Deep Brain Regions Research Articles

Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior

Neural population dynamics relevant to behavior vary over multiple spatial and temporal scales across three-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice, enabling the investigation of cell-type- and neurotransmitter-specific signals over arbitrary 3D volumes at a spatial resolution and coverage previously inaccessible. We applied this method to resolve rapid dopamine release dynamics across the striatum, revealing distinct, modality-specific spatiotemporal patterns in response to salient sensory stimuli extending over millimeters of tissue. Targeted optogenetics enabled flexible control of neural signaling on multiple spatial scales, better matching endogenous signaling patterns, and the spatial localization of behavioral function across large circuits.

Controlled noninvasive modulation of deep brain regions in humans

Transcranial focused ultrasound provides noninvasive and reversible approaches for precise and personalized manipulations of brain circuits, with the potential to transform our understanding of brain function and treatments of brain dysfunction. However, effective applications in humans have been limited by the human head, which attenuates and distorts ultrasound severely and unpredictably. This has led to uncertain ultrasound intensities delivered into the brain. Here, we address this lingering barrier using a direct measurement approach that can be repeatedly applied to the human brain. The approach uses an ultrasonic scan of the head to measure and compensate for the attenuation of the ultrasound by all obstacles within the ultrasound path. No other imaging modality is required and the method is parameter-free and personalized to each subject. The approach accurately restores operators’ intended intensities inside ex-vivo human skulls. Moreover, the approach is critical for effective modulation of deep brain regions in humans. When applied, the approach modulates fMRI Blood Oxygen Level Dependent (BOLD) activity in disease-relevant deep brain regions. This tool unlocks the potential of emerging approaches based on low-intensity ultrasound for controlled manipulations of neural circuits in humans.

Quantitative comparison of CSVD imaging markers between patients with possible amyloid small vessel disease and with non-amyloid small vessel disease

The spatial distribution patterns of cerebral microbleeds are associated with different types of cerebral small vessel disease (CSVD). This study aims to examine the disparities in brain imaging markers of CSVD among patients diagnosed with possible amyloid and non-amyloid small vessel disease. The head MR scans including susceptibility-weighted imaging (SWI) sequences from 351 patients at our institute were collected for analysis. CSVD imaging markers were quantified or graded across various CSVD dimensions in the patient images. Patients were categorized into the cerebral amyloid angiopathy group (CAA), hypertensive arteriopathy group (HA), or mixed small vessel disease group (Mixed), based on the spatial distribution of microbleeds. White matter lesions (WML) were segmented using an artificial neural network and assessed via a voxel-wise approach. Significant differences were observed among the three groups in several indices: microbleed count, lacune count at the centrum semiovale and basal ganglia levels, grade of enlarged perivascular space (EPVS) at the basal ganglia, and white matter lesion volume. These indices were substantially higher in the Mixed group compared to the other groups. Additionally, the incidences of cerebral hemorrhages (χ2 = 7.659, P = 0.006) and recent small subcortical infarcts (χ2 = 4.660, P = 0.031) were significantly more frequent in the HA group than in the CAA group. These results indicate that mixed spatial distribution patterns of microbleeds demonstrated the highest burden of cerebral small vessel disease. Microbleeds located in the deep brain regions were associated with a higher incidence of recent small subcortical infarcts and cerebral hemorrhages compared to those in the cortical areas.

Real-Time Precise Targeting of the Subthalamic Nucleus via Transfer Learning in a Rat Model of Parkinson's Disease Based on Microelectrode Arrays.

In neurodegenerative disorders, neuronal firing patterns and oscillatory activity are remarkably altered in specific brain regions, which can serve as valuable biomarkers for the identification of deep brain regions. The subthalamic nucleus (STN) has been the primary target for DBS in patients with Parkinson's disease (PD). In this study, changes in the spike firing patterns and spectral power of local field potentials (LFPs) in the pre-STN (zona incerta, ZI) and post-STN (cerebral peduncle, cp) regions were investigated in PD rats, providing crucial evidence for the functional localization of the STN. Sixteen-channel microelectrode arrays (MEAs) with sites distributed at different depths and widths were utilized to record neuronal activities. The spikes in the STN exhibited higher firing rates than those in the ZI and cp. Furthermore, the LFP power in the delta band in the STN was the greatest, followed by that in the ZI, and was greater than that in the cp. Additionally, increased LFP power was observed in the beta bands in the STN. To identify the best performing classification model, we applied various convolutional neural networks (CNNs) based on transfer learning to analyze the recorded raw data, which were processed using the Gram matrix of the spikes and the fast Fourier transform of the LFPs. The best transfer learning model achieved an accuracy of 95.16%. After fusing the spike and LFP classification results, the time precision for processing the raw data reached 500 ms. The pretrained model, utilizing raw data, demonstrated the feasibility of employing transfer learning for training models on neural activity. This approach highlights the potential for functional localization within deep brain regions.

Metabolic and vascular imaging markers for investigating Alzheimer's disease complicated by sleep fragmentation in mice.

Sleep problem is a common complication of Alzheimer's disease (AD). Extensive preclinical studies have been performed to investigate the AD pathology. However, the pathophysiological consequence of AD complicated by sleep problem remains to be further determined. To investigate brain metabolism and perfusion in an AD mouse model complicated by sleep problem, and subsequently identify potential imaging markers to better understand the associated pathophysiology. We examined the oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO2), and cerebral blood flow (CBF) using state-of-the-art MRI techniques in a cohort of 5xFAD model mice. Additionally, neuroinflammation, indicated by activated microglia, was assessed using histology techniques. Sleep fragmentation (SF) was utilized as a representative for sleep problems. SF was associated with significant increases in OEF (P = 0.023) and CMRO2 (P = 0.029), indicating a state of hypermetabolism. CBF showed a significant genotype-by-sleep interaction effect (P = 0.026), particularly in the deep brain regions such as the hippocampus and thalamus. Neuroinflammation was primarily driven by genotype rather than SF, especially in regions with significant interaction effect in CBF measurements. These results suggest that brain metabolism and perfusion measurements are promising markers for studying the co-pathogenesis of AD and SF.

Correlation between Cerebral Microbleeds and White Matter Changes on MRI using Microbleed Anatomical Rating and Fazekas Scales: A Cross-sectional Study

Introduction: Cerebral Microbleeds (CMBs) are small perivascular haemosiderin deposits in the brain that indicate bleeding events. The location of CMBs can provide insights into their underlying causes. CMBs found in peripheral lobar locations are often associated with cerebral amyloid angiopathy, while those occurring in deeper brain regions are more likely linked to hypertensive arteriopathy. White matter changes, known as Leukoaraiosis, have been linked to adverse cognitive functions, share risk factors with hypertension and microbleeds, and are associated with the severity of CMBs. Aim: To determine the correlation between CMBs and white matter changes on Magnetic Resonance Imagning (MRI) using the Microbleed Anatomical Rating Scale (MARS) and Fazekas scales. Materials and Methods: An analytical cross-sectional study was conducted in the Department of Radiodiagnosis, MS Ramaiah Hospitals, Bengaluru, Karnataka, India between November 2019 and June 2021, involving 65 subjects who underwent MRI brain scans at a tertiary care institute and were found to have microbleeds. Brain MRIs were performed using a 1.5 Tesla MRI Scanning Unit. Microbleeds were graded using the MARS, while white matter changes were graded using the Fazekas scale. The Chi-square test was employed to assess the significance of categorical data, and Spearman’s correlation was used to determine the correlation between MARS and Fazekas scale variables. Results: The subjects had a mean age range of 61 to 70 years, with a male-to-female ratio of 2:1. There was a significant correlation between MARS grade and Fazekas scale (p<0.001) with a correlation coefficient (r-value) of 1. The most commonly associated stroke subtype was lacunar infarct. Conclusion: There is a significant correlation between Leukoaraiosis (LA) and CMBs, indicating the end results of small vessel ischaemia and bleeding.

Development of wafer-scale multifunctional nanophotonic neural probes for brain activity mapping.

Optical techniques, such as optogenetic stimulation and functional fluorescence imaging, have been revolutionary for neuroscience by enabling neural circuit analysis with cell-type specificity. To probe deep brain regions, implantable light sources are crucial. Silicon photonics, commonly used for data communications, shows great promise in creating implantable devices with complex optical systems in a compact form factor compatible with high volume manufacturing practices. This article reviews recent developments of wafer-scale multifunctional nanophotonic neural probes. The probes can be realized on 200 or 300 mm wafers in commercial foundries and integrate light emitters for photostimulation, microelectrodes for electrophysiological recording, and microfluidic channels for chemical delivery and sampling. By integrating active optical devices to the probes, denser emitter arrays, enhanced on-chip biosensing, and increased ease of use may be realized. Silicon photonics technology makes possible highly versatile implantable neural probes that can transform neuroscience experiments.

Novel inductively coupled ear-bars (ICEs) to enhance restored fMRI signal from susceptibility compensation in rats.

Functional magnetic resonance imaging faces inherent challenges when applied to deep-brain areas in rodents, e.g. entorhinal cortex, due to the signal loss near the ear cavities induced by susceptibility artifacts and reduced sensitivity induced by the long distance from the surface array coil. Given the pivotal roles of deep brain regions in various diseases, optimized imaging techniques are needed. To mitigate susceptibility-induced signal losses, we introduced baby cream into the middle ear. To enhance the detection sensitivity of deep brain regions, we implemented inductively coupled ear-bars, resulting in approximately a 2-fold increase in sensitivity in entorhinal cortex. Notably, the inductively coupled ear-bar can be seamlessly integrated as an add-on device, without necessitating modifications to the scanner interface. To underscore the versatility of inductively coupled ear-bars, we conducted echo-planner imaging-based task functional magnetic resonance imaging in rats modeling Alzheimer's disease. As a proof of concept, we also demonstrated resting-state-functional magnetic resonance imaging connectivity maps originating from the left entorhinal cortex-a central hub for memory and navigation networks-to amygdala hippocampal area, Insular Cortex, Prelimbic Systems, Cingulate Cortex, Secondary Visual Cortex, and Motor Cortex. This work demonstrates an optimized procedure for acquiring large-scale networks emanating from a previously challenging seed region by conventional magnetic resonance imaging detectors, thereby facilitating improved observation of functional magnetic resonance imaging outcomes.

Simulation study on high spatio-temporal resolution acousto-electrophysiological neuroimaging.

Objective.Acousto-electrophysiological neuroimaging (AENI) is a technique hypothesized to record electrophysiological activity of the brain with millimeter spatial and sub-millisecond temporal resolution. This improvement is obtained by tagging areas with focused ultrasound (fUS). Due to mechanical vibration with respect to the measuring electrodes, the electrical activity of the marked region will be modulated onto the ultrasonic frequency. The region's electrical activity can subsequently be retrieved via demodulation of the measured signal. In this study, the feasibility of this hypothesized technique is tested.Approach.This is done by calculating the forward electroencephalography response under quasi-static assumptions. The head is simplified as a set of concentric spheres. Two sizes are evaluated representing human and mouse brains. Moreover, feasibility is assessed for wet and dry transcranial, and for cortically placed electrodes. The activity sources are modeled by dipoles, with their current intensity profile drawn from a power-law power spectral density.Results.It is shown that mechanical vibration modulates the endogenous activity onto the ultrasonic frequency. The signal strength depends non-linearly on the alignment between dipole orientation, vibration direction and recording point. The strongest signal is measured when these three dependencies are perfectly aligned. The signal strengths are in the pV-range for a dipole moment of 5 nAm and ultrasonic pressures within Food and Drug Administration (FDA)-limits. The endogenous activity can then be accurately reconstructed via demodulation. Two interference types are investigated: vibrational and static. Depending on the vibrational interference, it is shown that millimeter resolution signal detection is possible also for deep brain regions. Subsequently, successful demodulation depends on the static interference, that at MHz-range has to be sub-picovolt.Significance.Our results show that mechanical vibration is a possible underlying mechanism of acousto-electrophyisological neuroimaging. This paper is a first step towards improved understanding of the conditions under which AENI is feasible.

Noninvasive Deep Brain Stimulation via Temporal Interference Electric Fields Enhanced Motor Performance of Mice and Its Neuroplasticity Mechanisms.

A noninvasive deep brain stimulation via temporal interference (TI) electric fields is a novel neuromodulation technology, but few advances about TI stimulation effectiveness and mechanisms have been reported. One hundred twenty-six mice were selected for the experiment by power analysis. In the present study, TI stimulation was proved to stimulate noninvasively primary motor cortex (M1) of mice, and 7-day TI stimulation with an envelope frequency of 20 Hz (∆f =20 Hz), instead of an envelope frequency of 10 Hz (∆f =10 Hz), could obviously improve mice motor performance. The mechanism of action may be related to enhancing the strength of synaptic connections, improving synaptic transmission efficiency, increasing dendritic spine density, promoting neurotransmitter release, and increasing the expression and activity of synapse-related proteins, such as brain-derived neurotrophic factor (BDNF), postsynaptic density protein-95 (PSD-95), and glutamate receptor protein. Furthermore, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and its upstream BDNF play an important role in the enhancement of locomotor performance in mice by TI stimulation. To our knowledge, it is the first report about TI stimulation promoting multiple motor performances and describing its mechanisms. TI stimulation might serve as a novel promising approach to enhance motor performance and treat dysfunction in deep brain regions.

54 The Influence of Sex on Cognitive Control Performance and Frontoparietal Network Integrity in First-Episode Psychosis

Objective:Cognitive deficits in first-episode psychosis (FEP) are well documented, particularly aspects of cognitive control, which is one of the primary hypothesized functions of the frontoparietal network (FPN). The clinical features of psychotic disorders are known to differ between men and women, but little work has systematically studied neurobiological differences between the sexes, particularly in FEP. The current study aimed to examine sexual dimorphisms in structural integrity of the frontoparietal network (FPN) and its role in cognitive control in FEP.Participants and Methods:A total of 111 FEP patients (68 male, 43 female) and 55 healthy control participants (35 male, 20 female) from the Human Connectome Project for Early Psychosis underwent T1-weighted magnetic resonance imaging and neuropsychological testing were included in the study. Regions of interest (ROIs) included: left and right superior frontal gyrus, left and right middle frontal gyrus, left inferior frontal gyrus, left and right inferior parietal gyrus, right caudate and left thalamus. Using high-dimensional brain mapping procedures, surface shape of the caudate and thalamus was characterized using Large Deformation Diffeomorphic Metric Mapping, and cortical thickness of frontal and parietal regions was estimated using the FreeSurfer toolkit. Cognitive control was assessed using the Fluid Cognition Composite score from the NIH Toolbox Cognition Battery. Multivariate ANOVA models tested group differences, separated by sex, in cortical thickness ROIs, in addition to a whole-brain vertex-wise analysis. Vertex-wise statistical surface t-maps evaluated differences in subcortical surface shape, and Pearson correlations tested relationships between brain regions and Fluid Cognition performance.Results:Results of deep brain region comparisons between schizophrenia males (SCZM) and schizophrenia females (SCZF) groups revealed significant outward deformation at the tail of the right caudate and significant inward deformation along the dorsal aspects of the right caudate. Additionally, significant inward deformation in multiple nuclei of the left thalamus were revealed. Significant negative relationships between Fluid Cognition and the left superior/middle frontal gyrus (r = -0.24, p = 0.05) in the male FEP group were observed. Additionally, significant positive relationships between Fluid Cognition and left inferior frontal gyrus (r = 0.35, p = 0.02) and left inferior parietal gyrus (r = 0.35, p = 0.02) in the female FEP group were found.Conclusions:Overall, findings revealed significant brain differences of the FPN in deep-brain structures only, including abnormal caudal and thalamic shape, in male FEP compared to female FEP, providing evidence of the importance to examine sex differences in deep-brain regions at the first episode. Differential brain relationships with cognitive control also highlight sex-specific presentations that may aid in clinical management and further characterization of the illness in early stages.

Visualizing interferential stimulation of human brains.

Transcranial electrical stimulation (TES) is limited in focally stimulating deep-brain regions, even with optimized stimulation montages. Recently, interferential stimulation (IFS), also known as transcranial temporal interference stimulation (TI, TIS, or tTIS), has drawn much attention in the TES community as both computational and experimental studies show that IFS can reach deep-brain areas. However, the underlying electrodynamics of IFS is complicated and difficult to visualize. Existing literature only shows static visualization of the interfered electric field induced by IFS. These could result in a simplified understanding that there is always one static focal spot between the two pairs of stimulation electrodes. This static visualization can be frequently found in the IFS literature. Here, we aimed to systematically visualize the entire dynamics of IFS. Following the previous study, the lead field was solved for the MNI-152 head, and optimal montages using either two pairs of electrodes or two arrays of electrodes were found to stimulate a deep-brain region close to the left striatum with the highest possible focality. We then visualized the two stimulating electrical currents injected with similar frequencies. We animated the instant electric field vector at the target and one exemplary off-target location both in 3D space and as a 2D Lissajous curve. We finally visualized the distribution of the interfered electric field and the amplitude modulation envelope at an axial slice going through the target location. These two quantities were visualized in two directions: radial-in and posterior-anterior. We hope that with intuitive visualization, this study can contribute as an educational resource to the community's understanding of IFS as a powerful modality for non-invasive focal deep-brain stimulation.

Dual-color miniscope imaging of microvessels and neuronal activity in the hippocampus CA1 region of freely moving mice following alcohol administration.

Moderate-to-heavy episodic ("binge") drinking is the most common form of alcohol consumption in the United States. Alcohol at binge drinking concentrations reduces brain artery diameter in vivo and in vitro in many species including rats, mice, and humans. Despite the critical role played by brain vessels in maintaining neuronal function, there is a shortage of methodologies to simultaneously assess neuron and blood vessel function in deep brain regions. Here, we investigate cerebrovascular responses to ethanol by choosing a deep brain region that is implicated in alcohol disruption of brain function, the hippocampal CA1, and describe the process for obtaining simultaneous imaging of pyramidal neuron activity and diameter of nearby microvessels in freely moving mice via a dual-color miniscope. Recordings of neurovascular events were performed upon intraperitoneal injection of saline versus 3 g/kg ethanol in the same mouse. In male mice, ethanol mildly increased the amplitude of calcium signals while robustly decreasing their frequency. Simultaneously, ethanol decreased microvessel diameter. In females, ethanol did not change the amplitude or frequency of calcium signals from CA1 neurons but decreased microvessel diameter. A linear regression of ethanol-induced reduction in number of active neurons and microvessel constriction revealed a positive correlation (R = 0.981) in females. Together, these data demonstrate the feasibility of simultaneously evaluating neuronal and vascular components of alcohol actions in a deep brain area in freely moving mice, as well as the sexual dimorphism of hippocampal neurovascular responses to alcohol.

Upconversion-Luminescent Fiber Microchannel Sensors for Temperature Monitoring at High Spatial Resolution in the Brains of Freely Moving Animals.

Brain temperature is a critical factor affecting neural activity and function, whose fluctuations may result in acute life-threatening health complications and chronic neuropathology. To monitor brain temperature, luminescent nanothermometry (LN) based on upconversion nanoparticles (UCNPs) with low autofluorescence has received extensive attention for its advantages in high temperature sensitivity and high response speed. However, most of current the LNs are based on optical imaging, which fails in temperature monitoring in deep brain regions at high spatial resolution. Here, the fiber microchannel sensor (FMS) loaded with UCNPs (UCNP-FMS) is presented for temperature monitoring at high spatial resolution in the deep brains of freely moving animals. The UCNP-FMS is fabricated by incorporating UCNPs in microchannels of optical fibers, whose diameter is ∼50µm processed by femtosecond laser micromachining for spatially resolved sensing. The UCNPs provide thermal-sensitive upconversion emissions at dual wavelengths for ratiometric temperature sensing, ensuring a detection accuracy of ± 0.3°C at 37°C. Superior performances of UCNP-FMS are demonstrated by real-time temperature monitoring in different brain regions of freely moving animals under various conditions such as taking food, undergoing anesthesia/wakefulness, and suffering external temperature changes. Moreover, this study shows the capability of UCNP-FMS in distributed temperature sensing in mammalian brains in vivo.

Relation of MRI-Visible Perivascular Spaces and Other MRI Markers of Cerebral Small Vessel Disease.

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I-IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations.

Absence seizures in lesion-related epilepsy

BackgroundIn the new International League Against Epilepsy (ILAE) classification of seizure types, generalized seizures such as absence seizures (ASs) may originate from a focal point and rapidly spread to the bilaterally distributed brain network. Increasing evidence from animal and clinical studies has indicated that focal changes may occur prior to ASs; however, the relationship of ASs with epileptogenic lesions remains unclear.MethodsWe retrospectively collected and analyzed the clinical, imaging, and electrophysiological data of 16 patients who had ASs and structural lesions with seizure-free outcomes after lesion resection.ResultsIn semiology analysis, nine patients displayed focal onset; only two patients showed simple ASs, and seizure types other than ASs were observed in the remaining patients. On ictal electroencephalography (EEG), four patients showed bilateral synchronous symmetric 3 Hz generalized spike-wave discharges (GSWDs), and the remaining patients showed bilateral 1.5–2.5 Hz GSWDs. Moreover, most patients (13/16, 81.3%) exhibited focal features in addition to ASs, while interictal EEG was the same in 12 patients. Furthermore, on stereoelectroencephalogram (SEEG), 2/5 patients showed focal discharges before bilateral burst GSWDs. Additionally, all patients had structural lesions on imaging. In four typical AS patients, the lesions were located in deep brain regions. Notably, in 9 patients (9/16, 56%), the lesions were located in the posterior cortex. All patients underwent lesion resection and had seizure-free outcomes during follow-up, and intelligence quotient (IQ) also improved by 10.71 ± 3.90 one year after surgery.ConclusionsPatients with lesion-related epilepsy may present with ASs that have a focal onset and are associated with good surgical outcomes.

Effect of temporal interference electrical stimulation on phasic dopamine release in the striatum

BackgroundTemporal interference stimulation (TIS) is a neuromodulation technique that could stimulate deep brain regions by inducing interfering electrical signals based on high-frequency electrical stimulations of multiple electrode pairs from outside the brain. Despite numerous TIS studies, however, there has been limited investigation into the neurochemical effects of TIS. ObjectiveWe performed two experiments to investigate the effect of TIS on the medial forebrain bundle (MFB)-evoked phasic dopamine (DA) response. MethodsIn the first experiment, we applied TIS next to a carbon fiber microelectrode (CFM) to examine the modulation of the MFB-evoked phasic DA response in the striatum (STr). Beat frequencies and intensities of TIS were 0, 2, 6, 10, 20, 60, 130 Hz and 0, 100, 200, 300, 400, 500 μA. In the second experiment, we examined the effect of TIS with a 2 Hz beat frequency (based on the first experiment) on MFB-evoked phasic DA release when applied above the cortex (with a simulation-based stimulation site targeting the striatum). We employed 0 Hz and 2 Hz beat frequencies and a control condition without stimulation. ResultsIn the first experiment, TIS with a beat frequency of 2 Hz and an intensity of 400 μA or greater decreased MFB-evoked phasic DA release by roughly 40%, which continued until the experiment's end. In contrast, TIS at beat frequencies other than 2 Hz and intensities less than 400 μA did not affect MFB-evoked phasic DA release. In the second experiment, TIS with a 2 Hz beat frequency decreased only the MFB-evoked phasic DA response, but the reduction in DA release was not sustained. ConclusionsSTr-applied and cortex-applied TIS with delta frequency dampens evoked phasic DA release in the STr. These findings demonstrate that TIS could influence the neurochemical modulation of the brain.

Disrupting nociceptive information processing flow through transcranial focused ultrasound neuromodulation of thalamic nuclei

BackgroundMRI-guided transcranial focused ultrasound (MRgFUS) as a next-generation neuromodulation tool can precisely target and stimulate deep brain regions with high spatial selectivity. Combined with MR-ARFI (acoustic radiation force imaging) and using fMRI BOLD signal as functional readouts, our previous studies have shown that low-intensity FUS can excite or suppress neural activity in the somatosensory cortex. ObjectiveTo investigate whether low-intensity FUS can suppress nociceptive heat stimulation-induced responses in thalamic nuclei during hand stimulation, and to determine how this suppression influences the information processing flow within nociception networks. FindingsBOLD fMRI activations evoked by 47.5 °C heat stimulation of hand were detected in 24 cortical regions, which belong to sensory, affective, and cognitive nociceptive networks. Concurrent delivery of low-intensity FUS pulses (650 kHz, 550 kPa) to the predefined heat nociceptive stimulus-responsive thalamic centromedial_parafascicular (CM_para), mediodorsal (MD), ventral_lateral (VL_ and ventral_lateral_posteroventral (VLpv) nuclei suppressed their heat responses. Off-target cortical areas exhibited reduced, enhanced, or no significant fMRI signal changes, depending on the specific areas. Differentiable thalamocortical information flow during the processing of nociceptive heat input was observed, as indicated by the time to reach 10% or 30% of the heat-evoked BOLD signal peak. Suppression of thalamic heat responses significantly altered nociceptive processing flow and direction between the thalamus and cortical areas. Modulation of contralateral versus ipsilateral areas by unilateral thalamic activity differed. Signals detected in high-order cortical areas, such as dorsal frontal (DFC) and ventrolateral prefrontal (vlPFC) cortices, exhibited faster response latencies than sensory areas. ConclusionsThe concurrent delivery of FUS suppressed nociceptive heat response in thalamic nuclei and disrupted the nociceptive network. This study offers new insights into the causal functional connections within the thalamocortical networks and demonstrates the modulatory effects of low-intensity FUS on nociceptive information processing.

Depicting the anatomy of the gyral white matter: ubi sumus? quo vadimus?

Abstract A cerebral gyrus is made up of an external layer of folded cortex and an inner core of white matter. The architecture of the core has specific features that make it distinct from the white matter of the deep brain regions. Limited externally by the grey matter that covers the top of the gyrus and the neighbouring sulci, this gyral white matter is made up of a mix of fibre populations with multiple directions and destinations. The presence of densely packed fibres with multiple crossings, the proximity to the cortex and the existence of inter-regional and inter-individual variations make the task of depicting this microanatomy extremely challenging. The topic is, however, of paramount relevance for both fundamental and applied neurosciences. This fibre colocalization is crucial for the functional role of each cerebral region and is key to clinical manifestations in cases of parenchymal damage. As track tracing, imaging and dissection are based on different biological or physical principles, it is natural for their results to sometimes be different, but they are often complementary. As the amount of available information increases, it becomes fragmented due to the multiplicity of methods, target phenomena and studied species. In this scoping review, we present the key concepts and map the primary sources of evidence regarding identifying the fibre pathways that compose the gyral white matter, enabling the discussion of avenues for future research. The general pattern in which these pathways are distributed in the gyral white matter was detailed, and the main variations as a function of brain topography were explained and illustrated with typical examples.

Prefrontal stimulation as a tool to disrupt hippocampal and striatal reactivations underlying fast motor memory consolidation

BackgroundRecent evidence suggests that hippocampal replay in humans support rapid motor memory consolidation during epochs of wakefulness interleaved with task practice. Objectives/HypothesesThe goal of this study was to test whether such reactivation patterns can be modulated with experimental interventions and in turn influence fast consolidation. We hypothesized that non-invasive brain stimulation targeting hippocampal and striatal networks via the prefrontal cortex would influence brain reactivation and the rapid form of motor memory consolidation. MethodsTheta-burst stimulation was applied to a prefrontal cluster functionally connected to both the hippocampus and striatum of young healthy participants before they learned a motor sequence task in a functional magnetic resonance imaging (fMRI) scanner. Neuroimaging data acquired during task practice and the interleaved rest epochs were analyzed to comprehensively characterize the effect of stimulation on the neural processes supporting fast motor memory consolidation. ResultsOur results collectively show that active, as compared to control, theta-burst stimulation of the prefrontal cortex hindered fast motor memory consolidation. Converging evidence from both univariate and multivariate analyses of fMRI data indicate that active stimulation disrupted hippocampal and caudate responses during inter-practice rest, presumably altering the reactivation of learning-related patterns during the micro-offline consolidation episodes. Last, stimulation altered the link between the brain and the behavioral markers of the fast consolidation process. ConclusionThese results suggest that stimulation targeting deep brain regions via the prefrontal cortex can be used to modulate hippocampal and striatal reactivations in the human brain and influence motor memory consolidation.