Impact of sample size and regression of tissue-specific signals on effective connectivity within the core default mode network.

Interactions within brain networks are inherently directional, which are inaccessible to classical functional connectivity estimates from resting-state functional magnetic resonance imaging (fMRI) but can be detected using spectral dynamic causal modeling (DCM). The sample size and unavoidable presence of nuisance signals during fMRI measurement are the two important factors influencing the stability of group estimates of connectivity parameters. However, most recent studies exploring effective connectivity (EC) have been conducted with small sample sizes and minimally pre-processed datasets. We explore the impact of these two factors by analyzing clean resting-state fMRI data from 330 unrelated subjects from the Human Connectome Project database. We demonstrate that both the stability of the model selection procedures and the inference of connectivity parameters are highly dependent on the sample size. The minimum sample size required for stable DCM is approximately 50, which may explain the variability of the DCM results reported so far. We reveal a stable pattern of EC within the core default mode network computed for large sample sizes and demonstrate that the use of subject-specific thresholded whole-brain masks for tissue-specific signals regression enhances the detection of weak connections.

Form follows function: Applying photographic content analysis to forensic firearm identification.

Drawing forensic conclusions from an image or a video is known as "photographic content analysis." It involves the analysis of an image, as well as objects, actions, and events depicted in images or video. In recent years, photographic depictions of objects suspected as illegal firearms have substantially increased, appearing on CCTV surveillance footage, captured by mobile phones and shared on social media. However, the law in Israel states that a person can be charged with illegally possessing a firearm only if it can be proven that the object is capable of shooting with lethal bullet energy. This becomes more challenging in cases where the firearm was not physically seized, and the evidence exclusively consists of images and video. In this study, photographic content analysis was applied to images and video where objects suspected as commercial or improvised firearms had been depicted. An image and event sequence reconstruction video databases of both firearms and replicas were created in order to better define firearm-specific functional morphological features. We demonstrate that it is possible to classify an object as a firearm by analyzing the functional, and not only the esthetic, morphology in images and video. It is also shown that event sequence reconstruction in video may be used to infer that an object suspected as a firearm has the capacity to shoot by confirming the occurrence of a shooting act or shooting process. Thus, photographic content analysis may be used to forensically establish that an object depicted in an image or a video is a firearm by ruling out other known scenarios, and without physically seizing it.

How may analysis of an inner layer of clothing affect the scene reconstruction in a shooting incident?

Shooting distances are utilized, among other forensic input, to position shooters and victims at the crime scene. Shooting distance estimation is done, mainly under the knowledge or assumption, that no intervening object has been present between the target and the muzzle. In the analysis of clothing items of victims that have been involved in a shootout, it is assumed that most of the marks and materials are left on the outer layers of clothing. The outer layers, not the inner layers, are the first objects the bullet meets. Consequently, undergarments are often disregarded for shooting distance estimation as they are not assumed to contain sufficient information in the form of marks or materials. In light of the above, it is the standard operating procedure in some forensic laboratories not to examine underwear. In this case report, the forensic examiners started by the implementation of standard operating procedures, thus examining only the outer layers of clothing of the victims. A thorough visual examination of the various clothing items led a forensic examiner to decide to extend the standard operating procedures, and try and examine an undergarment of one of the victims as well. The interpretation of examination products led to different scene reconstruction, one that may have led to a different interpretation of evidence. In this case, simply sticking to standard operating procedures might have led to less accurate crime scene reconstruction. This case report comes to stress the importance of thorough inspection of forensic exhibits, and scientific and critical thinking about different scenarios. Moreover, it demonstrates how the case-by-case approach in shooting distance estimation may add meaningful information, and eventually-bring us even closer to the truth.

Treatment Tone Spacing and Acute Effects of Acoustic Coordinated Reset Stimulation in Tinnitus Patients.

Acoustic coordinated reset (aCR) therapy for tinnitus aims to desynchronize neuronal populations in the auditory cortex that exhibit pathologically increased coincident firing. The original therapeutic paradigm involves fixed spacing of four low-intensity tones centered around the frequency of a tone matching the tinnitus pitch, f T , but it is unknown whether these tones are optimally spaced for induction of desynchronization. Computational and animal studies suggest that stimulus amplitude, and relatedly, spatial stimulation profiles, of coordinated reset pulses can have a major impact on the degree of desynchronization achievable. In this study, we transform the tone spacing of aCR into a scale that takes into account the frequency selectivity of the auditory system at each therapeutic tone's center frequency via a measure called the gap index. Higher gap indices are indicative of more loosely spaced aCR tones. The gap index was found to be a significant predictor of symptomatic improvement, with larger gap indices, i.e., more loosely spaced aCR tones, resulting in reduction of tinnitus loudness and annoyance scores in the acute stimulation setting. A notable limitation of this study is the intimate relationship of hearing impairment with the gap index. Particularly, the shape of the audiogram in the vicinity of the tinnitus frequency can have a major impact on tone spacing. However, based on our findings we suggest hypotheses-based experimental protocols that may help to disentangle the impact of hearing loss and tone spacing on clinical outcome, to assess the electrophysiologic correlates of clinical improvement, and to elucidate the effects following chronic rather than acute stimulation.

Friction Marks of Stabbing Tools in Tires.

When receiving a stabbed tire for examination, forensic toolmark examiners can determine whether a suspect tool was used in a specific crime based on class-characteristics and individual-characteristics marks that have been left by the tool on the tire. This study discusses friction marks and their forensic value during the examination of a punctured tire. The term friction mark refers to the noticeable mark around the penetration area on a tire's surface. Tires designed to create high friction when contacting a road. Due to this design, friction is created between the stabbing tool shank and the sides of the hole. As a result of this friction, the shank of the stabbing tool wears the outer layer of tire around the hole. This leaves a friction mark whose general shape reflects the cross-sectional shape of the stabbing tool's shank. This phenomenon was observed and named by Locke (7) in his evaluation of tire puncture marks with knives. This article demonstrates the same phenomenon with other types of stabbing tools. Test stabs were produced with different tools representing a variety of cross-sectional shapes of shanks, and the resulting friction marks were photo-documented and discussed. Correlations between the various cross-sectional shapes and their corresponding friction marks are shown. Based on friction mark examination, the examiner: (i) can infer suspect tool shank cross-sectional shape with the evaluation of the friction mark shape and (ii) can deduce the maximum dimensions of the shank. This examination simplifies and accelerates the forensic comparison procedure and the investigation time.

Acoustic coordinated reset therapy for tinnitus with perceptually relevant frequency spacing and levels.

Acoustic coordinated reset (CR) therapy based on neuromodulation and neuroplasticity principles has been proposed for the treatment of tonal tinnitus. The original therapy involved periodic delivery of randomly ordered sequences of four low-level tones centered around the frequency of a tone that matched the tinnitus pitch, fT, with fixed ratios relative to fT and delivered several hours/day over several weeks. Here we transform the original CR tone selection method to a more perceptually-relevant equivalent rectangular bandwidth (ERB) frequency scale, the ERBN-number scale. Specifically, we provide a mathematical model that enables calculation of CR tones that accounts for fT- and hearing loss-related ERB widening and ERB overlaps and gaps of CR tone alignments. Further, the model ensures symmetric CR tone alignments based on modelling studies that indicate the effect is optimal if the CR stimuli are symmetrically spaced relative to the tinnitus-related population of abnormally synchronized cortical neurons to activate the adjacent sub-populations. We also present experimentally testable ERB-based CR tone alignment strategies and explain how to use the ERB-based model in experiments, clinical studies, other types of tinnitus sound treatment such as tailor-made notch music training and limitations of our approach.

Coordinated reset neuromodulation for Parkinson's disease: proof-of-concept study.

BACKGROUND: The discovery of abnormal synchronization of neuronal activity in the basal ganglia in Parkinson's disease (PD) has prompted the development of novel neuromodulation paradigms. Coordinated reset neuromodulation intends to specifically counteract excessive synchronization and to induce cumulative unlearning of pathological synaptic connectivity and neuronal synchrony. METHODS: In this prospective case series, six PD patients were evaluated before and after coordinated reset neuromodulation according to a standardized protocol that included both electrophysiological recordings and clinical assessments. RESULTS: Coordinated reset neuromodulation of the subthalamic nucleus (STN) applied to six PD patients in an externalized setting during three stimulation days induced a significant and cumulative reduction of beta band activity that correlated with a significant improvement of motor function. CONCLUSIONS: These results highlight the potential effects of coordinated reset neuromodulation of the STN in PD patients and encourage further development of this approach as an alternative to conventional high-frequency deep brain stimulation in PD.

Impact of acoustic coordinated reset neuromodulation on effective connectivity in a neural network of phantom sound.

Chronic subjective tinnitus is an auditory phantom phenomenon characterized by abnormal neuronal synchrony in the central auditory system. As recently shown in a proof of concept clinical trial, acoustic coordinated reset (CR) neuromodulation causes a significant relief of tinnitus symptoms combined with a significant decrease of pathological oscillatory activity in a network comprising auditory and non-auditory brain areas. The objective of the present study was to analyze whether CR therapy caused an alteration of the effective connectivity in a tinnitus related network of localized EEG brain sources. To determine which connections matter, in a first step, we considered a larger network of brain sources previously associated with tinnitus. To that network we applied a data-driven approach, combining empirical mode decomposition and partial directed coherence analysis, in patients with bilateral tinnitus before and after 12 weeks of CR therapy as well as in healthy controls. To increase the signal-to-noise ratio, we focused on the good responders, classified by a reliable-change-index (RCI). Prior to CR therapy and compared to the healthy controls, the good responders showed a significantly increased connectivity between the left primary cortex auditory cortex and the posterior cingulate cortex in the gamma and delta bands together with a significantly decreased effective connectivity between the right primary auditory cortex and the dorsolateral prefrontal cortex in the alpha band. Intriguingly, after 12 weeks of CR therapy most of the pathological interactions were gone, so that the connectivity patterns of good responders and healthy controls became statistically indistinguishable. In addition, we used dynamic causal modeling (DCM) to examine the types of interactions which were altered by CR therapy. Our DCM results show that CR therapy specifically counteracted the imbalance of excitation and inhibition. CR significantly weakened the excitatory connection between posterior cingulate cortex and primary auditory cortex and significantly strengthened inhibitory connections between auditory cortices and the dorsolateral prefrontal cortex. The overall impact of CR therapy on the entire tinnitus-related network showed up as a qualitative transformation of its spectral response, in terms of a drastic change of the shape of its averaged transfer function. Based on our findings we hypothesize that CR therapy restores a silence based cognitive auditory comparator function of the posterior cingulate cortex.

Data-driven approach to the estimation of connectivity and time delays in the coupling of interacting neuronal subsystems.

One of the challenges in neuroscience is the detection of directionality between signals reflecting neural activity. To reveal the directionality of coupling and time delays between interacting multi-scale signals, we use a combination of a data-driven technique called empirical mode decomposition (EMD) and partial directed coherence (PDC) together with the instantaneous causality test (ICT). EMD is used to separate multiple processes associated with different frequency bands, while PDC and ICT allow to explore directionality and characteristic time delays, respectively. We computationally validate our approach for the cases of both stochastic and chaotic oscillatory systems with different types of coupling. Moreover, we apply our approach to the analysis of the connectivity in different frequency bands between local field potentials (LFPs) bilaterally recorded from the left and right of subthalamic nucleus (STN) in patients with Parkinson's disease (PD). We reveal a bidirectional coupling between the left and right STN in the beta-band (10-30 Hz) for an akinetic PD patient and in the tremor band (3-5 Hz) for a tremor-dominant PD patient. We detect a short time delay, most probably reflecting the inter-hemispheric transmission time. Additionally, in both patients we observe a long time delay of approximately a mean period of the beta-band activity in the akinetic PD patient or the tremor band activity in the tremor-dominant PD patient. These long delays may emerge in subcortico-thalamic loops or longer pathways, comprising reflex loops, respectively. We show that the replacement of EMD by conventional bandpass filtering complicates the detection of directionality and leads to a spurious detection of time delays.

Computational modeling of paroxysmal depolarization shifts in neurons induced by the glutamate release from astrocytes.

Recent experimental studies have shown that astrocytes respond to external stimuli with a transient increase of the intracellular calcium concentration or can exhibit self-sustained spontaneous activity. Both evoked and spontaneous astrocytic calcium oscillations are accompanied by exocytosis of glutamate caged in astrocytes leading to paroxysmal depolarization shifts (PDS) in neighboring neurons. Here, we present a simple mathematical model of the interaction between astrocytes and neurons that is able to numerically reproduce the experimental results concerning the initiation of the PDS. The timing of glutamate release from the astrocyte is studied by means of a combined modeling of a vesicle cycle and the dynamics of SNARE-proteins. The neuronal slow inward currents (SICs), induced by the astrocytic glutamate and leading to PDS, are modeled via the activation of presynaptic glutamate receptors. The dependence of the bidirectional communication between neurons and astrocytes on the concentration of glutamate transporters is analyzed, as well. Our numerical results are in line with experimental findings showing that astrocyte can induce synchronous PDSs in neighboring neurons, resulting in a transient synchronous spiking activity.