Predicting Wrist Posture during Occupational Tasks Using Inertial Sensors and Convolutional Neural Networks.

Current methods for ergonomic assessment often use video-analysis to estimate wrist postures during occupational tasks. Wearable sensing and machine learning have the potential to automate this tedious task, and in doing so greatly extend the amount of data available to clinicians and researchers. A method of predicting wrist posture from inertial measurement units placed on the wrist and hand via a deep convolutional neural network has been developed. This study has quantified the accuracy and reliability of the postures predicted by this system relative to the gold standard of optoelectronic motion capture. Ten participants performed 3 different simulated occupational tasks on 2 occasions while wearing inertial measurement units on the hand and wrist. Data from the occupational task recordings were used to train a convolutional neural network classifier to estimate wrist posture in flexion/extension, and radial/ulnar deviation. The model was trained and tested in a leave-one-out cross validation format. Agreement between the proposed system and optoelectronic motion capture was 65% with κ = 0.41 in flexion/extension and 60% with κ = 0.48 in radial/ulnar deviation. The proposed system can predict wrist posture in flexion/extension and radial/ulnar deviation with accuracy and reliability congruent with published values for human estimators. This system can estimate wrist posture during occupational tasks in a small fraction of the time it takes a human to perform the same task. This offers opportunity to expand the capabilities of practitioners by eliminating the tedium of manual postural assessment.

Prefrontal and hippocampal theta rhythm show anxiolytic-like changes during periaqueductal-elicited "panic" in rats.

Anxiety and panic are both elicited by threat and co-occur clinically. But, at the neural level, anxiety appears to inhibit the generation of panic; and vice versa. Anxiety and panic are thought to engage more anterior (a) and mid-posterior (m) parts of the periaqueductal gray (PAG), respectively. Anxiety also engages the hippocampus and medial prefrontal cortex. Here, we tested if mPAG but not aPAG stimulation would suppress prefrontal and hippocampal theta rhythm as do anxiolytic drugs. Twelve male rats with implanted electrodes were stimulated alternately (30 s interval) in the left PAG or right reticular formation (reticularis pontis oralis [RPO]-as a positive control) with recording in the left prelimbic cortex and left and right hippocampus. PAG stimulation was set to produce freezing and RPO to produce 7-8 Hz theta rhythm before tests lasting 10 min on each of 5 days. mPAG stimulation decreased, and aPAG increased, theta power at all sites during elicited freezing. mPAG, but not aPAG, stimulation decreased prefrontal theta frequency. Stimulation did not substantially change circuit dynamics (pairwise phase consistency and partial directed coherence). Together with previous reports, our data suggest that panic- and anxiety-control systems are mutually inhibitory, and neural separation of anxiety and panic extends down to the aPAG and mPAG, respectively. Our findings are consistent with recent proposals that fear and anxiety are controlled by parallel neural hierarchies extending from PAG to the prefrontal cortex.

Novel multi jet fusion 3D-printed patient immobilization for radiation therapy.

PURPOSE: Thermoplastic immobilizers are used routinely in radiation therapy to achieve positioning accuracy. These devices are variable in quality as they are dependent on the skill of the human fabricator. We examine the potential multi jet fusion (MJF) 3D printing for the production immobilizers with a focus on the surface dosimetry of several MJF-printed PA12-based material candidates. Materials are compared with the goal of minimizing surface dose with comparison to standard thermoplastic. We introduce a novel metamaterial design for the shell of the immobilizer, with the aims of mechanical robustness and low-dose buildup. We demonstrate first examples of adult and pediatric cranial and head-and-neck immobilizers. METHODS: Three different PA12 materials were examined and compared to fused deposition modeling-printed polylactic acid (PLA), PLA with density lowered by adding hollow glass microspheres, and to perforated or perforated/stretched and solid status quo thermoplastic samples. Build-up dose measurements were made using a parallel plate chamber. A metamaterial design was established based on a packed hexagonal geometry. Radiochromic film dosimetry was performed to determine the dependence of surface dose on the metamaterial design. Full cranial and head-and-neck prototype immobilizers were designed, printed, and assessed with regard to dimensional accuracy. RESULTS: Build-up dose measurements demonstrated the superiority of the PA12 material with a light fusing agent, which yielded a ∼15% dose reduction compared to other MJF materials. Metamaterial samples provided dose reductions ranging from 11% to 40% compared to stretched thermoplastic. MJF-printed immobilizers were produced reliably, demonstrated the versatility of digital design, and showed dimensional accuracy with 97% of sampled points within ±2 mm. CONCLUSIONS: MJF is a promising technology for an automated fabrication of patient immobilizers. Material selection and metamaterial design can be leveraged to yield surface dose reduction of up to 40%. Immobilizer design is highly customizable, and the first examples of MJF-printed immobilizers demonstrate excellent dimensional accuracy.

Speed modulation of hippocampal theta frequency and amplitude predicts water maze learning.

Theta oscillations in the hippocampus have many behavioral correlates, with the magnitude and vigor of ongoing movement being the most salient. Many consider correlates of locomotion with hippocampal theta to be a confound in delineating theta contributions to cognitive processes. Theory and empirical experiments suggest theta-movement relationships are important if spatial navigation is to support higher cognitive processes. In the current study, we tested if variations in speed modulation of hippocampal theta can predict spatial learning rates in the water maze. Using multi-step regression, we find that the magnitude and robustness of hippocampal theta frequency versus speed scaling can predict water maze learning rates. Using a generalized linear model, we also demonstrate that speed and water maze learning are the best predictors of hippocampal theta frequency and amplitude. Our findings suggest movement-speed correlations with hippocampal theta frequency may be actively used in spatial learning.

Accuracy of a Low-Cost 3D-Printed Wearable Goniometer for Measuring Wrist Motion.

Wrist motion provides an important metric for disease monitoring and occupational risk assessment. The collection of wrist kinematics in occupational or other real-world environments could augment traditional observational or video-analysis based assessment. We have developed a low-cost 3D printed wearable device, capable of being produced on consumer grade desktop 3D printers. Here we present a preliminary validation of the device against a gold standard optical motion capture system. Data were collected from 10 participants performing a static angle matching task while seated at a desk. The wearable device output was significantly correlated with the optical motion capture system yielding a coefficient of determination (R2) of 0.991 and 0.972 for flexion/extension (FE) and radial/ulnar deviation (RUD) respectively (p < 0.0001). Error was similarly low with a root mean squared error of 4.9° (FE) and 3.9° (RUD). Agreement between the two systems was quantified using Bland-Altman analysis, with bias and 95% limits of agreement of 3.1° ± 7.4° and -0.16° ± 7.7° for FE and RUD, respectively. These results compare favourably with current methods for occupational assessment, suggesting strong potential for field implementation.

Venous ulcer: late complication of a traumatic arteriovenous fistula.

Arteriovenous fistula (AVF) formation after penetrating trauma is a well-described phenomenon. However, diagnosis of traumatic AVF is frequently delayed as patients often do not have hard signs of vascular injury at the initial presentation. Late complications of traumatic AVF include arterial and venous dilatation, distal ischemia, venous congestion, and congestive heart failure. This case report describes a traumatic femoral AVF causing distal venous ulceration 3 years after the injury. The AVF was treated with open repair. In the operating room, the Nicoladoni-Branham sign was elicited. The ulcer healed at 1 month and has not recurred at 1-year follow-up.

Dynamic interaction between hippocampus, orbitofrontal cortex, and subthalamic nucleus during goal conflict in the stop signal task in rats.

Action stopping depends on at least two (fast, slow) frontal circuits depending on the urgency of execution of the 'go' response. Human EEG suggests a third (even slower, limbic) circuit that activates frontal areas at frequencies typical of 'hippocampal theta'. Here we test in male rats whether stop-go conflict engages the hippocampus and so may send theta-modulated information via the frontal cortex to the subthalamic nucleus. We recorded from multi-electrode arrays in the hippocampus, orbitofrontal cortex, and subthalamus in 5 male Long Evans rats performing a stop signal task and, as in previous human experiments, assessed stop-signal specific power for effects of goal conflict. Conflict increased 11-12 Hz theta power modestly in all three structures but with the largest increase in power being at 5 Hz in the frontal cortex but not the hippocampus. There was increased conflict-related coherence in all circuits in the range 5-8 Hz and particularly at 5-6 Hz. Increased coherence coupled with an increase in conflict-induced low frequency power in the frontal cortex may reflect communication with the hippocampus. The data are consistent with a third limbic circuit that can generate stopping when go responses are particularly slow (as, e.g., in a go/no go task). [199 words; 200 max].

Sharp Tuning of Head Direction and Angular Head Velocity Cells in the Somatosensory Cortex.

Head direction (HD) cells form a fundamental component in the brain's spatial navigation system and are intricately linked to spatial memory and cognition. Although HD cells have been shown to act as an internal neuronal compass in various cortical and subcortical regions, the neural substrate of HD cells is incompletely understood. It is reported that HD cells in the somatosensory cortex comprise regular-spiking (RS, putative excitatory) and fast-spiking (FS, putative inhibitory) neurons. Surprisingly, somatosensory FS HD cells fire in bursts and display much sharper head-directionality than RS HD cells. These FS HD cells are nonconjunctive, rarely theta rhythmic, sparsely connected and enriched in layer 5. Moreover, sharply tuned FS HD cells, in contrast with RS HD cells, maintain stable tuning in darkness; FS HD cells' coexistence with RS HD cells and angular head velocity (AHV) cells in a layer-specific fashion through the somatosensory cortex presents a previously unreported configuration of spatial representation in the neocortex. Together, these findings challenge the notion that FS interneurons are weakly tuned to sensory stimuli, and offer a local circuit organization relevant to the generation and transmission of HD signaling in the brain.

Infraslow closed-loop brain training for anxiety and depression (ISAD): a protocol for a randomized, double-blind, sham-controlled pilot trial in adult females with internalizing disorders.

BACKGROUND: The core intrinsic connectivity networks (core-ICNs), encompassing the default-mode network (DMN), salience network (SN) and central executive network (CEN), have been shown to be dysfunctional in individuals with internalizing disorders (IDs, e.g. major depressive disorder, MDD; generalized anxiety disorder, GAD; social anxiety disorder, SOC). As such, source-localized, closed-loop brain training of electrophysiological signals, also known as standardized low-resolution electromagnetic tomography (sLORETA) neurofeedback (NFB), targeting key cortical nodes within these networks has the potential to reduce symptoms associated with IDs and restore normal core ICN function. We intend to conduct a randomized, double-blind (participant and assessor), sham-controlled, parallel-group (3-arm) trial of sLORETA infraslow (<0.1 Hz) fluctuation neurofeedback (sLORETA ISF-NFB) 3 times per week over 4 weeks in participants (n=60) with IDs. Our primary objectives will be to examine patient-reported outcomes (PROs) and neurophysiological measures to (1) compare the potential effects of sham ISF-NFB to either genuine 1-region ISF-NFB or genuine 2-region ISF-NFB, and (2) assess for potential associations between changes in PRO scores and modifications of electroencephalographic (EEG) activity/connectivity within/between the trained regions of interest (ROIs). As part of an exploratory analysis, we will investigate the effects of additional training sessions and the potential for the potentiation of the effects over time. METHODS: We will randomly assign participants who meet the criteria for MDD, GAD, and/or SOC per the MINI (Mini International Neuropsychiatric Interview for DSM-5) to one of three groups: (1) 12 sessions of posterior cingulate cortex (PCC) ISF-NFB up-training (n=15), (2) 12 sessions of concurrent PCC ISF up-training and dorsal anterior cingulate cortex (dACC) ISF-NFB down-training (n=15), or (3) 6 sessions of yoked-sham training followed by 6 sessions genuine ISF-NFB (n=30). Transdiagnostic PROs (Hospital Anxiety and Depression Scale, HADS; Inventory of Depression and Anxiety Symptoms - Second Version, IDAS-II; Multidimensional Emotional Disorder Inventory, MEDI; Intolerance of Uncertainty Scale - Short Form, IUS-12; Repetitive Thinking Questionnaire, RTQ-10) as well as resting-state neurophysiological measures (full-band EEG and ECG) will be collected from all subjects during two baseline sessions (approximately 1 week apart) then at post 6 sessions, post 12 sessions, and follow-up (1 month later). We will employ Bayesian methods in R and advanced source-localisation software (i.e. exact low-resolution brain electromagnetic tomography; eLORETA) in our analysis. DISCUSSION: This protocol will outline the rationale and research methodology for a clinical pilot trial of sLORETA ISF-NFB targeting key nodes within the core-ICNs in a female ID population with the primary aims being to assess its potential efficacy via transdiagnostic PROs and relevant neurophysiological measures. TRIAL REGISTRATION: Our study was prospectively registered with the Australia New Zealand Clinical Trials Registry (ANZCTR; Trial ID: ACTRN12619001428156). Registered on October 15, 2019.

Functional MRI response and correlated electrophysiological changes during posterior hypothalamic nucleus deep brain stimulation.

Identification of active networks involved in behavior is central to understanding brain function as an emergent property. Functional magnetic resonance imaging (fMRI) allows the identification of areas with increased or decreased activity, but the cellular correlates to changes in fMRI response is still controversial. Deep brain stimulation of the posterior hypothalamic nucleus (PH) is known to facilitate locomotor behaviors and rescue locomotion in rodent models of parkinsonian akinesia by an unknown mechanism. Here, we performed 9.4 T fMRI during deep brain stimulation of PH in the anesthetized rat as a model system to explore the network substrates for its behavioral consequences. In addition, multi-unit and field potential recordings were made to examine the physiological correlates to changes in fMRI response. The most robust and reliable MR signal increases were observed in the somatosensory and motor cortices, with minor limbic and sparse thalamic activation. Electrophysiological experiments demonstrated that increased fMRI response in the neocortex corresponds to general increases in spiking activity, decreased slow oscillations and increased delta band activity. Forelimb movements evoked by intracortical microstimulation had reduced thresholds and larger representational (motor map) areas during and following PH stimulation. These findings identify the sensorimotor cortices as major contributors for behavioral effects of PH stimulation, and that coincident increase in spiking, synaptic activity and MR signal reflect functional facilitation of neocortical output.

Behavioral significance of hippocampal θ oscillations: looking elsewhere to find the right answers.

The function of hippocampal theta oscillations has been subjected to constant speculation. Dynamic coupling of theta field potentials and spiking activity between the hippocampus and extra-hippocampal structures emphasizes the importance of theta-frequency oscillations in global spike-timing precision in the brain. Recent advances in understanding theta coupling between distant brain structures are discussed and explored in this article.

Minimal driving of hippocampal theta by the supramammillary nucleus during water maze learning.

Previous studies have shown only modest effects of supramammillary nucleus (SuM) dysfunction on theta frequency and learning in the water maze (WM), with larger effects in other tasks. However, theta recorded from SuM, and used to trigger the production of theta-like oscillations in the hippocampus, produced reversal of the deficit in WM learning produced by theta blocking. We explored this apparent inconsistency by analyzing the relationship between SuM and hippocampal theta in the control group of this theta-blocking experiment using coherence, phase analysis, and the directed transfer function. We found little evidence of an influence of SuM on the hippocampus in the bulk of WM learning-with some possibility of SuM becoming involved briefly later in learning. A learning-related increase in coherence was observed in conjunction with gradual phase reorganization of hippocampal theta in relation to SuM theta. This change in phase dynamics between the two structures was also correlated with a relative increase of the estimated direction of theta propagation from the SuM to the hippocampus. These results are consistent with the previous weak effects of SuM lesions and suggest that the use of SuM as a source to trigger hippocampal theta and recover function is likely to be due to coherence between SuM and some other structure that normally controls hippocampal theta during WM learning.

Thick primary melanoma has a heterogeneous tumor biology: an institutional series.

BACKGROUND: Thick melanomas (TM) ≥4 mm have a high risk for nodal and distant metastases. Optimal surgical management, prognostic significance of sentinel node biopsy (SLNB), and benefits of interferon (IFN) for these patients are unclear. As a continuum of increasing tumor thickness is placed into a single TM group, differences in biologic and clinical behavior may be lost. The purpose of this study was to better characterize the diverse biology in TM, including the value of increasing thickness and nodal status information, potentially identifying high risk TM subgroups that may warrant more aggressive treatment/follow up. METHODS: 155 consecutive TM patients treated at a single institution between 1971 and 2007 were retrospectively reviewed. Patient, disease and treatment features were analyzed with respect to disease-free (DFS) and overall survival (OS). RESULTS: Median patient age was 66 years and 68% of patients were men. The trunk was the most common TM location (35%), followed by the head and neck (29%) and lower extremities (20%). Median thickness was 6 mm and 61% were ulcerated. 6% patients had stage IV disease, 12% had clinical nodal metastases. Clinically negative lymph node basins were treated by observation (22 patients--15.4%), elective lymph node dissection (ELND) (24 patients--17.6%) or SLNB (91 patients--67%). 75% of ELND's and 53% of SLNB's were positive. Completion node dissection was performed in 38 SLNB+ patients and 22% had additional positive nodes. 17% of the study patients received IFN. At median follow up of 26 months, 5 year DFS and OS were 42% and 43.6%. For SLNB positive vs negative, median DFS were 22 vs 111 months (p = 0.006) and median OS were 41 vs 111 months (p = 0.006). When stratified by tumor thickness ≤ vs > 6 mm, 5 year DFS was 58.3% vs 20% (p < 0.0001) and OS was 62% vs 20% (P < 0.0001). IFN had no impact on DFS or OS (p = 0.98 and 0.8 respectively). CONCLUSION: Within the high risk group of patients with TM, cases with tumor thickness > 6 mm or a positive SLNB had a significantly worse DFS and OS (p < .0001, <.0001 and .006, .006).

Design and validation of a novel 3D-printed wearable device for monitoring knee joint kinematics.

Gait analysis provides an important tool for the study and clinical evaluation of conditions which affect knee joint biomechanics. Collection of knee joint kinematics in real world environments during locomotor activities of daily living could provide quantitative evidence to help understand functional impairment. Unfortunately, the high cost and necessary technical expertise associated with current commercially available systems for kinematic monitoring serve as an impediment to their adoption outside of specialized research groups. We have developed a low-cost, custom wearable device to address these shortcomings. The 3D printed device is capable of measuring knee flexion/extension (F/E) and adduction/abduction (AD/AB) angles. Here, we present a gold standard validation of the novel device against an optoelectronic motion capture system (MCS). Data were collected during a treadmill walking task from 8 participants on 2 separate occasions. Agreement with the MCS was quantified via root mean squared error (RMSE), coefficients of multiple correlation (CMC), paired dependent t-tests and Bland-Altman analyses. The wearable device had an overall RMSE of 3.0° and 2.7° and a CMC of 0.97 and 0.91 in F/E and AD/AB respectively. Wearable device error showed no significant differences between test occasions, and Bland-Altman analyses showed low bias with narrow limits of agreement. These results demonstrate the capability of the device to accurately and reliably monitor knee F/E and AD/AB angles showing strong potential for field implementation.

Coupling of theta oscillations between anterior and posterior midline cortex and with the hippocampus in freely behaving rats.

Theta oscillations in the hippocampus support cognitive processing. Theta-range rhythmicity has also been reported in frontal and posterior cortical areas--where it tends to show consistent phase-relations with hippocampal rhythmicity. Theta-range rhythmicity may, then, be important for cortico-cortical and/or cortico-hippocampal interactions. Here, we surveyed the rat frontal and posterior midline cortices for theta-related oscillations and examined their relationships with hippocampal activity in freely moving rats. Variation in electroencephalography across 4 general classes of spontaneous behavior demonstrated different profiles of theta-like activities through the rat midline cortices. Analysis of cortico-cortical and cortico-hippocampal coherences showed distinct, behavior-dependent, couplings of theta and delta oscillations. Increased theta coherence between structures was most obvious during nonautomatic behaviors and least during immobility or grooming. Extensive coupling of theta oscillations throughout the rat midline cortices and hippocampus occurred during rearing, and exploratory behavior. Such increases in coherence could reflect binding of cortico-hippocampal pathways into temporary functional units by behavioral demands. Extensive coupling of frontal delta, which lacked coherence with posterior areas (including the hippocampus), suggests that different frequencies of rhythmicity may act to bind groups of structures into different functional circuits on different occasions.

Mixed Effects of Low-dose Ethanol on Cortical and Hippocampal Theta Oscillations.

Ethanol is one of the most widely used drugs - with many psychoactive effects, including anxiolysis. The deleterious effects on brain function and general health of chronic and high-level ethanol use are well-studied. However, the neurophysiology of acute low dose ethanol has not been systematically investigated. Here, we examined the effects of low dose (0.25 and 0.5 g/kg) ethanol on midline (prefrontal, cingulate and retrosplenial) neocortical and hippocampal theta oscillations in freely moving rats. We also tested low dose ethanol on reticular-elicited and running-elicited hippocampal theta frequency and assessed the linear relationship of theta frequency to stimulation intensity and running speed, respectively. Low dose ethanol had mixed effects on neocortical theta oscillations. It most reliably reduced theta frequency, produced a weak inverted-U effect on theta power, and had no detectable effect on cortico-hippocampal theta coherence. Ethanol dose-dependently decreased the y-intercept of the speed-theta frequency function without affecting the slope, but decreased the slope of the stimulation intensity-theta frequency function without affecting the y-intercept; thus decreasing theta frequency in both cases. We conclude low dose ethanol has weak but detectable effects on neocortical and hippocampal theta oscillations. These effects may underlie positive cognitive and behavioural outcomes reported in the literature using low dose ethanol. The double dissociation of slope and y-intercept specific changes relating to different methods of hippocampal theta elicitation presents the potential to probe multiple mechanisms contributing to anxiolytic effects on theta and so hippocampal function.

An investigation of the pH dependence of copper-substituted anthrax lethal factor and its mechanistic implications.

Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of proteins critical to the maintenance of host signaling pathways during anthrax infections. Although zinc is typically regarded as the native metal ion in vivo, LF is highly tolerant to metal substitution, with its replacement by copper yielding an enzyme (CuLF) 4.5-fold more active than the native zinc protein (at pH 7). The current study demonstrates that by careful choice of the buffer, ionic strength, pH and substrate, the activity ratio of CuLF and native LF can be increased to >40-fold. Using a fluorogenic LF substrate, such optimized assay conditions can be exploited to detect LF concentrations as low as 2 pM. In contrast to the zinc form, CuLF was found to be inhibited by bromide and iodide ions, to be resistant to metal loss under acidic conditions, and to display a sharp pH dependence with significantly shifted alkaline limb towards more acidic conditions. The alkaline limb in the enzyme's pH profile is suggested to originate from changes in the protonation state of the metal-bound water molecule which serves as the nucleophile in the catalytic mechanism. Based on these observations and studies on other zinc proteases, a minimal mechanism for LF is proposed.

Bi-Directional Theta Modulation between the Septo-Hippocampal System and the Mammillary Area in Free-Moving Rats.

Hippocampal (HPC) theta oscillations have long been linked to various functions of the brain. Many cortical and subcortical areas that also exhibit theta oscillations have been linked to functional circuits with the hippocampus on the basis of coupled activities at theta frequencies. We examine, in freely moving rats, the characteristics of diencephalic theta local field potentials (LFPs) recorded in the supramammillary/mammillary (SuM/MM) areas that are bi-directionally connected to the HPC through the septal complex. Using partial directed coherence (PDC), we find support for previous suggestions that SuM modulates HPC theta at higher frequencies. We find weak separation of SuM and MM by dominant theta frequency recorded locally. Contrary to oscillatory cell activities under anesthesia where SuM is insensitive, but MM is sensitive to medial septal (MS) inactivation, theta LFPs persisted and became indistinguishable after MS-inactivation. However, MS-inactivation attenuated SuM/MM theta power, while increasing the frequency of SuM/MM theta. MS-inactivation also reduced root mean squared power in both HPC and SuM/MM equally, but reduced theta power differentially in the time domain. We provide converging evidence that SuM is preferentially involved in coding HPC theta at higher frequencies, and that the MS-HPC circuit normally imposes a frequency-limiting modulation over the SuM/MM area as suggested by cell-based recordings in anesthetized animals. In addition, we provide evidence that the postulated SuM-MS-HPC-MM circuit is under complex bi-directional control, rather than SuM and MM having roles as unidirectional relays in the network.

A Critical Assessment of Directed Connectivity Estimates with Artificially Imposed Causality in the Supramammillary-Septo-Hippocampal Circuit.

Algorithms for estimating directed connectivity have become indispensable to further understand the neurodynamics between functionally coupled brain areas. The evaluation of directed connectivity on the propagation of brain activity has largely been based on simulated data or toy models, where various hidden properties of neurophysiological data may not be fully recapitulated. In this study, directionality was unequivocally manipulated in the freely moving rat in a unique dataset, where normal oscillatory interactions between the supramammillary nucleus (SuM) and hippocampus (HPC) were attenuated by temporary medial septal (MS) inactivation, and replaced by electrical stimulation of the fornix to evaluate the performance of several directed connectivity assessment methods. The directed transfer function, partial directed coherence, directed coherence, pair-wise Geweke-Granger causality, phase slope index, and phase transfer entropy, all found SuM to HPC theta propagation when the MS is inactivated, and HPC activity was driven by peaks of simultaneously recorded SuM theta. As expected from theoretical expectations and simulated data, signal features including coupling strength, signal-to-noise ratio, and stationarity all weakly affected directed connectivity measures. We conclude that all the examined directed connectivity estimates correctly identify artificially imposed uni-directionality of brain oscillations in freely moving animals. Non-auto-regressive modeling based methods appear to be the most robust, and are least affected by inherent features in data such as signal-to-noise ratio and stationarity.