Heuristic Spike Sorting Tuner (HSST), a framework to determine optimal parameter selection for a generic spike sorting algorithm

Extracellular microelectrodes frequently record neural activity from more than one neuron in the vicinity of the electrode. The process of labeling each recorded spike waveform with the identity of its source neuron is called spike sorting and is often approached from an abstracted statistical perspective. However, these approaches do not consider neurophysiological realities and may ignore important features that could improve the accuracy of these methods. Further, standard algorithms typically require selection of at least one free parameter, which can have significant effects on the quality of the output. We describe a Heuristic Spike Sorting Tuner (HSST) that determines the optimal choice of the free parameters for a given spike sorting algorithm based on the neurophysiological qualification of unit isolation and signal discrimination. A set of heuristic metrics are used to score the output of a spike sorting algorithm over a range of free parameters resulting in optimal sorting quality. We demonstrate that these metrics can be used to tune parameters in several spike sorting algorithms. The HSST algorithm shows robustness to variations in signal to noise ratio, number and relative size of units per channel. Moreover, the HSST algorithm is computationally efficient, operates unsupervised, and is parallelizable for batch processing

Heuristic Spike Sorting Tuner (HSST), a framework to determine optimal parameter selection for a generic spike sorting algorithm

Extracellular microelectrodes frequently record neural activity from more than one neuron in the vicinity of the electrode. The process of labeling each recorded spike waveform with the identity of its source neuron is called spike sorting and is often approached from an abstracted statistical perspective. However, these approaches do not consider neurophysiological realities and may ignore important features that could improve the accuracy of these methods. Further, standard algorithms typically require selection of at least one free parameter, which can have significant effects on the quality of the output. We describe a Heuristic Spike Sorting Tuner (HSST) that determines the optimal choice of the free parameters for a given spike sorting algorithm based on the neurophysiological qualification of unit isolation and signal discrimination. A set of heuristic metrics are used to score the output of a spike sorting algorithm over a range of free parameters resulting in optimal sorting quality. We demonstrate that these metrics can be used to tune parameters in several spike sorting algorithms. The HSST algorithm shows robustness to variations in signal to noise ratio, number and relative size of units per channel. Moreover, the HSST algorithm is computationally efficient, operates unsupervised, and is parallelizable for batch processing

Intracortical microstimulation of human somatosensory cortex induces natural perceptual biases

Time-order error, a psychophysical phenomenon in which the duration in between successive stimuli alters perception, has been studied for decades by neuroscientists and psychologists. To date, however, the locus of these effects is unknown. We use intracortical microstimulation of somatosensory cortex in three humans with spinal cord injury as a tool to bypass initial stages of processing and restrict the possible locations that signals could be modified. Using a 2-interval forced choice amplitude discrimination paradigm, we first assessed the extent to which order effects are observed. Comparing trials where the standard stimulus was in the first or second interval, we found that systematic biases are exhibited, typically causing the intensity of the second stimulus to be overestimated The degree of this overestimation for individual electrodes was dependent on the perceptual sensitivity to changes in stimulus amplitude. To investigate the role of memory on this phenomenon, we implemented a 2-interval magnitude estimation task in which participants were instructed to ignore the first stimulus and again found that the perceptual intensity of the second stimulus tended to be enhanced by the first in a manner that depended on the amplitude and duration of the first stimulus. Finally, we repeated both paradigms while varying the inter-stimulus interval to examine the timescale over which these effects occur and found that longer inter-stimulus intervals reduced the effect size. These results show that direct activation of primary somatosensory cortex is sufficient to induce time-order errors

Limb-state information encoded by peripheral and central somatosensory neurons:Implications for an afferent interface

A major issue to be addressed in the development of neural interfaces for prosthetic control is the need for somatosensory feedback. Here, we investigate two possible strategies: electrical stimulation of either dorsal root ganglia (DRG) or primary somatosensory cortex (S1). In each approach, we must determine a model that reflects the representation of limb state in terms of neural discharge. This model can then be used to design stimuli that artificially activate the nervous system to convey information about limb state to the subject. Electrically activating DRG neurons using naturalistic stimulus patterns, modeled on recordings made during passive limb movement, evoked activity in S1 that was similar to that of the original movement. We also found that S1 neural populations could accurately discriminate different patterns of DRG stimulation across a wide range of stimulus pulse-rates. In studying the neural coding in S1, we also decoded the kinematics of active limb movement using multi-electrode recordings in the monkey. Neurons having both proprioceptive and cutaneous receptive fields contributed equally to this decoding. Some neurons were most informative of limb state in the recent past, but many others appeared to signal upcoming movements suggesting that they also were modulated by an efference copy signal. Finally, we show that a monkey was able to detect stimulation through a large percentage of electrodes implanted in area 2. We discuss the design of appropriate stimulus paradigms for conveying time-varying limb state information, and the relative merits and limitations of central and peripheral approaches

Complex-Temperature Singularities in the d=2d=2 Ising Model. III. Honeycomb Lattice

We study complex-temperature properties of the uniform and staggered susceptibilities $\chi$ and $\chi^{(a)}$ of the Ising model on the honeycomb lattice. From an analysis of low-temperature series expansions, we find evidence that $\chi$ and $\chi^{(a)}$ both have divergent singularities at the point $z=-1 \equiv z_{\ell}$ (where $z=e^{-2K}$), with exponents $\gamma_{\ell}'= \gamma_{\ell,a}'=5/2$. The critical amplitudes at this singularity are calculated. Using exact results, we extract the behaviour of the magnetisation $M$ and specific heat $C$ at complex-temperature singularities. We find that, in addition to its zero at the physical critical point, $M$ diverges at $z=-1$ with exponent $\beta_{\ell}=-1/4$, vanishes continuously at $z=\pm i$ with exponent $\beta_s=3/8$, and vanishes discontinuously elsewhere along the boundary of the complex-temperature ferromagnetic phase. $C$ diverges at $z=-1$ with exponent $\alpha_{\ell}'=2$ and at $v=\pm i/\sqrt{3}$ (where $v = \tanh K$) with exponent $\alpha_e=1$, and diverges logarithmically at $z=\pm i$. We find that the exponent relation $\alpha'+2\beta+\gamma'=2$ is violated at $z=-1$; the right-hand side is 4 rather than 2. The connections of these results with complex-temperature properties of the Ising model on the triangular lattice are discussed.Comment: 22 pages, latex, figures appended after the end of the text as a compressed, uuencoded postscript fil

St. Louis Area Earthquake Hazards Mapping Project: Seismic and Liquefaction Hazard Maps

We present probabilistic and deterministic seismic and liquefaction hazard maps for the densely populated St. Louis metropolitan area that account for the expected effects of surficial geology on earthquake ground shaking. Hazard calculations were based on a map grid of 0.005°, or about every 500 m, and are thus higher in resolution than any earlier studies. To estimate ground motions at the surface of the model (e.g., site amplification), we used a new detailed near-surface shear-wave velocity model in a 1D equivalent- linear response analysis. When compared with the 2014 U.S. Geological Survey (USGS) National Seismic Hazard Model, which uses a uniform firm-rock-site condition, the new probabilistic seismic-hazard estimates document much more variability. Hazard levels for upland sites (consisting of bedrock and weathered bedrock overlain by loess-covered till and drift deposits), show up to twice the ground-motion values for peak ground acceleration (PGA), and similar ground-motion values for 1.0 s spectral acceleration (SA). Probabilistic ground-motion levels for lowland alluvial floodplain sites (generally the 20-40-m-thick modern Mississippi and Missouri River floodplain deposits overlying bedrock) exhibit up to twice the ground-motion levels for PGA, and up to three times the ground-motion levels for 1.0 s SA. Liquefaction probability curves were developed from available standard penetration test data assuming typical lowland and upland water table levels. A simplified liquefaction hazard map was created from the 5%-in-50-year probabilistic ground-shaking model. The liquefaction hazard ranges from low (\u3c40% of area expected to liquefy) in the uplands to severe (\u3e60% of area expected to liquefy) in the lowlands. Because many transportation routes, power and gas transmission lines, and population centers exist in or on the highly susceptible lowland alluvium, these areas in the St. Louis region are at significant potential risk from seismically induced liquefaction and associated ground deformation

Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial.

BACKGROUND: Adjuvant chemotherapy for early breast cancer has improved outcomes but causes toxicity. The UK TACT2 trial used a 2×2 factorial design to test two hypotheses: whether use of accelerated epirubicin would improve time to tumour recurrence (TTR); and whether use of oral capecitabine instead of cyclophosphamide would be non-inferior in terms of patients' outcomes and would improve toxicity, quality of life, or both. METHODS: In this multicentre, phase 3, randomised, controlled trial, we enrolled patients aged 18 years or older from 129 UK centres who had histologically confirmed node-positive or high-risk node-negative operable breast cancer, had undergone complete excision, and were due to receive adjuvant chemotherapy. Patients were randomly assigned to receive four cycles of 100 mg/m2 epirubicin either every 3 weeks (standard epirubicin) or every 2 weeks with 6 mg pegfilgrastim on day 2 of each cycle (accelerated epirubicin), followed by four 4-week cycles of either classic cyclophosphamide, methotrexate, and fluorouracil (CMF; 600 mg/m2 cyclophosphamide intravenously on days 1 and 8 or 100 mg/m2 orally on days 1-14; 40 mg/m2 methotrexate intravenously on days 1 and 8; and 600 mg/m2 fluorouracil intravenously on days 1 and 8 of each cycle) or four 3-week cycles of 2500 mg/m2 capecitabine (1250 mg/m2 given twice daily on days 1-14 of each cycle). The randomisation schedule was computer generated in random permuted blocks, stratified by centre, number of nodes involved (none vs one to three vs four or more), age (≤50 years vs >50 years), and planned endocrine treatment (yes vs no). The primary endpoint was TTR, defined as time from randomisation to first invasive relapse or breast cancer death, with intention-to-treat analysis of standard versus accelerated epirubicin and per-protocol analysis of CMF versus capecitabine. This trial is registered with ISRCTN, number 68068041, and with ClinicalTrials.gov, number NCT00301925. FINDINGS: From Dec 16, 2005, to Dec 5, 2008, 4391 patients (4371 women and 20 men) were recruited. At a median follow-up of 85·6 months (IQR 80·6-95·9) no significant difference was seen in the proportions of patients free from TTR events between the accelerated and standard epirubicin groups (overall hazard ratio [HR] 0·94, 95% CI 0·81-1·09; stratified p=0·42). At 5 years, 85·9% (95% CI 84·3-87·3) of patients receiving standard epirubicin and 87·1% (85·6-88·4) of those receiving accelerated epirubicin were free from TTR events. 4358 patients were included in the per-protocol analysis, and no difference was seen in the proportions of patients free from TTR events between the CMF and capecitabine groups (HR 0·98, 95% CI 0·85-1.14; stratified p=0·00092 for non-inferiority). Compared with baseline, significantly more patients taking CMF than those taking capecitabine had clinically relevant worsening of quality of life at end of treatment (255 [58%] of 441 vs 235 [50%] of 475; p=0·011) and at 12 months (114 [34%] of 334 vs 89 [22%] of 401; p<0·001 at 12 months) and had worse quality of life over time (p<0·0001). Detailed toxicity and quality-of-life data were collected from 2115 (48%) of treated patients. The most common grade 3 or higher adverse events in cycles 1-4 were neutropenia (175 [16%]) and fatigue (56 [5%]) of the 1070 patients treated with standard epirubicin, and fatigue (63 [6%]) and infection (34 [3%]) of the 1045 patients treated with accelerated epirubicin. In cycles 5-8, the most common grade 3 or higher adverse events were neutropenia (321 [31%]) and fatigue (109 [11%]) in the patients treated with CMF, and hand-foot syndrome (129 [12%]) and diarrhoea (67 [6%]) in the 1044 patients treated with capcitabine. INTERPRETATION: We found no benefit from increasing the dose density of the anthracycline component of chemotherapy. However, capecitabine could be used in place of CMF without significant loss of efficacy and with improved quality of life. FUNDING: Cancer Research UK, Amgen, Pfizer, and Roche

Discovery of mating in the major African livestock pathogen Trypanosoma congolense

The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen

Study of the Potts Model on the Honeycomb and Triangular Lattices: Low-Temperature Series and Partition Function Zeros

We present and analyze low-temperature series and complex-temperature partition function zeros for the $q$-state Potts model with $q=4$ on the honeycomb lattice and $q=3,4$ on the triangular lattice. A discussion is given as to how the locations of the singularities obtained from the series analysis correlate with the complex-temperature phase boundary. Extending our earlier work, we include a similar discussion for the Potts model with $q=3$ on the honeycomb lattice and with $q=3,4$ on the kagom\'e lattice.Comment: 33 pages, Latex, 9 encapsulated postscript figures, J. Phys. A, in pres

Microstimulation of human somatosensory cortex evokes task-dependent, spatially patterned responses in motor cortex

The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded – in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands – the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger’s movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation