A multicenter effectiveness trial of QEEG-informed neurofeedback in ADHD: Replication and treatment prediction.

INTRODUCTION: Quantitative Electroencephalogram-(QEEG-)informed neurofeedback is a method in which standard neurofeedback protocols are assigned, based on individual EEG characteristics in order to enhance effectiveness. Thus far clinical effectiveness data have only been published in a small sample of 21 ADHD patients. Therefore, this manuscript aims to replicate this effectiveness in a new sample of 114 patients treated with QEEG-informed neurofeedback, from a large multicentric dataset and to investigate potential predictors of neurofeedback response. METHODS: A sample of 114 patients were included as a replication sample. Patients were treated with standard neurofeedback protocols (Sensori-Motor-Rhythm (SMR), Theta-Beta (TBR), or Slow Cortical Potential (SCP) neurofeedback), in combination with coaching and sleep hygiene advice. The ADHD Rating Scale (ADHD-RS) and Pittsburgh Sleep Quality Index (PSQI) were assessed at baseline, every 10th session, and at outtake. Holland Sleep Disorder Questionnaire (HSDQ) was assessed at baseline and outtake. Response was defined as ≥25% reduction (R25), ≥50% reduction (R50), and remission. Predictive analyses were focused on predicting remission status. RESULTS: In the current sample, response rates were 85% (R25), 70% (R50), and remission was 55% and clinical effectiveness was not significantly different from the original 2012 sample. Non-remitters exhibited significantly higher baseline hyperactivity ratings. Women who remitted had significantly shorter P300 latencies and boys who remitted had significantly lower iAPF's. DISCUSSION: In the current sample, clinical effectiveness was replicated, suggesting it is possible to assign patients to a protocol based on their individual baseline QEEG to enhance signal-to-noise ratio. Furthermore, remitters had lower baseline hyperactivity scores. Likewise, female remitters had shorter P300 latencies, whereas boys who remitted have a lower iAPF. Our data suggests initial specificity in treatment allocation, yet further studies are needed to replicate the predictors of neurofeedback remission.

Effects of Mindfulness-Based Cognitive Therapy on Body Awareness in Patients with Chronic Pain and Comorbid Depression.

Body awareness has been proposed as one of the major mechanisms of mindfulness interventions, and it has been shown that chronic pain and depression are associated with decreased levels of body awareness. We investigated the effect of Mindfulness-Based Cognitive Therapy (MBCT) on body awareness in patients with chronic pain and comorbid active depression compared to treatment as usual (TAU; N = 31). Body awareness was measured by a subset of the Multidimensional Assessment of Interoceptive Awareness (MAIA) scales deemed most relevant for the population. These included: Noticing, Not-Distracting, Attention Regulation, Emotional Awareness, and Self-Regulation. In addition, pain catastrophizing was measured by the Pain Catastrophizing Scale (PCS). These scales had adequate to high internal consistency in the current sample. Depression severity was measured by the Quick Inventory of Depressive Symptomatology-Clinician rated (QIDS-C16). Increases in the MBCT group were significantly greater than in the TAU group on the "Self-Regulation" and "Not Distracting" scales. Furthermore, the positive effect of MBCT on depression severity was mediated by "Not Distracting." These findings provide preliminary evidence that a mindfulness-based intervention may increase facets of body awareness as assessed with the MAIA in a population of pain patients with depression. Furthermore, they are consistent with a long hypothesized mechanism for mindfulness and emphasize the clinical relevance of body awareness.

4-Hz Transcranial Alternating Current Stimulation Phase Modulates Hearing.

BACKGROUND: Non-invasive brain stimulation with transcranial alternating currents (tACS) has been shown to entrain slow cortical oscillations and thereby influence various aspects of visual perception. Much less is known about its potential effects on auditory perception. OBJECTIVE: In the present study, we apply a novel variant that enables near-equivalent stimulation of both auditory cortices to investigate the causal role of the phase of 4-Hz cortical oscillations for auditory perception. METHODS: We measured detection performance for near-threshold auditory stimuli (4-Hz click trains) that were presented at various moments during ongoing tACS (two synchronous 4-Hz alternating currents applied transcranially to the two cerebral hemispheres). RESULTS: We found that changes in the relative timing of acoustic and electric stimulation cause corresponding perceptual changes that oscillate predominantly at the 4-Hz frequency of the electric stimulation, which is consistent with previous results based on 10-Hz tACS. CONCLUSION: TACS at various frequencies can affect auditory perception. Together with converging previous results based on acoustic stimulation (rather than tACS), this finding implies that fundamental aspects of auditory cognition are mediated by the temporal coherence of sound-induced cortical activity with ongoing cortical oscillations at multiple time scales.

Transcutaneous vagus nerve stimulation boosts associative memory in older individuals.

Direct vagus nerve stimulation (dVNS) is known to improve mood, epilepsy, and memory. Memory improvements have been observed in Alzheimer's disease patients after long-term stimulation. The potential of transcutaneous vagus nerve stimulation (tVNS), a noninvasive alternative to dVNS, to alter memory performance remains unknown. We aimed to investigate the effect of a single-session tVNS on associative memory performance in healthy older individuals. To investigate this, we performed a single-blind sham-controlled randomized crossover pilot study in healthy older individuals (n = 30, 50% female). During the stimulation or sham condition, participants performed an associative face-name memory task. tVNS enhanced the number of hits of the memory task, compared with the sham condition. This effect was specific to the experimental task. Participants reported few side effects. We conclude that tVNS is a promising neuromodulatory technique to improve associative memory performance in older individuals, even after a single session. More research is necessary to investigate its underlying neural mechanisms, the impact of varying stimulation parameters, and its applicability in patients with cognitive decline.

Out of control: evidence for anterior insula involvement in motor impulsivity and reactive aggression.

Inhibiting impulsive reactions while still defending one's vital resources is paramount to functional self-control and successful development in a social environment. However, this ability of successfully inhibiting, and thus controlling one's impulsivity, often fails, leading to consequences ranging from motor impulsivity to aggressive reactions following provocation. Although inhibitory failure represents the underlying mechanism, the neurocognition of social aggression and motor response inhibition have traditionally been investigated in separation. Here, we aimed to directly investigate and compare the neural mechanisms underlying the failure of inhibition across those different modalities of self-control. We used functional imaging to reveal the overlap in neural correlates between failed motor response inhibition (measured by a go/no-go task) and reactive aggression (measured by the Taylor aggression paradigm) in healthy males. The core overlap of neural correlates was located in the anterior insula, suggesting common anterior insula involvement in motor impulsivity as well as reactive aggression. This evidence regarding an overarching role of the anterior insula across different modalities of self-control enables an integrative perspective on insula function and a better integration of cognitive, social and emotional factors into a comprehensive model of impulsivity. Furthermore, it can eventually lead to a better understanding of clinical syndromes involving inhibitory deficits.

Current directions in non-invasive low intensity electric brain stimulation for depressive disorder.

Non-invasive stimulation of the human brain to improve depressive symptoms is increasingly finding its way in clinical settings as a viable form of somatic treatment. Following successful modulation of neural excitability with subsequent antidepressant effects, neural polarization by administrating weak direct currents to the scalp has gained renewed interest. A new wave of basic and clinical studies seems to underscore the potential therapeutic value of direct current stimulation in the treatment of depression. Issues concerning the lack of mechanistic insights into the workings of modifying brain function through neural polarization and how this process translates to its antidepressant properties calls for additional research. The range of its clinical applicability has yet to be established.

Dissecting hemisphere-specific contributions to visual spatial imagery using parametric brain mapping.

In the current study we aimed to empirically test previously proposed accounts of a division of labour between the left and right posterior parietal cortices during visuospatial mental imagery. The representation of mental images in the brain has been a topic of debate for several decades. Although the posterior parietal cortex is involved bilaterally, previous studies have postulated that hemispheric specialisation might result in a division of labour between the left and right parietal cortices. In the current fMRI study, we used an elaborated version of a behaviourally-controlled spatial imagery paradigm, the mental clock task, which involves mental image generation and a subsequent spatial comparison between two angles. By systematically varying the difference between the two angles that are mentally compared, we induced a symbolic distance effect: smaller differences between the two angles result in higher task difficulty. We employed parametrically weighed brain imaging to reveal brain areas showing a graded activation pattern in accordance with the induced distance effect. The parametric difficulty manipulation influenced behavioural data and brain activation patterns in a similar matter. Moreover, since this difficulty manipulation only starts to play a role from the angle comparison phase onwards, it allows for a top-down dissociation between the initial mental image formation, and the subsequent angle comparison phase of the spatial imagery task. Employing parametrically weighed fMRI analysis enabled us to top-down disentangle brain activation related to mental image formation, and activation reflecting spatial angle comparison. The results provide first empirical evidence for the repeatedly proposed division of labour between the left and right posterior parietal cortices during spatial imagery.

The cross-functional role of frontoparietal regions in cognition: internal attention as the overarching mechanism.

Neuroimaging studies have repeatedly reported findings of activation in frontoparietal regions that largely overlap across various cognitive functions. Part of this frontoparietal activation has been interpreted as reflecting attentional mechanisms that can adaptively be directed towards external stimulation as well as internal representations (internal attention), thereby generating the experience of distinct cognitive functions. Nevertheless, findings of material- and task-specific activation in frontal and parietal regions challenge this internal attention hypothesis and have been used to support more modular hypotheses of cognitive function. The aim of this review is twofold: First, it discusses evidence in support of the concept of internal attention and the so-called dorsal attention network (DAN) as its neural source with respect to three cognitive functions (working memory, episodic retrieval, and mental imagery). While DAN activation in all three functions has been separately linked to internal attention, a comprehensive and integrative review has so far been lacking. Second, the review examines findings of material- and process-specific activation within frontoparietal regions, arguing that these results are well compatible with the internal attention account of frontoparietal activation. A new model of cognition is presented, proposing that supposedly different cognitive concepts actually rely on similar attentional network dynamics to maintain, reactivate and newly create internal representations of stimuli in various modalities. Attentional as well as representational mechanisms are assigned to frontal and parietal regions, positing that some regions are implicated in the allocation of attentional resources to perceptual or internal representations, but others are involved in the representational processes themselves.

Brain networks underlying mental imagery of auditory and visual information.

Mental imagery is a complex cognitive process that resembles the experience of perceiving an object when this object is not physically present to the senses. It has been shown that, depending on the sensory nature of the object, mental imagery also involves correspondent sensory neural mechanisms. However, it remains unclear which areas of the brain subserve supramodal imagery processes that are independent of the object modality, and which brain areas are involved in modality-specific imagery processes. Here, we conducted a functional magnetic resonance imaging study to reveal supramodal and modality-specific networks of mental imagery for auditory and visual information. A common supramodal brain network independent of imagery modality, two separate modality-specific networks for imagery of auditory and visual information, and a common deactivation network were identified. The supramodal network included brain areas related to attention, memory retrieval, motor preparation and semantic processing, as well as areas considered to be part of the default-mode network and multisensory integration areas. The modality-specific networks comprised brain areas involved in processing of respective modality-specific sensory information. Interestingly, we found that imagery of auditory information led to a relative deactivation within the modality-specific areas for visual imagery, and vice versa. In addition, mental imagery of both auditory and visual information widely suppressed the activity of primary sensory and motor areas, for example deactivation network. These findings have important implications for understanding the mechanisms that are involved in generation of mental imagery.

Hemispheric Differences within the Fronto-Parietal Network Dynamics Underlying Spatial Imagery.

Spatial imagery refers to the inspection and evaluation of spatial features (e.g., distance, relative position, configuration) and/or the spatial manipulation (e.g., rotation, shifting, reorienting) of mentally generated visual images. In the past few decades, psychophysical as well as functional brain imaging studies have indicated that any such processing of spatially coded information and/or manipulation based on mental images (i) is subject to similar behavioral demands and limitations as in the case of spatial processing based on real visual images, and (ii) consistently activates several nodes of widely distributed cortical networks in the brain. These nodes include areas within both, the dorsal fronto-parietal as well as ventral occipito-temporal visual processing pathway, representing the "what" versus "where" aspects of spatial imagery. We here describe evidence from functional brain imaging and brain interference studies indicating systematic hemispheric differences within the dorsal fronto-parietal networks during the execution of spatial imagery. Importantly, such hemispheric differences and functional lateralization principles are also found in the effective brain network connectivity within and across these networks, with a direction of information flow from anterior frontal/premotor regions to posterior parietal cortices. In an attempt to integrate these findings of hemispheric lateralization and fronto-to-parietal interactions, we argue that spatial imagery constitutes a multifaceted cognitive construct that can be segregated in several distinct mental sub processes, each associated with activity within specific lateralized fronto-parietal (sub) networks, forming the basis of the here proposed dynamic network model of spatial imagery.

Integration of "what" and "where" in frontal cortex during visual imagery of scenes.

Imagination is a key function for many human activities, such as reminiscing, learning, or planning. Unravelling its neuro-biological basis is paramount to grasp the essence of our thoughts. Previous neuroimaging studies have identified brain regions subserving the visualisation of "what?" (e.g. faces or objects) and "where?" (e.g. spatial layout) content of mental images. However, the functional role of a common set of involved regions - the frontal regions - and their interplay with the "what" and "where" regions, has remained largely unspecified. This study combines functional MRI and electroencephalography to examine the full-brain network that underlies the visual imagery of complex scenes and to investigate the spectro-temporal properties of its nodes, especially of the frontal cortex. Our results indicate that frontal regions integrate the "what" and "where" content of our thoughts into one visually imagined scene. We link early synchronisation of anterior theta and beta oscillations to regional activation of right and central frontal cortices, reflecting retrieval and integration of information. These frontal regions orchestrate remote occipital-temporal regions (including calcarine sulcus and parahippocampal gyrus) that encode the detailed representations of the objects, and parietal "where" regions that encode the spatial layout into forming one coherent mental picture. Specifically the mesial superior frontal gyrus appears to have a principal integrative role, as its activity during the visualisation of the scene predicts subsequent performance on the imagery task.

Pain attenuation through mindfulness is associated with decreased cognitive control and increased sensory processing in the brain.

Pain can be modulated by several cognitive techniques, typically involving increased cognitive control and decreased sensory processing. Recently, it has been demonstrated that pain can also be attenuated by mindfulness. Here, we investigate the underlying brain mechanisms by which the state of mindfulness reduces pain. Mindfulness practitioners and controls received unpleasant electric stimuli in the functional magnetic resonance imaging scanner during a mindfulness and a control condition. Mindfulness practitioners, but not controls, were able to reduce pain unpleasantness by 22% and anticipatory anxiety by 29% during a mindful state. In the brain, this reduction was associated with decreased activation in the lateral prefrontal cortex and increased activation in the right posterior insula during stimulation and increased rostral anterior cingulate cortex activation during the anticipation of pain. These findings reveal a unique mechanism of pain modulation, comprising increased sensory processing and decreased cognitive control, and are in sharp contrast to established pain modulation mechanisms.

Dynamic premotor-to-parietal interactions during spatial imagery.

The neurobiological processes underlying mental imagery are a matter of debate and controversy among neuroscientists, cognitive psychologists, philosophers, and biologists. Recent neuroimaging studies demonstrated that the execution of mental imagery activates large frontoparietal and occipitotemporal networks in the human brain. These previous imaging studies, however, neglected the crucial interplay within and across the widely distributed cortical networks of activated brain regions. Here, we combined time-resolved event-related functional magnetic resonance imaging with analyses of interactions between brain regions (functional and effective brain connectivity) to unravel the premotor-parietal dynamics underlying spatial imagery. Participants had to sequentially construct and spatially transform a mental visual object based on either verbal or visual instructions. By concurrently accounting for the full spatiotemporal pattern of brain activity and network connectivity, we functionally segregated an early from a late premotor-parietal imagery network. Moreover, we revealed that the modality-specific information upcoming from sensory brain regions is first sent to the premotor cortex and then to the medial-dorsal parietal cortex, i.e., top-down from the motor to the perceptual pole during spatial imagery. Importantly, we demonstrate that the premotor cortex serves as the central relay station, projecting to parietal cortex at two functionally distinct stages during spatial imagery. Our approach enabled us to disentangle the multicomponential cognitive construct of mental imagery into its different cognitive subelements. We discuss and explicitly assign these mental subprocesses to each of the revealed effective brain connectivity networks and present an integrative neurobiological model of spatial imagery.

Enhanced vividness of mental imagery as a trait marker of schizophrenia?

We assessed the vividness of mental imagery in schizophrenia patients in the context of psychopathology and cognitive abilities. A questionnaire on the vividness of mental imagery (Questionnaire Upon Mental Imagery [QMI]) and a hallucination scale were administered to 50 patients with paranoid schizophrenia. The related perceptual and cognitive skills, general intelligence level, and psychomotor speed were measured as covariates with a battery of performance tests. All measures were statistically compared to a group of 50 age- and sex-matched healthy controls. The schizophrenia group obtained higher values both for vividness of imagery and occurrence of hallucinations. These differences were independent of general intelligence and psychomotor speed and did not correlate with individual psychopathology. The correlation between the hallucination and imagery scales themselves was very low. These results suggest that patients with schizophrenia experience a significantly greater vividness of mental imagery than healthy controls, which does not seem to be an effect of other group differences or individual psychopathology (e.g., frequency of hallucinations). Vividness of mental imagery might thus prove to be an independent trait marker of schizophrenia.

Tracking the mind's image in the brain I: time-resolved fMRI during visuospatial mental imagery.

Mental imagery, the generation and manipulation of mental representations in the absence of sensory stimulation, is a core element of numerous cognitive processes. We investigate the cortical mechanisms underlying imagery and spatial analysis in the visual domain using event-related functional magnetic resonance imaging during the mental clock task. The time-resolved analysis of cortical activation from auditory perception to motor response reveals a sequential activation of the left and right posterior parietal cortex, suggesting that these regions perform distinct functions in this imagery task. This is confirmed by a trial-by-trial analysis of correlations between reaction time and onset, width, and amplitude of the hemodynamic response. These findings pose neurophysiological constraints on cognitive models of mental imagery.

Tracking the mind's image in the brain II: transcranial magnetic stimulation reveals parietal asymmetry in visuospatial imagery.

The functional relevance of brain activity during visuospatial tasks was investigated by combining functional magnetic resonance imaging with unilateral repetitive transcranial magnetic stimulation (rTMS). The cognitive tasks involved visuospatial operations on visually presented and mentally imagined material ("mental clock task"). While visuospatial operations were associated with activation of the intraparietal sulcus region bilaterally, only the group which received rTMS to the right parietal lobe showed an impairment of performance during and immediately after rTMS. This functional parietal asymmetry might indicate a capacity of the right parietal lobe to compensate for a temporary suppression of the left. This is compatible with current theories of spatial hemineglect and constitutes a constraint for models of distributed information processing in the parietal lobes.