White matter fibre density in the brain's inhibitory control network is associated with falling in low activity older adults.

Recent research has indicated that the relationship between age-related cognitive decline and falling may be mediated by the individual's capacity to quickly cancel or inhibit a motor response. This longitudinal investigation demonstrates that higher white matter fibre density in the motor inhibition network paired with low physical activity was associated with falling in elderly participants. We measured the density of white matter fibre tracts connecting key nodes in the inhibitory control network in a large sample (n = 414) of older adults. We modelled their self-reported frequency of falling over a 4-year period with white matter fibre density in pathways corresponding to the direct and hyperdirect cortical-subcortical loops implicated in the inhibitory control network. Only connectivity between right inferior frontal gyrus and right subthalamic nucleus was associated with falling as measured cross-sectionally. The connectivity was not, however, predictive of future falling when measured 2 and 4 years later. Higher white matter fibre density was associated with falling, but only in combination with low levels of physical activity. No such relationship existed for selected control brain regions that are not implicated in the inhibitory control network. Albeit statistically robust, the direction of this effect was counterintuitive (more dense connectivity associated with falling) and warrants further longitudinal investigation into whether white matter fibre density changes over time in a manner correlated with falling, and mediated by physical activity.

Ca(II) and Zn(II) Cooperate To Modulate the Structure and Self-Assembly of S100A12.

S100A12 is a member of the Ca2+ binding S100 family of proteins that functions within the human innate immune system. Zinc sequestration by S100A12 confers antimicrobial activity when the protein is secreted by neutrophils. Here, we demonstrate that Ca2+ binding to S100A12's EF-hand motifs and Zn2+ binding to its dimeric interface cooperate to induce reversible self-assembly of the protein. Solution and magic angle spinning nuclear magnetic resonance spectroscopy on apo-, Ca2+-, Zn2+-, and Ca2+,Zn2+-S100A12 shows that significant metal binding-induced chemical shift perturbations, indicative of conformational changes, occur throughout the polypeptide chain. These perturbations do not originate from changes in the secondary structure of the protein, which remains largely preserved. While the overall structure of S100A12 is dominated by Ca2+ binding, Zn2+ binding to Ca2+-S100A12 introduces additional structural changes to helix II and the hinge domain (residues 38-53). The hinge domain of S100A12 is involved in the molecular interactions that promote chemotaxis for human monocyte, acute inflammatory responses and generates edema. In Ca2+-S100A12, helix II and the hinge domain participate in binding with the C-type immunoglobulin domain of the receptor for advanced glycation products (RAGE). We discuss how the additional conformational changes introduced to these domains upon Zn2+ binding may also impact the interaction of S100A12 and target proteins such as RAGE.

A biradical-tagged phospholipid as a polarizing agent for solid-state MAS Dynamic Nuclear Polarization NMR of membrane proteins.

A novel Dynamic Nuclear Polarization (DNP) NMR polarizing agent ToSMTSL-PTE representing a phospholipid with a biradical TOTAPOL tethered to the polar head group has been synthesized, characterized, and employed to enhance solid-state Nuclear Magnetic Resonance (SSNMR) signal of a lipid-reconstituted integral membrane protein proteorhodopsin (PR). A matrix-free PR formulation for DNP improved the absolute sensitivity of NMR signal by a factor of ca. 4 compared to a conventional preparation with TOTAPOL dispersed in a glassy glycerol/water matrix. DNP enhancements measured at 400 MHz/263 GHz and 600 MHz/395 GHz showed a strong field dependence but remained moderate at both fields, and comparable to those obtained for PR covalently modified with ToSMTSL. Additional continuous wave (CW) X-band electron paramagnetic resonance (EPR) experiments with ToSMTSL-PTE in solutions and in lipid bilayers revealed that an unfavorable conformational change of the linker connecting mononitroxides could be one of the reasons for moderate DNP enhancements. Further, differential scanning calorimetry (DSC) and CW EPR experiments indicated an inhomogeneous distribution and/or a possibility of a partial aggregation of ToSMTSL-PTE in DMPC:DMPA bilayers when the concentration of the polarizing agent was increased to 20 mol% to maximize the DNP enhancement. Thus, conformational changes and an inhomogeneous distribution of the lipid-based biradicals in lipid bilayers emerged as important factors to consider for further development of this matrix-free approach for DNP of membrane proteins.

Exposure to Trauma and Mental Health Service Engagement Among Adults Who Were Children of the Northern Ireland Troubles of 1968 to 1998.

Northern Ireland is an appropriate region to examine the impact of traumatic experiences, owing to the many years of civil violence that have characterized its recent history, known colloquially as the "Troubles." Given the prominence of traumatic experiences among the aging population of Northern Ireland (NI), an evidence base is required to inform the planning and provision of effective mental health and other services. We analyzed the follow-up interviews (n = 225) of individuals from the Northern Ireland Study of Health and Stress (NISHS), aged 45 years and older, who experienced one or more conflict-related traumatic events. This study demonstrated that in NI traumatic events, such as being involved in an explosion, seeing someone killed or seriously injured, and living in a region of terror were most likely to be related to the Troubles. However, event types that we had not previously known to be related to conflict (such as the sudden death of a loved one), were also often related to the Troubles. Two-thirds of participants (67.1%) reported exposure to a Troubles-related event, and 57.8% reported being a civilian in a region of terror. The vast majority (85.9%) of participants who experienced a Troubles-related trauma never sought help, despite 59.1% meeting the criteria for a lifetime mental disorder. The reasons for not seeking help and sources of help are outlined. Policy makers must address Troubles-related mental health effects, in terms of how they carry forward into aging, and consider ways of improving engagement with services and treatments.

The Economic Burden of PTSD in Northern Ireland.

The objective of this study was to estimate the economic costs of posttraumatic stress disorder (PTSD) among the Northern Ireland (NI) adult population. The authors present a prevalence-based, bottom-up study based primarily on data from 1,986 participants in the Northern Ireland Study of Health and Stress (NISHS). Both direct costs of treatment and indirect costs of productivity losses were included. Units of service and medication resource use were obtained from the NISHS and combined with their relevant unit costs from the Personal Social Services Research Unit and Prescription Costs Analysis data for NI. Indirect costs included the costs of incapacity days due to PTSD and presenteeism costs, with gender-specific wage rates used as the relevant unit costs. The total direct and indirect cost of PTSD in NI (2008) was £172,756,062. This figure is likely to be conservative due to the exclusion of a number of cost categories. Nevertheless, comparison of estimates of the burden of PTSD with the estimated cost of treating all adults with PTSD with the recommended treatments shows the potential for substantial economic gains to be made through extension and investment in effective evidence-based treatments.

Intracellular distribution of differentially phosphorylated dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A).

The gene encoding dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is located within the Down syndrome (DS) critical region of chromosome 21. DYRK1A interacts with a plethora of substrates in the cytosol, cytoskeleton, and nucleus. Its overexpression is a contributing factor to the developmental alterations and age-associated pathology observed in DS. We hypothesized that the intracellular distribution of DYRK1A and cell-compartment-specific functions are associated with DYRK1A posttranslational modifications. Fractionation showed that, in both human and mouse brain, almost 80% of DYRK1A was associated with the cytoskeleton, and the remaining DYRK1A was present in the cytosolic and nuclear fractions. Coimmunoprecipitation revealed that DYRK1A in the brain cytoskeleton fraction forms complexes with filamentous actin, neurofilaments, and tubulin. Two-dimensional gel analysis of the fractions revealed DYRK1A with distinct isoelectric points: 5.5-6.5 in the nucleus, 7.2-8.2 in the cytoskeleton, and 8.7 in the cytosol. Phosphate-affinity gel electrophoresis demonstrated several bands of DYRK1A with different mobility shifts for nuclear, cytoskeletal, and cytosolic DYRK1A, indicating modification by phosphorylation. Mass spectrometry analysis disclosed one phosphorylated site in the cytosolic DYRK1A and multiple phosphorylated residues in the cytoskeletal DYRK1A, including two not previously described. This study supports the hypothesis that intracellular distribution and compartment-specific functions of DYRK1A may depend on its phosphorylation pattern.

Prefrontal activation when suppressing an automatic balance recovery step.

BACKGROUND: The present study investigated neural mechanisms for suppressing a highly automatic balance recovery step. Response inhibition has typically been researched using focal hand reaction tasks performed by seated participants, and this has revealed a neural stopping network including the Inferior Frontal Gyrus (IFG). It is unclear if the same neural networks contribute to suppressing an unwanted balance reaction. RESEARCH QUESTION: Is there greater IFG activation when suppressing an automatic balance recovery step? METHODS: Functional near-infrared spectroscopy (fNIRS) was used to measure brain activity in 21 young adults as they performed a balance recovery task that demanded rapid step suppression following postural perturbation. The hypothesis was that the IFG would show heightened activity when suppressing an automatic balance recovery step. A lean and-release system was used to impose temporally unpredictable forward perturbations by releasing participants from a supported forward lean. For most trials (80%), participants were told to recover balance by quickly stepping forward (STEP). However, on 20% of trials at random, a high-pitch tone was played immediately after postural perturbation signaling participants to suppress a step and fully relax into a catch harness (STOP). This allowed us to target the ability to cancel an already initiated step in a balance recovery context. Average oxygenated hemoglobin changes were contrasted between STEP and STOP trials, 1-6 s post perturbation. RESULTS: The results showed a greater bilateral prefrontal response during STOP trials, supporting the idea that executive brain networks are active when suppressing a balance recovery step. SIGNIFICANCE: Our study demonstrates one way in which higher brain processes may help us prevent falls in complex environments where behavioral flexibility is necessary. This study also presents a novel method for assessing response inhibition in an upright postural context where rapid stepping reactions are required.

Evaluating possible maternal effect lethality and genetic background effects in Naa10 knockout mice.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting approximately 80% of all human proteins. The human essential X-linked gene, NAA10, encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. There is extensive genetic variation in humans with missense, splice-site, and C-terminal frameshift variants in NAA10. In mice, Naa10 is not an essential gene, as there exists a paralogous gene, Naa12, that substantially rescues Naa10 knockout mice from embryonic lethality, whereas double knockouts (Naa10-/Y Naa12-/-) are embryonic lethal. However, the phenotypic variability in the mice is nonetheless quite extensive, including piebaldism, skeletal defects, small size, hydrocephaly, hydronephrosis, and neonatal lethality. Here we replicate these phenotypes with new genetic alleles in mice, but we demonstrate their modulation by genetic background and environmental effects. We cannot replicate a prior report of "maternal effect lethality" for heterozygous Naa10-/X female mice, but we do observe a small amount of embryonic lethality in the Naa10-/Y male mice on the inbred genetic background in this different animal facility.

Evaluating possible maternal effect lethality and genetic background effects in Naa10 knockout mice.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting approximately 80% of all human proteins. The human essential X-linked gene, NAA10, encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. There is extensive genetic variation in humans with missense, splice-site, and C-terminal frameshift variants in NAA10. In mice, Naa10 is not an essential gene, as there exists a paralogous gene, Naa12, that substantially rescues Naa10 knockout mice from embryonic lethality, whereas double knockouts (Naa10-/Y Naa12-/-) are embryonic lethal. However, the phenotypic variability in the mice is nonetheless quite extensive, including piebaldism, skeletal defects, small size, hydrocephaly, hydronephrosis, and neonatal lethality. Here we replicate these phenotypes with new genetic alleles in mice, but we demonstrate their modulation by genetic background and environmental effects. We cannot replicate a prior report of "maternal effect lethality" for heterozygous Naa10-/X female mice, but we do observe a small amount of embryonic lethality in the Naa10-/y male mice on the inbred genetic background in this different animal facility.

Trauma associated with civil conflict and posttraumatic stress disorder: evidence from the Northern Ireland study of health and stress.

The authors provide epidemiological estimates of trauma, posttraumatic stress disorder (PTSD), and associated mental disorders in Northern Ireland (NI) with a focus on the impact of civil conflict using data from the NI Study of Health and Stress (NISHS), a representative epidemiological survey of adults in NI. Overall 60.6% had a lifetime traumatic event, and 39.0% experienced a presumed conflict-related event. Men were significantly more likely to experience any traumatic event and most conflict-related event types (p < .05). The lifetime and 12-month prevalence of PTSD were 8.8% and 5.1%, respectively. Furthermore, the lifetime prevalence of any mental disorder among men and women who experienced a conflict-related trauma (46.0% and 55.9%, respectively) was significantly higher than the prevalence among men and women who did not experience this type of traumatic event (27.2% and 31.1%, respectively). Given the public health burden posed by PTSD and additional impact of conflict, specific attention must be paid to the policy, service, and clinical challenge of delivering evidence-based treatments in the wake of a tumultuous period of conflict.

Foreshock properties illuminate nucleation processes of slow and fast laboratory earthquakes.

Understanding the connection between seismic activity and the earthquake nucleation process is a fundamental goal in earthquake seismology with important implications for earthquake early warning systems and forecasting. We use high-resolution acoustic emission (AE) waveform measurements from laboratory stick-slip experiments that span a spectrum of slow to fast slip rates to probe spatiotemporal properties of laboratory foreshocks and nucleation processes. We measure waveform similarity and pairwise differential travel-times (DTT) between AEs throughout the seismic cycle. AEs broadcasted prior to slow labquakes have small DTT and high waveform similarity relative to fast labquakes. We show that during slow stick-slip, the fault never fully locks, and waveform similarity and pairwise differential travel times do not evolve throughout the seismic cycle. In contrast, fast laboratory earthquakes are preceded by a rapid increase in waveform similarity late in the seismic cycle and a reduction in differential travel times, indicating that AEs begin to coalesce as the fault slip velocity increases leading up to failure. These observations point to key differences in the nucleation process of slow and fast labquakes and suggest that the spatiotemporal evolution of laboratory foreshocks is linked to fault slip velocity.

Functional near-infrared spectroscopy measures of neural activity in children with and without developmental language disorder during a working memory task.

INTRODUCTION: Children with developmental language disorder (DLD) exhibit cognitive deficits that interfere with their ability to learn language. Little is known about the functional neuroanatomical differences between children developing typically (TD) and children with DLD. METHODS: Using functional near-infrared spectroscopy, we recorded oxygenated hemoglobin (O2 hb) concentration values associated with neural activity in children with and without DLD during an auditory N-back task that included 0-back, 1-back, and 2-back conditions. Analyses focused on the left dorsolateral prefrontal cortex (DLPFC) and left inferior parietal lobule (IPL). Multilevel models were constructed with accuracy, response time, and O2 hb as outcome measures, with 0-back outcomes as fixed effects to control for sustained attention. RESULTS: Children with DLD were significantly less accurate than their TD peers at both the 1-back and 2-back tasks, and they demonstrated slower response times during 2-back. In addition, children in the TD group demonstrated significantly greater sensitivity to increased task difficulty, showing increased O2 hb to the IPL during 1-back and to the DLPFC during the 2-back, whereas the DLD group did not. A secondary analysis revealed that higher O2 hb in the DLPFC predicted better task accuracy across groups. CONCLUSION: When task difficulty increased, children with DLD failed to recruit the DLPFC for monitoring information and the IPL for processing information. Reduced memory capacity and reduced engagement likely contribute to the language learning difficulties of children with DLD.

Suppressing a Blocked Balance Recovery Step: A Novel Method to Assess an Inhibitory Postural Response.

Stepping to recover balance is an important way we avoid falling. However, when faced with obstacles in the step path, we must adapt such reactions. Physical obstructions are typically detected through vision, which then cues step modification. The present study describes a novel method to assess visually prompted step inhibition in a reactive balance context. In our task, participants recovered balance by quickly stepping after being released from a supported forward lean. On rare trials, however, an obstacle blocked the stepping path. The timing of vision relative to postural perturbation was controlled using occlusion goggles to regulate task difficulty. Furthermore, we explored step suppression in our balance task related to inhibitory capacity measured at the hand using a clinically feasible handheld device (ReacStick). Our results showed that ReacStick and step outcomes were significantly correlated in terms of successful inhibition (r = 0.57) and overall reaction accuracy (r = 0.76). This study presents a novel method for assessing rapid inhibition in a dynamic postural context, a capacity that appears to be a necessary prerequisite to a subsequent adaptive strategy. Moreover, this capacity is significantly related to ReacStick performance, suggesting a potential clinical translation.

Contribution of primary motor cortex to compensatory balance reactions.

BACKGROUND: Rapid compensatory arm reactions represent important response strategies following an unexpected loss of balance. While it has been assumed that early corrective actions arise largely from sub-cortical networks, recent findings have prompted speculation about the potential role of cortical involvement. To test the idea that cortical motor regions are involved in early compensatory arm reactions, we used continuous theta burst stimulation (cTBS) to temporarily suppress the hand area of primary motor cortex (M1) in participants prior to evoking upper limb balance reactions in response to whole body perturbation. We hypothesized that following cTBS to the M1 hand area evoked EMG responses in the stimulated hand would be diminished. To isolate balance reactions to the upper limb participants were seated in an elevated tilt-chair while holding a stable handle with both hands. The chair was held vertical by a magnet and was triggered to fall backward unpredictably. To regain balance, participants used the handle to restore upright stability as quickly as possible with both hands. Muscle activity was recorded from proximal and distal muscles of both upper limbs. RESULTS: Our results revealed an impact of cTBS on the amplitude of the EMG responses in the stimulated hand muscles often manifest as inhibition in the stimulated hand. The change in EMG amplitude was specific to the target hand muscles and occasionally their homologous pairs on the non-stimulated hand with no consistent effects on the remaining more proximal arm muscles. CONCLUSIONS: Present findings offer support for cortical contributions to the control of early compensatory arm reactions following whole-body perturbation.

Theta burst repetitive transcranial magnetic stimulation attenuates somatosensory evoked potentials from the lower limb.

BACKGROUND: Continuous theta burst stimulation (cTBS) is a form of repetitive transcranial magnetic stimulation which has been shown to alter cortical excitability in the upper limb representation of primary somatosensory cortex (SI). However, it is unknown whether cTBS modulates cortical excitability within the lower limb representation in SI. The present study investigates the effects of cTBS over the SI lower limb representation on cortical somatosensory evoked potentials (SEPs) and Hoffmann reflex (H-reflex) following tibial nerve stimulation at the knee. SEPs and H-reflex were recorded before and in four time blocks up to 30 minutes following cTBS targeting the lower limb representation within SI. RESULTS: Following cTBS, the P1-N1 first cortical potential was significantly decreased at 12-16 minutes. CTBS also suppressed the P2-N2 second cortical potential for up to 30 minutes following stimulation. The H-reflex remained statistically unchanged following cTBS although there was a modest suppression observed. CONCLUSION: We conclude that cTBS decreases cortical excitability of the lower limb representation of SI as evidenced by suppressed SEP amplitude. The duration and magnitude of the cTBS after effects are similar to those observed in upper limb studies.

Catching and throwing exercises to improve reactive balance: A randomized controlled trial protocol for the comparison of aquatic and dry-land exercise environments.

Reactive balance, a critical automatic movement pattern in response to a perturbation, is directly linked to fall prevention in older adults. Various exercise interventions have been broadly performed to improve reactive balance and thus prevent falls. Curiously, aquatic exercises have been suggested as an effective balance intervention and a safer alternative to exercises on dry land yet the efficacy of aquatic exercises on reactive balance has not been formally investigated. The present clinical trial aims to identify if skills acquired during aquatic exercise are more effectively transferred to a reactive balance task than land exercise. This study is designed as a double-blinded, randomized controlled clinical trial. Forty-four older adults aged 65 years or above who meet the eligibility criteria will be recruited and randomized into an aquatic exercise group or land exercise group. Each group will participate in the same single bout intervention that includes a ball throwing and catching task. A modified lean-and-release test will be implemented on land immediately before, after, and one week after the single bout intervention. The outcomes will include reaction time, rapid response accuracy, and mini-BESTest scores obtained from stepping and grasping reactions. All statistical analyses will be conducted using an intention-to-treat approach. Our conceptual hypothesis is that participants in the aquatic exercise group will demonstrate more improved outcome scores in the lean-and-release test when compared to those in the land exercise group. The results of the present study are expected to provide evidence to support the benefits of aquatic exercises for improving reactive balance in older adults. Further, participants may find aquatic exercises safer and more motivating, thus encouraging them to participate in further aquatic exercise programs.

A method to assess response inhibition during a balance recovery step.

BACKGROUND: Correlations between falls and individual differences in inhibitory control, suggest the ability to suppress automatic, but unwanted, action is important in fall prevention. Response inhibition has been a topic of considerable interest in the cognitive neuroscience community for many decades, bringing a wealth of techniques that could potentially inform assessment of reactive balance. For example, the stop signal task is a popular method to quantify inhibitory control ability. RESEARCH QUESTION: Can we apply the stop signal task to measure response inhibition in a balance recovery task? METHODS: Twenty healthy, young adults completed a novel reactive balance test that required occasional suppression of a balance recovery step. Participants were released from a supported lean ('Go' cue) requiring them to quickly step forward to regain balance. On some trials, a tone ('Stop' cue) instructed participants to suppress a step and relax into a harness. Step trials were more frequent (80%) than stop trials (20%) to bias a rapid stepping response. The stop tone was presented at various delays following cable release, to manipulate task difficulty (i.e., longer delays make step suppression difficult). Individual differences in inhibitory control were determined using lift off times from force plates, and by contrasting muscle activation in failed compared to successful stop trials. RESULTS: Most participants were able to successfully suppress a balance recovery step on occasion, allowing for accurate estimation of individual differences in inhibitory control. The successful suppression of a balance recovery step was more likely in the group (n = 10) where shorter stop signal delays were used (i.e., the task was easier). SIGNIFICANCE: While balance assessments often stress reflexive action, there is a need for methods that evaluate response inhibition. The present study leveraged a well-established cognitive test of inhibitory control to develop a method to quantify stopping ability in a reactive balance context.

The High-Frequency Signature of Slow and Fast Laboratory Earthquakes.

Tectonic faults fail through a spectrum of slip modes, ranging from slow aseismic creep to rapid slip during earthquakes. Understanding the seismic radiation emitted during these slip modes is key for advancing earthquake science and earthquake hazard assessment. In this work, we use laboratory friction experiments instrumented with ultrasonic sensors to document the seismic radiation properties of slow and fast laboratory earthquakes. Stick-slip experiments were conducted at a constant loading rate of 8 µm/s and the normal stress was systematically increased from 7 to 15 MPa. We produced a full spectrum of slip modes by modulating the loading stiffness in tandem with the fault zone normal stress. Acoustic emission data were recorded continuously at 5 MHz. We demonstrate that the full continuum of slip modes radiate measurable high-frequency energy between 100 and 500 kHz, including the slowest events that have peak fault slip rates <100 µm/s. The peak amplitude of the high-frequency time-domain signals scales systematically with fault slip velocity. Stable sliding experiments further support the connection between fault slip rate and high-frequency radiation. Experiments demonstrate that the origin of the high-frequency energy is fundamentally linked to changes in fault slip rate, shear strain, and breaking of contact junctions within the fault gouge. Our results suggest that having measurements close to the fault zone may be key for documenting seismic radiation properties and fully understanding the connection between different slip modes.

The impact of light fingertip touch on haptic cortical processing during a standing balance task.

Availability of fingertip touch onto a stable surface reduces body sway for subjects standing with eyes closed. This is largely associated with sensory feedback from the fingertip when mechanical load is limited. Here, it is possible that the central nervous system facilitates cortical sensory processing to augment feedback to control upright stance. To test this, we compared cortical sensory excitability between tasks with and without light finger touch while standing. Subjects stood in tandem on a force plate with eyes closed while lightly touching a stable surface with the index finger. This was, in two different studies, compared to: (1) no haptic contact or (2) light touch on an object not referenced to balance. Throughout testing, the median nerve was stimulated and electroencephalography was used to measure somatosensory evoked potentials (SEPs). As expected, availability of stable light touch reduced medial-lateral COP sway. Peak amplitudes for SEP components revealed reduced P100 (48%), but increased P50 (31%), N140 (80%), and P200 (20%) during stable touch versus no touch. The modulation of P50 and N140 was no longer present when comparing stable to control (touch), which suggested that attending to touch on either surface, regardless of stability reference, accounted for these changes. Conversely, P200 was increased (19%) when touching the stable surface. Our data show SEP modulation during a standing balance task related to hand contact. Facilitation of P200 in particular may indicate task-specific regulation of the cortical representation of fingertip afferent input when it is relevant to providing stable cues for static balance control.

Frequency-Magnitude Statistics of Laboratory Foreshocks Vary With Shear Velocity, Fault Slip Rate, and Shear Stress.

Understanding the temporal evolution of foreshocks and their relation to earthquake nucleation is important for earthquake early warning systems, earthquake hazard assessment, and earthquake physics. Laboratory experiments on intact rock and rough fractures have demonstrated that the number and size of acoustic emission (AE) events increase and that the Gutenberg-Richter b-value decreases prior to coseismic failure. However, for lab fault zones of finite width, where shear occurs within gouge, the physical processes that dictate temporal variations in frequency-magnitude (F/M) statistics of lab foreshocks are unclear. Here, we report on a series of laboratory experiments to illuminate the physical processes that govern temporal variations in b-value and AE size. We record AE data continuously for hundreds of lab seismic cycles and report F/M statistics. Our foreshock catalogs include cases where F/M data are not exponentially distributed, but we retain the concept of b-value for comparison with other works. We find that b-value decreases as the fault approaches failure, consistent with previous works. We also find that b-value scales inversely with shear velocity and fault slip rate, suggesting that fault slip acceleration during earthquake nucleation could impact foreshock F/M statistics. We propose that fault zone dilation and grain mobilization have a strong influence on foreshock magnitude. Fault dilation at higher shearing rates increases porosity and results in larger foreshocks and smaller b-values. Our observations suggest that lab earthquakes are preceded by a preparatory nucleation phase with systematic variations in AE and fault zone properties.