The changes of neuroactivity of Tui Na (Chinese massage) at Hegu acupoint on sensorimotor cortex in stroke patients with upper limb motor dysfunction: a fNIRS study.

BACKGROUND: Tui Na (Chinese massage) is a relatively simple, inexpensive, and non-invasive intervention, and has been used to treat stroke patients for many years in China. Tui Na acts on specific parts of the body which are called meridians and acupoints to achieve the role of treating diseases. Yet the underlying neural mechanism associated with Tui Na is not clear due to the lack of detection methods. OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) was used to explore the changes of sensorimotor cortical neural activity in patients with upper limb motor dysfunction of stroke and healthy control groups during Tui Na Hegu Point. METHODS: Ten patients with unilateral upper limb motor dysfunction after stroke and eight healthy subjects received Tui Na. fNIRS was used to record the hemodynamic data in the sensorimotor cortex and the changes in blood flow were calculated based on oxygenated hemoglobin (Oxy-Hb), the task session involved repetitive Tui Na on Hegu acupoint, using a block design [six cycles: rest (20 seconds); Tui Na (20 seconds); rest (30 seconds)]. The changes in neural activity in sensorimotor cortex could be inferred according to the principle of neurovascular coupling, and the number of activated channels in the bilateral hemisphere was used to calculate the lateralization index. RESULT: 1. For hemodynamic response induced by Hegu acupoint Tui Na, a dominant increase in the contralesional primary sensorimotor cortex during Hegu point Tui Na of the less affected arm in stroke patients was observed, as well as that in healthy controls, while this contralateral pattern was absent during Hegu point Tui Na of the affected arm in stroke patients. 2. Concerning the lateralization index in stroke patients, a significant difference was observed between lateralization index values for the affected arm and the less affected arm (P < 0.05). Wilcoxon tests showed a significant difference between lateralization index values for the affected arm in stroke patients and lateralization index values for the dominant upper limb in healthy controls (P < 0.05), and no significant difference between lateralization index values for the less affected arm in stroke patients and that in healthy controls (P = 0.36). CONCLUSION: The combination of Tui Na and fNIRS has the potential to reflect the functional status of sensorimotor neural circuits. The changes of neuroactivity in the sensorimotor cortex when Tui Na Hegu acupoint indicate that there is a certain correlation between acupoints in traditional Chinese medicine and neural circuits.

Imbalance Between Prefronto-Thalamic and Sensorimotor-Thalamic Circuitries Associated with Working Memory Deficit in Schizophrenia.

BACKGROUND: Thalamocortical circuit imbalance characterized by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity has been consistently documented at rest in schizophrenia (SCZ). However, this thalamocortical imbalance has not been studied during task engagement to date, limiting our understanding of its role in cognitive dysfunction in schizophrenia. METHODS: Both n-back working memory (WM) task-fMRI and resting-state fMRI data were collected from 172 patients with SCZ and 103 healthy control subjects (HC). A replication sample with 49 SCZ and 48 HC was independently obtained. Sixteen thalamic subdivisions were employed as seeds for the analysis. RESULTS: During both task-performance and rest, SCZ showed thalamic hyperconnectivity with sensorimotor cortices, but hypoconnectivity with prefrontal-cerebellar regions relative to controls. Higher sensorimotor-thalamic connectivity and lower prefronto-thalamic connectivity both relate to poorer WM performance (lower task accuracy and longer response time) and difficulties in discriminating target from nontarget (lower d' score) in n-back task. The prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity were anti-correlated both in SCZ and HCs; this anti-correlation was more pronounced with less cognitive demand (rest>0-back>2-back). These findings replicated well in the second sample. Finally, the hypo- and hyper-connectivity patterns during resting-state positively correlated with the hypo- and hyper-connectivity during 2-back task-state in SCZ respectively. CONCLUSIONS: The thalamocortical imbalance reflected by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity is present both at rest and during task engagement in SCZ and relates to working memory performance. The frontal reduction, sensorimotor enhancement pattern of thalamocortical imbalance is a state-invariant feature of SCZ that affects a core cognitive function.

Longitudinal Changes of Sensorimotor Resting-State Functional Connectivity Differentiate between Patients with Thalamic Infarction and Pontine Infarction.

Purpose. We investigated the disparate influence of lesion location on functional damage and reorganization of the sensorimotor brain network in patients with thalamic infarction and pontine infarction. Methods. Fourteen patients with unilateral infarction of the thalamus and 14 patients with unilateral infarction of the pons underwent longitudinal fMRI measurements and motor functional assessment five times during a 6-month period (<7 days, at 2 weeks, 1 month, 3 months, and 6 months after stroke onset). Twenty-five age- and sex-matched controls underwent MRI examination across five consecutive time points in 6 months. Functional images from patients with left hemisphere lesions were first flipped from the left to the right side. The voxel-wise connectivity analyses between the reference time course of each ROI (the contralateral dorsal lateral putamen (dl-putamen), pons, ventral anterior (VA), and ventral lateral (VL) nuclei of the thalamus) and the time course of each voxel in the sensorimotor area were performed for all five measurements. One-way ANOVA was used to identify between-group differences in functional connectivity (FC) at baseline stage (<7 days after stroke onset), with infarction volume included as a nuisance variable. The family-wise error (FWE) method was used to account for multiple comparison issues using SPM software. Post hoc repeated-measure ANOVA was applied to examine longitudinal FC reorganization. Results. At baseline stage, significant differences were detected between the contralateral VA and ipsilateral postcentral gyrus (cl_VA-ip_postcentral), contralateral VL and ipsilateral precentral gyrus (cl_VL-ip_precentral). Repeated measures ANOVA revealed that the FC change of cl_VA-ip_postcentral differ significantly among the three groups over time. The significant changes of FC between cl_VA and ip_postcentral at different time points in the thalamic infarction group showed that compared with 7 days after stroke onset, there was significantly increased FC of cl_VA-ip_postcentral at 1 month, 3 months, and 6 months after stroke onset. Conclusions. The different patterns of sensorimotor functional damage and reorganization in patients with pontine infarction and thalamic infarction may provide insights into the neural mechanisms underlying functional recovery after stroke.

fMRI neurofeedback in the motor system elicits bidirectional changes in activity and in white matter structure in the adult human brain.

White matter (WM) plasticity supports skill learning and memory. Up- and downregulation of brain activity in animal models lead to WM alterations. But can bidirectional brain-activity manipulation change WM structure in the adult human brain? We employ fMRI neurofeedback to endogenously and directionally modulate activity in the sensorimotor cortices. Diffusion tensor imaging is acquired before and after two separate conditions, involving regulating sensorimotor activity either up or down using real or sham neurofeedback (n = 20 participants × 4 scans). We report rapid opposing changes in corpus callosum microstructure that depend on the direction of activity modulation. Our findings show that fMRI neurofeedback can be used to endogenously and directionally alter not only brain-activity patterns but also WM pathways connecting the targeted brain areas. The level of associated brain activity in connected areas is therefore a possible mediator of previously described learning-related changes in WM.

Characterizing effects of age, sex and psychosis symptoms on thalamocortical functional connectivity in youth.

The thalamus is composed of multiple nuclei densely connected with the cortex in an organized manner, forming parallel thalamocortical networks critical to sensory, motor, and cognitive functioning. Thalamocortical circuit dysfunction has been implicated in multiple neurodevelopmental disorders, including schizophrenia, which also often exhibit sex differences in prevalence, clinical characteristics, and neuropathology. However, very little is known about developmental and sex effects on thalamocortical networks in youth. The present study characterized the effects of age, sex and psychosis symptomatology in anatomically constrained thalamocortical networks in a large community sample of youth (n = 1100, aged 8-21) from the Philadelphia Neurodevelopmental Cohort (PNC). Cortical functional connectivity of seven anatomically defined thalamic nuclear groups were examined: anterior, mediodorsal, ventral lateral, ventral posterolateral, pulvinar, medial and lateral geniculate nuclear groups. Age and sex effects were characterized using complementary thalamic region-of-interest (ROI) to cortical ROI and voxel-wise analyses. Effects of clinical symptomatology were analyzed by separating youth into three groups based on their clinical symptoms; typically developing youth (n = 298), psychosis spectrum youth (n = 320), and youth with other psychopathologies (n = 482). As an exploratory analysis, association with PRIME scores were used as a dimensional measure of psychopathology. Age effects were broadly characterized by decreasing connectivity with sensory/motor cortical areas, and increasing connectivity with heteromodal prefrontal and parietal cortical areas. This pattern was most pronounced for thalamic motor and sensory nuclei. Females showed greater connectivity between multiple thalamic nuclear groups and the visual cortex compared to males, while males showed greater connectivity with the inferior frontal and orbitofrontal cortices. Youth with psychosis spectrum symptoms showed a subtle decrease in thalamic connectivity with the premotor and prefrontal cortices. Across all youth, greater PRIME scores were associated with lower connectivity between the prefrontal cortex and mediodorsal thalamus. By characterizing typical development in anatomically constrained thalamocortical networks, this study provides an anchor for conceptualizing disruptions to the integrity of these networks observed in neurodevelopmental disorders.

Altered sensorimotor integration in multiple sclerosis: A combined neurophysiological and functional MRI study.

OBJECTIVE: To explore whether abnormal thalamic resting-state functional connectivity (rsFC) contributes to altered sensorimotor integration and hand dexterity impairment in multiple sclerosis (MS). METHODS: To evaluate sensorimotor integration, we recorded kinematic features of index finger abductions during somatosensory temporal discrimination threshold (STDT) testing in 36 patients with relapsing-remitting MS and 39 healthy controls (HC). Participants underwent a multimodal 3T structural and functional MRI protocol. RESULTS: Patients had lower index finger abduction velocity during STDT testing compared to HC. Thalamic rsFC with the precentral and postcentral gyri, supplementary motor area (SMA), insula, and basal ganglia was higher in patients than HC. Intrathalamic rsFC and thalamic rsFC with caudate and insula bilaterally was lower in patients than HC. Finger movement velocity positively correlated with intrathalamic rsFC and negatively correlated with thalamic rsFC with the precentral and postcentral gyri, SMA, and putamen. CONCLUSIONS: Abnormal thalamic rsFC is a possible substrate for altered sensorimotor integration in MS, with high intrathalamic rsFC facilitating finger movements and increased thalamic rsFC with the basal ganglia and sensorimotor cortex contributing to motor performance deterioration. SIGNIFICANCE: The combined study of thalamic functional connectivity and upper limb sensorimotor integration may be useful in identifying patients who can benefit from early rehabilitation to prevent upper limb motor impairment.

Kinesthetic illusion induced by visual stimulation influences sensorimotor event-related desynchronization in stroke patients with severe upper-limb paralysis: A pilot study.

BACKGROUND: Repetition of motor imagery improves the motor function of patients with stroke. However, patients who develop severe upper-limb paralysis after chronic stroke often have an impaired ability to induce motor imagery. We have developed a method to passively induce kinesthetic perception using visual stimulation (kinesthetic illusion induced by visual stimulation [KINVIS]). OBJECTIVE: This pilot study further investigated the effectiveness of KINVIS in improving the induction of kinesthetic motor imagery in patients with severe upper-limb paralysis after stroke. METHODS: Twenty participants (11 with right hemiplegia and 9 with left hemiplegia; mean time from onset [±standard deviation], 67.0±57.2 months) with severe upper-limb paralysis who could not extend their paretic fingers were included in this study. The ability to induce motor imagery was evaluated using the event-related desynchronization (ERD) recorded during motor imagery before and after the application of KINVIS for 20 min. The alpha- and beta-band ERDs around the premotor, primary sensorimotor, and posterior parietal cortices of the affected and unaffected hemispheres were evaluated during kinesthetic motor imagery of finger extension and before and after the intervention. RESULTS: Beta-band ERD recorded from the affected hemisphere around the sensorimotor area showed a significant increase after the intervention, while the other ERDs remained unchanged. CONCLUSIONS: In patients with chronic stroke who were unable to extend their paretic fingers for a prolonged period of time, the application of KINVIS, which evokes kinesthetic perception, improved their ability to induce motor imagery. Our findings suggest that although KINVIS is a passive intervention, its short-term application can induce changes related to the motor output system.

Hyperactive sensorimotor cortex during voice perception in spasmodic dysphonia.

Spasmodic dysphonia (SD) is characterized by an involuntary laryngeal muscle spasm during vocalization. Previous studies measured brain activation during voice production and suggested that SD arises from abnormal sensorimotor integration involving the sensorimotor cortex. However, it remains unclear whether this abnormal sensorimotor activation merely reflects neural activation produced by abnormal vocalization. To identify the specific neural correlates of SD, we used a sound discrimination task without overt vocalization to compare neural activation between 11 patients with SD and healthy participants. Participants underwent functional MRI during a two-alternative judgment task for auditory stimuli, which could be modal or falsetto voice. Since vocalization in falsetto is intact in SD, we predicted that neural activation during speech perception would differ between the two groups only for modal voice and not for falsetto voice. Group-by-stimulus interaction was observed in the left sensorimotor cortex and thalamus, suggesting that voice perception activates different neural systems between the two groups. Moreover, the sensorimotor signals positively correlated with disease severity of SD, and classified the two groups with 73% accuracy in linear discriminant analysis. Thus, the sensorimotor cortex and thalamus play a central role in SD pathophysiology and sensorimotor signals can be a new biomarker for SD diagnosis.

Effect of combined neurofeedback and game-based cognitive training on the treatment of ADHD: A randomized controlled study.

Neurofeedback (NF) is referred to as a "possibly efficacious" treatment in the current evidence-based reviews; therefore, more research is needed to determine its effects especially in combination with other treatments. The present study examines the effect of NF and game-based cognitive training on children with attention deficit hyperactivity disorder (ADHD). Thirty-two male students with ADHD were assigned to NF (N = 16; Mage=10.20; SD = 1.03) and waiting list control (N = 16; Mage = 10.05; SD = 0.83) in a randomized double-blind trial. The children in the NF group based on quantitative electroencephalography (QEEG) attended 30 three times-weekly sessions. The children were examined in pretest and post-test with EEG, Integrated Visual and Auditory Continuous Performance (IVA), and Conners Parent, and Teacher Rating Scales-Revised. The treatment was found significant all the symptom variables except for attention deficit (AD) and auditory response control (ARC). Normalization of the atypical EEG features with reduced [Formula: see text] wave and increased sensory motor (SMR) activity in central zero (Cz) was recorded in the NF condition participants. However, except for SMR activity there were no significant changes in the waves of frontocentral zero (FCz). It is concluded that technology developments provide an interesting vehicle for interposing interventions and that combined NF and game-based cognitive training can produce positive therapeutic effects on brainwaves and ADHD symptomatology.

A feasibility study of brain-targeted treatment for people with painful knee osteoarthritis in tertiary care.

Purpose: To assess the feasibility and clinical impact of brain-targeted treatment (BT; aiming to target sensorimotor processing) in knee osteoarthritis patients attending tertiary care. Methods: Randomized replicated case series. The study involved three phases, each of 2 weeks duration: (1) no-treatment phase; (2) BT phase (left/right judgments and touch discrimination training); and (3) usual care (education, strengthening, and stretching training). Primary outcomes were: timely recruitment; number of participants completing the interventions; treatment compliance and barriers; follow-up rates; and treatment impact on pain and function. Fear-avoidance beliefs and clinical measures of cortical body representation (tactile acuity and left/right judgment performance) were secondary outcomes. Results: A total of 5% (19/355) of all assessed patients were eligible to participate and of these, 58% (11/19) agreed to participate. Ten patients completed the study, and 9 were successfully followed up, with treatment compliance varying between interventions. Compliance was poor for the touch discrimination component of BT. No significant effects were observed for pain relief or knee function after any treatment. A positive impact of treatment was found for fear-avoidance beliefs (usual care vs. washout, p = 0.007; BT vs. washout, p = 0.029) and left/right judgment accuracy (usual care vs. washout; p = 0.006). Conclusions: Clear barriers were identified to implementing BT in tertiary care for knee osteoarthritis. Access to all available services (especially the use of interpreters), and treatment options that do not require additional assistance to perform (e.g., touch discrimination training) represent the main lessons learned.

Abnormal Functional Relationship of Sensorimotor Network With Neurotransmitter-Related Nuclei via Subcortical-Cortical Loops in Manic and Depressive Phases of Bipolar Disorder.

OBJECTIVE: Manic and depressive phases of bipolar disorder (BD) show opposite psychomotor symptoms. Neuronally, these may depend on altered relationships between sensorimotor network (SMN) and subcortical structures. The study aimed to investigate the functional relationships of SMN with substantia nigra (SN) and raphe nuclei (RN) via subcortical-cortical loops, and their alteration in bipolar mania and depression, as characterized by psychomotor excitation and inhibition. METHOD: In this resting-state functional magnetic resonance imaging (fMRI) study on healthy (n = 67) and BD patients (n = 100), (1) functional connectivity (FC) between thalamus and SMN was calculated and correlated with FC from SN or RN to basal ganglia (BG)/thalamus in healthy; (2) using an a-priori-driven approach, thalamus-SMN FC, SN-BG/thalamus FC, and RN-BG/thalamus FC were compared between healthy and BD, focusing on manic (n = 34) and inhibited depressed (n = 21) patients. RESULTS: (1) In healthy, the thalamus-SMN FC showed a quadratic correlation with SN-BG/thalamus FC and a linear negative correlation with RN-BG/thalamus FC. Accordingly, the SN-related FC appears to enable the thalamus-SMN coupling, while the RN-related FC affects it favoring anti-correlation. (2) In BD, mania showed an increase in thalamus-SMN FC toward positive values (ie, thalamus-SMN abnormal coupling) paralleled by reduction of RN-BG/thalamus FC. By contrast, inhibited depression showed a decrease in thalamus-SMN FC toward around-zero values (ie, thalamus-SMN disconnection) paralleled by reduction of SN-BG/thalamus FC (and RN-BG/thalamus FC). The results were replicated in independent HC and BD datasets. CONCLUSIONS: These findings suggest an abnormal relationship of SMN with neurotransmitters-related areas via subcortical-cortical loops in mania and inhibited depression, finally resulting in psychomotor alterations.

Sensorimotor Connectivity after Motor Exercise with Neurofeedback in Post-Stroke Patients with Hemiplegia.

Impaired finger motor function in post-stroke hemiplegia is a debilitating condition with no evidence-based or accessible treatments. Here, we evaluated the neurophysiological effectiveness of direct brain control of robotic exoskeleton that provides movement support contingent with brain activity. To elucidate the mechanisms underlying the neurofeedback intervention, we assessed resting-state functional connectivity with functional magnetic resonance imaging (rsfcMRI) between the ipsilesional sensory and motor cortices before and after a single 1-h intervention. Eighteen stroke patients were randomly assigned to crossover interventions in a double-blind and sham-controlled design. One patient dropped out midway through the study, and 17 patients were included in this analysis. Interventions involved motor imagery, robotic assistance, and neuromuscular electrical stimulation administered to a paretic finger. The neurofeedback intervention delivered stimulations contingent on desynchronized ipsilesional electroencephalographic (EEG) oscillations during imagined movement, and the control intervention delivered sensorimotor stimulations that were independent of EEG oscillations. There was a significant time × intervention interaction in rsfcMRI in the ipsilesional sensorimotor cortex. Post-hoc analysis showed a larger gain in increased functional connectivity during the neurofeedback intervention. Although the neurofeedback intervention delivered fewer total sensorimotor stimulations compared to the sham-control, rsfcMRI in the ipsilesional sensorimotor cortices was increased during the neurofeedback intervention compared to the sham-control. Higher coactivation of the sensory and motor cortices during neurofeedback intervention enhanced rsfcMRI in the ipsilesional sensorimotor cortices. This study showed neurophysiological evidence that EEG-contingent neurofeedback is a promising strategy to induce intrinsic ipsilesional sensorimotor reorganization, supporting the importance of integrating closed-loop sensorimotor processing at a neurophysiological level.

Cause or effect: Altered brain and network activity in cervical dystonia is partially normalized by botulinum toxin treatment.

BACKGROUND: Idiopathic cervical dystonia (CD) is a chronic movement disorder characterized by impressive clinical symptoms and the lack of clear pathological findings in clinical diagnostics and imaging. At present, the injection of botulinum toxin (BNT) in dystonic muscles is an effective therapy to control motor symptoms and pain in CD. OBJECTIVES: We hypothesized that, although it is locally injected to dystonic muscles, BNT application leads to changes in brain and network activity towards normal brain function. METHODS: Using 3 T functional MR imaging along with advanced analysis techniques (functional connectivity, Granger causality, and regional homogeneity), we aimed to characterize brain activity in CD (17 CD patients vs. 17 controls) and to uncover the effects of BNT treatment (at 6 months). RESULTS: In CD, we observed an increased information flow within the basal ganglia, the thalamus, and the sensorimotor cortex. In parallel, some of these structures became less responsive to regulating inputs. Furthermore, our results suggested an altered somatosensory integration. Following BNT administration, we noted a shift towards normal brain function in the CD patients, especially within the motor cortex, the somatosensory cortex, and the basal ganglia. CONCLUSION: The changes in brain function and network activity in CD can be interpreted as related to the underlying cause, the effort to compensate or a mixture of both. Although BNT is applied in the last stage of the cortico-neuromuscular pathway, brain patterns are shifted towards those of healthy controls.

Association between Thalamocortical Functional Connectivity Abnormalities and Cognitive Deficits in Schizophrenia.

Cognitive deficits are considered a core component of schizophrenia and may predict functional outcome. However, the neural underpinnings of neuropsychological impairment remain to be fully elucidated. Data of 59 schizophrenia patients and 72 healthy controls from a public resting-state fMRI database was employed in our study. Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery was used to measure deficits of cognitive abilities in schizophrenia. Neural correlates of cognitive deficits in schizophrenia were examined by linear regression analysis of the thalamocortical network activity with scores of seven cognitive domains. We confirmed the combination of reduced prefrontal-thalamic connectivity and increased sensorimotor-thalamic connectivity in patients with schizophrenia. Correlation analysis with cognition revealed that in schizophrenia (1) the thalamic functional connectivity in the bilateral pre- and postcentral gyri was negatively correlated with attention/vigilance and speed of processing (Pearson's r ≤ -0.443, p ≤ 0.042, FWE corrected), and positively correlated with patients' negative symptoms (Pearson's r ≥ 0.375, p ≤ 0.003, FWE corrected); (2) the thalamic functional connectivity in the right cerebellum was positively correlated with speed of processing (Pearson's r = 0.388, p = 0.01, FWE corrected). Our study demonstrates that thalamic hyperconnectivity with sensorimotor areas is related to the severity of cognitive deficits and clinical symptoms, and extends our understanding of the neural underpinnings of "cognitive dysmetria" in schizophrenia.

Post-Weaning Social Isolation Disturbs Gene Expression in Rat Brain Structures.

Post-weaning social isolation of male Wistar rats for 10 weeks led to an increase of their aggressiveness, sensorimotor reactivity, and cognitive deficiency, manifesting in training disorders evaluated by the acoustic startle response (amplitude of the response decreasing). Expression of gene encoding serine protease prolyl endopeptidase (EC 3.4.21.26) in the frontal cortex was higher than in control rats kept in groups, while the level of mRNA of the gene encoding dipeptidyl peptidase IV (EC 3.4.14.5) did not differ from the control in any of the brain structures. The levels of serotonin transporter gene mRNA in the striatum and hypothalamus were higher than in the control. No appreciable changes in the expression of genes encoding tryptophan hydroxylase-2 and monoaminoxidase A and B in the frontal cortex, striatum, amygdala, hypothalamus, and hippocampus were detected. The data indicated the involvement of genes associated with the serotoninergic system in the mechanisms of mental disorders induced by post-weaning social isolation and suggest the gene encoding prolyl endopeptidase as a candidate gene involved in the pathogenesis of these disorders.

The Brain Network in a Model of Thalamocortical Dysrhythmia.

Sensory information processing and higher cognitive functions rely on the interactions between thalamus and cortex. Many types of neurological and psychiatric disorders are accompanied or driven by alterations in the brain connectivity. In this study, putative changes in functional and effective corticocortical (CC), thalamocortical (TC), and corticothalamic (CT) connectivity during wakefulness and slow-wave sleep (SWS) in a model of thalamocortical dysrhythmia, TRIP8b-/- mice, and in control (wild-type or WT) mice are described. Coherence and nonlinear Granger causality (GC) were calculated for twenty 10 s length epochs of SWS and active wakefulness (AW) of each animal. Coherence was reduced between 4 and ca 20 Hz in the cortex and between cortex and thalamus during SWS compared with AW in WT but not in TRIP8b-/- mice. Moreover, TRIP8b-/- mice showed lower CT coherence during AW compared with WT mice; these differences were no longer present during SWS. Unconditional GC analysis also showed sleep-related reductions in TC and CT couplings in WT mice, while TRIP8b-/- mice showed diminished wake and enhanced sleep CC coupling and rather strong CT-directed coupling during wake and sleep, although smaller during sleep. Conditional GC coupling analysis confirmed the diminished CC and enhanced CT coupling in TRIP8b-/- mice. Our findings indicate that altered properties of hyperpolarization-activated cyclic nucleotide-gated cation channels, characterizing TRIP8b-/- mice, have clear effects on CC, TC, and CT networks. A more complete understanding of the function of the altered communication within these networks awaits detailed phenotyping of TRIP8b-/- mice aimed at specifics of sensory and attentional processes.

Dissociable Disruptions in Thalamic and Hippocampal Resting-State Functional Connectivity in Youth with 22q11.2 Deletions.

The 22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant with high penetrance for developmental neuropsychiatric disorders. Study of individuals with 22q11DS therefore may offer key insights into neural mechanisms underlying such complex illnesses. Resting-state functional connectivity MRI studies in idiopathic schizophrenia have consistently revealed disruption of thalamic and hippocampal circuitry. Here, we sought to test whether this circuitry is similarly disrupted in the context of this genetic high-risk condition. To this end, resting-state functional connectivity patterns were assessed in a sample of human youth with 22q11DS (n = 42; 59.5% female) and demographically matched healthy controls (n = 39; 53.8% female). Neuroimaging data were acquired via single-band protocols and analyzed in line with methods provided by the Human Connectome Project. We computed functional relationships between individual-specific anatomically defined thalamic and hippocampal seeds and all gray matter voxels in the brain. Whole-brain Type I error protection was achieved through nonparametric permutation-based methods. The 22q11DS patients displayed dissociable disruptions in thalamic and hippocampal functional connectivity relative to control subjects. Thalamocortical coupling was increased in somatomotor regions and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to somatomotor and associative network connectivity. The thalamic and hippocampal dysconnectivity observed in 22q11DS suggests that high genetic risk for psychiatric illness is linked with disruptions in large-scale corticosubcortical networks underlying higher-order cognitive functions. These effects highlight the translational importance of large-effect copy number variants for informing mechanisms underlying neural disruptions observed in idiopathic developmental neuropsychiatric disorders.SIGNIFICANCE STATEMENT Investigation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biologically tractable approach to identify neural circuit disruptions underlying developmental neuropsychiatric conditions. The 22q11.2 deletion syndrome confers particularly high risk for psychotic disorders and is thus an important translational model in which to investigate systems-level mechanisms implicated in idiopathic illness. Here, we show resting-state fMRI evidence of large-scale sensory and executive network disruptions in youth with 22q11DS. In particular, this study provides the first evidence that these networks are disrupted in a dissociable fashion with regard to the functional connectivity of the thalamus and hippocampus, suggesting circuit-level dysfunction.

Using EEG-based brain computer interface and neurofeedback targeting sensorimotor rhythms to improve motor skills: Theoretical background, applications and prospects.

Many Brain Computer Interface (BCI) and neurofeedback studies have investigated the impact of sensorimotor rhythm (SMR) self-regulation training procedures on motor skills enhancement in healthy subjects and patients with motor disabilities. This critical review aims first to introduce the different definitions of SMR EEG target in BCI/Neurofeedback studies and to summarize the background from neurophysiological and neuroplasticity studies that led to SMR being considered as reliable and valid EEG targets to improve motor skills through BCI/neurofeedback procedures. The second objective of this review is to introduce the main findings regarding SMR BCI/neurofeedback in healthy subjects. Third, the main findings regarding BCI/neurofeedback efficiency in patients with hypokinetic activities (in particular, motor deficit following stroke) as well as in patients with hyperkinetic activities (in particular, Attention Deficit Hyperactivity Disorder, ADHD) will be introduced. Due to a range of limitations, a clear association between SMR BCI/neurofeedback training and enhanced motor skills has yet to be established. However, SMR BCI/neurofeedback appears promising, and highlights many important challenges for clinical neurophysiology with regards to therapeutic approaches using BCI/neurofeedback.

Reconfiguration of Dynamic Functional Connectivity in Sensory and Perceptual System in Schizophrenia.

Schizophrenia is thought as a self-disorder with dysfunctional brain connectivity. This self-disorder is often attributed to high-order cognitive impairment. Yet due to the frequent report of sensorial and perceptual deficits, it has been hypothesized that self-disorder in schizophrenia is dysfunctional communication between sensory and cognitive processes. To further verify this assumption, the present study comprehensively examined dynamic reconfigurations of resting-state functional connectivity (rsFC) in schizophrenia at voxel level, region level, and network levels (102 patients vs. 124 controls). We found patients who show consistently increased rsFC variability in sensory and perceptual system, including visual network, sensorimotor network, attention network, and thalamus at all the three levels. However, decreased variability in high-order networks, such as default mode network and frontal-parietal network were only consistently observed at region and network levels. Taken together, these findings highlighted the rudimentary role of elevated instability of information communication in sensory and perceptual system and attenuated whole-brain integration of high-order network in schizophrenia, which provided novel neural evidence to support the hypothesis of disrupted perceptual and cognitive function in schizophrenia. The foci of effects also highlighted that targeting perceptual deficits can be regarded as the key to enhance our understanding of pathophysiology in schizophrenia and promote new treatment intervention.

EEG Neurofeedback Is Under Strong Control of Psychosocial Factors.

Recently, a deep impact of psychosocial effects on the outcomes of neurofeedback training was suggested. Previous findings point out an association between locus of control in dealing with technology and the individual ability to up-regulate the sensorimotor rhythm (12-15 Hz) in the EEG. Since the antecedents of locus of control in dealing with technology differ between males and females, we have investigated the effect of sex of participant and experimenter on the outcomes of neurofeedback training. Mindfulness and SMR baseline power also were assessed as possible confounding variables. Undergraduate psychology students (n = 142) took part in a single session of neurofeedback training conducted by either male or female experimenters. Male participants as well as those female participants instructed by male experimenters were able to upregulate SMR, while female participants trained by female experimenters were not. A strong positive correlation between training outcomes and locus of control in dealing with technology was observed only in the female participants trained by female experimenters. These results are suggestive about the impact of psychosocial factors-particularly gender-related effects-on neurofeedback training outcomes and the urgent need to document it in neurofeedback studies.