Beta Modulation Research Articles

Integration of valence and conflict processing through cellular-field interactions in human subgenual cingulate during emotional face processing in treatment-resistant depression.

The subgenual anterior cingulate cortex (sgACC) has been identified as a key brain area involved in various cognitive and emotional processes. While the sgACC has been implicated in both emotional valuation and emotional conflict monitoring, it is still unclear how this area integrates multiple functions. We characterized both single neuron and local field oscillatory activity in 14 patients undergoing sgACC deep brain stimulation for treatment-resistant depression. During recording, patients were presented with a modified Stroop task containing emotional face images that varied in valence and congruence. We further analyzed spike-field interactions to understand how network dynamics influence single neuron activity in this area. Most single neurons responded to both valence and congruence, revealing that sgACC neuronal activity can encode multiple processes within the same task, indicative of multifunctionality. During peak neuronal response, we observed increased spectral power in low frequency oscillations, including theta-band synchronization (4-8 Hz), as well as desynchronization in beta-band frequencies (13-30 Hz). Theta activity was modulated by current trial congruency with greater increases in spectral power following non-congruent stimuli, while beta desynchronizations occurred regardless of emotional valence. Spike-field interactions revealed that local sgACC spiking was phase-locked most prominently to the beta band, whereas phase-locking to the theta band occurred in fewer neurons overall but was modulated more strongly for neurons that were responsive to task. Our findings provide the first direct evidence of spike-field interactions relating to emotional cognitive processing in the human sgACC. Furthermore, we directly related theta oscillatory dynamics in human sgACC to current trial congruency, demonstrating it as an important regulator during conflict detection. Our data endorse the sgACC as an integrative hub for cognitive emotional processing through modulation of beta and theta network activity.

Contingent magnetic variation and beta-band oscillations in sensorimotor temporal decision-making

The ability to accurately encode the temporal information of sensory events and hence to make prompt action is fundamental to humans’ prompt behavioral decision-making. Here we examined the ability of ensemble coding (averaging multiple inter-intervals in a sound sequence) and subsequent immediate reproduction of target duration at half, equal, or double that of the perceived mean interval in a sensorimotor loop. With magnetoencephalography (MEG), we found that the contingent magnetic variation (CMV) in the central scalp varied as a function of the averaging tasks, with a faster rate for buildup amplitudes and shorter peak latencies in the “half” condition as compared to the “double” condition. ERD (event-related desynchronization) -to-ERS (event-related synchronization) latency was shorter in the ”half” condition. A robust beta band (15–23 Hz) power suppression and recovery between the final tone and the action of key pressing was found for time reproduction. The beta modulation depth (i.e., the ERD-to-ERS power difference) was larger in motor areas than in primary auditory areas. Moreover, results of phase slope index (PSI) indicated that beta oscillations in the left supplementary motor area (SMA) led those in the right superior temporal gyrus (STG), showing SMA to STG directionality for the processing of sequential (temporal) auditory interval information. Our findings provide the first evidence to show that CMV and beta oscillations predict the coupling between perception and action in time averaging.

Effects of Single-Session Practice Structure on Motor Skill Acquisition and Alpha and Beta EEG Oscillations

Background: Although it is known that practicing a motor skill updates the associated internal model, it is still unclear as to how cortical oscillations linked with the motor skill change under differing practice schedules. The current study investigated α- and β-power changes associated with motor skill acquisition. Objectives: Firstly, we investigated the behavioral effects of practice on motor learning and retention during repetitive (RP) and variable (VP) practice schedules on an anticipation timing task. Secondly, we investigated changes in cortical α (10 - 13 Hz) and β (15 - 30 Hz) event-related synchronization and desynchronization (ERS/ERD) under RP and VP during early (EP) and late (LP) stages of practice. Methods: To investigate the behavioral effects of practice on learning and retention, participants were pretested, post-tested at 5 min (retention), and tested twice at 30 min (one for longer retention, one for transfer to a novel velocity). To investigate electroencephalography (EEG) α and β power changes, data were collected from electrode sites T7, T8, C3, C4, CP3, CP4, FCz, AFz, and Pz. Results: Based on a 2 × 4 (practice group × test block) ANOVA, results indicated a significant learning effect for both group participants, with VP participants performing better on the 30-min transfer test. To investigate EEG α and β power changes, data were analyzed using separate, 2 × 2 repeated measures ANOVA (group [RP and VP] × practice trial blocks [EP and LP]). Power analyses revealed (1) attenuated α ERD at T7 (cognitive/verbal rehearsal), C3 (motor cortex), CP3, CP4, and FCz (pooled data representing premotor cortices), and AFz (frontal cortex and attentional processes) during LP, with greater changes observed in premotor activity (PMA), T7, and AFz electrode sites in RP participants. β frequency analysis, using beta modulation depth (BMD), revealed that participants in both groups had increased BMD at premotor, motor, and frontal electrode sites at LP, with RP participants exhibiting greater changes. Conclusions: Results are in accordance with previous research indicating that practicing under a VP schedule leads to superior motor skill transfer than practicing under an RP schedule. Moreover, lesser changes in α ERD along and lower BMD observed in VP participants might be responsible for a more adaptable and flexible motor program, allowing for greater skill retention and transfer in individuals practicing under VP conditions.

Tracking the neurodevelopmental trajectory of beta band oscillations with optically pumped magnetometer-based magnetoencephalography.

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform - optically pumped magnetometer-based magnetoencephalography (OPM-MEG) - to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment.

Tracking the neurodevelopmental trajectory of beta band oscillations with optically pumped magnetometer-based magnetoencephalography

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform – optically pumped magnetometer-based magnetoencephalography (OPM-MEG) – to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment.

Cross-Day Data Diversity Improves Inter-Individual Emotion Commonality of Spatio-Spectral EEG Signatures Using Independent Component Analysis

Electroencephalogram (EEG) variability poses a great challenge to the affective brain-computer interface (aBCI) for practical applications. Most aBCI frameworks have been demonstrated successfully but deliberated on single-day data, which can be realistically susceptible to psychophysiological changes and further hinder the exploration of inter-individual EEG commonality. This study proposes a multiple-day scenario that learns exclusively from diverse EEG correlates of emotional responses on different days (i.e., enriched data diversity) by using a unified independent components analysis framework. Given an eight-day dataset of 10 subjects ( <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">i.e</i> ., 80 sessions), the results demonstrated that the multiple-day scenario intensified the inter-subject emotion commonality ( <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">i.e</i> ., the percentage of subjects with the same signature) to a certain extent when considering sufficient cross-day sessions, whereas the most commonly adopted single-day analysis (i.e., diversity-confined) led to session-dependent inferior outcomes. Given the best case, the emotional valence dimension was associated with relatively reproducible frontal beta, central midline gamma, and occipital beta modulations with 30%–40% subject commonality, whereas the arousal counterpart suffered more substantially from EEG variability and barely returned representative signatures. These results suggest that EEG signature representation may be substantially compromised by limited data diversity, impeding the efficacy and generalizability of the aBCI model in real-life settings.

Altered excitation-inhibition balance in the primary sensorimotor cortex to proprioceptive hand stimulation in cerebral palsy

ObjectiveOur objective was to clarify the primary sensorimotor (SM1) cortex excitatory and inhibitory alterations in hemiplegic (HP) and diplegic (DP) cerebral palsy (CP) by quantifying SM1 cortex beta power suppression and rebound with magnetoencephalography (MEG). MethodsMEG was recorded from 16 HP and 12 DP adolescents, and their 32 healthy controls during proprioceptive stimulation of the index fingers evoked by a movement actuator. The related beta power changes were computed with Temporal Spectral Evolution (TSE). Peak strengths of beta suppression and rebound were determined from representative channels over the SM1 cortex. ResultsBeta suppression was stronger contralateral to the stimulus and rebound was weaker ipsilateral to the stimulation in DP compared to controls. Beta modulation strengths did not differ significantly between HP and the control group. ConclusionsThe emphasized beta suppression in DP suggests less efficient proprioceptive processing in the SM1 contralateral to the stimulation. Their weak rebound further indicates reduced intra- and/or interhemispheric cortical inhibition, which is a potential neuronal mechanism for their bilateral motor impairments. SignificanceThe excitation-inhibition balance of the SM1 cortex related to proprioception is impaired in diplegic CP. Therefore, the cortical and behavioral proprioceptive deficits should be better diagnosed and considered to better target individualized effective rehabilitation in CP.

TRPC4 Channel Knockdown in the Hippocampal CA1 Region Impairs Modulation of Beta Oscillations in Novel Context.

Hippocampal local field potentials (LFP) are highly related to behavior and memory functions. It has been shown that beta band LFP oscillations are correlated with contextual novelty and mnemonic performance. Evidence suggests that changes in neuromodulators, such as acetylcholine and dopamine, during exploration in a novel environment underlie changes in LFP. However, potential downstream mechanisms through which neuromodulators may alter the beta band oscillation in vivo remain to be fully understood. In this paper, we study the role of the membrane cationic channel TRPC4, which is modulated by various neuromodulators through G-protein-coupled receptors, by combining shRNA-mediated TRPC4 knockdown (KD) with LFP measurements in the CA1 region of the hippocampus in behaving mice. We demonstrate that the increased beta oscillation power seen in the control group mice in a novel environment is absent in the TRPC4 KD group. A similar loss of modulation was also seen in the low-gamma band oscillations in the TRPC4 KD group. These results demonstrate that TRPC4 channels are involved in the novelty-induced modulation of beta and low-gamma oscillations in the CA1 region.

Multi-channel EEG-based BCI using regression and classification methods for attention training by serious game

Background and Objective:Most of the existing brain–computer interfaces (BCIs) for attention cognitive training provide feedback only according to the classifier’s output, instead of biomarker of interest. This work aims to develop an electroencephalogram (EEG)-based BCI for sustained attention training, which monitors the user’s attention level by acquiring his/her neural information from specific brain regions, and translates it into control commands for a game, enhancing the modulation of theta (θ: 4–7 Hz) and beta (β: 13–30 Hz) rhythms over the attention network. Methods:The proposed BCI filters short-time EEG periods in a frequency range from 1 to 30 Hz, to later calculate covariance matrices and immediately extract feature vectors onto the Riemannian geometry space. Then, the support vector machine with the radial basic function kernel is trained to classify the attention and non-attention states. As a novelty, the designed BCI provides visual feedback more correlated with the user’s attention level and θ/β modulation, using a control strategy that combines the classifier’s output and the output of a cubic regression model. This model is fitted by weighting the feature vectors by considering the θ/β power ratios, in order to translate the neural information into control commands for the serious game. Twenty healthy subjects were divided into three groups to test the proposed BCI with different control strategies. The collected data were also used to evaluate both the BCI performance and the effect of adding θ/β in the control model. Results:The BCI reached accuracy up to 98% recognizing both attention and non-attention states. The average θ/β distribution on the user’s scalp showed reduction of this ratio in brain regions that play an important role during sustained attention tasks, such as frontal, temporal, parietal, and occipital lobes. This finding confirms that the control strategy considering θ/β from the frontotemporal cortex forced the modulation of this biomarker. Conclusions:Our approach and findings can contribute to the development of more effective EEG technologies for cognitive attention training.

Oscillatory neurofeedback networks and poststroke rehabilitative potential in severely impaired stroke patients

Motor restoration after severe stroke is often limited. However, some of the severely impaired stroke patients may still have a rehabilitative potential. Biomarkers that identify these patients are sparse.Eighteen severely impaired chronic stroke patients with a lack of volitional finger extension participated in an EEG study. During sixty-six trials of kinesthetic motor imagery, a brain-machine interface turned event-related beta-band desynchronization of the ipsilesional sensorimotor cortex into opening of the paralyzed hand by a robotic orthosis. A subgroup of eight patients participated in a subsequent four-week rehabilitation training. Changes of the movement extent were captured with sensors which objectively quantified even discrete improvements of wrist movement. Albeit with the same motor impairment level, patients could be differentiated into two groups, i.e., with and without task-related increase of bilateral cortico-cortical phase synchronization between frontal/premotor and parietal areas. This fronto-parietal integration (FPI) was associated with a significantly higher volitional beta modulation range in the ipsilesional sensorimotor cortex. Following the four-week training, patients with FPI showed significantly higher improvement in wrist movement than those without FPI. Moreover, only the former group improved significantly in the upper extremity Fugl-Meyer-Assessment score.Neurofeedback-related long-range oscillatory coherence may differentiate severely impaired stroke patients with regard to their rehabilitative potential, a finding that needs to be confirmed in larger patient cohorts.

Early lysosome defects precede neurodegeneration with Aβ and tau aggregation

AbstractBackgroundLoss‐of‐function mutations in the X‐linked endosomal Na+/H+ Exchanger 6 (NHE6) cause Christianson syndrome (CS) in males. CS involves endosome dysfunction leading to early cerebellar degeneration, as well as later‐onset cortical and subcortical neurodegeneration, potentially including tau deposition as reported in postmortem studies. In addition, there is reported evidence of modulation of amyloid beta (Aβ) levels in experimental models wherein NHE6 expression was targeted. For in vivo studies, rat models may have an advantage over mouse models for the study of neurodegeneration, as rat brain can demonstrate robust deposition of endogenously‐expressed Aβ and tau in certain pathological states. Mouse models generally do not show the accumulation of insoluble, endogenously‐expressed (non‐transgenic) tau or Aβ.MethodWe generated an NHE6‐null rat model of CS using CRISPR‐Cas9 genome‐editing technologies to study neurodegeneration in CS and the possibility of Aβ and tau pathology.ResultUsing this novel rat model, we were able to follow the sequence of pathogenic events in CS. NHE6‐null rats demonstrate an early and rapid loss of Purkinje cells in the cerebellum, as well as a more protracted neurodegenerative course in the cerebrum. In both the cerebellum and cerebrum, lysosome deficiency is an early pathogenic event, preceding autophagic dysfunction. Microglial and astrocyte activation also occur early. In the hippocampus and cortex, lysosome defects precede loss of pyramidal cells. Importantly, we subsequently observe biochemical and in situ evidence of both Aβ and tau aggregation in the aged NHE6‐null hippocampus and cortex (but not in the cerebellum). Tau deposition is widely distributed, including cortical and subcortical distributions. Interestingly, we observe tau deposition in both neurons and glia, as has been reported in CS postmortem studies previously.ConclusionThis new model is among very few examples of a genetically modified animal that exhibits neurodegeneration with deposition of endogenously‐expressed Aβ and tau. This NHE6‐null rat will serve as a new robust model for CS. Furthermore, these studies provide evidence for linkages between endo‐lysosome dysfunction and neurodegeneration involving protein aggregations, including Aβ and tau. Therefore these studies may provide insight into mechanisms of more common neurodegenerative disorders, including Alzheimer’s Disease and related dementias.

Movement-related beta ERD and ERS abnormalities in neuropsychiatric disorders.

Movement-related oscillations in the beta range (from 13 to 30 Hz) have been observed over sensorimotor areas with power decrease (i.e., event-related desynchronization, ERD) during motor planning and execution followed by an increase (i.e., event-related synchronization, ERS) after the movement's end. These phenomena occur during active, passive, imaged, and observed movements. Several electrophysiology studies have used beta ERD and ERS as functional indices of sensorimotor integrity, primarily in diseases affecting the motor system. Recent literature also highlights other characteristics of beta ERD and ERS, implying their role in processes not strictly related to motor function. Here we review studies about movement-related ERD and ERS in diseases characterized by motor dysfunction, including Parkinson's disease, dystonia, stroke, amyotrophic lateral sclerosis, cerebral palsy, and multiple sclerosis. We also review changes of beta ERD and ERS reported in physiological aging, Alzheimer's disease, and schizophrenia, three conditions without overt motor symptoms. The review of these works shows that ERD and ERS abnormalities are present across the spectrum of the examined pathologies as well as development and aging. They further suggest that cognition and movement are tightly related processes that may share common mechanisms regulated by beta modulation. Future studies with a multimodal approach are warranted to understand not only the specific topographical dynamics of movement-related beta modulation but also the general meaning of beta frequency changes occurring in relation to movement and cognitive processes at large. Such an approach will provide the foundation to devise and implement novel therapeutic approaches to neuropsychiatric disorders.

Electrophysiological and Clinical Predictors of Methylphenidate, Guanfacine, and Combined Treatment Outcomes in Children With Attention-Deficit/Hyperactivity Disorder

The combination of d-methylphenidate and guanfacine (an α-2A agonist) has emerged as a potential alternative to either monotherapy in children with attention-deficit/hyperactivity disorder (ADHD), but it is unclear what predicts response to these treatments. This study is the first to investigate pretreatment clinical and electroencephalography (EEG) profiles as predictors of treatment outcome in children randomized to these different medications. A total of 181 children with ADHD (aged 7-14 years; 123 boys) completed an 8-week randomized, double-blind, comparative study with d-methylphenidate, guanfacine, or combined treatments. Pretreatment assessments included ratings on ADHD, anxiety, and oppositional behavior. EEG activity from cortical sources localized within midfrontal and midoccipital regions was measured during a spatial working memory task with encoding, maintenance, and retrieval phases. Analyses tested whether pretreatment clinical and EEG measures predicted treatment-related change in ADHD severity. Higher pretreatment hyperactivity-impulsivity and oppositional symptoms and lower anxiety predicted greater ADHD improvements across all medication groups. Pretreatment event-related midfrontal beta power predicted treatment outcome with combined and monotherapy treatments, albeit in different directions. Weaker beta modulations predicted improvements with combined treatment, whereas stronger modulation during encoding and retrieval predicted improvements with d-methylphenidate and guanfacine, respectively. A multivariate model including EEG and clinical measures explained twice as much variance in ADHD improvement with guanfacine and combined treatment (R2= 0.34-0.41) as clinical measures alone (R2= 0.14-.21). We identified treatment-specific and shared predictors of response to different pharmacotherapies in children with ADHD. If replicated, these findings would suggest that aggregating information from clinical and brain measures may aid personalized treatment decisions in ADHD. Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; https://clinicaltrials.gov; NCT00429273.

Differential motor system entrainment to auditory and visual rhythms.

Perception of, and synchronization to, auditory rhythms is known to be more accurate than with flashing visual rhythms. The motor system is known to play a role in the processing of timing information for auditory rhythm perception, but it is unclear if the motor system plays the same role for visual rhythm perception. One demonstrated component of auditory rhythm perception is neural entrainment at the frequency of the auditory rhythm. In this study, we use EEG to measure the entrainment of both auditory and visual rhythms from the motor cortex while subjects either tapped in synchrony with or passively attended to the presented rhythms. To isolate activity from motor cortex, we used independent component analysis to first separate out neural sources, then selected components using a combination of component topography, dipole location, mu activation, and beta modulation. This process took advantage of the fact that tapping activity results in reduced mu power, and characteristic beta modulation, which helped select motor components. Our findings suggest neural entrainment in motor components was stronger for visual rhythms than auditory rhythms and strongest during the tapping conditions for both modalities. We also find mu power increased in response to both auditory and visual rhythms. These findings indicate that the generally greater rhythm perception capabilities of the auditory system over the visual system may not depend entirely on neural entrainment in the motor system, but rather how the motor system is able to use the timing information made available to it. NEW & NOTEWORTHY We investigated neural entrainment in the motor system for both auditory and visual isochronous rhythms using electroencephalogram. Counter to expectations, our findings suggest stronger entrainment for visual rhythms than for auditory rhythms. Motor system activity was isolated with a novel procedure using independent component analysis as a means of blind source separation, along with known markers of mu activity from the motor system to identify motor components.

Reduced sensorimotor beta dynamics could represent a “slowed movement state” in healthy individuals

It is well established that the amplitude of beta oscillations (∼13–30 Hz)—recorded over the sensorimotor cortex—distinctly change throughout movement. Specifically, a movement-related beta decrease (MRBD) occurs before and during movement, and a post-movement beta rebound (PMBR) follows. We investigated how the magnitude of the MRBD and PMBR vary when participants are put in an experimentally induced slow versus fast movement state. Individuals performed a task with blocks that elicited longer reaction times (RTs) and shorter RTs (SLOW and FAST blocks, respectively) while scalp-electroencephalography (EEG) was recorded. The timing of an upcoming movement was also modulated to create blocks with certain and uncertain response timing (FIXED and VARIED blocks, respectively). We found that beta modulation was reduced in SLOW blocks compared to FAST blocks (i.e., a less negative MRBD and less positive PMBR). For the movement certainty manipulation, we saw mixed behavioral and EEG results. Our primary finding of reduced beta modulation during an experimentally induced “slowed movement state” aligns with previous work showing reduced movement-related beta activity in patients with Parkinson's disease.

Dorsal-to-ventral imbalance in the superior longitudinal fasciculus mediates methylphenidate's effect on beta oscillations in ADHD.

While pharmacological treatment with methylphenidate (MPH) is a first line intervention for ADHD, its mechanisms of action have yet to be elucidated. We here seek to identify the white matter tracts that mediate MPH’s effect on beta oscillations. We implemented a double‐blind placebo‐controlled crossover design, where boys diagnosed with ADHD underwent behavioral and MEG measurements during a spatial attention task while on and off MPH. The results were compared with an age/IQ‐matched control group. Estimates of white matter tracts were obtained using diffusion tensor imaging (DTI). Via a stepwise model selection strategy, we identified the fiber tracts (regressors) significantly predicting values of the dependent variables of interest (i.e., oscillatory power, behavioral performance, and clinical symptoms): the anterior thalamic radiation (ATR), the superior longitudinal fasciculus (“parietal endings”) (SLFp), and superior longitudinal fasciculus (“temporal endings”) (SLFt). ADHD symptoms severity was associated with lower fractional anisotropy (FA) within the ATR. In addition, individuals with relatively higher FA in SLFp compared to SLFt, led to stronger behavioral effects of MPH in the form of faster and more accurate responses. Furthermore, the same parietotemporal FA gradient explained the effects of MPH on beta modulation: subjects with ADHD exhibiting higher FA in SLFp compared to SLFt also displayed greater effects of MPH on beta power during response preparation. Our data suggest that the behavioral deficits and aberrant oscillatory modulations observed in ADHD depend on a possibly detrimental structural connectivity imbalance within the SLF, caused by a diffusivity gradient in favor of parietal rather than temporal, fiber tracts.

Modulation of VEGF and TGF beta in 5-FU induced inflammation in MCF-7 using an herbal formulation

Acquired drug resistance is an increasing challenge in treating cancer with chemotherapy. One mechanism behind this resistance is the increased inflammation that supports the progression and development of cancer that arises because of the drug’s presence.&#x0D; Integrative oncology is the field that focuses on including natural products alongside traditional therapy to create a treatment that focuses on holistic patient well-being. In this in vitro study, we hypothesized that the use of an herbal formulation, consisting of turmeric and green tea, alongside a traditional chemotherapeutic drug, 5-fluorouracil (5-FU), can reduce the expression of two pro-cancer cytokines in breast cancer cells.&#x0D; Breast cancer cells were cultured and then treated with both 5-FU and the herbal formulation. We conducted enzyme-linked immunosorbent assays (ELISAs) to measure VEGF and TGFβ in the cell culture supernatant. The results clearly demonstrate that the use of the herbal formulation alongside the chemo drug significantly decreases the level of cytokines produced when compared to the levels produced when exposed solely to the chemo drug.&#x0D; Hence, we conclude that this combination of treatment, based on the principle of integrative oncology, shows potential for reducing the resistance against treatment conferred through increased inflammation. Consequently, this suggests a prospective way forward in improving the efficacy of cancer treatment.

Pop-out search instigates beta-gated feature selectivity enhancement across V4 layers

Visual search is a workhorse for investigating how attention interacts with processing of sensory information. Attentional selection has been linked to altered cortical sensory responses and feature preferences (i.e., tuning). However, attentional modulation of feature selectivity during search is largely unexplored. Here we map the spatiotemporal profile of feature selectivity during singleton search. Monkeys performed a search where a pop-out feature determined the target of attention. We recorded laminar neural responses from visual area V4. We first identified "feature columns" which showed preference for individual colors. In the unattended condition, feature columns were significantly more selective in superficial relative to middle and deep layers. Attending a stimulus increased selectivity in all layers but not equally. Feature selectivity increased most in the deep layers, leading to higher selectivity in extragranular layers as compared to the middle layer. This attention-induced enhancement was rhythmically gated in phase with the beta-band local field potential. Beta power dominated both extragranular laminar compartments, but current source density analysis pointed to an origin in superficial layers, specifically. While beta-band power was present regardless of attentional state, feature selectivity was only gated by beta in the attended condition. Neither the beta oscillation nor its gating of feature selectivity varied with microsaccade production. Importantly, beta modulation of neural activity predicted response times, suggesting a direct link between attentional gating and behavioral output. Together, these findings suggest beta-range synaptic activation in V4's superficial layers rhythmically gates attentional enhancement of feature tuning in a way that affects the speed of attentional selection.

Donepezil modulation of beta- amyloid oligomer phagocytosis in peripheral monocytes. Bed to bench observations from Alzheimer's disease patients

Beta-Amyloid (Abeta) aggregates are reputed to play a central role in AD pathogenesis, partly by triggering neuroinflammation. Peripheral monocytes can shift into the CNS, hence participating in Abeta oligomer clearance. Donepezil's anti-AD mechanism remains largely elusive; however, it can interact with monocyte α7nAChR that is involved in Abeta phagocytosis. We believe that by binding to α7nAChR, Donepezil can modulate Abeta internalization driven by both α7nAChR and TREM2.

Stimulation of the left dorsolateral prefrontal cortex with slow rTMS enhances verbal memory formation.

Encoding of episodic memories relies on stimulus-specific information processing and involves the left prefrontal cortex. We here present an incidental finding from a simultaneous EEG-TMS experiment as well as a replication of this unexpected effect. Our results reveal that stimulating the left dorsolateral prefrontal cortex (DLPFC) with slow repetitive transcranial magnetic stimulation (rTMS) leads to enhanced word memory performance. A total of 40 healthy human participants engaged in a list learning paradigm. Half of the participants (N = 20) received 1 Hz rTMS to the left DLPFC, while the other half (N = 20) received 1 Hz rTMS to the vertex and served as a control group. Participants receiving left DLPFC stimulation demonstrated enhanced memory performance compared to the control group. This effect was replicated in a within-subjects experiment where 24 participants received 1 Hz rTMS to the left DLPFC and vertex. In this second experiment, DLPFC stimulation also induced better memory performance compared to vertex stimulation. In addition to these behavioural effects, we found that 1 Hz rTMS to DLPFC induced stronger beta power modulation in posterior areas, a state that is known to be beneficial for memory encoding. Further analysis indicated that beta modulations did not have an oscillatory origin. Instead, the observed beta modulations were a result of a spectral tilt, suggesting inhibition of these parietal regions. These results show that applying 1 Hz rTMS to DLPFC, an area involved in episodic memory formation, improves memory performance via modulating neural activity in parietal regions.