code/sim_worker.py

#!/usr/bin/env python3
"""
sim_worker.py — Standalone circuit simulator for subprocess-based parallelism.

Called by batch_generate_v2.py via subprocess.Popen:
    python3 sim_worker.py <config_json_path> <output_dir> <ach_model>

Reads circuit config from JSON, builds HH network in Jaxley, sweeps 11 ACh
levels, computes 11 summary statistics, writes output JSON.

ACh models:
    v14a: Synaptic suppression only (same as v13 production data)
    v14b: Mild depolarization only (0.0002 nA max, sigmoid onset at ach=0.3)
    v14c: Both mechanisms combined

Output: <output_dir>/circuit_XXXXX.json (list of 11 dicts, one per ACh level)
On error: <output_dir>/circuit_XXXXX.error (error message)

Exit codes: 0 = success, 1 = failure
"""

import sys
import json
import math
import os
import time
import traceback

# Suppress Jaxley's verbose per-synapse/per-recording print() noise
# (Jaxley uses print(), not logging, so we redirect stdout temporarily)
import logging
logging.getLogger("jaxley").setLevel(logging.ERROR)
logging.getLogger("jax").setLevel(logging.WARNING)

# ---------------------------------------------------------------------------
# Constants (must match batch_generate.py / training pipeline)
# ---------------------------------------------------------------------------
ACH_LEVELS = [0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0]

# OU noise parameters (Destexhe 2001 background synaptic bombardment)
OU_MU = -0.001       # nA — mean current (below rheobase ~0.003)
OU_SIGMA = 0.001     # nA — noise amplitude
OU_TAU = 5.0         # ms — correlation time

# Synaptic conductances — very weak coupling (AI regime)
EXC_GS = 0.000005    # μS (0.05× default)
INH_GS = 0.00003     # μS (inhibition-dominant)
E_SYN_EXC = 0.0      # mV (excitatory reversal)
E_SYN_INH = -80.0    # mV (inhibitory reversal — GABA-A like)


# ---------------------------------------------------------------------------
# ACh Model Functions
# ---------------------------------------------------------------------------
def ach_to_mu_shift_v14a(ach: float) -> float:
    """v14a: No depolarization (synaptic suppression only)."""
    return 0.0

def ach_to_syn_scale_v14a(ach: float) -> float:
    """v14a: E2 exponential synaptic suppression (Ramaswamy 2018 Table 2)."""
    return max(0.05, math.exp(-2.3 * ach))

def ach_to_mu_shift_v14b(ach: float) -> float:
    """v14b: Mild depolarization only.
    
    +0.0002 nA max (6× smaller than v10's 0.0012 which caused synchrony).
    Sigmoid onset at ach=0.3 to avoid low-ACh correlation spikes.
    """
    return 0.0002 / (1.0 + math.exp(-10.0 * (ach - 0.3)))

def ach_to_syn_scale_v14b(ach: float) -> float:
    """v14b: No synaptic suppression (depolarization only)."""
    return 1.0

def ach_to_mu_shift_v14c(ach: float) -> float:
    """v14c: Same depolarization as v14b."""
    return 0.0002 / (1.0 + math.exp(-10.0 * (ach - 0.3)))

def ach_to_syn_scale_v14c(ach: float) -> float:
    """v14c: Same synaptic suppression as v14a."""
    return max(0.05, math.exp(-2.3 * ach))


ACH_MODELS = {
    "v14a": (ach_to_mu_shift_v14a, ach_to_syn_scale_v14a),
    "v14b": (ach_to_mu_shift_v14b, ach_to_syn_scale_v14b),
    "v14c": (ach_to_mu_shift_v14c, ach_to_syn_scale_v14c),
}


# ---------------------------------------------------------------------------
# OU Noise Generator
# ---------------------------------------------------------------------------
def generate_ou_current(dt_ms, n_steps, mu, sigma, tau_ms, rng):
    """Ornstein-Uhlenbeck process: colored noise for background synaptic input."""
    import numpy as np
    x = np.zeros(n_steps)
    x[0] = mu
    dt_s = dt_ms / 1000.0
    tau_s = tau_ms / 1000.0
    noise_coeff = sigma * math.sqrt(2.0 * dt_s / tau_s)
    for step in range(1, n_steps):
        x[step] = x[step-1] + dt_s * (mu - x[step-1]) / tau_s + noise_coeff * rng.randn()
    return x


# ---------------------------------------------------------------------------
# Statistics (character-for-character match with batch_generate.py)
# ---------------------------------------------------------------------------
def compute_statistics(spike_trains, n_exc, n_inh, duration_ms):
    """Compute population-level summary statistics from spike trains."""
    import numpy as np

    n_total = n_exc + n_inh
    duration_s = duration_ms / 1000.0

    # Firing Rates
    rates = [len(st) / duration_s for st in spike_trains]
    exc_rates = rates[:n_exc]
    inh_rates = rates[n_exc:]

    mean_rate = float(np.mean(rates)) if rates else 0.0
    mean_exc_rate = float(np.mean(exc_rates)) if exc_rates else 0.0
    mean_inh_rate = float(np.mean(inh_rates)) if inh_rates else 0.0

    # CV of ISI
    cv_isis = []
    for st in spike_trains:
        if len(st) > 2:
            isis = np.diff(st)
            if np.mean(isis) > 0:
                cv_isis.append(float(np.std(isis) / np.mean(isis)))
    mean_cv_isi = float(np.mean(cv_isis)) if cv_isis else 0.0

    # Fano Factor
    bin_size_ms = 50.0
    n_bins = int(duration_ms / bin_size_ms)
    if n_bins > 0:
        bin_counts = np.zeros((n_total, n_bins))
        for i, st in enumerate(spike_trains):
            for t in st:
                b = min(int(t / bin_size_ms), n_bins - 1)
                bin_counts[i, b] += 1
        fano_factors = []
        for i in range(n_total):
            m = np.mean(bin_counts[i])
            if m > 0:
                fano_factors.append(float(np.var(bin_counts[i]) / m))
        mean_fano = float(np.mean(fano_factors)) if fano_factors else 1.0
    else:
        mean_fano = 1.0

    # Population Synchrony
    pop_bin_ms = 5.0
    n_pop_bins = int(duration_ms / pop_bin_ms)
    if n_pop_bins > 0:
        pop_rate = np.zeros(n_pop_bins)
        for st in spike_trains:
            for t in st:
                b = min(int(t / pop_bin_ms), n_pop_bins - 1)
                pop_rate[b] += 1
        pop_rate /= n_total
        pop_mean = np.mean(pop_rate)
        synchrony_index = float(np.var(pop_rate) / pop_mean) if pop_mean > 0 else 0.0
    else:
        synchrony_index = 0.0

    # Pairwise Correlations (sample)
    n_sample = min(100, n_exc * (n_exc - 1) // 2)
    if n_sample > 0 and n_pop_bins > 0:
        corr_bin_ms = 10.0
        n_corr_bins = int(duration_ms / corr_bin_ms)
        binned = np.zeros((n_exc, n_corr_bins))
        for i in range(n_exc):
            for t in spike_trains[i]:
                b = min(int(t / corr_bin_ms), n_corr_bins - 1)
                binned[i, b] += 1
        pair_rng = np.random.RandomState(0)
        correlations = []
        for _ in range(n_sample):
            i, j = pair_rng.choice(n_exc, 2, replace=False)
            x, y = binned[i], binned[j]
            if np.std(x) > 0 and np.std(y) > 0:
                r = float(np.corrcoef(x, y)[0, 1])
                if not np.isnan(r):
                    correlations.append(r)
        mean_pairwise_corr = float(np.mean(correlations)) if correlations else 0.0
    else:
        mean_pairwise_corr = 0.0

    # Power Spectrum
    if n_pop_bins > 10:
        from scipy import signal
        freqs, psd = signal.welch(pop_rate, fs=1000.0 / pop_bin_ms, nperseg=min(256, n_pop_bins))
        peak_freq = float(freqs[np.argmax(psd)])
        total_power = float(np.sum(psd))
    else:
        peak_freq = 0.0
        total_power = 0.0

    return {
        "mean_firing_rate": round(mean_rate, 3),
        "mean_exc_rate": round(mean_exc_rate, 3),
        "mean_inh_rate": round(mean_inh_rate, 3),
        "mean_cv_isi": round(mean_cv_isi, 3),
        "mean_fano_factor": round(mean_fano, 3),
        "synchrony_index": round(synchrony_index, 4),
        "mean_pairwise_corr": round(mean_pairwise_corr, 4),
        "peak_frequency_hz": round(peak_freq, 3),
        "total_spectral_power": round(total_power, 6),
        "n_active_neurons": sum(1 for r in rates if r > 0.5),
        "total_spikes": sum(len(st) for st in spike_trains),
    }


# ---------------------------------------------------------------------------
# Main Simulation
# ---------------------------------------------------------------------------
def simulate_circuit(config: dict, output_dir: str, ach_model: str):
    """Build one circuit, sweep all 11 ACh levels, save results."""
    import numpy as np
    import copy

    # Lazy imports — each subprocess gets its own JAX runtime
    import jaxley as jx
    from jaxley.channels import HH
    from jaxley.synapses import IonotropicSynapse

    # Get ACh functions for this model
    mu_shift_fn, syn_scale_fn = ACH_MODELS[ach_model]

    circuit_id = config["circuit_id"]
    n_exc = config["n_exc"]
    n_inh = config["n_inh"]
    conn_prob = config["conn_prob"]
    sim_duration_ms = config["sim_duration_ms"]
    seed = config["seed"]

    n_total = n_exc + n_inh
    rng = np.random.RandomState(seed)
    dt = 0.025
    n_steps = int(sim_duration_ms / dt)

    t_start = time.time()

    # === Phase 1: Build network ONCE ===
    cells = []
    for i in range(n_total):
        comp = jx.Compartment()
        comp.insert(HH())
        cells.append(comp)
    net = jx.Network(cells)

    # Connect with pre-computed adjacency
    adjacency = rng.random((n_total, n_total)) < conn_prob
    np.fill_diagonal(adjacency, False)

    syn_count = 0
    for pre_idx in range(n_total):
        for post_idx in range(n_total):
            if adjacency[pre_idx, post_idx]:
                jx.connect(net.cell(pre_idx), net.cell(post_idx), IonotropicSynapse())
                syn_count += 1

    t_build = time.time() - t_start

    # Set per-synapse gS and e_syn based on E/I identity
    if syn_count > 0:
        gs_arr = np.empty(syn_count)
        esyn_arr = np.empty(syn_count)
        syn_idx = 0
        for pre_idx in range(n_total):
            for post_idx in range(n_total):
                if adjacency[pre_idx, post_idx]:
                    if pre_idx < n_exc:
                        gs_arr[syn_idx] = EXC_GS
                        esyn_arr[syn_idx] = E_SYN_EXC
                    else:
                        gs_arr[syn_idx] = INH_GS
                        esyn_arr[syn_idx] = E_SYN_INH
                    syn_idx += 1
        net.edges["IonotropicSynapse_gS"] = gs_arr
        net.edges["IonotropicSynapse_e_syn"] = esyn_arr
        net.edges["IonotropicSynapse_s"] = 0.0  # CRITICAL: no phantom current

    mean_in_degree = max(1.0, syn_count / n_total)

    # Pre-generate per-neuron noise seeds (shared across ACh levels)
    noise_seeds = rng.randint(0, 1000000, n_total)
    stim_len = int(sim_duration_ms / dt) + 1

    # === Phase 2: Sequential ACh sweep using deepcopy ===
    results = []

    for ach_idx, ach in enumerate(ACH_LEVELS):
        t0 = time.time()

        net_copy = copy.deepcopy(net)

        # ACh modulates EXCITATORY synapses (muscarinic suppression)
        syn_scale = syn_scale_fn(ach)
        if syn_count > 0:
            exc_mask = net_copy.edges["IonotropicSynapse_e_syn"] == E_SYN_EXC
            net_copy.edges.loc[exc_mask, "IonotropicSynapse_gS"] = EXC_GS * syn_scale

        # ACh shifts mean current toward threshold
        mu_shift = mu_shift_fn(ach)
        mu_eff = OU_MU + mu_shift
        sigma_eff = OU_SIGMA  # ACh does NOT change noise amplitude

        # Stimulate each neuron with independent OU noise
        for i in range(n_total):
            neuron_rng = np.random.RandomState(noise_seeds[i])
            ou_trace = generate_ou_current(dt, n_steps, mu_eff, sigma_eff, OU_TAU, neuron_rng)
            i_stim = np.zeros(stim_len)
            ou_len = min(len(ou_trace), stim_len)
            i_stim[:ou_len] = ou_trace[:ou_len]
            net_copy.cell(i).stimulate(i_stim)
            net_copy.cell(i).record("v")

        voltages = jx.integrate(net_copy, delta_t=dt)
        t_sim = time.time() - t0

        # Extract spikes (only from stable period: after 200ms warmup)
        v_np = np.array(voltages)
        warmup_steps = int(200.0 / dt)
        spike_trains = []
        for i in range(n_total):
            v_stable = v_np[i, warmup_steps:]
            crossings = np.where((v_stable[:-1] < 0.0) & (v_stable[1:] >= 0.0))[0]
            spike_times_ms = ((crossings + warmup_steps) * dt).tolist()
            spike_trains.append(spike_times_ms)

        # Compute statistics on stable period only
        stable_duration_ms = sim_duration_ms - 200.0
        stats = compute_statistics(spike_trains, n_exc, n_inh, stable_duration_ms)

        results.append({
            "circuit_id": circuit_id,
            "ach_level": ach,
            "ach_model": ach_model,
            "n_exc": n_exc,
            "n_inh": n_inh,
            "n_total": n_total,
            "conn_prob": conn_prob,
            "n_synapses": syn_count,
            "mean_in_degree": round(mean_in_degree, 1),
            "gS_exc_effective": round(EXC_GS * syn_scale, 8),
            "ou_mu_effective": round(mu_eff, 6),
            "ou_sigma_effective": round(sigma_eff, 6),
            "ou_tau": OU_TAU,
            "sim_duration_ms": sim_duration_ms,
            "seed": seed,
            "sim_time_s": round(t_sim, 2),
            "statistics": stats,
        })

    total_time = time.time() - t_start

    # === Save results ===
    os.makedirs(output_dir, exist_ok=True)
    outpath = os.path.join(output_dir, f"circuit_{circuit_id:05d}.json")
    with open(outpath, "w") as f:
        json.dump(results, f)

    # Print summary to stderr (stdout may be suppressed)
    print(
        f"OK circuit={circuit_id} model={ach_model} "
        f"build={t_build:.1f}s total={total_time:.1f}s "
        f"rate@0={results[0]['statistics']['mean_firing_rate']:.1f}Hz "
        f"corr@0={results[0]['statistics']['mean_pairwise_corr']:.4f} "
        f"corr@1={results[-1]['statistics']['mean_pairwise_corr']:.4f}",
        file=sys.stderr,
    )

    return results


# ---------------------------------------------------------------------------
# Entry point
# ---------------------------------------------------------------------------
def main():
    if len(sys.argv) != 4:
        print(f"Usage: python3 {sys.argv[0]} <config_json_path> <output_dir> <ach_model>",
              file=sys.stderr)
        print(f"  ach_model: v14a | v14b | v14c", file=sys.stderr)
        sys.exit(1)

    config_path = sys.argv[1]
    output_dir = sys.argv[2]
    ach_model = sys.argv[3]

    if ach_model not in ACH_MODELS:
        print(f"ERROR: Unknown ACh model '{ach_model}'. Must be one of: {list(ACH_MODELS.keys())}",
              file=sys.stderr)
        sys.exit(1)

    # Read config
    with open(config_path, "r") as f:
        config = json.load(f)

    circuit_id = config["circuit_id"]

    try:
        simulate_circuit(config, output_dir, ach_model)
    except Exception as e:
        # Write error marker
        os.makedirs(output_dir, exist_ok=True)
        error_path = os.path.join(output_dir, f"circuit_{circuit_id:05d}.error")
        with open(error_path, "w") as f:
            f.write(f"{type(e).__name__}: {e}\n")
            f.write(traceback.format_exc())
        print(f"FAIL circuit={circuit_id}: {e}", file=sys.stderr)
        sys.exit(1)


if __name__ == "__main__":
    main()