Neurovascular Coupling Analysis Based on Multivariate Variational Gaussian Process Convergent Cross-Mapping.

Neurovascular coupling (NVC) provides important insights into the intricate activity of brain functioning and may aid in the early diagnosis of brain diseases. Emerging evidences have shown that NVC could be assessed by the coupling between electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). However, this endeavor presents significant challenges due to the absence of standardized methodologies and reliable techniques for coupling analysis of these two modalities. In this study, we introduced a novel method, i.e., the collaborative multi-output variational Gaussian process convergent cross-mapping (CMVGP-CCM) approach to advance coupling analysis of EEG and fNIRS. To validate the robustness and reliability of the CMVGP-CCM method, we conducted extensive experiments using chaotic time series models with varying noise levels, sequence lengths, and causal driving strengths. In addition, we employed the CMVGP-CCM method to explore the NVC between EEG and fNIRS signals collected from 26 healthy participants using a working memory (WM) task. Results revealed a significant causal effect of EEG signals, particularly the delta, theta, and alpha frequency bands, on the fNIRS signals during WM. This influence was notably observed in the frontal lobe, and its strength exhibited a decline as cognitive demands increased. This study illuminates the complex connections between brain electrical activity and cerebral blood flow, offering new insights into the underlying NVC mechanisms of WM.

Study on Improving the Modulatory Effect of Rhythmic Oscillations by Transcranial Magneto-Acoustic Stimulation.

In hippocampus, synaptic plasticity and rhythmic oscillations reflect the cytological basis and the intermediate level of cognition, respectively. Transcranial ultrasound stimulation (TUS) has demonstrated the ability to elicit changes in neural response. However, the modulatory effect of TUS on synaptic plasticity and rhythmic oscillations was insufficient in the present studies, which may be attributed to the fact that TUS acts mainly through mechanical forces. To enhance the modulatory effect on synaptic plasticity and rhythmic oscillations, transcranial magneto-acoustic stimulation (TMAS) which induced a coupled electric field together with TUS's ultrasound field was applied. The modulatory effect of TMAS and TUS with a pulse repetition frequency of 100 Hz were compared. TMAS/TUS were performed on C57 mice for 7 days at two different ultrasound intensities (3 W/cm2 and 5 W/cm [Formula: see text]. Behavioral tests, long-term potential (LTP) and local field potentials in vivo were performed to evaluate TUS/TMAS modulatory effect on cognition, synaptic plasticity and rhythmic oscillations. Protein expression based on western blotting were used to investigate the under- lying mechanisms of these beneficial effects. At 5 W/cm2, TMAS-induced LTP were 113.4% compared to the sham group and 110.5% compared to TUS. Moreover, the relative power of high gamma oscillations (50-100Hz) in the TMAS group ( 1.060±0.155 %) was markedly higher than that in the TUS group ( 0.560±0.114 %) and sham group ( 0.570±0.088 %). TMAS significantly enhanced the synchronization of theta and gamma oscillations as well as theta-gamma cross-frequency coupling. Whereas, TUS did not show relative enhancements. TMAS provides enhanced effect for modulating the synaptic plasticity and rhythmic oscillations in hippocampus.

Theta and alpha oscillations may underlie improved attention and working memory in musically trained children.

INTRODUCTION: Attention and working memory are key cognitive functions that allow us to select and maintain information in our mind for a short time, being essential for our daily life and, in particular, for learning and academic performance. It has been shown that musical training can improve working memory performance, but it is still unclear if and how the neural mechanisms of working memory and particularly attention are implicated in this process. In this work, we aimed to identify the oscillatory signature of bimodal attention and working memory that contributes to improved working memory in musically trained children. MATERIALS AND METHODS: We recruited children with and without musical training and asked them to complete a bimodal (auditory/visual) attention and working memory task, whereas their brain activity was measured using electroencephalography. Behavioral, time-frequency, and source reconstruction analyses were made. RESULTS: Results showed that, overall, musically trained children performed better on the task than children without musical training. When comparing musically trained children with children without musical training, we found modulations in the alpha band pre-stimuli onset and the beginning of stimuli onset in the frontal and parietal regions. These correlated with correct responses to the attended modality. Moreover, during the end phase of stimuli presentation, we found modulations correlating with correct responses independent of attention condition in the theta and alpha bands, in the left frontal and right parietal regions. CONCLUSIONS: These results suggest that musically trained children have improved neuronal mechanisms for both attention allocation and memory encoding. Our results can be important for developing interventions for people with attention and working memory difficulties.

Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole.

AIMS: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. METHODS: Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. RESULTS: We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. CONCLUSIONS: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.

A randomized controlled trial of intermittent theta burst stimulation to the medial prefrontal cortex for tobacco use disorder: Clinical efficacy and safety.

OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of administering intermittent theta burst stimulation (iTBS) to the medial prefrontal cortex for tobacco use disorder. METHODS: A randomized sham-controlled trial was conducted, with 38 participants receiving 28 sessions of active (n=25) or sham (n=13) iTBS (2 sessions/day, 600 pulses/session, 110% resting motor threshold, AFz target) along with smoking cessation education (Forever Free © booklets) over 14 visits. Primary outcomes included self-reported cigarette consumption and abstinence, verified by urinary cotinine tests. Secondary outcomes included symptoms of tobacco use disorder, negative mood, and safety/tolerability. RESULTS: Both active and sham groups reported reduced cigarette consumption (ß = -0.12, p = 0.015), cigarette craving (ß = -0.16, p = 0.002), and tobacco withdrawal symptoms (ß = -0.05, p < 0.001). However, there were no significant time x group interaction effects for any measure. Similarly, the two groups had no significant differences in urinary cotinine-verified abstinence. Adverse events occurred with similar frequency in both groups. CONCLUSION: There were no differences in cigarette consumption between the active and sham iTBS groups, both groups decreased cigarette consumption similarly. Further research is needed to compare iTBS to standard high-frequency rTMS and explore the potential differences in efficacy. Despite limitations, this study contributes to experimental design considerations for TMS as a novel intervention for tobacco and other substance use disorders, emphasizing the need for a more comprehensive understanding of the stimulation parameters and target sites.

Single session of intermittent theta burst stimulation alters brain activity of patients in vegetative state.

BACKGROUND: Non-invasive brain stimulation is considered as a promising technology for treating patients with disorders of consciousness (DOC). Various approaches and protocols have been proposed; however, few of them have shown potential effects on patients with vegetative state (VS). This study aimed to explore the neuro-modulation effects of intermittent theta burst stimulation (iTBS) on the brains of patients with VS and to provide a pilot investigation into its possible role in treating such patients. METHODS: We conducted a sham-controlled crossover study, a real and a sham session of iTBS were delivered over the left dorsolateral prefrontal cortex of such patients. A measurement of an electroencephalography (EEG) and a behavioral assessment of the Coma Recovery Scale-Revised (CRS-R) were applied to evaluate the modulation effects of iTBS before and after stimulation. RESULTS: No meaningful changes of CRS-R were found. The iTBS altered the spectrum, complexity and functional connectivity of the patients. The real stimulation induced a trend of decreasing of delta power at T1 and T2 in the frontal region, significant increasing of permutation entropy at the T2 in the left frontal region. In addition, brain functional connectivity, particularly inter-hemispheric connectivity, was strengthened between the electrodes of the frontal region. The sham stimulation, however, did not induce any significant changes of the brain activity. CONCLUSIONS: One session of iTBS significantly altered the oscillation power, complexity and functional connectivity of brain activity of VS patients. It may be a valuable tool on modulating the brain activities of patients with VS.

Frontal Theta Asymmetry may be a new target for reducing the severity of depression and improving cognitive function in depressed patients.

BACKGROUND: The prevalence of depressive disorder is increasing due to a variety of factors, which brings a huge strain on individuals, families and society. This study aims to investigate whether there is Frontal Theta Asymmetry (FTA) in depressed patients, and whether FTAs are related to depression severity and cognitive function changes in depressed patients. METHODS: Participants who met the inclusion criteria were enrolled in this study. Socio-demographic data of each participant were recorded. Zung's self-rating Depression Scale was used to assess the depression status of participants. P300 was used to evaluate the cognitive function of participants. EEG data from participants were collected by the NeuroScan SynAmps RT EEG system. t-test, Wilcoxon rank-sum test and Chi-square test were used to detect the differences of different variables between the two groups. Multiple linear regression analysis and multiple logistic regression analysis were used to analyze relationships between FTAs in different regions and participants' depression status and cognitive function. RESULTS: A total of 66 depressed participants and 47 healthy control participants were included in this study. The theta spectral power of the left frontal lobe was slightly stronger than that of the right frontal lobe in the depression group, while the opposite was true in the healthy control group. The FTA in F3/F4 had certain effects on the emergence of depression in participants, the emergence of depression in participants and Changes in cognitive function. CONCLUSIONS: FTAs are helpful to assess the severity of depression and early identify cognitive impairment in patients with depression.

Morpho-electric diversity of human hippocampal CA1 pyramidal neurons.

Hippocampal pyramidal neuron activity underlies episodic memory and spatial navigation. Although extensively studied in rodents, extremely little is known about human hippocampal pyramidal neurons, even though the human hippocampus underwent strong evolutionary reorganization and shows lower theta rhythm frequencies. To test whether biophysical properties of human Cornu Amonis subfield 1 (CA1) pyramidal neurons can explain observed rhythms, we map the morpho-electric properties of individual CA1 pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery. Human CA1 pyramidal neurons have much larger dendritic trees than mouse CA1 pyramidal neurons, have a large number of oblique dendrites, and resonate at 2.9 Hz, optimally tuned to human theta frequencies. Morphological and biophysical properties suggest cellular diversity along a multidimensional gradient rather than discrete clustering. Across the population, dendritic architecture and a large number of oblique dendrites consistently boost memory capacity in human CA1 pyramidal neurons by an order of magnitude compared to mouse CA1 pyramidal neurons.

Prefrontal-subthalamic theta signaling mediates delayed responses during conflict processing.

While medial frontal cortex (MFC) and subthalamic nucleus (STN) have been implicated in conflict monitoring and action inhibition, respectively, an integrated understanding of the spatiotemporal and spectral interaction of these nodes and how they interact with motor cortex (M1) to definitively modify motor behavior during conflict is lacking. We recorded neural signals intracranially across presupplementary motor area (preSMA), M1, STN, and globus pallidus internus (GPi), during a flanker task in 20 patients undergoing deep brain stimulation implantation surgery for Parkinson disease or dystonia. Conflict is associated with sequential and causal increases in local theta power from preSMA to STN to M1 with movement delays directly correlated with increased STN theta power, indicating preSMA is the MFC locus that monitors conflict and signals STN to implement a 'break.' Transmission of theta from STN-to-M1 subsequently results in a transient increase in M1-to-GPi beta flow immediately prior to movement, modulating the motor network to actuate the conflict-related action inhibition (i.e., delayed response). Action regulation during conflict relies on two distinct circuits, the conflict-related theta and movement-related beta networks, that are separated spatially, spectrally, and temporally, but which interact dynamically to mediate motor performance, highlighting complex parallel yet interacting networks regulating movement.

Control of working memory by phase-amplitude coupling of human hippocampal neurons.

Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta-gamma phase-amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3-5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.

Cross-strata co-occurrence of ripples with theta-frequency oscillations in the hippocampus of foraging rats.

Brain rhythms have been postulated to play central roles in animal cognition. A prominently reported dichotomy of hippocampal rhythms links theta-frequency oscillations (4-12 Hz) and ripples (120-250 Hz) exclusively to preparatory and consummatory behaviours, respectively. However, because of the differential power expression of these two signals across hippocampal strata, such exclusivity requires validation through analyses of simultaneous multi-strata recordings. We assessed co-occurrence of theta-frequency oscillations with ripples in multi-channel recordings of extracellular potentials across hippocampal strata from foraging rats. We detected all ripple events from an identified stratum pyramidale (SP) channel. We then defined theta epochs based on theta oscillations detected from the stratum lacunosum-moleculare (SLM) or the stratum radiatum (SR). We found ∼20% of ripple events (in SP) to co-occur with theta epochs identified from SR/SLM channels, defined here as theta ripples. Strikingly, when theta epochs were instead identified from the SP channel, such co-occurrences were significantly reduced because of a progressive reduction in theta power along the SLM-SR-SP axis. Behaviourally, we found most theta ripples to occur during immobile periods, with comparable theta power during exploratory and immobile theta epochs. Furthermore, the progressive reduction in theta power along the SLM-SR-SP axis was common to exploratory and immobile periods. Finally, we found a strong theta-phase preference of theta ripples within the fourth quadrant [3π/2 - 2π] of the associated theta oscillation. The prevalence of theta ripples expands the potential roles of ripple-frequency oscillations to span the continuum of encoding, retrieval and consolidation, achieved through interactions with theta oscillations. KEY POINTS: The brain manifests oscillations in recorded electrical potentials, with different frequencies of oscillation associated with distinct behavioural states. A prominently reported dichotomy assigns theta-frequency oscillations (4-12 Hz) and ripples (120-250 Hz) recorded in the hippocampus to be exclusively associated with preparatory and consummatory behaviours, respectively. Our multi-strata recordings from the rodent hippocampus coupled with cross-strata analyses provide direct quantitative evidence for the occurrence of ripple events nested within theta oscillations. These results highlight the need for an analysis pipeline that explicitly accounts for the specific strata where individual oscillatory power is high, in analysing simultaneously recorded data from multiple strata. Our observations open avenues for investigations involving cross-strata interactions between theta oscillations and ripples across different behavioural states.

Theta Phase Entrainment of Single-Cell Spiking in Rat Somatosensory Barrel Cortex and Secondary Visual Cortex Is Enhanced during Multisensory Discrimination Behavior.

Phase entrainment of cells by theta oscillations is thought to globally coordinate the activity of cell assemblies across different structures, such as the hippocampus and neocortex. This coordination is likely required for optimal processing of sensory input during recognition and decision-making processes. In quadruple-area ensemble recordings from male rats engaged in a multisensory discrimination task, we investigated phase entrainment of cells by theta oscillations in areas along the corticohippocampal hierarchy: somatosensory barrel cortex (S1BF), secondary visual cortex (V2L), perirhinal cortex (PER), and dorsal hippocampus (dHC). Rats discriminated between two 3D objects presented in tactile-only, visual-only, or both tactile and visual modalities. During task engagement, S1BF, V2L, PER, and dHC LFP signals showed coherent theta-band activity. We found phase entrainment of single-cell spiking activity to locally recorded as well as hippocampal theta activity in S1BF, V2L, PER, and dHC. While phase entrainment of hippocampal spikes to local theta oscillations occurred during sustained epochs of task trials and was nonselective for behavior and modality, somatosensory and visual cortical cells were only phase entrained during stimulus presentation, mainly in their preferred modality (S1BF, tactile; V2L, visual), with subsets of cells selectively phase-entrained during cross-modal stimulus presentation (S1BF: visual; V2L: tactile). This effect could not be explained by modulations of firing rate or theta amplitude. Thus, hippocampal cells are phase entrained during prolonged epochs, while sensory and perirhinal neurons are selectively entrained during sensory stimulus presentation, providing a brief time window for coordination of activity.

Electrophysiological Properties of the Medial Mammillary Bodies across the Sleep-Wake Cycle.

The medial mammillary bodies (MBs) play an important role in the formation of spatial memories; their dense inputs from hippocampal and brainstem regions makes them well placed to integrate movement-related and spatial information, which is then extended to the anterior thalamic nuclei and beyond to the cortex. While the anatomical connectivity of the medial MBs has been well studied, much less is known about their physiological properties, particularly in freely moving animals. We therefore carried out a comprehensive characterization of medial MB electrophysiology across arousal states by concurrently recording from the medial MB and the CA1 field of the hippocampus in male rats. In agreement with previous studies, we found medial MB neurons to have firing rates modulated by running speed and angular head velocity, as well as theta-entrained firing. We extended the characterization of MB neuron electrophysiology in three key ways: (1) we identified a subset of neurons (25%) that exhibit dominant bursting activity; (2) we showed that ∼30% of theta-entrained neurons exhibit robust theta cycle skipping, a firing characteristic that implicates them in a network for prospective coding of position; and (3) a considerable proportion of medial MB units showed sharp-wave ripple (SWR) responsive firing (∼37%). The functional heterogeneity of MB electrophysiology reinforces their role as an integrative node for mnemonic processing and identifies potential roles for the MBs in memory consolidation through propagation of SWR-responsive activity to the anterior thalamus and prospective coding in the form of theta cycle skipping.

Two are better than one: Differences in cortical EEG patterns during auditory and visual verbal working memory processing between Unilateral and Bilateral Cochlear Implanted children.

Despite the proven effectiveness of cochlear implant (CI) in the hearing restoration of deaf or hard-of-hearing (DHH) children, to date, extreme variability in verbal working memory (VWM) abilities is observed in both unilateral and bilateral CI user children (CIs). Although clinical experience has long observed deficits in this fundamental executive function in CIs, the cause to date is still unknown. Here, we have set out to investigate differences in brain functioning regarding the impact of monaural and binaural listening in CIs compared with normal hearing (NH) peers during a three-level difficulty n-back task undertaken in two sensory modalities (auditory and visual). The objective of this pioneering study was to identify electroencephalographic (EEG) marker pattern differences in visual and auditory VWM performances in CIs compared to NH peers and possible differences between unilateral cochlear implant (UCI) and bilateral cochlear implant (BCI) users. The main results revealed differences in theta and gamma EEG bands. Compared with hearing controls and BCIs, UCIs showed hypoactivation of theta in the frontal area during the most complex condition of the auditory task and a correlation of the same activation with VWM performance. Hypoactivation in theta was also observed, again for UCIs, in the left hemisphere when compared to BCIs and in the gamma band in UCIs compared to both BCIs and NHs. For the latter two, a correlation was found between left hemispheric gamma oscillation and performance in the audio task. These findings, discussed in the light of recent research, suggest that unilateral CI is deficient in supporting auditory VWM in DHH. At the same time, bilateral CI would allow the DHH child to approach the VWM benchmark for NH children. The present study suggests the possible effectiveness of EEG in supporting, through a targeted approach, the diagnosis and rehabilitation of VWM in DHH children.

Preoperative recovery sleep ameliorates postoperative cognitive dysfunction aggravated by sleep fragmentation in aged mice by enhancing EEG delta-wave activity and LFP theta oscillation in hippocampal CA1.

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

Event-related theta and gamma band oscillatory dynamics during visuo-spatial sequence memory in younger and older adults.

Visuo-spatial working memory (VSWM) for sequences is thought to be crucial for daily behaviors. Decades of research indicate that oscillations in the gamma and theta bands play important functional roles in the support of visuo-spatial working memory, but the vast majority of that research emphasizes measures of neural activity during memory retention. The primary aims of the present study were (1) to determine whether oscillatory dynamics in the Theta and Gamma ranges would reflect item-level sequence encoding during a computerized spatial span task, (2) to determine whether item-level sequence recall is also related to these neural oscillations, and (3) to determine the nature of potential changes to these processes in healthy cognitive aging. Results indicate that VSWM sequence encoding is related to later (∼700 ms) gamma band oscillatory dynamics and may be preserved in healthy older adults; high gamma power over midline frontal and posterior sites increased monotonically as items were added to the spatial sequence in both age groups. Item-level oscillatory dynamics during the recall of VSWM sequences were related only to theta-gamma phase amplitude coupling (PAC), which increased monotonically with serial position in both age groups. Results suggest that, despite a general decrease in frontal theta power during VSWM sequence recall in older adults, gamma band dynamics during encoding and theta-gamma PAC during retrieval play unique roles in VSWM and that the processes they reflect may be spared in healthy aging.

Unlocking Therapeutic Potential: The Role of Theta Burst Stimulation in Multiple Sclerosis Management.

Objective: Current therapies for multiple sclerosis (MS) often have limited efficacy and side effects, necessitating alternative approaches. Noninvasive brain stimulation (NIBS), such as transcranial direct current stimulation and transcranial magnetic stimulation (TMS), offers potential solutions. Among NIBS techniques, theta burst stimulation (TBS) is notable for its ability to modulate cortical activity. The objective of this systematic review is to assess the impact of TBS on MS symptoms.Data Sources: The study conducted rigorous systematic searches in PubMed, Google Scholar, and Scopus databases up to June 2023, using specific Medical Subject Headings terms related to NIBS and MS, such as TMS and TBS, in conjunction with terms like MS or demyelinating disease. Additionally, the bibliographic references of included studies, book chapters, and original articles were manually reviewed.Study Selection: The study selection process involved a 2-tiered screening mechanism, beginning with an evaluation of titles and abstracts, followed by a full-text review of selected articles. Inclusion criteria incorporated randomized controlled trials (RCTs) focusing on TBS with MS patients. Exclusion criteria included non-qualitative, non-MS, and non-TBS studies. Risk of bias assessment was conducted using the 2008 Cochrane Risk of Bias 2 Scale for RCTs.Data Extraction: Data extraction was conducted by thoroughly reviewing each research article and systematically recording the relevant information using a standardized data extraction form, ensuring consistency and accuracy throughout the process.Results: In a systematic review encompassing 5 randomized controlled trials involving 117 individuals with relapsing-remitting or secondary progressive MS across Italy, France, and Russia, various forms of TBS were applied. These interventions ranged from intermittent TBS (iTBS) to continuous intermittent TBS (c-iTBS) that demonstrated favorable outcomes. Notably, TBS interventions led to significant reductions in spasticity, fatigue, and pain, with c-iTBS combined with vestibular rehabilitation showing additional improvements in vestibular-ocular reflexes, gait, and balance. While specific protocols varied among the studies, collectively, the results suggest promise for TBS approaches in alleviating MS-related symptoms.Conclusions: The findings of this review suggest that TBS may hold promise in addressing specific MS symptoms, notably fatigue and spasticity. Future research should include a more diverse participant pool to explore TBS effects across different MS subtypes and aim for larger sample sizes to enhance statistical power and result reliability.Prim Care Companion CNS Disord 2024;26(2):23r03645. Author affiliations are listed at the end of this article.

Increases in pre-stimulus theta and alpha oscillations precede successful encoding of crossmodal associations.

A central aspect of episodic memory is the formation of associations between stimuli from different modalities. Current theoretical approaches assume a functional role of ongoing oscillatory power and phase in the theta band (3-7 Hz) for the encoding of crossmodal associations. Furthermore, ongoing activity in the theta range as well as alpha (8-12 Hz) and low beta activity (13-20 Hz) before the presentation of a stimulus is thought to modulate subsequent cognitive processing, including processes that are related to memory. In this study, we tested the hypothesis that pre-stimulus characteristics of low frequency activity are relevant for the successful formation of crossmodal memory. The experimental design that was used specifically allowed for the investigation of associative memory independent from individual item memory. Participants (n = 51) were required to memorize associations between audiovisual stimulus pairs and distinguish them from newly arranged ones consisting of the same single stimuli in the subsequent recognition task. Our results show significant differences in the state of pre-stimulus theta and alpha power between remembered and not remembered crossmodal associations, clearly relating increased power to successful recognition. These differences were positively correlated with memory performance, suggesting functional relevance for behavioral measures of associative memory. Further analysis revealed similar effects in the low beta frequency ranges, indicating the involvement of different pre-stimulus-related cognitive processes. Phase-based connectivity measures in the theta band did not differ between remembered and not remembered stimulus pairs. The findings support the assumed functional relevance of theta band oscillations for the formation of associative memory and demonstrate that an increase of theta as well as alpha band oscillations in the pre-stimulus period is beneficial for the establishment of crossmodal memory.

The Important Role of the Right Dorsolateral Prefrontal Cortex in Conflict Adaptation: A Combined Voxel-Based Morphometry and Continuous Theta Burst Stimulation Study.

Humans can flexibly adjust their executive control to resolve conflicts. Conflict adaptation and conflict resolution are crucial aspects of conflict processing. Functional neuroimaging studies have associated the dorsolateral prefrontal cortex (DLPFC) with conflict processing, but its causal role remains somewhat controversial. Moreover, the neuroanatomical basis of conflict processing has not been thoroughly examined. In this study, the Stroop task, a well-established measure of conflict, was employed to investigate (1) the neuroanatomical basis of conflict resolution and conflict adaptation with the voxel-based morphometry analysis, (2) the causal role of DLPFC in conflict processing with the application of the continuous theta burst stimulation to DLPFC. The results revealed that the Stroop effect was correlated to the gray matter volume of the precuneus, postcentral gyrus, and cerebellum, and the congruency sequence effect was correlated to the gray matter volume of superior frontal gyrus, postcentral gyrus, and lobule paracentral gyrus. These findings indicate the neuroanatomical basis of conflict resolution and adaptation. In addition, the continuous theta burst stimulation over the right DLPFC resulted in a significant reduction in the Stroop effect of RT after congruent trials compared with vertex stimulation and a significant increase in the Stroop effect of accuracy rate after incongruent trials than congruent trials, demonstrating the causal role of right DLPFC in conflict adaptation. Moreover, the DLPFC stimulation did not affect the Stroop effect of RT and accuracy rate. Overall, our study offers further insights into the neural mechanisms underlying conflict resolution and adaptation.

Optogenetic stimulation of medial septal glutamatergic neurons modulates theta-gamma coupling in the hippocampus.

Hippocampal cross-frequency theta-gamma coupling (TGC) is a basic mechanism for information processing, retrieval, and consolidation of long-term and working memory. While the role of entorhinal afferents in the modulation of hippocampal TGC is widely accepted, the influence of other main input to the hippocampus, from the medial septal area (MSA, the pacemaker of the hippocampal theta rhythm) is poorly understood. Optogenetics allows us to explore how different neuronal populations of septohippocampal circuits control neuronal oscillations in vivo. Rhythmic activation of septal glutamatergic neurons has been shown to drive hippocampal theta oscillations, but the role of these neuronal populations in information processing during theta activation has remained unclear. Here we investigated the influence of phasic activation of MSA glutamatergic neurons expressing channelrhodopsin II on theta-gamma coupling in the hippocampus. During the experiment, local field potentials of MSA and hippocampus of freely behaving mice were modulated by 470 nm light flashes with theta frequency (2-10) Hz. It was shown that both the power and the strength of modulation of gamma rhythm nested on hippocampal theta waves depend on the frequency of stimulation. The modulation of the amplitude of slow gamma rhythm (30-50 Hz) prevailed over modulation of fast gamma (55-100 Hz) during flash trains and the observed effects were specific for theta stimulation of MSA. We discuss the possibility that phasic depolarization of septal glutamatergic neurons controls theta-gamma coupling in the hippocampus and plays a role in memory retrieval and consolidation.