A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum.

OBJECTIVES: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD. MATERIALS AND METHODS: Twelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs). RESULTS: VC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion. CONCLUSIONS: This study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD.

Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.

Background: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets. Results: We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine's data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. Conclusions: These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry. Funding: This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1-190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016-0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 - 2056) (FXV). Clinical trial number: NCT03842800.

Ketamine is a widely used anesthetic as well as a popular illegal recreational drug. Recently, it has also gained attention as a potential treatment for depression, particularly in cases that don't respond to conventional therapies. However, individuals can vary in their response to ketamine. For example, the drug can alter some people's perception, such as seeing objects as larger or small than they are, while other individuals are unaffected. Although a single dose of ketamine was shown to improve depression symptoms in approximately 65% of patients, the treatment does not work for a significant portion of patients. Understanding why ketamine does not work for everyone could help to identify which patients would benefit most from the treatment. Previous studies investigating ketamine as a treatment for depression have typically included a group of individuals given ketamine and a group given a placebo drug. Assuming people respond similarly to ketamine, the responses in each group were averaged and compared to one another. However, this averaging of results may have masked any individual differences in response to ketamine. As a result, Moujaes et al. set out to investigate whether individuals show differences in brain activity and behavior in response to ketamine. Moujaes et al. monitored the brain activity and behavior of 40 healthy individuals that were first given a placebo drug and then ketamine. The results showed that brain activity and behavior varied significantly between individuals after ketamine administration. Genetic analysis revealed that different gene expression patterns paired with differences in ketamine response in individuals ­ an effect that was hidden when the results were averaged. Ketamine also caused greater differences in brain activity and behavior between individuals than other drugs, such as psychedelics, suggesting ketamine generates a particularly complex response in people. In the future, extending these findings in healthy individuals to those with depression will be crucial for determining whether differences in response to ketamine align with how effective ketamine treatment is for an individual.

Apparent diffusion coefficient values predict response to brachytherapy in bulky cervical cancer.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer. METHODS: Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden's J statistic was used to identify a threshold value. RESULTS: Among 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10- 3 mm2/s were 5.33 (95% CI, 1.35-24.4) times more likely to achieve CMR. CONCLUSIONS: Clinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.

Thermal stimulus task fMRI in the cervical spinal cord at 7 Tesla.

Although functional magnetic resonance imaging (fMRI) is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0 . Increasing field strength enables higher spatial resolution and improved sensitivity to blood oxygenation level-dependent (BOLD) signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D echo-planar imaging (EPI) protocols, which differ in sensitivity to spatial and temporal B0 inhomogeneity. The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. All protocols used 3 mm slice thickness. For each protocol, the BOLD response to 13 10-s noxious thermal stimuli applied to the right thumb was acquired in a 10-min fMRI run. Image quality, temporal signal to noise ratio (SNR), and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment. PRACTITIONER POINTS: First stimulus task fMRI results in the spinal cord at 7 T. Single-shot 0.75 mm 2D EPI produced the highest mean z-statistic. Multi-shot 0.60 mm 2D EPI provided the best-localized activation and least distortion.

A study on the promotion effect of government guidance on the construction of a national unified market logistics channel.

Logistics channel is the lifeblood to ensure that logistics serves the circulation inside and outside the region, and to realize regional economic integration, it greatly contributes to the implementation of the national unified market strategy. As the government plays an important role in the construction of logistics channels, this paper further clarifies the effect of government participation and support policies by defining the role and functions of the government in the construction of logistics channels. Based on the evolutionary game theory, the paper reveals the equilibrium conditions of logistics channel construction under the market mechanism and government guidance under the assumption of bounded rationality. We construct an evolutionary game model among participating stakeholders, then study the evolutionary stability strategy of logistics channel participation behavior using the stability theorem for the model's differential equations. In order to explore the dynamic evolution process of both parties' choices under the two modes, we investigates the influence of the initial intention, cooperative income, cost proportion, penalty coefficient and construction cost of participating enterprises on both parties' strategic decisions under the market mechanism and government guidance modes through numerical simulation. We find that: (1) under the market mechanism and government guidance modes, there is a game equilibrium in the participation behavior of logistics enterprises in the national unified market, and that the conditions for realizing the equilibrium of cooperation among stakeholders under the guidance of the government are easier to meet; (2) The initial intentions of the two players in the game along the logistics channel influence each other, and government participation can change the effects of cooperative income, the penalty coefficient and construction cost on the system game strategy, which has a positive effect on the channel construction; (3) At the same time the simulation shows that the government's promotion effect has certain limitations, and the government should provide reasonable guidance to prevent enterprises from hindering the healthy development of logistics channels. This study provides a theoretical reference for the government and logistics enterprises, especially relying on logistics channels to support the regional coordination of national unified market development.

Predictive values of spinal cord diffusion magnetic resonance imaging to characterize outcomes after contusion injury.

OBJECTIVES: To explore filtered diffusion-weighted imaging (fDWI), in comparison with conventional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), as a predictor for long-term locomotor and urodynamic (UD) outcomes in Yucatan minipig model of spinal cord injury (SCI). Additionally, electrical conductivity of neural tissue using D-waves above and below the injury was measured to assess correlations between fDWI and D-waves data. METHODS: Eleven minipigs with contusion SCI at T8-T10 level underwent MRI at 3T 4 h. post-SCI. Parameters extracted from region of interest analysis included Daxial from fDWI at injury site, fractional anisotropy and radial diffusivity from DTI above the injury site along with measures of edema length and cord width at injury site from T2 -weighted images. Locomotor recovery was assessed pre- and weekly post-SCI through porcine thoracic injury behavior scale (PTIBS) and UD were performed pre- and at 12 weeks of SCI. D-waves latency and amplitude differences were recorded before and immediately after SCI. RESULTS: Two groups of pigs were found based on the PTIBS at week 12 (p < 0.0001) post-SCI and were labeled "poor" and "good" recovery. D-waves amplitude decreased below injury and increased above injury. UD outcomes pre/post SCI changed significantly. Conventional MRI metrics from T2 -weighted images were significantly correlated with diffusion MRI metrics. Daxial at injury epicenter was diminished by over 50% shortly after SCI, and it differentiated between good and poor locomotor recovery and UD outcomes. INTERPRETATION: Similar to small animal studies, fDWI from acute imaging after SCI is a promising predictor for functional outcomes in large animals.

Thermal Stimulus Task fMRI in the Cervical Spinal Cord at 7 Tesla.

PURPOSE: Although functional MRI is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0. Increasing field strength enables higher spatial resolution and improved sensitivity to BOLD signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first stimulus task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D EPI protocols, as they differ in sensitivity to spatial and temporal B0 inhomogeneity. METHODS: The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. For each protocol, the BOLD response to thirteen 10-second noxious thermal stimuli applied to the right thumb was acquired in a 10-minute fMRI run. Image quality, temporal SNR, and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. RESULTS: Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. CONCLUSION: Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment.

Neural function underlying reward expectancy and attainment in adolescents with diverse psychiatric symptoms.

Reward dysfunction has been hypothesized to play a key role in the development of psychiatric conditions during adolescence. To help capture the complexity of reward function in youth, we used the Reward Flanker fMRI Task, which enabled us to examine neural activity during expectancy and attainment of both certain and uncertain rewards. Participants were 84 psychotropic-medication-free adolescents, including 67 with diverse psychiatric conditions and 17 healthy controls. Functional MRI used high-resolution acquisition and high-fidelity processing techniques modeled after the Human Connectome Project. Analyses examined neural activation during reward expectancy and attainment, and their associations with clinical measures of depression, anxiety, and anhedonia severity, with results controlled for family-wise errors using non-parametric permutation tests. As anticipated, reward expectancy activated regions within the fronto-striatal reward network, thalamus, occipital lobe, superior parietal lobule, temporoparietal junction, and cerebellum. Unexpectedly, however, reward attainment was marked by widespread deactivation in many of these same regions, which we further explored using cosine similarity analysis. Across all subjects, striatum and thalamus activation during reward expectancy negatively correlated with anxiety severity, while activation in numerous cortical and subcortical regions during reward attainment positively correlated with both anxiety and depression severity. These findings highlight the complexity and dynamic nature of neural reward processing in youth.

Prefrontal-habenular microstructural impairments in human cocaine and heroin addiction.

The habenula (Hb) is central to adaptive reward- and aversion-driven behaviors, comprising a hub for higher-order processing networks involving the prefrontal cortex (PFC). Despite an established role in preclinical models of cocaine addiction, the translational significance of the Hb and its connectivity with the PFC in humans is unclear. Using diffusion tractography, we detailed PFC structural connectivity with the Hb and two control regions, quantifying tract-specific microstructural features in healthy and cocaine-addicted individuals. White matter was uniquely impaired in PFC-Hb projections in both short-term abstainers and current cocaine users. Abnormalities in this tract further generalized to an independent sample of heroin-addicted individuals and were associated, in an exploratory analysis, with earlier onset of drug use across the addiction subgroups, potentially serving as a predisposing marker amenable for early intervention. Importantly, these findings contextualize a plausible PFC-Hb circuit in the human brain, supporting preclinical evidence for its impairment in cocaine addiction.

Impact of autocalibration method on accelerated EPI of the cervical spinal cord at 7 T.

PURPOSE: The spinal cord contains sensorimotor neural circuits of scientific and clinical interest. However, spinal cord functional MRI (fMRI) is significantly more technically demanding than brain fMRI, due primarily to its proximity to the lungs. Accelerated echo-planar imaging (EPI) at 7 T is particularly vulnerable to k-space phase inconsistencies induced by motion or B0 fluctuation, during either autocalibration signal (ACS) or time-series acquisition. For 7 T brain fMRI, sensitivity to motion and B0 fluctuation can be reduced using a re-ordered segmented EPI ACS based on the fast low-angle excitation echo-planar technique (FLEET). However, respiration-induced B0 fluctuations (exceeding 100 Hz at C7) are greater, and fewer k-space lines per slice are required for cervical spinal cord fMRI at 7 T, necessitating a separate evaluation of ACS methods. METHODS: We compared 24-line single-shot EPI with 48-line two-shot segmented EPI, two-shot FLEET, and gradient echo (GRE)-based ACS acquisition methods, performed under various physiological conditions, in terms of temporal signal-to-noise ratio and prevalence of artifacts in generalized autocalibrating partially parallel acquisition (GRAPPA)-accelerated EPI of the cervical spinal cord at 7 T. RESULTS: Segmented EPI and FLEET ACS produce images with nearly identical patterns of severe image artifacts. GRE and single-shot EPI ACS consistently produce images free from significant artifacts, and temporal signal-to-noise ratio is significantly greater for GRE ACS, particularly in lower slices where through-slice dephasing is most severe. CONCLUSIONS: GRE and single-shot EPI-ACS acquisition methods, which are robust to respiration-induced phase errors between k-space segments, produce images with fewer and less severe artifacts than either FLEET or conventionally segmented EPI for accelerated EPI of the cervical spinal cord at 7 T.

Empirical transmit field bias correction of T1w/T2w myelin maps.

T1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a 'pseudo-transmit' approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected T1w/T2w myelin maps are both better neuroanatomical measures (e.g., for use in cross-species comparisons), and more appropriate for statistical comparisons of relative T1w/T2w differences across individuals and groups (e.g., sex, age, or body-mass-index) within a consistently acquired study at 3T. We recommend that investigators who use the T1w/T2w approach for mapping cortical myelin use these B1+ transmit field corrected myelin maps going forward.

Regional differences of high-quality development level for manufacturing industry in China.

The development of China's manufacturing industry is still facing the challenge of regional imbalance. To solve the problem of development imbalance, it is necessary to realize regional development. First, we must analyze the development characteristics of different regions. To this end, we consider the requirements of the new development era and design an evaluation index system for the high-quality development level of the manufacturing industry from the dimensions of innovation, green, and efficiency. Then construct a novel hybrid model which combines the grey incidence clustering model and AP algorithm for panel data in this paper. According to the statistical data from 2014 to 2018, we find out the high-quality development of China's manufacturing industry is characterized by obvious regional differences, different development stages and different constraints.

Comparison of multicenter MRI protocols for visualizing the spinal cord gray matter.

PURPOSE: Spinal cord gray-matter imaging is valuable for a number of applications, but remains challenging. The purpose of this work was to compare various MRI protocols at 1.5 T, 3 T, and 7 T for visualizing the gray matter. METHODS: In vivo data of the cervical spinal cord were collected from nine different imaging centers. Data processing consisted of automatically segmenting the spinal cord and its gray matter and co-registering back-to-back scans. We computed the SNR using two methods (SNR_single using a single scan and SNR_diff using the difference between back-to-back scans) and the white/gray matter contrast-to-noise ratio per unit time. Synthetic phantom data were generated to evaluate the metrics performance. Experienced radiologists qualitatively scored the images. We ran the same processing on an open-access multicenter data set of the spinal cord MRI (N = 267 participants). RESULTS: Qualitative assessments indicated comparable image quality for 3T and 7T scans. Spatial resolution was higher at higher field strength, and image quality at 1.5 T was found to be moderate to low. The proposed quantitative metrics were found to be robust to underlying changes to the SNR and contrast; however, the SNR_single method lacked accuracy when there were excessive partial-volume effects. CONCLUSION: We propose quality assessment criteria and metrics for gray-matter visualization and apply them to different protocols. The proposed criteria and metrics, the analyzed protocols, and our open-source code can serve as a benchmark for future optimization of spinal cord gray-matter imaging protocols.

Selective augmentation of corticospinal motor drive with trans-spinal direct current stimulation in the cat.

BACKGROUND: A key outcome for spinal cord stimulation for neurorehabilitation after injury is to strengthen corticospinal system control of the arm and hand. Non-invasive, compared with invasive, spinal stimulation minimizes risk but depends on muscle-specific actions for restorative functions. OBJECTIVE: We developed a large-animal (cat) model, combining computational and experimental techniques, to characterize neuromodulation with transcutaneous spinal direct current stimulation (tsDCS) for facilitation of corticospinal motor drive to specific forelimb muscles. METHODS: Acute modulation of corticospinal function by tsDCS was measured using motor cortex-evoked muscle potentials (MEPs). The effects of current intensity, polarity (cathodal, anodal), and electrode position on specific forelimb muscle (biceps vs extensor carpi radialis, ECR) MEP modulation were examined. Locations of a key target, the motoneuron pools, were determined using neuronal tracing. A high-resolution anatomical (MRI and CT) model was developed for computational simulation of spinal current flow during tsDCS. RESULTS: Effects of tsDCS on corticospinal excitability were robust and immediate, therefore supporting MEPs as a sensitive marker of tsDCS targeting. Varying cathodal/anodal current intensity modulated MEP enhancement/suppression, with higher cathodal sensitivity. Muscle-specificity depended on cathode position; the rostral position preferentially augmented biceps responses and the caudal position, ECR responses. Precise anatomical current-flow modeling, supplemented with target motor pool distributions, can explain tsDCS focality on muscle groups. CONCLUSION: Anatomical current-flow modeling with physiological validation based on MEPs provides a framework to optimize muscle-specific tsDCS interventions. tsDCS targeting of representative motor pools enables muscle- and response-specific neuromodulation of corticospinal motor drive.

Long-term ecological assessment of intracranial electrophysiology synchronized to behavioral markers in obsessive-compulsive disorder.

Detection of neural signatures related to pathological behavioral states could enable adaptive deep brain stimulation (DBS), a potential strategy for improving efficacy of DBS for neurological and psychiatric disorders. This approach requires identifying neural biomarkers of relevant behavioral states, a task best performed in ecologically valid environments. Here, in human participants with obsessive-compulsive disorder (OCD) implanted with recording-capable DBS devices, we synchronized chronic ventral striatum local field potentials with relevant, disease-specific behaviors. We captured over 1,000 h of local field potentials in the clinic and at home during unstructured activity, as well as during DBS and exposure therapy. The wide range of symptom severity over which the data were captured allowed us to identify candidate neural biomarkers of OCD symptom intensity. This work demonstrates the feasibility and utility of capturing chronic intracranial electrophysiology during daily symptom fluctuations to enable neural biomarker identification, a prerequisite for future development of adaptive DBS for OCD and other psychiatric disorders.

Decoding Neural Activity in Sulcal and White Matter Areas of the Brain to Accurately Predict Individual Finger Movement and Tactile Stimuli of the Human Hand.

Millions of people worldwide suffer motor or sensory impairment due to stroke, spinal cord injury, multiple sclerosis, traumatic brain injury, diabetes, and motor neuron diseases such as ALS (amyotrophic lateral sclerosis). A brain-computer interface (BCI), which links the brain directly to a computer, offers a new way to study the brain and potentially restore impairments in patients living with these debilitating conditions. One of the challenges currently facing BCI technology, however, is to minimize surgical risk while maintaining efficacy. Minimally invasive techniques, such as stereoelectroencephalography (SEEG) have become more widely used in clinical applications in epilepsy patients since they can lead to fewer complications. SEEG depth electrodes also give access to sulcal and white matter areas of the brain but have not been widely studied in brain-computer interfaces. Here we show the first demonstration of decoding sulcal and subcortical activity related to both movement and tactile sensation in the human hand. Furthermore, we have compared decoding performance in SEEG-based depth recordings versus those obtained with electrocorticography electrodes (ECoG) placed on gyri. Initial poor decoding performance and the observation that most neural modulation patterns varied in amplitude trial-to-trial and were transient (significantly shorter than the sustained finger movements studied), led to the development of a feature selection method based on a repeatability metric using temporal correlation. An algorithm based on temporal correlation was developed to isolate features that consistently repeated (required for accurate decoding) and possessed information content related to movement or touch-related stimuli. We subsequently used these features, along with deep learning methods, to automatically classify various motor and sensory events for individual fingers with high accuracy. Repeating features were found in sulcal, gyral, and white matter areas and were predominantly phasic or phasic-tonic across a wide frequency range for both HD (high density) ECoG and SEEG recordings. These findings motivated the use of long short-term memory (LSTM) recurrent neural networks (RNNs) which are well-suited to handling transient input features. Combining temporal correlation-based feature selection with LSTM yielded decoding accuracies of up to 92.04 ± 1.51% for hand movements, up to 91.69 ± 0.49% for individual finger movements, and up to 83.49 ± 0.72% for focal tactile stimuli to individual finger pads while using a relatively small number of SEEG electrodes. These findings may lead to a new class of minimally invasive brain-computer interface systems in the future, increasing its applicability to a wide variety of conditions.

Historical perspectives, challenges, and future directions of implantable brain-computer interfaces for sensorimotor applications.

Almost 100 years ago experiments involving electrically stimulating and recording from the brain and the body launched new discoveries and debates on how electricity, movement, and thoughts are related. Decades later the development of brain-computer interface technology began, which now targets a wide range of applications. Potential uses include augmentative communication for locked-in patients and restoring sensorimotor function in those who are battling disease or have suffered traumatic injury. Technical and surgical challenges still surround the development of brain-computer technology, however, before it can be widely deployed. In this review we explore these challenges, historical perspectives, and the remarkable achievements of clinical study participants who have bravely forged new paths for future beneficiaries.

Evoking highly focal percepts in the fingertips through targeted stimulation of sulcal regions of the brain for sensory restoration.

BACKGROUND: Paralysis and neuropathy, affecting millions of people worldwide, can be accompanied by significant loss of somatosensation. With tactile sensation being central to achieving dexterous movement, brain-computer interface (BCI) researchers have used intracortical and cortical surface electrical stimulation to restore somatotopically-relevant sensation to the hand. However, these approaches are restricted to stimulating the gyral areas of the brain. Since representation of distal regions of the hand extends into the sulcal regions of human primary somatosensory cortex (S1), it has been challenging to evoke sensory percepts localized to the fingertips. OBJECTIVE/HYPOTHESIS: Targeted stimulation of sulcal regions of S1, using stereoelectroencephalography (SEEG) depth electrodes, can evoke focal sensory percepts in the fingertips. METHODS: Two participants with intractable epilepsy received cortical stimulation both at the gyri via high-density electrocorticography (HD-ECoG) grids and in the sulci via SEEG depth electrode leads. We characterized the evoked sensory percepts localized to the hand. RESULTS: We show that highly focal percepts can be evoked in the fingertips of the hand through sulcal stimulation. fMRI, myelin content, and cortical thickness maps from the Human Connectome Project elucidated specific cortical areas and sub-regions within S1 that evoked these focal percepts. Within-participant comparisons showed that percepts evoked by sulcal stimulation via SEEG electrodes were significantly more focal (80% less area; p = 0.02) and localized to the fingertips more often, than by gyral stimulation via HD-ECoG electrodes. Finally, sulcal locations with consistent modulation of high-frequency neural activity during mechanical tactile stimulation of the fingertips showed the same somatotopic correspondence as cortical stimulation. CONCLUSIONS: Our findings indicate minimally invasive sulcal stimulation via SEEG electrodes could be a clinically viable approach to restoring sensation.

Angiogenic gene networks are dysregulated in opioid use disorder: evidence from multi-omics and imaging of postmortem human brain.

Opioid use disorder (OUD) is a public health crisis in the U.S. that causes over 50 thousand deaths annually due to overdose. Using next-generation RNA sequencing and proteomics techniques, we identified 394 differentially expressed (DE) coding and long noncoding (lnc) RNAs as well as 213 DE proteins in Brodmann Area 9 of OUD subjects. The RNA and protein changes converged on pro-angiogenic gene networks and cytokine signaling pathways. Four genes (LGALS3, SLC2A1, PCLD1, and VAMP1) were dysregulated in both RNA and protein. Dissecting these DE genes and networks, we found cell type-specific effects with enrichment in astrocyte, endothelial, and microglia correlated genes. Weighted-genome correlation network analysis (WGCNA) revealed cell-type correlated networks including an astrocytic/endothelial/microglia network involved in angiogenic cytokine signaling as well as a neuronal network involved in synaptic vesicle formation. In addition, using ex vivo magnetic resonance imaging, we identified increased vascularization in postmortem brains from a subset of subjects with OUD. This is the first study integrating dysregulation of angiogenic gene networks in OUD with qualitative imaging evidence of hypervascularization in postmortem brain. Understanding the neurovascular effects of OUD is critical in this time of widespread opioid use.

Smoking status links habenular volume to glycated hemoglobin: Findings from the Human Connectome Project-Young Adult.

BACKGROUND: The habenula-pancreas axis regulates the stimulatory effects of nicotine on blood glucose levels and may participate in the emergence of type 2 diabetes in human tobacco smokers. This secondary analysis of young adults from the Human Connectome Project (HCP-YA) evaluated whether smoking status links the relationship between habenular volume and glycated hemoglobin (HbA1c), a marker of long-term glycemic control. METHODS: Habenula segmentation was performed using a fully-automated myelin content-based approach in HCP-YA participants and the results were inspected visually (n = 693; aged 22-37 years). A linear regression analysis was used with habenular volume as the dependent variable, the smoking-by-HbA1c interaction as the independent variable of interest, and age, gender, race, ethnicity, education, income, employment status, body mass index, and total gray matter volume as covariates. RESULTS: Habenula volume and HbA1c were similar in smokers and nonsmokers. There was a significant interaction effect (F(1, 673)= 5.03, p = 0.025) indicating that habenular volume was related to HbA1c in a manner that depended on smoking status. Among participants who were smokers (n = 120), higher HbA1c was associated with apparently larger habenular volume (ß = 6.74, standard error=2.36, p = 0.005). No such association between habenular volume and HbA1c was noted among participants who were nonsmokers (n = 573). DISCUSSION: Blood glucose levels over an extended time period, reflected by HbA1c, were correlated with habenular volume in smokers, consistent with a relationship between the habenula and blood glucose homeostasis in smokers. Future studies are needed to evaluate how habenular function relates to glycemic control in smokers and nonsmokers.