Odor cueing of declarative memories during sleep enhances coordinated spindles and slow oscillations.

Long-term memories are formed by repeated reactivation of newly encoded information during sleep. This process can be enhanced by using memory-associated reminder cues like sounds and odors. While auditory cueing has been researched extensively, few electrophysiological studies have exploited the various benefits of olfactory cueing. We used high-density electroencephalography in an odor-cueing paradigm that was designed to isolate the neural responses specific to the cueing of declarative memories. We show widespread cueing-induced increases in the duration and rate of sleep spindles. Higher spindle rates were most prominent over centro-parietal areas and largely overlapping with a concurrent increase in the amplitude of slow oscillations (SOs). Interestingly, greater SO amplitudes were linked to a higher likelihood of coupling a spindle and coupled spindles expressed during cueing were more numerous in particular around SO up states. We thus identify temporally and spatially coordinated enhancements of sleep spindles and slow oscillations as a candidate mechanism behind cueing-induced memory processing. Our results further demonstrate the feasibility of studying neural activity patterns linked to such processing using olfactory cueing during sleep.

Functional MRI Neurofeedback Outperforms Cognitive Behavioral Therapy for Reducing Tinnitus Distress: A Prospective Randomized Clinical Trial.

Background Cognitive behavioral therapy (CBT) is the current standard treatment for chronic severe tinnitus; however, preliminary evidence suggests that real-time functional MRI (fMRI) neurofeedback therapy may be more effective. Purpose To compare the efficacy of real-time fMRI neurofeedback against CBT for reducing chronic tinnitus distress. Materials and Methods In this prospective controlled trial, participants with chronic severe tinnitus were randomized from December 2017 to December 2021 to receive either CBT (CBT group) for 10 weekly group sessions or real-time fMRI neurofeedback (fMRI group) individually during 15 weekly sessions. Change in the Tinnitus Handicap Inventory (THI) score (range, 0-100) from baseline to 6 or 12 months was assessed. Secondary outcomes included four quality-of-life questionnaires (Beck Depression Inventory, Pittsburgh Sleep Quality Index, State-Trait Anxiety Inventory, and World Health Organization Disability Assessment Schedule). Questionnaire scores between treatment groups and between time points were assessed using repeated measures analysis of variance and the nonparametric Wilcoxon signed rank test. Results The fMRI group included 21 participants (mean age, 49 years ± 11.4 [SD]; 16 male participants) and the CBT group included 22 participants (mean age, 53.6 years ± 8.8; 16 male participants). The fMRI group showed a greater reduction in THI scores compared with the CBT group at both 6 months (mean score change, -28.21 points ± 18.66 vs -12.09 points ± 18.86; P = .005) and 12 months (mean score change, -30 points ± 25.44 vs -4 points ± 17.2; P = .01). Compared with baseline, the fMRI group showed improved sleep (mean score, 8.62 points ± 4.59 vs 7.25 points ± 3.61; P = .006) and trait anxiety (mean score, 44 points ± 11.5 vs 39.84 points ± 10.5; P = .02) at 1 month and improved depression (mean score, 13.71 points ± 9.27 vs 6.53 points ± 5.17; P = .01) and general functioning (mean score, 24.91 points ± 17.05 vs 13.06 points ± 10.1; P = .01) at 6 months. No difference in these metrics over time was observed for the CBT group (P value range, .14 to >.99). Conclusion Real-time fMRI neurofeedback therapy led to a greater reduction in tinnitus distress than the current standard treatment of CBT. ClinicalTrials.gov registration no.: NCT05737888; Swiss Ethics registration no.: BASEC2017-00813 © RSNA, 2024 Supplemental material is available for this article.

Author Correction: Closed-loop brain training: the science of neurofeedback.

In this article, the affiliation for Mohit Rana was incorrectly listed as the Institute for Biological and Medical Engineering, Department of Psychiatry, and Section of Neuroscience, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860 Hernán Briones, piso 2, Macul 782-0436, Santiago, Chile. The listed affiliation should have been the following: Departamento de Psiquiatría, Escuela de Medicina, Centro Interdisciplinario de Neurociencias, Pontificia Universidad Católica de Chile, Santiago, Chile; and the Laboratory for Brain-Machine Interfaces and Neuromodulation, Pontificia Universidad Católica de Chile, Santiago, Chile. An acknowledgement to Mohit Rana's funding source was also missing. The following sentence should have been included in the acknowledgments section: M.R. is supported by a Fondecyt postdoctoral fellowship (project no. 3100648).

Closed-loop brain training: the science of neurofeedback.

Neurofeedback is a psychophysiological procedure in which online feedback of neural activation is provided to the participant for the purpose of self-regulation. Learning control over specific neural substrates has been shown to change specific behaviours. As a progenitor of brain-machine interfaces, neurofeedback has provided a novel way to investigate brain function and neuroplasticity. In this Review, we examine the mechanisms underlying neurofeedback, which have started to be uncovered. We also discuss how neurofeedback is being used in novel experimental and clinical paradigms from a multidisciplinary perspective, encompassing neuroscientific, neuroengineering and learning-science viewpoints.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

Involvement of top-down networks in the perception of facial emotions: A magnetoencephalographic investigation.

Conscious perception of the emotional valence of faces has been proposed to involve top-down and bottom-up information processing. Yet, the underlying neuronal mechanisms of these two processes and the implementation of their cooperation is still unclear. According to the global workspace model, higher level cognitive processing of visual emotional stimuli relies on both bottom-up and top-down processing. Using masking stimuli in a visual backward masking paradigm with delays at the perceptual threshold, at which stimuli can only partly be detected, suggests that only top-down processing differs between correctly and incorrectly perceived stimuli, while bottom-up visual processing is not compromised and comparable for both conditions. Providing visual stimulation near the perceptual threshold in the backward masking paradigm thus enabled us to compare differences in top-down modulation of the visual information of correctly and incorrectly recognized facial emotions in 12 healthy individuals using magnetoencephalography (MEG). For correctly recognized facial emotions, we found a right-hemispheric fronto-parietal network oscillating in the high-beta and low-gamma band and exerting top-down control as determined by the causality measure of phase slope index (PSI). In contrast, incorrect recognition was associated with enhanced coupling in the gamma band between left frontal and right parietal regions. Our results indicate that the perception of emotional face stimuli relies on the right-hemispheric dominance of synchronized fronto-parietal gamma-band activity.

Spatial characteristics of spontaneous and stimulus-induced individual functional connectivity networks in severe disorders of consciousness.

BACKGROUND: Functional connectivity (fcMRI) analyses of resting state functional magnetic resonance imaging (fMRI) data revealed substantial differences between states of consciousness. The underlying cause-effect linkage, however, remains unknown to the present day. The aim of this study was to examine the relationship between fcMRI measures and Disorders of Consciousness (DOC) in resting state and under adequate stimulation. METHODS AND FINDINGS: fMRI data from thirteen patients with unresponsive wakefulness syndrome, eight patients in minimally conscious state, and eleven healthy controls were acquired in rest and during the application of nociceptive and emotional acoustic stimuli. We compared spatial characteristics and anatomical topography of seed-based fcMRI networks on group and individual levels. The anatomical topography of fcMRI networks of patients was altered in all three conditions as compared with healthy controls. Spread and distribution of individual fcMRI networks, however, differed significantly between patients and healthy controls in stimulation conditions only. The exploration of individual metric values identified two patients whose spatial metrics did not deviate from metric distributions of healthy controls in a statistically meaningful manner. CONCLUSIONS: These findings suggest that the disturbance of consciousness in DOC is related to deficits in global topographical network organization rather than a principal inability to establish long-distance connections. In addition, the results question the claim that task-free measurements are particularly valuable as a tool for individual diagnostics in severe neurological disorders. Further studies comparing connectivity indices with outcome of DOC patients are needed to determine the clinical relevance of spatial metrics and stimulation paradigms for individual diagnosis, prognosis and treatment in DOC.

Learned control of inter-hemispheric connectivity: Effects on bimanual motor performance.

Bimanual movements involve the interactions between both primary motor cortices. These interactions are assumed to involve phase-locked oscillatory brain activity referred to as inter-hemispheric functional coupling. So far, inter-hemispheric functional coupling has been investigated as a function of motor performance. These studies report mostly a negative correlation between the performance in motor tasks and the strength of functional coupling. However, correlation might not reflect a causal relationship. To overcome this limitation, we opted for an alternative approach by manipulating the strength of inter-hemispheric functional coupling and assessing bimanual motor performance as a dependent variable. We hypothesize that an increase/decrease of functional coupling deteriorates/facilitates motor performance in an out-of-phase bimanual finger-tapping task. Healthy individuals were trained to volitionally regulate functional coupling in an operant conditioning paradigm using real-time magnetoencephalography neurofeedback. During operant conditioning, two discriminative stimuli were associated with upregulation and downregulation of functional coupling. Effects of training were assessed by comparing motor performance prior to (pre-test) and after the training (post-test). Participants receiving contingent feedback learned to upregulate and downregulate functional coupling. Comparing motor performance, as indexed by the ratio of tapping speed for upregulation versus downregulation trials, no change was found in the control group between pre- and post-test. In contrast, the group receiving contingent feedback evidenced a significant decrease of the ratio implicating lower tapping speed with stronger functional coupling. Results point toward a causal role of inter-hemispheric functional coupling for the performance in bimanual tasks. Hum Brain Mapp 38:4353-4369, 2017. © 2017 Wiley Periodicals, Inc.

How feedback, motor imagery, and reward influence brain self-regulation using real-time fMRI.

The learning process involved in achieving brain self-regulation is presumed to be related to several factors, such as type of feedback, reward, mental imagery, duration of training, among others. Explicitly instructing participants to use mental imagery and monetary reward are common practices in real-time fMRI (rtfMRI) neurofeedback (NF), under the assumption that they will enhance and accelerate the learning process. However, it is still not clear what the optimal strategy is for improving volitional control. We investigated the differential effect of feedback, explicit instructions and monetary reward while training healthy individuals to up-regulate the blood-oxygen-level dependent (BOLD) signal in the supplementary motor area (SMA). Four groups were trained in a two-day rtfMRI-NF protocol: GF with NF only, GF,I with NF + explicit instructions (motor imagery), GF,R with NF + monetary reward, and GF,I,R with NF + explicit instructions (motor imagery) + monetary reward. Our results showed that GF increased significantly their BOLD self-regulation from day-1 to day-2 and GF,R showed the highest BOLD signal amplitude in SMA during the training. The two groups who were instructed to use motor imagery did not show a significant learning effect over the 2 days. The additional factors, namely motor imagery and reward, tended to increase the intersubject variability in the SMA during the course of training. Whole brain univariate and functional connectivity analyses showed common as well as distinct patterns in the four groups, representing the varied influences of feedback, reward, and instructions on the brain. Hum Brain Mapp 37:3153-3171, 2016. © 2016 Wiley Periodicals, Inc.

Simultaneous epidural functional near-infrared spectroscopy and cortical electrophysiology as a tool for studying local neurovascular coupling in primates.

Simultaneous measurements of intra-cortical electrophysiology and hemodynamic signals in primates are essential for relating human neuroimaging studies with intra-cortical electrophysiology in monkeys. Previously, technically challenging and resourcefully demanding techniques such as fMRI and intrinsic-signal optical imaging have been used for such studies. Functional near-infrared spectroscopy is a relatively less cumbersome neuroimaging method that uses near-infrared light to detect small changes in concentrations of oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR) and total hemoglobin (HbT) in a volume of tissue with high specificity and temporal resolution. FNIRS is thus a good candidate for hemodynamic measurements in primates to acquire local hemodynamic signals during electrophysiological recordings. To test the feasibility of using epidural fNIRS with concomitant extracellular electrophysiology, we recorded neuronal and hemodynamic activity from the primary visual cortex of two anesthetized monkeys during visual stimulation. We recorded fNIRS epidurally, using one emitter and two detectors. We performed simultaneous cortical electrophysiology using tetrodes placed between the fNIRS sensors. We observed robust and reliable responses to the visual stimulation in both [HbO] and [HbR] signals, and quantified the signal-to-noise ratio of the epidurally measured signals. We also observed a positive correlation between stimulus-induced modulation of [HbO] and [HbR] signals and strength of neural modulation. Briefly, our results show that epidural fNIRS detects single-trial responses to visual stimuli on a trial-by-trial basis, and when coupled with cortical electrophysiology, is a promising tool for studying local hemodynamic signals and neurovascular coupling.

Flagrant Misconduct of Reviewers and Editor: A Case Study.

A case of a particularly severe misbehavior in a review process is described. Two reviewers simply copied and pasted their critical comments from their previous reviews without reading the reviewed manuscript. The editor readily accepted the reviewers' opinion and rejected the manuscript. These facts give rise to some general questions about possible factors affecting the ethical behavior of reviewers and editors, as well as possible countermeasures to prevent ethical violations.

Clinical Potential of Transcranial Focused Ultrasound for Neurorehabilitation in Pediatric Cancer Survivors.

Cancer survivors are at a high risk for treatment-related late effects, particularly neurocognitive impairment in the attention and executive function domains. These can be compounded in pediatric populations still undergoing neural development, which has increased interest in survivorship studies and neurorehabilitation approaches to mitigate these effects. Cognitive training regimens have shown promise as a therapeutic intervention for improving cognitive function. Therapist-guided and computerized training programs with adaptive paradigms have been successfully implemented in pediatric populations, with positive outcomes on attention and working memory. Another interventional approach is neuromodulation to alter plasticity. Transcranial electrical stimulation can modulate cortical surface activity, and cranial nerve stimulation alters autonomic activity in afferent brainstem pathways. However, they are more systemic in nature and have diffuse spatial targeting. Transcranial focused ultrasound (tFUS) modulation overcomes these limitations with high spatial specificity and the ability to target deeper brain regions. In this review, we discuss the efficacy of tFUS for modulating specific brain regions and its potential utility to augment cognitive training programs as a complementary intervention.

Self-Regulation of the Posterior-Frontal Brain Activity with Real-Time fMRI Neurofeedback to Influence Perceptual Discrimination.

The Global Neuronal Workspace (GNW) hypothesis states that the visual percept is available to conscious awareness only if recurrent long-distance interactions among distributed brain regions activate neural circuitry extending from the posterior areas to prefrontal regions above a certain excitation threshold. To directly test this hypothesis, we trained 14 human participants to increase blood oxygenation level-dependent (BOLD) signals with real-time functional magnetic resonance imaging (rtfMRI)-based neurofeedback simultaneously in four specific regions of the occipital, temporal, insular and prefrontal parts of the brain. Specifically, we hypothesized that the up-regulation of the mean BOLD activity in the posterior-frontal brain regions lowers the perceptual threshold for visual stimuli, while down-regulation raises the threshold. Our results showed that participants could perform up-regulation (Wilcoxon test, session 1: p = 0.022; session 4: p = 0.041) of the posterior-frontal brain activity, but not down-regulation. Furthermore, the up-regulation training led to a significant reduction in the visual perceptual threshold, but no substantial change in perceptual threshold was observed after the down-regulation training. These findings show that the up-regulation of the posterior-frontal regions improves the perceptual discrimination of the stimuli. However, further questions as to whether the posterior-frontal regions can be down-regulated at all, and whether down-regulation raises the perceptual threshold, remain unanswered.

Functional MRI Assessment of Brain Activity Patterns Associated with Reading in Medulloblastoma Survivors.

Medulloblastoma, a malignant brain tumor primarily affecting children, poses significant challenges to patients and clinicians due to its complex treatment and potential long-term cognitive consequences. While recent advancements in treatment have significantly improved survival rates, survivors often face cognitive impairments, particularly in reading, impacting their quality of life. According to the double deficit theory, reading impairments are caused by deficits in one or both of two independent reading-related functions: phonological awareness and rapid visual naming. This longitudinal study investigates neurofunctional changes related to reading in medulloblastoma survivors in comparison to controls using functional MRI acquired during rapid automatized naming tasks over three annual visits. Support vector machine classification of functional MRI data reveals a progressive divergence in brain activity patterns between medulloblastoma survivors and healthy controls over time, suggesting delayed effects of cancer treatment on brain function. Alterations in brain regions involved in visual processing and orthographic recognition during rapid naming tasks imply disruptions in the ventral visual pathway associated with normal orthographic processing. These alterations are correlated with performance in tasks involving sound awareness, reading fluency, and word attack. These findings underscore the dynamic nature of post-treatment neurofunctional alterations and the importance of early identification and intervention to address cognitive deficits in survivors.

Real-Time fMRI Neurofeedback Training of Selective Attention in Older Adults.

BACKGROUND: Selective attention declines with age, due to age-related functional changes in dorsal anterior cingulate cortex (dACC). Real-time functional magnetic resonance imaging (rtfMRI) neurofeedback has been used in young adults to train volitional control of brain activity, including in dACC. METHODS: For the first time, this study used rtfMRI neurofeedback to train 19 young and 27 older adults in volitional up- or down-regulation of bilateral dACC during a selective attention task. RESULTS: Older participants in the up-regulation condition (experimental group) showed greater reward points and dACC BOLD signal across training sessions, reflective of neurofeedback training success; and faster reaction time and better response accuracy, suggesting behavioral benefits on selective attention. These effects were not observed for older participants in the down-regulation condition (inverse condition control group), supporting specificity of volitional dACC up-regulation training in older adults. These effects were, unexpectedly, also not observed for young participants in the up-regulation condition (age control group), perhaps due to a lack of motivation to continue the training. CONCLUSIONS: These findings provide promising first evidence of functional plasticity in dACC in late life via rtfMRI neurofeedback up-regulation training, enhancing selective attention, and demonstrate proof of concept of rtfMRI neurofeedback training in cognitive aging.

Motor Intentions Decoded from fMRI Signals.

Motor intention is a high-level brain function related to planning for movement. Although studies have shown that motor intentions can be decoded from brain signals before movement execution, it is unclear whether intentions relating to mental imagery of movement can be decoded. Here, we investigated whether differences in spatial and temporal patterns of brain activation were elicited by intentions to perform different types of motor imagery and whether the patterns could be used by a multivariate pattern classifier to detect such differential intentions. The results showed that it is possible to decode intentions before the onset of different types of motor imagery from functional MR signals obtained from fronto-parietal brain regions, such as the premotor cortex and posterior parietal cortex, while controlling for eye movements and for muscular activity of the hands. These results highlight the critical role played by the aforementioned brain regions in covert motor intentions. Moreover, they have substantial implications for rehabilitating patients with motor disabilities.

Comparison of LED- and LASER-based fNIRS technologies to record the human peri­spinal cord neurovascular response.

Recently, functional Near-Infrared Spectroscopy (fNIRS) was applied to obtain, non-invasively, the human peri­spinal Neuro-Vascular Response (NVR) under a non-noxious electrical stimulation of a peripheral nerve. This method allowed the measurements of changes in the concentration of oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) from the peri­spinal vascular network. However, there is a lack of clarity about the potential differences in perispinal NVR recorded by the different fNIRS technologies currently available. In this work, the two main noninvasive fNIRS technologies were compared, i.e., LED and LASER-based. The recording of the human peri­spinal NVR induced by non-noxious electrical stimulation of a peripheral nerve was recorded simultaneously at C7 and T10 vertebral levels. The amplitude, rise time, and full width at half maximum duration of the perispinal NVRs were characterized in healthy volunteers and compared between both systems. The main difference was that the LED-based system shows about one order of magnitude higher values of amplitude than the LASER-based system. No statistical differences were found for rise time and for duration parameters (at thoracic level). The comparison of point-to-point wave patterns did not show significant differences between both systems. In conclusion, the peri­spinal NRV response obtained by different fNIRS technologies was reproducible, and only the amplitude showed differences, probably due to the power of the system which should be considered when assessing the human peri­spinal vascular network.

Imaging Assessment of Radiation Therapy-Related Normal Tissue Injury in Children: A PENTEC Visionary Statement.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium has made significant contributions to understanding and mitigating the adverse effects of childhood cancer therapy. This review addresses the role of diagnostic imaging in detecting, screening, and comprehending radiation therapy-related late effects in children, drawing insights from individual organ-specific PENTEC reports. We further explore how the development of imaging biomarkers for key organ systems, alongside technical advancements and translational imaging approaches, may enhance the systematic application of imaging evaluations in childhood cancer survivors. Moreover, the review critically examines knowledge gaps and identifies technical and practical limitations of existing imaging modalities in the pediatric population. Addressing these challenges may expand access to, minimize the risk of, and optimize the real-world application of, new imaging techniques. The PENTEC team envisions this document as a roadmap for the future development of imaging strategies in childhood cancer survivors, with the overarching goal of improving long-term health outcomes and quality of life for this vulnerable population.

Hydroxyurea maintains working memory function in pediatric sickle cell disease.

Sickle cell disease (SCD) decreases the oxygen-carrying capacity of red blood cells. Children with SCD have reduced/restricted cerebral blood flow, resulting in neurocognitive deficits. Hydroxyurea is the standard treatment for SCD; however, whether hydroxyurea influences such effects is unclear. A key area of SCD-associated neurocognitive impairment is working memory, which is implicated in other cognitive and academic skills. The neural correlates of working memory can be tested using n-back tasks. We analyzed functional magnetic resonance imaging (fMRI) data of patients with SCD (20 hydroxyurea-treated patients and 11 controls, aged 7-18 years) while they performed n-back tasks. Blood-oxygenation level-dependent (BOLD) signals were assessed during working memory processing at 2 time points: before hydroxyurea treatment and ~1 year after treatment was initiated. Neurocognitive measures were also assessed at both time points. Our results suggested that working memory was stable in the treated group. We observed a treatment-by-time interaction in the right cuneus and angular gyrus for the 2- >0-back contrast. Searchlight-pattern classification of the 2 time points of the 2-back tasks identified greater changes in the pattern and magnitude of BOLD signals, especially in the posterior regions of the brain, in the control group than in the treated group. In the control group at 1-year follow-up, 2-back BOLD signals increased across time points in several clusters (e.g., right inferior temporal lobe, right angular gyrus). We hypothesize that these changes resulted from increased cognitive effort during working memory processing in the absence of hydroxyurea. In the treated group, 0- to 2-back BOLD signals in the right angular gyrus and left cuneus increased continuously with increasing working memory load, potentially related to a broader dynamic range in response to task difficulty and cognitive effort. These findings suggest that hydroxyurea treatment helps maintain working memory function in SCD.

Secondary cerebro-cerebellar and intra-cerebellar dysfunction in cerebellar mutism syndrome.

BACKGROUND: Cerebellar mutism syndrome (CMS) is characterized by deficits of speech, movement, and affect that can occur following tumor removal from the posterior fossa. The role of cerebro-cerebellar tract injuries in the etiology of CMS remains unclear, with recent studies suggesting that cerebro-cerebellar dysfunction may be related to chronic, rather than transient, symptomatology. METHODS: We measured functional connectivity between the cerebellar cortex and functional nodes throughout the brain using fMRI acquired after tumor removal but prior to adjuvant therapy in a cohort of 70 patients diagnosed with medulloblastoma. Surgical lesions were mapped to the infratentorial anatomy, and connectivity with cerebral cortex was tested for statistical dependence on extent of cerebellar outflow pathway injury. RESULTS: CMS diagnosis was associated with an increase in connectivity between the right cerebellar and left cerebral hemisphere, maximally between cerebellum and ventromedial prefrontal cortex (VM-PFC). Connectivity dependence on cerebellar outflow was significant for some speech nodes but not for VM-PFC, suggesting altered input to the cerebellum. Connectivity between posterior regions of cerebellar cortex and ipsilateral dentate nuclei was abnormal in CMS participants, maximally within the right cerebellar hemisphere. CONCLUSIONS: The functional abnormalities we identified are notably upstream of where causal surgical injury is thought to occur, indicating a secondary phenomenon. The VM-PFC is involved in several functions that may be relevant to the symptomatology of CMS, including emotional control and motor learning. We hypothesize that these abnormalities may reflect maladaptive learning within the cerebellum consequent to disordered motor and limbic function by the periaqueductal gray and other critical midbrain targets.