Modulation Of Brain Activity Research Articles

Understanding the effects of cortical gyrification in tACS: insights from experiments and computational models.

The alpha rhythm is often associated with relaxed wakefulness or idling and is altered by various factors. Abnormalities in the alpha rhythm have been linked to several neurological and psychiatric disorders, including Alzheimer's disease. Transcranial alternating current stimulation (tACS) has been proposed as a potential tool to restore a disrupted alpha rhythm in the brain by stimulating at the individual alpha frequency (IAF), although some research has produced contradictory results. In this study, we applied an IAF-tACS protocol over parieto-occipital areas to a sample of healthy subjects and measured its effects over the power spectra. Additionally, we used computational models to get a deeper understanding of the results observed in the experiment. Both experimental and numerical results showed an increase in alpha power of 8.02% with respect to the sham condition in a widespread set of regions in the cortex, excluding some expected parietal regions. This result could be partially explained by taking into account the orientation of the electric field with respect to the columnar structures of the cortex, showing that the gyrification in parietal regions could generate effects in opposite directions (hyper-/depolarization) at the same time in specific brain regions. Additionally, we used a network model of spiking neuronal populations to explore the effects that these opposite polarities could have on neural activity, and we found that the best predictor of alpha power was the average of the normal components of the electric field. To sum up, our study sheds light on the mechanisms underlying tACS brain activity modulation, using both empirical and computational approaches. Non-invasive brain stimulation techniques hold promise for treating brain disorders, but further research is needed to fully understand and control their effects on brain dynamics and cognition. Our findings contribute to this growing body of research and provide a foundation for future studies aimed at optimizing the use of non-invasive brain stimulation in clinical settings.

A voltage-controlled current source for temporal interference stimulation: Analysis, design, and study.

The temporal interference stimulation is a new technique to modulate brain activity by applying multiple channels of voltage-controlled current source (VCCS) simultaneously to the receptor surface. In this paper, the envelopes of the overlapped current waves at several areas of the receptor were analyzed and discussed with different circuit structures of VCCS. A complementary differential current source (CDCS) was designed to fit the best circuit topology based on the analysis of the enhanced Howland current source structure. Experiments were conducted by injecting current to a swine tissue using the CDCS and conventional VCCS and acquiring the voltage waveform data from different parts of the tissue. The waveforms were compared and analyzed, revealing that the conventional VCCS may generate an interference envelope in unexpected regions, while the CDCS did not. The CDCS design approach in this paper provides a new solution for temporal interference stimulation VCCS.

Disturbance of information in superior parietal lobe during dual-task interference in a simulated driving task

Performing a secondary task while driving causes a decline in driving performance. This phenomenon, called dual-task interference, can have lethal consequences. Previous fMRI studies have looked at the changes in the average brain activity to uncover the neural correlates of dual-task interference. From these results, it is unclear whether the overall modulations in brain activity result from general effects such as task difficulty, attentional modulations, and mental effort or whether it is caused by a change in the responses specific to each condition due to dual-task interference. To overcome this limitation, here, we used multi-voxel pattern analysis (MVPA) to interrogate the change in the information content in multiple brain regions during dual-task interference in simulated driving. Participants performed a lane-change task in a simulated driving environment, along with a tone discrimination task with either short or long onset time difference (Stimulus Onset Asynchrony, SOA) between the two tasks. Behavioral results indicated a robust dual-task effect on lane-change reaction time (RT). MVPA revealed regions that carry information about the driving lane-change direction (shift right/shift left), including the superior parietal lobe (SPL), visual, and motor regions. Comparison of decoding accuracies across SOA conditions in the SPL region revealed lower accuracy in the short compared to the long SOA condition. This change in accuracy was not observed in the visual and motor regions. These findings suggest that the dual-task interference in driving may be related to the disturbance of information processing in the SPL region.

Characteristics of EEG power spectra involved in the proficiency of motor learning.

Neuromodulation techniques for modulating brain activity can affect performance in a variety of behaviors. Techniques including transcranial alternating current stimulation and random noise stimulation can modulate neural oscillations. However, the intervention effect of neuromodulation approaches on motor learning is poor, partly because the electroencephalography (EEG) power spectra associated with the motor learning process has not yet been fully elucidated. Therefore, we investigated the characteristics of EEG power spectra in the process of motor learning in 15 right-handed healthy participants (5 females; mean age = 22.8 ± 3.0 years). The motor task was a ball-rotation task in which participants rotated two balls in the palm of their left hand. Participants performed a pre-test, the motor learning tasks, and a post-test. In the motor learning tasks, twenty 60 s trials were performed in the clockwise (CW) direction. Before and after the motor learning tasks, CW and counterclockwise (CCW; control condition) tasks were performed for 60 s each as pre- and post-tests. Therefore, CW direction was set as a motor learning task, while CCW was a test-only control task. EEG was recorded during the tests and tasks, and the power spectra in the alpha, beta, and gamma oscillations were calculated and compared between pre- and post-tests. The results showed that in the CW post-test, the power of the gamma band in the left parietal areas and the right frontal area was significantly higher than in the pre-test. In the CCW, there was no significant difference in each band at each area between the pre- and post-tests. Our findings reveal the characteristics of the EEG spectra related to the motor learning process. These results may help to establish more effective neuromodulation approaches to modifying neural oscillations in motor learning, including in rehabilitation fields.

Anatomical and Functional Connectivity of Critical Deep Brain Structures and Their Potential Clinical Application in Brain Stimulation

Subcortical structures, such as the hippocampus, amygdala, and nucleus accumbens (NAcc), play crucial roles in human cognitive, memory, and emotional processing, chronic pain pathophysiology, and are implicated in various psychiatric and neurological diseases. Interventions modulating the activities of these deep brain structures hold promise for improving clinical outcomes. Recently, non-invasive brain stimulation (NIBS) has been applied to modulate brain activity and has demonstrated its potential for treating psychiatric and neurological disorders. However, modulating the above deep brain structures using NIBS may be challenging due to the nature of these stimulations. This study attempts to identify brain surface regions as source targets for NIBS to reach these deep brain structures by integrating functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). We used resting-state functional connectivity (rsFC) and probabilistic tractography (PTG) analysis to identify brain surface stimulation targets that are functionally and structurally connected to the hippocampus, amygdala, and NAcc in 119 healthy participants. Our results showed that the medial prefrontal cortex (mPFC) is functionally and anatomically connected to all three subcortical regions, while the precuneus is connected to the hippocampus and amygdala. The mPFC and precuneus, two key hubs of the default mode network (DMN), as well as other cortical areas distributed at the prefrontal cortex and the parietal, temporal, and occipital lobes, were identified as potential locations for NIBS to modulate the function of these deep structures. The findings may provide new insights into the NIBS target selections for treating psychiatric and neurological disorders and chronic pain.

Low-frequency repetitive transcranial magnetic stimulation alters the individual functional dynamical landscape.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive approach to modulate brain activity and behavior in humans. Still, how individual resting-state brain dynamics after rTMS evolves across different functional configurations is rarely studied. Here, using resting state fMRI data from healthy subjects, we aimed to examine the effects of rTMS to individual large-scale brain dynamics. Using Topological Data Analysis based Mapper approach, we construct the precise dynamic mapping (PDM) for each participant. To reveal the relationship between PDM and canonical functional representation of the resting brain, we annotated the graph using relative activation proportion of a set of large-scale resting-state networks (RSNs) and assigned the single brain volume to corresponding RSN-dominant or a hub state (not any RSN was dominant). Our results show that (i) low-frequency rTMS could induce changed temporal evolution of brain states; (ii) rTMS didn't alter the hub-periphery configurations underlined resting-state brain dynamics; and (iii) the rTMS effects on brain dynamics differ across the left frontal and occipital lobe. In conclusion, low-frequency rTMS significantly alters the individual temporo-spatial dynamics, and our finding further suggested a potential target-dependent alteration of brain dynamics. This work provides a new perspective to comprehend the heterogeneous effect of rTMS.

The neurobiology of insulin-like growth factor I: From neuroprotection to modulation of brain states.

After decades of research in the neurobiology of IGF-I, its role as a prototypical neurotrophic factor is undisputed. However, many of its actions in the adult brain indicate that this growth factor is not only involved in brain development or in the response to injury. Following a three-layer assessment of its role in the central nervous system, we consider that at the cellular level, IGF-I is indeed a bona fide neurotrophic factor, modulating along ontogeny the generation and function of all the major types of brain cells, contributing to sculpt brain architecture and adaptive responses to damage. At the circuit level, IGF-I modulates neuronal excitability and synaptic plasticity at multiple sites, whereas at the system level, IGF-I intervenes in energy allocation, proteostasis, circadian cycles, mood, and cognition. Local and peripheral sources of brain IGF-I input contribute to a spatially restricted, compartmentalized, and timed modulation of brain activity. To better define these variety of actions, we consider IGF-I a modulator of brain states. This definition aims to reconcile all aspects of IGF-I neurobiology, and may provide a new conceptual framework in the design of future research on the actions of this multitasking neuromodulator in the brain.

Identification of Parkinson's Disease Subtypes from Resting-State Electroencephalography.

Parkinson's disease (PD) patients present with a heterogeneous clinical phenotype, including motor, cognitive, sleep, and affective disruptions. However, this heterogeneity is often either ignored or assessed using only clinical assessments. We aimed to identify different PD sub-phenotypes in a longitudinal follow-up analysis and their electrophysiological profile based on resting-state electroencephalography (RS-EEG) and to assess their clinical significance over the course of the disease. Using electrophysiological features obtained from RS-EEG recordings and data-driven methods (similarity network fusion and source-space spectral analysis), we have performed a clustering analysis to identify disease sub-phenotypes and we examined whether their different patterns of disruption are predictive of disease outcome. We showed that PD patients (n = 44) can be sub-grouped into three phenotypes with distinct electrophysiological profiles. These clusters are characterized by different levels of disruptions in the somatomotor network (Δ and β band), the frontotemporal network (α2 band) and the default mode network (α1 band), which consistently correlate with clinical profiles and disease courses. These clusters are classified into either moderate (only-motor) or mild-to-severe (diffuse) disease. We showed that EEG features can predict cognitive evolution of PD patients from baseline, when the cognitive clinical scores were overlapped. The identification of novel PD subtypes based on electrical brain activity signatures may provide a more accurate prognosis in individual patients in clinical practice and help to stratify subgroups in clinical trials. Innovative profiling in PD can also support new therapeutic strategies that are brain-based and designed to modulate brain activity disruption. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Versatile In-Ear Biosensing System and Body-Area Network for Unobtrusive Continuous Health Monitoring.

To enable continuous, mobile health monitoring, body-worn sensors need to offer comparable performance to clinical devices in a lightweight, unobtrusive package. This work presents a complete versatile wireless electrophysiology data acquisition system (weDAQ) that is demonstrated for in-ear electroencephalography (EEG) and other on-body electrophysiology with user-generic dry-contact electrodes made from standard printed circuit boards (PCBs). Each weDAQ device provides 16 recording channels, driven right leg (DRL), a 3-axis accelerometer, local data storage, and adaptable data transmission modes. The weDAQ wireless interface supports deployment of a body area network (BAN) capable of aggregating various biosignal streams over multiple worn devices simultaneously, on the 802.11n WiFi protocol. Each channel resolves biopotentials ranging over 5 orders of magnitude with a noise level of 0.52 μVrms over a 1000-Hz bandwidth, and a peak SNDR of 119 dB and CMRR of 111 dB at 2 ksps. The device leverages in-band impedance scanning and an input multiplexer to dynamically select good skin contacting electrodes for reference and sensing channels. In-ear and forehead EEG measurements taken from subjects captured modulation of alpha brain activity, electrooculogram (EOG) characteristic eye movements, and electromyogram (EMG) from jaw muscles. Simultaneous ECG and EMG measurements were demonstrated on multiple, freely-moving subjects in their natural office environment during periods of rest and exercise. The small footprint, performance, and configurability of the open-source weDAQ platform and scalable PCB electrodes presented, aim to provide the biosensing community greater experimental flexibility and lower the barrier to entry for new health monitoring research.

Offline 20 Hz transcranial alternating current stimulation over the right inferior frontal gyrus increases theta activity during a motor response inhibition task

ObjectivesPrevious studies have shown that the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (preSMA) play an important role in motor inhibitory control. The aim of the study was to use theta frequency transcranial alternating current stimulation (tACS) to modulate brain activity in the rIFG and preSMA and to test the effects of stimulation using a motor response inhibition task. MethodsIn four sessions, 20 healthy participants received tACS at 6 Hz over preSMA or rIFG, or 20 Hz over rIFG (to test frequency specificity), or sham stimulation before task processing. After each type of stimulation, the participants performed the Go/NoGo task with simultaneous electroencephalogram (EEG) recording. ResultsBy stimulating rIFG and preSMA with 6 Hz tACS, we were not able to modulate either behavioral performance nor the EEG correlate. Interestingly, 20 Hz tACS over the rIFG significantly increased theta activity, however without behavioral effects. This increased theta activity did not coincide with the stimulation area and was localized in the fronto-central and centro-parietal areas. ConclusionsThe inclusion of a control frequency is crucial to test for frequency specificity. Our findings are in accordance with previous studies showing that after effects of tACS are not restricted to the stimulation frequency but can also occur in other frequency bands.

0416 Preliminary Study of the Effects of Continuous Theta Burst Stimulation of the Default Mode Network on Subjective Sleepiness

Abstract Introduction Repetitive transcranial Magnetic Stimulation (rTMS) is a noninvasive intervention commonly used to treat clinical depression by modulating brain activity in specific regions. We investigated rTMS of the default mode network (DMN) as a potential treatment for insomnia. The DMN is associated with internally focused cognition and rumination. Therefore, we expected that modulation of this network would improve sleep. As reported elsewhere, this trial showed that active cTBS to the DMN improved polysomnographically (PSG) measured sleep. Here, we hypothesized that participants who were treated with active continuous theta burst stimulation (cTBS) rTMS over the DMN versus sham cTBS would report reduced subjective sleepiness following post-treatment sleep. Methods Twenty adults with clinical insomnia completed this study (Mage=26.90, SD=6.56). Participants completed two overnight visits; one where they received active cTBS treatment and one where they received sham TMS treatment. We analyzed the Karolinska Sleepiness Scale (KSS), which was administered six times throughout each visit. KSS 1-3 were administered prior to treatment and KSS 4-6 were post TMS treatment. We used a repeated measures ANOVA to analyze effects of TMS on reported daytime sleepiness. Results There was no main effect of condition on sleepiness score F(1,18 )=1.165, p=0.295, ηp 2=0.061. There was a significant interaction effect of condition and pre/post intervention on reported subjective sleepiness F(1,18)=3.079, p=0.013, ηp 2 = 0.146, although follow-up analyses did not reveal significant differences. Nonetheless, there was a continuous negative trend toward reduced sleepiness for post TMS administration after overnight sleep in active cTBS (M = 4.8, SD = 1.96) compared to the sham cTBS session (M = 5.2, SD = 1.91) (p = 0.366). Conclusion As reported elsewhere, this trial of a single administration of cTBS showed improved PSG sleep. Here we saw that there was no significant change in subjective sleepiness following a night of sleep with or without the trial of cTBS, but there was a nonsignificant trend toward declining sleepiness for the active cTBS group relative to the sham condition. This preliminary study is encouraging and suggests that further research into this approach is warranted. Support (if any) W81XWH2010173

NET-TEN: a silicon neuromorphic network for low-latency detection of seizures in local field potentials

Objective. Therapeutic intervention in neurological disorders still relies heavily on pharmacological solutions, while the treatment of patients with drug resistance remains an unresolved issue. This is particularly true for patients with epilepsy, 30% of whom are refractory to medications. Implantable devices for chronic recording and electrical modulation of brain activity have proved a viable alternative in such cases. To operate, the device should detect the relevant electrographic biomarkers from local field potentials (LFPs) and determine the right time for stimulation. To enable timely interventions, the ideal device should attain biomarker detection with low latency while operating under low power consumption to prolong battery life. Approach. Here we introduce a fully-analog neuromorphic device implemented in CMOS technology for analyzing LFP signals in an in vitro model of acute ictogenesis. Neuromorphic networks have progressively gained a reputation as low-latency low-power computing systems, which makes them a promising candidate as processing core of next-generation implantable neural interfaces. Main results. The developed system can detect ictal and interictal events with ms-latency and with high precision, consuming on average 3.50 nW during the task. Significance. The work presented in this paper paves the way to a new generation of brain implantable devices for personalized closed-loop stimulation for epilepsy treatment.

Can vibrotactile stimulation and tDCS help inefficient BCI users?

Brain-computer interface (BCI) has helped people by allowing them to control a computer or machine through brain activity without actual body movement. Despite this advantage, BCI cannot be used widely because some people cannot achieve controllable performance. To solve this problem, researchers have proposed stimulation methods to modulate relevant brain activity to improve BCI performance. However, multiple studies have reported mixed results following stimulation, and the comparative study of different stimulation modalities has been overlooked. Accordingly, this study was designed to compare vibrotactile stimulation and transcranial direct current stimulation’s (tDCS) effects on brain activity modulation and motor imagery BCI performance among inefficient BCI users. We recruited 44 subjects and divided them into sham, vibrotactile stimulation, and tDCS groups, and low performers were selected from each stimulation group. We found that the latter’s BCI performance in the vibrotactile stimulation group increased significantly by 9.13% (p < 0.01), and while the tDCS group subjects’ performance increased by 5.13%, it was not significant. In contrast, sham group subjects showed no increased performance. In addition to BCI performance, pre-stimulus alpha band power and the phase locking values (PLVs) averaged over sensory motor areas showed significant increases in low performers following stimulation in the vibrotactile stimulation and tDCS groups, while sham stimulation group subjects and high performers showed no significant stimulation effects across all groups. Our findings suggest that stimulation effects may differ depending upon BCI efficiency, and inefficient BCI users have greater plasticity than efficient BCI users.

Aberrant adenosine signaling in patients with focal cortical dysplasia.

Focal cortical dysplasia (FCD), a common malformation of cortical development, is frequently associated with pharmacoresistant epilepsy in both children and adults. Adenosine is an inhibitory modulator of brain activity and a prospective anti-seizure agent with potential for clinical translation. Our previous results demonstrated that the major adenosine-metabolizing enzyme adenosine kinase (ADK) was upregulated in balloon cells (BCs) within FCD type IIB lesions, suggesting that dysfunction of the adenosine system is implicated in the pathophysiology of FCD. In our current study, we therefore performed a comprehensive analysis of adenosine signaling in surgically resected cortical specimens from patients with FCD type I and type II via immunohistochemistry and immunoblot analysis. Adenosine enzyme signaling was assessed by quantifying the levels of the key enzymes of adenosine metabolism, i.e., ADK, adenosine deaminase (ADA), and ecto-5'-nucleotidase (CD73). Adenosine receptor signaling was assessed by quantifying the levels of adenosine A2A receptor (A2AR) and putative downstream mediators of adenosine, namely, glutamate transporter-1 (GLT-1) and mammalian target of rapamycin (mTOR). Within lesions in FCD specimens, we found that the adenosine-metabolizing enzymes ADK and ADA, as well as the adenosine-producing enzyme CD73, were upregulated. We also observed an increase in A2AR density, as well as a decrease in GLT-1 levels and an increase in mTOR levels, in FCD specimens compared with control tissue. These results suggest that dysregulation of the adenosine system is a common pathologic feature of both FCD type I and type II. The adenosine system might therefore be a therapeutic target for the treatment of epilepsy associated with FCD.

Medial prefrontal transcranial alternating current stimulation for apathy in Huntington's disease

We investigated the effects of transcranial alternating current stimulation (tACS) targeted to the bilateral medial prefrontal cortex (mPFC) and administered at either delta or alpha frequencies, on brain activity and apathy in people with Huntington's disease (HD) (n = 17). Given the novelty of the protocol, neurotypical controls (n = 20) were also recruited. All participants underwent three 20-min sessions of tACS; one session at alpha frequency (Individualised Alpha Frequency (IAF), or 10 Hz when an IAF was not detected); one session at delta frequency (2 Hz); and a session of sham tACS. Participants completed the Monetary Incentive Delay (MID) task with simultaneous recording of EEG immediately before and after each tACS condition. The MID task presents participants with cues signalling potential monetary gains or losses that increase activity in key regions of the cortico-basal ganglia-thalamocortical networks, with dysfunction of the latter network being implicated in the pathophysiology of apathy. We used the P300 and Contingent Negative Variation (CNV) event-related potentials elicited during the MID task as markers of mPFC engagement. HD participants' CNV amplitude significantly increased in response to alpha-tACS, but not delta-tACS or sham. Neurotypical controls' P300 and CNV were not modulated by any of the tACS conditions, but they did demonstrate a significant decrease in post-target response times following alpha-tACS. We present this as preliminary evidence of the ability of alpha-tACS to modulate brain activity associated with apathy in HD.

Resting-State Electroencephalography Reveals Three Subphenotypes of Parkinson’s Disease (P6-11.002)

<h3>Objective:</h3> To identify different Parkinson’s disease (PD) sub-phenotypes and their electrophysiological profile based on resting-state electroencephalography (RS-EEG). <h3>Background:</h3> Parkinson’s disease is a complex brain disorder characterised mainly by motor signs, with clinical evidence of cognitive and behavioural deficits in up to 40% of cases in early stage. Clinical and biological manifestations are very heterogeneous among individuals with PD and subgrouping was mainly performed using clinical parameters. However, these subgroups do not take into account underlying disease physiopathology, and were shown not entirely predictive of disease prognosis. <h3>Design/Methods:</h3> Resting-state electroencephalography (EEG) is a powerful tool to identify abnormal patterns of motor and cognitive deficits in PD. These disruptions have previously been identified across multiple frequency bands using cortical spectral power and functional connectivity from longitudinal high-density EEG recordings (baseline, 3 years follow-up and 5 years follow-up). In this study, using data-driven methods (similarity network fusion and source-space spectral analysis), we have performed a clustering analysis to identify disease sub-phenotypes and to determine whether different patterns of disruption are predictive of disease outcome. <h3>Results:</h3> We showed that PD patients (N = 44) can be subgrouped into three phenotypes with distinct electrophysiological profiles. These clusters are characterised by different levels of disruptions in the somatomotor network (delta and beta band), the frontotemporal network (alpha2 band) and the default mode network (alpha1 band), which consistently correlate with clinical profiles and disease courses. We showed that these clusters are statistically robust, and can predict the clinical trajectory and disease outcome. <h3>Conclusions:</h3> Our findings show that novel phenotyping using electric brain signal analysis can distinguish PD subtypes based exclusively on different patterns of brain oscillations. These patterns can reflect underlying disease neurobiology. Innovative profiling in PD has clear potential in patient’s stratification and can also support new therapeutic strategies that are brain-based and designed to modulate brain activity disruption. <b>Disclosure:</b> Mrs. Yassine has nothing to disclose. Ute Gschwandtner has nothing to disclose. Dr. Auffret has received personal compensation for serving as an employee of France Développement Electronique. The institution of Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Britannia. Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Britannia. Dr. Auffret has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Britannia. Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aguettant. The institution of Dr. Auffret has received research support from Association France Parkinson. The institution of Dr. Auffret has received research support from Homeperf. The institution of Dr. Auffret has received research support from LVL. The institution of Dr. Auffret has received research support from University of Rennes 1. The institution of Dr. Auffret has received research support from Aguettant. The institution of Dr. Auffret has received research support from Linde. The institution of Dr. Auffret has received research support from Plateforme Nationale pour la recherche sur la fin de vie. Dr. Auffret has received publishing royalties from a publication relating to health care. Dr. Duprez has nothing to disclose. Mr. Verin has nothing to disclose. The institution of Dr. Fuhr has received research support from Roche. Mr. HASSAN has nothing to disclose.

Factors Mediating Public Perceptions of Therapeutic Closed-Loop Brain Implants for Epilepsy and Mood Disorders (P6-9.002)

<h3>Objective:</h3> To examine perceptions of implanted neural devices among groups underserved by prevailing neuropsychiatric treatment approaches. <h3>Background:</h3> “Closed-loop” devices that both sense and modulate brain activity represent a new paradigm for neuropsychiatric treatment. However, neurotechnologists and even neuroethicists are not demographically representative of U.S. society, so the concerns of groups most in need of new paradigms may not be reflected in current neurotechnology development. <h3>Design/Methods:</h3> We fielded a nationally representative survey (n=1047) oversampling non-Hispanic Black (n=214), Hispanic (n=210), and rural Americans (n=219), eliciting treatment preferences in scenarios comparing (1) a therapeutic closed-loop brain implant versus surgical resection for refractory epilepsy, and (2) an investigational closed-loop brain implant versus medications for mood disorders. We asked respondents to rate the importance of differing considerations favoring either the implanted device or traditional treatment. We examined whether such considerations mediate demographic differences in treatment preferences using survey-weighted logistic regression models. <h3>Results:</h3> In both scenarios, non-Hispanic Black Americans were less likely to prefer the implanted neural device than non-Hispanic White Americans (epilepsy OR 0.28, p&lt;0.001; mood OR 0.23, p=0.008); there was no main effect contrasting Hispanic with non-Hispanic White Americans, or contrasting rural with urban/suburban Americans. In the epilepsy scenario the difference between non-Hispanic Black and non-Hispanic White Americans’ treatment preferences was partially mediated by preference for established treatments, concerns about privacy, and concerns about hacking. In the mood scenario the difference between non-Hispanic Black and non-Hispanic White Americans’ treatment preferences was partially mediated by indifference to temporally specific action of a closed-loop device, concerns about changes to core traits, and preference for established treatments. <h3>Conclusions:</h3> Black Americans are less likely than White Americans to prefer closed-loop brain implants to traditional treatment, with specific concerns that may be informed by the history of unethical medical experimentation targeting Black people. <b>Disclosure:</b> Mr. Dada has received personal compensation for serving as an employee of Dreem Health. The institution of Mr. Chen has received research support from the National Institutes of Health (NIH). The institution of Dr. Haeusermann has received research support from the National Institutes of Health (NIH). Ms. Fong has nothing to disclose. Dr. Hamilton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Hamilton has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Highland Instruments. Dr. Hamilton has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology (Journal). The institution of Dr. Hamilton has received research support from NIH. The institution of Dr. Hamilton has received research support from Department of Defense. The institution of Dr. James has received research support from National Institute of Health. The institution of Dr. James has received research support from Society of Family Planning . The institution of Dr. James has received research support from Greenwall Foundation. Prof. Dohan has nothing to disclose. The institution of Dr. Chiong has received research support from the National Institutes of Health. The institution of Dr. Chiong has received research support from the Dana Foundation. Dr. Chiong has received personal compensation in the range of $500-$4,999 for serving as a member, NeuroEthics Working Group with National Institutes of Health.

A comparison of how deep brain stimulation in two targets with anti-compulsive efficacy modulates brain activity using fMRI in awake rats.

Deep brain stimulation (DBS) is an established neuromodulatory intervention against otherwise treatment-refractory obsessive-compulsive disorder (OCD). Several DBS targets, all of which are part of brain networks connecting basal ganglia and prefrontal cortex, alleviate OCD symptoms. Stimulation of these targets is thought to unfold its therapeutic effect by modulation of network activity through internal capsule (IC) connections. Research into DBS-induced network changes and the nature of IC-related effects of DBS in OCD is needed to further improve DBS. Here, we studied the effects of DBS at the ventral medial striatum (VMS) and IC on blood-oxygen level dependent (BOLD) responses in awake rats using functional magnetic resonance imaging (fMRI). BOLD-signal intensity was measured in five regions of interest (ROIs): medial and orbital prefrontal cortex, nucleus accumbens (NAc), IC area, and mediodorsal thalamus. In previous rodent studies, stimulation at both target locations resulted in a reduction of OCD-like behavior and activation of prefrontal cortical areas. Therefore, we hypothesized that stimulation at both targets would result in partially overlapping BOLD responses. Both differential and overlapping activity between VMS and IC stimulation was found. Stimulating the caudal part of the IC resulted in activation around the electrode, while stimulating the rostral part of the IC resulted in increased cross-correlations between the IC area, orbitofrontal cortex, and NAc. Stimulation of the dorsal part of the VMS resulted in increased activity in the IC area, suggesting this area is activated during both VMS and IC stimulation. This activation is also indicative of VMS-DBS impacting corticofugal fibers running through the medial caudate into the anterior IC, and both VMS and IC DBS might act on these fibers to induce OCD-reducing effects. These results show that rodent fMRI with simultaneous electrode stimulation is a promising approach to study the neural mechanisms of DBS. Comparing the effects of DBS in different target areas has the potential to improve our understanding of the neuromodulatory changes that take place across various networks and connections in the brain. Performing this research in animal disease models will lead to translational insights in the mechanisms underlying DBS, and can aid improvement and optimization of DBS in patient populations.

A Brief History of Transcranial Magnetic Stimulation

A Brief History of Transcranial Magnetic Stimulation

Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder

The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior. To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD. This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021. Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo. Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal. Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02). Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire. isrctn.org Identifier: ISRCTN17271094.