seal brain: bringing pinnipeds into the neurobiological study of vocal learning.

Comparative animal studies of complex behavioural traits, and their neurobiological underpinnings, can increase our understanding of their evolution, including in humans. Vocal learning, a potential precursor to human speech, is one such trait. Mammalian vocal learning is under-studied: most research has either focused on vocal learning in songbirds or its absence in non-human primates. Here, we focus on a highly promising model species for the neurobiology of vocal learning: grey seals (Halichoerus grypus). We provide a neuroanatomical atlas (based on dissected brain slices and magnetic resonance images), a labelled MRI template, a three-dimensional model with volumetric measurements of brain regions, and histological cortical stainings. Four main features of the grey seal brain stand out: (i) it is relatively big and highly convoluted; (ii) it hosts a relatively large temporal lobe and cerebellum; (iii) the cortex is similar to that of humans in thickness and shows the expected six-layered mammalian structure; (iv) there is expression of FoxP2 present in deeper layers of the cortex; FoxP2 is a gene involved in motor learning, vocal learning, and spoken language. Our results could facilitate future studies targeting the neural and genetic underpinnings of mammalian vocal learning, thus bridging the research gap from songbirds to humans and non-human primates. Our findings are relevant not only to vocal learning research but also to the study of mammalian neurobiology and cognition more in general. This article is part of the theme issue 'Vocal learning in animals and humans'.

Improving cognition in severe mental illness by combining cognitive remediation and transcranial direct current stimulation: study protocol for a pragmatic randomized controlled pilot trial (HEADDSET).

BACKGROUND: A fundamental challenge for many people with severe mental illness (SMI) is how to deal with cognitive impairments. Cognitive impairments are common in this population and limit daily functioning. Moreover, neural plasticity in people with SMI appears to be reduced, a factor that might hinder newly learned cognitive skills to sustain. The objective of this pilot trial is to investigate the effects of cognitive remediation (CR) on cognitive and daily functioning in people dependent on residential settings. In addition, transcranial direct current stimulation (tDCS) is used to promote neural plasticity. It is expected that the addition of tDCS can enhance learning and will result in longer-lasting improvements in cognitive and daily functioning. METHODS: This is a pragmatic, triple-blinded, randomized, sham-controlled, pilot trial following a non-concurrent multiple baseline design with the participants serving as their own control. We will compare (1) CR to treatment as usual, (2) active/sham tDCS+CR to treatment as usual, and (3) active tDCS+CR to sham tDCS+CR. Clinical relevance, feasibility, and acceptability of the use of CR and tDCS will be evaluated. We will recruit 26 service users aged 18 years or older, with a SMI and dependent on residential facilities. After a 16-week waiting period (treatment as usual), which will serve as a within-subject control condition, participants will be randomized to 16 weeks of twice weekly CR combined with active (N = 13) or sham tDCS (N = 13). Cognitive, functional, and clinical outcome assessments will be performed at baseline, after the control (waiting) period, directly after treatment, and 6-months post-treatment. DISCUSSION: The addition of cognitive interventions to treatment as usual may lead to long-lasting improvements in the cognitive and daily functioning of service users dependent on residential facilities. This pilot trial will evaluate whether CR on its own or in combination with tDCS can be a clinically relevant addition to further enhance recovery. In case the results indicate that cognitive performance can be improved with CR, and whether or not tDCS will lead to additional improvement, this pilot trial will be extended to a large randomized multicenter study. TRIAL REGISTRATION: Dutch Trial Registry NL7954 . Prospectively registered on August 12, 2019.

Similar EEG Activity Patterns During Experimentally-Induced Auditory Illusions and Veridical Perceptions.

Hallucinations and illusions are two instances of perceptual experiences illustrating how perception might diverge from external sensory stimulations and be generated or altered based on internal brain states. The occurrence of these phenomena is not constrained to patient populations. Similar experiences can be elicited in healthy subjects by means of suitable experimental procedures. Studying the neural mechanisms underlying these experiences not only has the potential to expand our understanding of the brain's perceptual machinery but also of how it might get impaired. In the current study, we employed an auditory signal detection task to induce auditory illusions by presenting speech snippets at near detection threshold intensity embedded in noise. We investigated the neural correlates of auditory false perceptions by examining the EEG activity preceding the responses in speech absent (false alarm, FA) trials and comparing them to speech present (hit) trials. The results of the comparison of event-related potentials (ERPs) in the activation period vs. baseline revealed the presence of an early negativity (EN) and a late positivity (LP) similar in both hits and FAs, which were absent in misses, correct rejections (CR) and control button presses (BPs). We postulate that the EN and the LP might represent the auditory awareness negativity (AAN) and centro-parietal positivity (CPP) or P300, respectively. The event-related spectral perturbations (ERSPs) exhibited a common power enhancement in low frequencies (<4 Hz) in hits and FAs. The low-frequency power enhancement has been frequently shown to be accompanied with P300 as well as separately being a marker of perceptual awareness, referred to as slow cortical potentials (SCP). Furthermore, the comparison of hits vs. FAs showed a significantly higher LP amplitude and low frequency power in hits compared to FAs. Generally, the observed patterns in the present results resembled some of the major neural correlates associated with perceptual awareness in previous studies. Our findings provide evidence that the neural correlates associated with conscious perception, can be elicited in similar ways in both presence and absence of externally presented sensory stimuli. The present findings did not reveal any pre-stimulus alpha and beta modulations distinguishing conscious vs. unconscious perceptions.

White matter alterations in glaucoma and monocular blindness differ outside the visual system.

The degree to which glaucoma has effects in the brain beyond the eye and the visual pathways is unclear. To clarify this, we investigated white matter microstructure (WMM) in 37 tracts of patients with glaucoma, monocular blindness, and controls. We used brainlife.io for reproducibility. White matter tracts were subdivided into seven categories ranging from those primarily involved in vision (the visual white matter) to those primarily involved in cognition and motor control. In the vision tracts, WMM was decreased as measured by fractional anisotropy in both glaucoma and monocular blind subjects compared to controls, suggesting neurodegeneration due to reduced sensory inputs. A test-retest approach was used to validate these results. The pattern of results was different in monocular blind subjects, where WMM properties increased outside the visual white matter as compared to controls. This pattern of results suggests that whereas in the monocular blind loss of visual input might promote white matter reorganization outside of the early visual system, such reorganization might be reduced or absent in glaucoma. The results provide indirect evidence that in glaucoma unknown factors might limit the reorganization as seen in other patient groups following visual loss.

Widespread white matter aberration is associated with the severity of apathy in amnestic Mild Cognitive Impairment: Tract-based spatial statistics analysis.

Apathy is recognized as a prevalent behavioral symptom of amnestic Mild Cognitive Impairment (aMCI). In aMCI, apathy is associated with an increased risk and increases the risk of progression to Alzheimer's Disease (AD). Previous DTI study in aMCI showed that apathy has been associated with white matter alterations in the cingulum, middle and inferior longitudinal fasciculus, fornix, and uncinate fasciculus. However, the underlying white matter correlates associated with apathy in aMCI are still unclear. We investigated this relationship using whole-brain diffusion tensor imaging (DTI). Twenty-nine aMCI patients and 20 matched cognitively healthy controls were included. Apathy severity was assessed using the Apathy Evaluation Scale Clinician version. We applied the tract-based spatial statistics analyses to DTI parameters: fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity to investigate changes in white matter pathways associated with the severity of apathy. No significant difference was found in any of the DTI parameters between aMCI and the control group. In aMCI, higher severity of apathy was associated with lower FA in various white matter pathways including the left anterior part of inferior fronto-occipital fasciculus/uncinate fasciculus, genu and body of the corpus callosum, superior and anterior corona radiata, anterior thalamic radiation of both hemispheres and in the right superior longitudinal fasciculus/anterior segment of arcuate fasciculus (p < .05, TFCE-corrected) after controlling for age, gender and GDS non-apathy. A trend association was observed in the right posterior corona radiata and corticospinal tract/internal capsule, and bilateral forceps minor (p < .065, TFCE-corrected). In conclusion, in aMCI, severity of apathy is associated with aberrant white matter integrity in widely distributed pathways, within and between hemispheres.

Insight does not come at random: Individual gray matter networks relate to clinical and cognitive insight in schizophrenia.

BACKGROUND: Impaired clinical and cognitive insight are prevalent in schizophrenia and relate to poorer outcome. Good insight has been suggested to depend on social cognitive and metacognitive abilities requiring global integration of brain signals. Impaired insight has been related to numerous focal gray matter (GM) abnormalities distributed across the brain suggesting dysconnectivity at the global level. In this study, we test whether global integration deficiencies reflected in gray matter network connectivity underlie individual variations in insight. METHODS: We used graph theory to examine whether individual GM-network metrics relate to insight in patients with a psychotic disorder (n = 114). Clinical insight was measured with the Schedule for the Assessment of Insight-Expanded and item G12 of the Positive and Negative Syndrome Scale, and cognitive insight with the Beck Cognitive Insight Scale. Individual GM-similarity networks were created from GM-segmentations of T1-weighted MRI-scans. Graph metrics were calculated using the Brain Connectivity Toolbox. RESULTS: Networks of schizophrenia patients with poorer clinical insight showed less segregation (i.e. clustering coefficient) into specialized subnetworks at the global level. Schizophrenia patients with poorer cognitive insight showed both less segregation and higher connectedness (i.e. lower path length) of their brain networks, making their network topology more "random". CONCLUSIONS: Our findings suggest less segregated processing of information in patients with poorer cognitive and clinical insight, in addition to higher connectedness in patients with poorer cognitive insight. The ability to take a critical perspective on one's symptoms (clinical insight) or views (cognitive insight) might depend especially on segregated specialized processing within distinct subnetworks.

Spontaneous brain activity underlying auditory hallucinations in the hearing-impaired.

Auditory hallucinations, the perception of a sound without a corresponding source, are common in people with hearing impairment. Two forms can be distinguished: simple (i.e., tinnitus) and complex hallucinations (speech and music). Little is known about the precise mechanisms underlying these types of hallucinations. Here we tested the assumption that spontaneous activity in the auditory pathways, following deafferentation, underlies these hallucinations and is related to their phenomenology. By extracting (fractional) Amplitude of Low Frequency Fluctuation [(f)ALFF] scores from resting state fMRI of 18 hearing impaired patients with complex hallucinations (voices or music), 18 hearing impaired patients with simple hallucinations (tinnitus or murmuring), and 20 controls with normal hearing, we investigated differences in spontaneous brain activity between these groups. Spontaneous activity in the anterior and posterior cingulate cortex of hearing-impaired groups was significantly higher than in the controls. The group with complex hallucinations showed elevated activity in the bilateral temporal cortex including Wernicke's area, while spontaneous activity of the group with simple hallucinations was mainly located in the cerebellum. These results suggest a decrease in error monitoring in both hearing-impaired groups. Spontaneous activity of language-related areas only in complex hallucinations suggests that the manifestation of the spontaneous activity represents the phenomenology of the hallucination. The link between cerebellar activity and simple hallucinations, such as tinnitus, is new and may have consequences for treatment.

Alpha Power and Functional Connectivity in Cognitive Decline: A Systematic Review and Meta-Analysis.

BACKGROUND: Mild cognitive impairment (MCI) is a stage between expected age-related cognitive decline and dementia. Dementias have been associated with changes in neural oscillations across the frequency spectrum, including the alpha range. Alpha is the most prominent rhythm in human EEG and is best detected during awake resting state (RS). Though several studies measured alpha power and synchronization in MCI, findings have not yet been integrated. OBJECTIVE: To consolidate findings on power and synchronization of alpha oscillations across stages of cognitive decline. METHODS: We included studies published until January 2020 that compared power or functional connectivity between 1) people with MCI and cognitively healthy older adults (OA) or people with a neurodegenerative dementia, and 2) people with progressive and stable MCI. Random-effects meta-analyses were performed when enough data was available. RESULTS: Sixty-eight studies were included in the review. Global RS alpha power was lower in AD than in MCI (ES = -0.30; 95% CI = -0.51, -0.10; k = 6), and in MCI than in OA (ES = -1.49; 95% CI = -2.69, -0.29; k = 5). However, the latter meta-analysis should be interpreted cautiously due to high heterogeneity. The review showed lower RS alpha power in progressive than in stable MCI, and lower task-related alpha reactivity in MCI than in OA. People with MCI had both lower and higher functional connectivity than OA. Publications lacked consistency in MCI diagnosis and EEG measures. CONCLUSION: Research indicates that RS alpha power decreases with increasing impairment, and could-combined with measures from other frequency bands-become a biomarker of early cognitive decline.

Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders: a meta-analysis.

BACKGROUND: Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis. METHODS: A PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition. RESULTS: We included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains. CONCLUSIONS: Our results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention).

Abnormal dynamic resting-state brain network organization in auditory verbal hallucination.

Auditory-verbal hallucinations (AVH) are a key symptom of schizophrenia. Recent neuroimaging studies examining dynamic functional connectivity suggest that disrupted dynamic interactions between brain networks characterize complex symptoms in mental illness including schizophrenia. Studying dynamic connectivity may be especially relevant for hallucinations, given their fluctuating phenomenology. Indeed, it remains unknown whether AVH in schizophrenia are directly related to altered dynamic connectivity within and between key brain networks involved in auditory perception and language, emotion processing, and top-down control. In this study, we used dynamic connectivity approaches including sliding window and k-means to examine dynamic interactions among brain networks in schizophrenia patients with and without a recent history of AVH. Dynamic brain network analysis revealed that patients with AVH spent less time in a 'network-antagonistic' brain state where the default mode network (DMN) and the language network were anti-correlated, and had lower probability to switch into this brain state. Moreover, patients with AVH showed a lower connectivity within the language network and the auditory network, and lower connectivity was observed between the executive control and the language networks in certain dynamic states. Our study provides the first neuroimaging evidence of altered dynamic brain networks for understanding neural mechanisms of AVH in schizophrenia. The findings may inform and further strengthen cognitive models of AVH that aid the development of new coping strategies for patients.