High Probability Of Connectivity Research Articles

A structural connectivity atlas of limbic brainstem nuclei.

Understanding the structural connectivity of key brainstem nuclei with limbic cortical regions is essential to the development of therapeutic neuromodulation for depression, chronic pain, addiction, anxiety and movement disorders. Several brainstem nuclei have been identified as the primary central nervous system (CNS) source of important monoaminergic ascending fibers including the noradrenergic locus coeruleus, serotonergic dorsal raphe nucleus, and dopaminergic ventral tegmental area. However, due to practical challenges to their study, there is limited data regarding their in vivo anatomic connectivity in humans. To evaluate the structural connectivity of the following brainstem nuclei with limbic cortical areas: locus coeruleus, ventral tegmental area, periaqueductal grey, dorsal raphe nucleus, and nucleus tractus solitarius. Additionally, to develop a group average atlas of these limbic brainstem structures to facilitate future analyses. Each nucleus was manually masked from 197 Human Connectome Project (HCP) structural MRI images using FSL software. Probabilistic tractography was performed using FSL's FMRIB Diffusion Toolbox. Connectivity with limbic cortical regions was calculated and compared between brainstem nuclei. Results were aggregated to produce a freely available MNI structural atlas of limbic brainstem structures. A general trend was observed for a high probability of connectivity to the amygdala, hippocampus and DLPFC with relatively lower connectivity to the orbitofrontal cortex, NAc, hippocampus and insula. The locus coeruleus and nucleus tractus solitarius demonstrated significantly greater connectivity to the DLPFC than amygdala while the periaqueductal grey, dorsal raphe nucleus, and ventral tegmental area did not demonstrate a significant difference between these two structures. Monoaminergic and other modulatory nuclei in the brainstem project widely to cortical limbic regions. We describe the structural connectivity across the several key brainstem nuclei theorized to influence emotion, reward, and cognitive functions. An increased understanding of the anatomic basis of the brainstem's role in emotion and other reward-related processing will support targeted neuromodulatary therapies aimed at alleviating the symptoms of neuropsychiatric disorders.

Infrastructure Allocation for Improving Sensing Accuracy and Connectivity Probability Based on Combination Strategy in Vehicular Networks

Sensing and communication are the two major concerns in vehicle-road collaboration system, whose function realization needs the support of RSE (roadside equipment). A misleading deployment incurs in waste of valuable resources and degradation of the network performance. Based on the combination strategy, this study proposed a hybrid allocation method to deploy RSE on a highway by considering the sensing capability of traditional ITS sensors and the communication feature of popular networking devices. Two sorts of RSE, the one integrated ITS sensor and networking device, named sensing & communication-RSE (scRSE), and the other belongs to networking devices, named communication-RSE (cRSE), were involved. A hybrid RSE allocation framework was proposed, in which an optimal method was adopted to deploy scRSE on key points for data acquisition and a connectivity probability-based uniform method was used to deploy cRSE for communication. The effectiveness of these methods was verified by case analysis. The results indicated that the proposed hybrid method was very effective and outperformed the conventional uniform deployment method. The key parameters, including the coverage range, RSE spacing, and vehicle density, had an important impact on network connectivity probability. To obtain high connectivity probability, a lower density of connected vehicles (CVs) needs the support of wide coverage of RSE, and vice versa. When the density of CVs reaches to a certain value, vehicular networks could be realized without the help of RSE. Benefitting from the mobility of CVs, increasing their transmission range was better than increasing RSE coverage radius in improving connectivity probability.

Delineating Functional Corridors Linking Leopard Habitat in the Eastern and Western Cape, South Africa

Natural landscapes are increasingly fragmented due to human activity. This contributes to isolation and inadequate gene flow among wildlife populations. These threats intensify where populations are already low, and gene flow is compromised. Ensuring habitat connectivity despite transformed landscapes can mitigate these risks. Leopards are associated with high levels of biodiversity and are the last widely occurring, free-roaming apex predator in South Africa. Although highly adaptable, leopard survival is reduced by human-caused mortality and habitat destruction. We aimed to assess the connectivity of leopard habitat in the Eastern Cape and Western Cape, South Africa. We predicted leopard habitat by correlating GPS data from 31 leopards to environmental features that included human-associated and natural landscapes. We used circuit theory to delineate corridors linking known leopard populations. Finally, using camera traps, we tested whether five predicted corridors were used by leopards. Leopard habitat was strongly correlated to moderate slopes and areas of natural land-cover and plantations, highlighting mountainous areas as important habitat with high connectivity probability. While most habitat patches showed some level of connectivity, leopards avoided highly transformed landscapes, potentially isolating some populations. Where corridors are not functional, active conservation measures for species connectivity becomes important.

NDNF interneurons, Spartans of the cortical column: Small in number, strong in impact

NDNF selectively labels neurogliaform inhibitory interneurons of layer 1. In this issue of Neuron, Cohen-Kashi Malina etal. (2021) show that NDNF activity is highly correlated with arousal level. During high arousal state, NDNF inhibits the dendrites while disinhibiting the soma of nearby pyramidal neurons.

Coral cover surveys corroborate predictions on reef adaptive potential to thermal stress

As anomalous heat waves are causing the widespread decline of coral reefs worldwide, there is an urgent need to identify coral populations tolerant to thermal stress. Heat stress adaptive potential is the degree of tolerance expected from evolutionary processes and, for a given reef, depends on the arrival of propagules from reefs exposed to recurrent thermal stress. For this reason, assessing spatial patterns of thermal adaptation and reef connectivity is of paramount importance to inform conservation strategies. In this work, we applied a seascape genomics framework to characterize the spatial patterns of thermal adaptation and connectivity for coral reefs of New Caledonia (Southern Pacific). In this approach, remote sensing of seascape conditions was combined with genomic data from three coral species. For every reef of the region, we computed a probability of heat stress adaptation, and two indices forecasting inbound and outbound connectivity. We then compared our indicators to field survey data, and observed that decrease of coral cover after heat stress was lower at reefs predicted with high probability of adaptation and inbound connectivity. Last, we discussed how these indicators can be used to inform local conservation strategies and preserve the adaptive potential of New Caledonian reefs.

Applied connectivity modelling at local to regional scale: The potential for sea lice transmission between Scottish finfish aquaculture management areas

Due to the importance of parasite and disease controls for animal welfare, environmental sustainability and the economic viability of the finfish aquaculture industry in coastal waters, spatial management measures need to take into account the degree of connectivity between management areas. This paper describes the model integration (one-way nesting) of local high-resolution and wider domain hydrodynamic models around Scotland and the combination of their outputs to force a bio-physical modelling application to support marine spatial management. We used climatological flow fields from a hydrodynamic modelling framework (the “Scottish Shelf Model”) to estimate the degree of connectivity between Scottish finfish aquaculture Farm Management Areas (FMA) using bio-physical simulations of virtual organisms representing the planktonic phase of parasitic sea lice, an important problem for the aquaculture industry. Three types of analysis are carried out: presence/absence of connections between FMAs as the most extreme case, connection probabilities above a defined biologically-meaningful threshold, and above-threshold connection probabilities with a weighting associated with farmed fish within-area biomass (as a proxy for sea lice production) as a more realistic scenario. We find a general northward flow of particles from mainland farms aligned with the prevailing circulation and high connection probability towards the north. Some regions (Loch Linnhe/Sound of Mull) can be classified as net exporters and some (east coast of the Western Isles, the north-west coast) as net receivers of particles. A few selected regions show far reaching connections above the biologically-meaningful probability threshold, for example across the Minch between the Scottish mainland and the Western Isles. Other areas such as Shetland appear to be self-contained and internally well inter-connected. Our results are relevant to the marine aquaculture industry and regulators as they can provide useful information that can be used to develop effective strategies for parasite control.

Anterior Thalamic Excitation and Feedforward Inhibition of Presubicular Neurons Projecting to Medial Entorhinal Cortex.

The presubiculum contains head direction cells that are crucial for spatial orientation. Here, we examined the connectivity and strengths of thalamic inputs to presubicular layer 3 neurons projecting to the medial entorhinal cortex in the mouse. We recorded pairs of projection neurons and interneurons while optogenetically stimulating afferent fibers from the anterior thalamic nuclei. Thalamic input differentially affects presubicular neurons: layer 3 pyramidal neurons and fast-spiking parvalbumin-expressing interneurons are directly and monosynaptically activated, with depressing dynamics, whereas somatostatin-expressing interneurons are indirectly excited, during repetitive anterior thalamic nuclei activity. This arrangement ensures that the thalamic excitation of layer 3 cells is often followed by disynaptic inhibition. Feedforward inhibition is largely mediated by parvalbumin interneurons, which have a high probability of connection to presubicular pyramidal cells, and it may enforce temporally precise head direction tuning during head turns. Our data point to the potential contribution of presubicular microcircuits for fine-tuning thalamic head direction signals transmitted to medial entorhinal cortex.SIGNIFICANCE STATEMENT How microcircuits participate in shaping neural inputs is crucial to understanding information processing in the brain. Here, we show how the presubiculum may process thalamic head directional information before transmitting it to the medial entorhinal cortex. Synaptic inputs from the anterior thalamic nuclei excite layer 3 pyramidal cells and parvalbumin interneurons, which mediate disynaptic feedforward inhibition. Somatostatin interneurons are excited indirectly. Presubicular circuits may switch between two regimens depending on the angular velocity of head movements. During immobility, somatostatin-pyramidal cell interactions could support maintained head directional firing with attractor-like dynamics. During rapid head turns, in contrast, parvalbumin-mediated feedforward inhibition may act to tune the head direction signal transmitted to medial entorhinal cortex.

Cortical Dynamics in Presence of Assemblies of Densely Connected Weight-Hub Neurons.

Experimental measurements of pairwise connection probability of pyramidal neurons together with the distribution of synaptic weights have been used to construct randomly connected model networks. However, several experimental studies suggest that both wiring and synaptic weight structure between neurons show statistics that differ from random networks. Here we study a network containing a subset of neurons which we call weight-hub neurons, that are characterized by strong inward synapses. We propose a connectivity structure for excitatory neurons that contain assemblies of densely connected weight-hub neurons, while the pairwise connection probability and synaptic weight distribution remain consistent with experimental data. Simulations of such a network with generalized integrate-and-fire neurons display regular and irregular slow oscillations akin to experimentally observed up/down state transitions in the activity of cortical neurons with a broad distribution of pairwise spike correlations. Moreover, stimulation of a model network in the presence or absence of assembly structure exhibits responses similar to light-evoked responses of cortical layers in optogenetically modified animals. We conclude that a high connection probability into and within assemblies of excitatory weight-hub neurons, as it likely is present in some but not all cortical layers, changes the dynamics of a layer of cortical microcircuitry significantly.

White Matter Microstructural Damage on Diffusion Tensor Imaging in Cerebral Small Vessel Disease

Cerebral small vessel disease (SVD) is a major health problem for its contribution to ≈45% of dementias, and about a fifth of all strokes worldwide, representing one of the most important causes of disabilities.1 The term SVD refers to a group of pathological processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. The most common forms are age- and hypertension-related SVD and cerebral amyloid angiopathy (CAA).2 Vessel wall changes may lead to both ischemic and hemorrhagic consequences: (1) a state of chronic hypoperfusion or vascular dysfunction responsible for incomplete infarction,3,4 (2) acute focal necrosis (lacunar infarct), or (3) vessel rupture manifesting as hemorrhagic SVD. The clinical consequences of SVD are various and mainly consist of cognitive, mood, and motor dysfunctions leading to functional disability in the late stages of the disease. Magnetic resonance imaging (MRI) has become crucial in the diagnosis of SVD enabling the evaluation of the disease progression both in the clinical and research settings. However, correlations between clinical features of SVD and conventional MRI measures have been partially discordant. Some authors suggested that the cumulative effect of SVD lesions, rather than the individual lesions themselves determines the clinical impact,5 whereas others suggested that the presence and severity of alterations nonvisible on conventional MRI might also be an explanation.6 In the past decade, diffusion tensor imaging (DTI) has been increasingly used for the evaluation of SVD patients because it is sensitive to tissue damage and can show abnormalities in both areas of white matter hyperintensities (WMH) and in normal appearing WM (NAWM). Despite the high sensitivity in detecting cerebral damage, DTI has a low specificity in detecting the underlying cause. In fact, we can only infer that DTI changes reflect a loss of WM …

Research of Resource Optimization Technology Based on Connectivity Probability in Vehicular Network

Multi-lane connectivity probability analysis model based on vehicle speed is studied under free flow state, which focuses on connectivity probability of various road segments, and deduces multilane connectivity probability. For unicast/multicast end-to-end message delivery scenario, connectivity probability based resource optimization algorithm in vehicular network is proposed with the consideration of vehicle speed and direction. On a macro level, the best road segment with high connectivity probability is selected to forward packets. On a micro level, in order to improve the efficiency of data delivery, the neighbor information based multi-hop broadcasting is proceeded to quickly transmit packets from the selected segments to another one. NS2 simulation results show that the proposed resource optimization algorithm improves the effectiveness of the packet forwarding, and reduces the packet transmission delay in vehicular network.

A high-resolution map of direct and indirect connectivity of erosion risk areas to surface waters in Switzerland—A risk assessment tool for planning and policy-making

Off-site effects of soil erosion are becoming increasingly important, particularly the pollution of surface waters. In order to develop environmentally efficient and cost effective mitigation options it is essential to identify areas that bear both a high erosion risk and high connectivity to surface waters. This paper introduces a simple risk assessment tool that allows the delineation of potential critical source areas (CSA) of sediment input into surface waters concerning the agricultural areas of Switzerland. The basis are the erosion risk map with a 2m resolution (ERM2) and the drainage network, which is extended by drained roads, farm tracks, and slope depressions. The probability of hydrological and sedimentological connectivity is assessed by combining soil erosion risk and extended drainage network with flow distance calculation. A GIS-environment with multiple-flow accumulation algorithms is used for routing runoff generation and flow pathways. The result is a high resolution connectivity map of the agricultural area of Switzerland (888,050ha). Fifty-five percent of the computed agricultural area is potentially connected with surface waters, 45% is not connected. Surprisingly, the larger part of 34% (62% of the connected area) is indirectly connected with surface waters through drained roads, and only 21% are directly connected. The reason is the topographic complexity and patchiness of the landscape due to a dense road and drainage network. A total of 24% of the connected area and 13% of the computed agricultural area, respectively, are rated with a high connectivity probability. On these CSA an adapted land use is recommended, supported by vegetated buffer strips preventing sediment load. Even areas that are far away from open water bodies can be indirectly connected and need to be included in planning of mitigation measures. Thus, the connectivity map presented is an important decision-making tool for policy-makers and extension services. The map is published on the web and thus available for application.

Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts.

To study remote effects distant from acute ischemic infarcts by measuring longitudinal changes of cortical thickness in connected brain regions as well as changes in microstructural integrity in connecting fiber tracts. Thirty-two patients (mean age 71 years) underwent a standardized protocol including multimodal MRI and clinical assessment both at stroke onset and 6 months after the event. Cortex connected to acute infarcts was identified by probabilistic diffusion tensor tractography starting from the acute lesion. Changes of cortical thickness were measured using the longitudinal stream of FreeSurfer. Microstructural damage in white matter tracts was assessed by changes of mean diffusivity. We found focal cortical thinning specifically in areas connected to acute infarcts (p < 0.001). Thinning was more pronounced in regions showing a high probability of connectivity to infarcts. Microstructural damage in white matter tracts connecting acute infarcts with distant cortex significantly correlated with thickness changes in that region (ρ = -0.39, p = 0.028). There was no indication of an influence of cavitation status or infarct etiology on the observed changes in cortex and white matter. These findings identify secondary degeneration of connected white matter tracts and remote cortex as key features of acute ischemic infarcts. Our observations may have implications for the understanding of structural and functional reorganization after stroke.

A Novel Hybrid Key Management Scheme for Establishing Secure Communication in Wireless Sensor Networks

Security is a critical issue when sensor nodes are deployed in a hostile environment. This paper proposes a novel Polynomial based Q composite random scheme for the establishment of triple key among communicating nodes in a network. The proposed scheme combines the robustness of Q-Composite Key Generation Scheme with the Polynomial Pool-Based Schemethat enables a secure communication between wireless sensor nodes. The security analysis shows that our scheme assures a high probability of secure communication with a low communication overhead. The simulation results prove that our scheme performs better in terms of network resilience against node capture attacks with a high probability of connectivity. The proposed scheme shows an improvement in compromised data links between non compromised sensors.Our scheme also provides high resilience in terms of the fraction of unaffected communication links against the compromised nodes even in the presence of a large number of malicious nodes.

Diffusion pattern analysis for social networking sites using small-world network multiple influence model

Despite the rapid proliferation of social networking sites (SNSs), most of the relevant research remains at the level of the analysis of their apparent characteristics. The kernel of the question, though, is the causal relationship between those characteristics and their diffusion patterns. Even though it is axiomatic that SNS diffusion patterns are highly affected by SNS characteristics, there has been little research focusing on the influence of the latter on the former. In response to this research lacuna, the present study aimed, first, to find key SNS characteristics that can be directly related to their diffusion patterns; second, to classify existing SNSs according to those derived characteristics, and finally, to examine whether the different types of SNS actually lead to distinct diffusion patterns or not. SNS diffusion patterns were analyzed using the Small-World Network Multiple Influence (SWMI) model which can explain the characteristics of social systems. The analysis results show that SNSs having a high degree of relationship extension represent a high-connection probability to users not already connected, and also, that SNSs having a high degree of shared interest have a relatively stronger external effect than other SNSs.

Functional Coupling from Simple to Complex Cells in the Visually Driven Cortical Circuit

In the classic model of the primary visual cortex, upper-layer complex cells are driven by feedforward inputs from layer 4 simple cells. Based on spike cross-correlation, previous in vivo work has suggested that this connection is strong and dense, with a high probability of connection (50%) and significant strength in connected pairs. A much sparser projection has been found in brain slices, however, with the probability of layer 4 cells connecting to layer 2/3 cells being relatively low (10%). Here, we explore this connection in vivo in the cat primary visual cortex by recording simultaneously spikes of layer 4 simple cells and the membrane potential (V(m)) of layer 2/3 complex cells. By triggering the average of the complex cell's V(m) on the spikes of the simple cell (V(m)-STA), we found functional coupling to be very common during visual stimulation: the simple cell's spikes tended to occur near the troughs of the complex cell's V(m) fluctuations and were, on average, followed by a significant (~1 mV) fast-rising (10 ms) depolarization in the complex cell. In the absence of visual stimulation, however, when single simple cells were activated electrically through the recording electrode, no significant depolarization, or at most a very weak input (0.1-0.2 mV), was detected in the complex cell. We suggest that the functional coupling observed during visual stimulation arises from coordinated or nearly synchronous activity among a large population of simple cells, only a small fraction of which are presynaptic to the recorded complex cell.

Probabilistic tractography of the posterior subthalamic area in Parkinson’s disease patients

Deep brain stimulation (DBS) is a non-pharmacological treatment for Parkinson’s disease (PD), and its efficacy depends largely on which anatomical structure (target) is stimulated. The subthalamic nucleus (STN) is one of the most commonly used targets, but stimulation of new targets within the posterior sub-thalamic area (PSA), comprising a group of white matter fibers known as prelemniscal radiations (Raprl), as well as the caudal zonaincerta nucleus (Zic), have proven to be superior at improving certain clinical symptoms. Despite their clinical usefulness, their anatomical connectivity has not been completely described in humans. We performed constrained spherical deconvolution of the signal in diffusion-weighted images and subsequent tractography as a means to non-invasively define the connectivity of the Raprl and Zic in a group of five patients with PD. Further, we used track-density imaging, a novel method to improve the spatial resolution of the acquired images, in order to visualize the small subregions that comprise the PSA with a voxel resolution of 0.2 × 0.2 × 0.2 mm3. Both Raprl and Zic demonstrated high probability of connectivity with the dorsal brainstem, cerebellum, subcortical nuclei (globus pallidum ventral, lateral thalamic nuclei), and cortical areas (orbitofrontal cortex, primary and supplementary motor cortex areas). The connectivity patterns were re-producible between patients and were discretely organized as the tracts entered/exited the PSA, depending on their end points. These findings indicate that the PSA is part of the neuronal circuitry controlling movement, and the precise characterization of its connectivity will aid in our understanding of the net-works involved in PD and how they can be modulated with DBS in order to alleviate symptoms.

Incident subcortical infarcts induce focal thinning in connected cortical regions

Brain atrophy is common in subcortical ischemic vascular disease, but the underlying mechanisms are poorly understood. We set out to examine the effects of incident subcortical infarcts on cortical morphology. A total of 276 subjects with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, an inherited small vessel disease, were enrolled in a prospective study. Incident subcortical infarcts were identified on follow-up magnetic resonance scans after 18, 36, and 54 months using difference images. Probabilistic fiber tracking and cortical thickness measurements were applied to study the longitudinal relationship between incident infarcts and connected cortical areas. Cortical thickness was assessed before and after infarction using FreeSurfer software. Focal cortical thinning was defined as change of cortical thickness in the connected region of interest exceeding the global change of cortical thickness. Nine subjects had a single incident infarct during the follow-up and were suitable for analysis. There was a strong correlation between the probability of connectivity and mean focal cortical thinning (p = 0.0039). In all subjects, there was focal cortical thinning in cortical regions with high probability of connectivity with the incident infarct. This pattern was not observed when using control tractography seeds. Our findings provide in vivo evidence for secondary cortical neurodegeneration after subcortical ischemia as a mechanism for brain atrophy in cerebrovascular disease.

Optogenetic Probing of Fast Glutamatergic Transmission from Hypocretin/Orexin to Histamine NeuronsIn Situ

Hypothalamic hypocretin/orexin (hcrt/orx) neurons coordinate sleep-wake cycles, reward seeking, and body energy balance. Neurochemical data suggest that hcrt/orx cells contain several transmitters, but what hcrt/orx cells release onto their projection targets is unknown. A major pathway by which hcrt/orx neurons are thought to promote arousal is through projections to tuberomammillary histamine (HA) neurons. To study the impact of the electrical activity in hcrt/orx cells on HA neurons, we genetically targeted the light-activated excitatory ion channel channelrhodopsin-2 (ChR2) to the plasma membrane of hcrt/orx cells, and performed patch-clamp recordings from HA cells in acute mouse brain slices. Stimulation of ChR2-containing fibers with millisecond flashes of blue light produced fast postsynaptic currents in HA neurons, with a high connection probability (≈60% of HA cells were connected to ≈40% of hcrt/orx cells expressing ChR2). These inputs depended on tetrodotoxin-sensitive action potentials, had kinetics typical of glutamatergic responses mediated by AMPA receptors, were blocked by the AMPA receptor blocker CNQX, and displayed multiple forms of short-term plasticity (depression in ≈70% trials, facilitation in ≈30% trials, both often in the same cell). Furthermore, stimulation of hcrt/orx axons at physiological frequencies rapidly and reversibly increased action potential firing in HA cells, an effect that was abolished by blockade of AMPA receptors. These results provide the first functional evidence that hcrt/orx neurons are capable of fast glutamatergic control of their projection targets, and suggest that variations in electrical activity of hcrt/orx axons can induce rapid changes in long-range signals generated by HA neurons.

Multi-institutional evaluation of deep brain stimulation targeting using probabilistic connectivity-based thalamic segmentation

Due to the lack of internal anatomical detail with traditional MR imaging, preoperative stereotactic planning for the treatment of tremor usually relies on indirect targeting based on atlas-derived coordinates. The object of this study was to preliminarily investigate the role of probabilistic tractography-based thalamic segmentation for deep brain stimulation (DBS) targeting for the treatment of tremor. Six patients undergoing bilateral implantation of DBS electrodes in the thalamus for the treatment of upper-extremity tremor were studied. All patients underwent stereotactic surgical implantation using traditional methods (based on indirect targeting methodologies and intraoperative macrostimulation findings) that were programmed for optimal efficacy, independent of tractography-based segmentations described in this report. Connectivity-based thalamic segmentations were derived by identifying with which of 7 cortical target regions each thalamic voxel had the highest probability of connectivity. The authors retrospectively analyzed the location of the optimal contact for treatment of tremor with connectivity-based thalamic segmentations. Findings from one institution (David Geffen School of Medicine at UCLA) were validated with results from 4 patients at another institution (University of Virginia Health System). Of 12 electrodes implanted using traditional methodologies, all but one resulted in efficacious tremor control. Connectivity-based thalamic segmentation consistently revealed discrete thalamic regions having unique connectivity patterns with distinct cortical regions. Although the authors initially hypothesized that the most efficacious DBS contact for controlling tremor would colocalize with the thalamic region most highly connected with the primary motor cortex, they instead found it to highly colocalize with those thalamic voxels demonstrating a high probability of connectivity with premotor cortex (center-to-center distance: 0.36 ± 0.55 mm). In contrast to the high degree of colocalization with optimal stimulation site, the precise localization of the premotor cortex-defined thalamic region relative to the anterior and posterior commissures was highly variable. Having defined a connectivity-based target for thalamic stimulation in a cohort of patients at David Geffen School of Medicine at UCLA, the authors validated findings in 4 patients (5 electrodes) who underwent surgery at a different institution (University of Virginia Health System) by a different surgeon. This report identifies and provides preliminary external validation of a novel means of targeting a patient-specific therapeutic thalamic target for the treatment of tremor based on individualized analysis of thalamic connectivity patterns. This novel thalamic targeting approach is based on identifying the thalamic region with the highest probability of connectivity with premotor and supplementary motor cortices. This approach may prove to be advantageous over traditional preoperative methods of indirect targeting, providing patient-specific targets that could improve the precision, efficacy, and efficiency of deep brain stimulation surgery. Prospective evaluation and development of methodologies to make these analyses more widely available to neurosurgeons are likely warranted.

Preparation of Coverslips for Neuronal Cultures

INTRODUCTIONThis protocol describes methods for preparing glass coverslips to use with three different types of dissociated neuronal cultures: mass culture, microisland culture, and macroisland culture. In mass culture, the entire glass coverslip is precoated with poly-D-lysine and laminin and then plated with astrocytes followed by dissociated neurons. In this system, the plated neurons tend to form an extensive and widespread network of synapses. However, depending on the origin of the neurons, proximity might not be a good predictor of the presence of synapses between any two cells. Microisland culture aims to increase the probability of identifying neurons synaptically connected to each other; its basic principle is to restrict spatially the choice of connections. This is done by plating neurons on astrocyte-seeded collagen dots on a background of a nonadhesive agarose substrate. Synaptic interactions between dorsal horn (DH) neurons or between dorsal-root ganglion (DRG) and DH neurons on the microislands are reliably found using this system, whereas they are much harder to find in mass culture. The macroisland approach is similar, but generates larger islands. It was developed specifically to improve neuronal survival in DRG/DH cocultures while still providing a high probability of connection between DRG and DH neurons. For DH-DH synapses however, microislands are still the best system.