[Eeglablist] Open online discussion: How Do Cable Theory and AMPA/GABA Balance Compare in Their Contributions to 1/f?

[Ching-Ming Lee]

Hello Makoto and the 1/f community,

Inspired by this discussion, I would like to share some empirical data that
might help quantify the relative contributions of cable theory versus E/I
balance.

As a physicist working on materials science and EEG, I conducted an N-of-1
longitudinal study on a 65-year-old subject (a senior physicist). We
delivered four consecutive sessions of alpha-tuned rTMS (totaling 8,600
pulses) within 3.5 hours and monitored the state evolution.

*Key Findings:*

   1.

   *Dramatic Exponent Shift:* We observed the 1/f exponent (FOOOF) drifting
   from ~1.2 (baseline) up to ~1.8 at Stage 4.
   2.

   *Structural Stability vs. Dynamic Change:* Since the subject's neuronal
   morphology (cable theory properties) cannot change by 60% within 3 hours,
   this massive shift provides strong evidence that *E/I balance
   (GABA-mediated inhibition)* is the primary driver of 1/f *dynamics*,
   even if cable theory sets the *baseline*.
   3.

   *The "Collapse" Threshold:* Our WPLI network analysis shows that while
   the "Small-World" topology optimizes initially, it undergoes a *"Network
   Collapse"* beyond a certain exponent threshold (Stage 5), where global
   efficiency drops and local clustering disintegrates.

*Implications for the Discussion:* This data supports the idea that
1/f-ness is not just a passive physical property but a dynamic biomarker of
functional boundaries. It also challenges the clinical "more is better"
approach in TMS therapy, suggesting that we can push the brain into an
over-inhibited disordered phase.

These findings are part of a manuscript currently in preparation.

I look forward to discussing how we might use such longitudinal
"perturbation" data to weigh the factors Makoto and DeepSeek mentioned.

Best regards,

Ching-Ming Lee

Graduate School of Materials Science

National Yunlin University of Science and Technology

Евгений Машеров via eeglablist <eeglablist at sccn.ucsd.edu> 於 2026年4月13日週一
上午9:38寫道：

> This is wonderful.
> I tried to devise an experiment that would allow me to choose between the
> hypotheses. Due to my laziness, I asked DeepSeek about it, but he suggested
> what was probably a wonderful plan, but it required methods unavailable to
> me (perhaps I could interest colleagues from another institute, but the
> chances are slim).
> Here's his advice:
> "Excellent question. This moves the discussion from theory to experimental
> testing.
>
> The main problem is that in real EEG/LFP, all four mechanisms act
> simultaneously. The task is not to choose "the one true one" but to
> estimate the relative contribution of each in a specific context (type of
> activity, brain region, state, species, age).
>
> Below is one "clean" experiment (or type of analysis) for testing the
> primacy of each hypothesis. The gold standard is to compare model
> predictions with data, manipulating only one parameter at a time.
>
> 1. Testing hypothesis 2.1 (spatial averaging / source size)
> What experiment: Simultaneous scalp EEG + intracortical LFP (high-density
> linear array) in the same animal/human (intraoperatively).
>
> Logic:
>
> LFP registers local sources with a radius of ~0.5–2 mm — here, the mutual
> cancellation between spatially separated generators is minimal.
>
> Scalp EEG is the result of averaging over areas of several cm².
>
> Prediction: If spatial averaging is the main contributor to the 1/f slope:
>
> In LFP, the spectral slope will be significantly flatter (closer to
> 1/f⁰…¹) compared to EEG.
>
> The difference in slope (EEG minus LFP) will be positive and correlate
> with the size of the coherent region, estimated via cross-coherence on LFP.
>
> Control: If there is no difference, then the 1/f on the scalp is mainly
> shaped by local membrane/synaptic mechanisms (2.2, 2.3).
>
> 2. Testing hypothesis 2.2 (cable theory / dendritic filtering)
> What experiment: Patch-clamp from the soma + simultaneous activation of
> distal and proximal dendritic synapses (optogenetics or focal glutamate
> stimulation) in a single neuron in slice / in vivo.
>
> Logic:
>
> Stimulate proximal synapses (near the soma) — record EPSP at the soma.
>
> Stimulate distal synapses (on the same neuron) — record EPSP at the soma.
>
> Compare the spectra of these two response types.
>
> Prediction: If cable filtering is significant:
>
> EPSPs from distal inputs will have a steeper 1/f roll-off (less
> high-frequency power) compared to proximal ones.
>
> The peak amplitude (20–50 Hz) will be significantly reduced.
>
> Key experiment: Do the same in the presence of separate AMPA and GABA-A
> blockers to eliminate their kinetics. The remaining difference is purely
> passive filtering.
>
> Quantitative check: Compare with a cable model (Rall, NEURON) — match the
> spectral slope at different distances.
>
> 3. Testing hypothesis 2.3 (AMPA vs GABA-A kinetics)
> What experiment: Dynamic pharmacological manipulation (and optogenetics
> with different kinetics) at the same LFP site.
>
> Logic:
>
> Block GABA-A (bicuculline) — get predominance of fast AMPA-EPSPs.
>
> Block AMPA (CNQX) — leave slow GABA-A-IPSPs.
>
> Then restore the original balance.
>
> Compare the 1/f slope (2–100 Hz range).
>
> Prediction (per Gao & Donoghue 2016):
>
> AMPA-dominant → flatter spectrum (weak 1/f dependence).
>
> GABA-A-dominant → steeper spectrum (strong 1/f dependence).
>
> Critical control: Simultaneously monitor spatial coherence (to rule out
> mechanism 2.1) and vary stimulation distance from soma (to rule out 2.2).
>
> If effect exists — receptor kinetics make an independent contribution.
> If no effect — the 1/f slope is not primarily determined by kinetics
> (unlikely but possible).
>
> 4. Testing hypothesis 2.4 (slow ion concentration / open-loop current)
> What experiment: Long-duration (>10–20 min) recording of LFP +
> ion-selective microelectrodes (K⁺, Ca²⁺) in cortex without external
> stimulation (spontaneous activity).
>
> Logic:
>
> Standard microelectrodes record high-frequency LFP (0.5–200 Hz).
>
> Ion-selective electrodes give extracellular K⁺ concentration with ~0.1–1
> Hz temporal resolution.
>
> Prediction: If slow ionic shifts affect 1/f:
>
> The spectral slope in the 0.05–1 Hz range will correlate with K⁺
> concentration.
>
> When the "closed-loop" current is disrupted (e.g., via Na⁺-K⁺-ATPase
> blockade with ouabain, or during hypoxia), the 1/f slope will first change,
> then return with a time constant of tens of seconds to minutes.
>
> Key test: Look at 40 Hz ASSR in two groups (red vs blue, as in your
> example) — if the difference in 1/f is at frequencies <<1 Hz but not at >10
> Hz, that supports 2.4. If the difference is at high frequencies, that
> points to 2.1–2.3.
>
> Summary: which single experiment is the most powerful for disentangling
> these?
> There isn't one. But there is a combinatorial protocol that could yield a
> weighted contribution:
>
> Step    Manipulation    Tests
> 1       Scalp EEG vs intracortical LFP  2.1
> 2       Proximal vs distal responses (optogenetics)     2.2
> 3       Pharmacology (CNQX + bicuculline) at same LFP site      2.3
> 4       Long-term recording + ion-selective electrodes + ouabain        2.4
> If after step 2 (distance control) the pharmacological effect remains —
> 2.3 is real.
> If after step 1 (accounting for source size) the 1/f almost disappears —
> 2.1 is the main contributor.
> If slope changes appear only in the very low-frequency range (<<1 Hz) —
> that's 2.4.
>
> This is a complex experiment, but it is already being partially performed
> in neurophysiology using optogenetics and high-density probe arrays."
>
> In the meantime, I'll try to come up with a way to differentiate between
> the two using existing EEG recordings of people in different states. I'm
> not sure it will work, but maybe it will be informative.
>
> Eugen Masherov
>
>
>
> > Hello 1/f people,
> >
> > Gin Estrella Cruz and I will meet online to discuss whether it is
> possible
> > to quantitatively compare the contributions of cable theory and AMPA/GABA
> > (i.e., E/I) balance to EEG's 1/f power distribution. At this point, I do
> > not know whether such a comparison is feasible. Anyone is welcome to join
> > if the timing works, I'd love to hear your opinions and advice. Since
> there
> > is a 12-hour time difference between us, the meeting time is a bit
> awkward.
> >
> > *Time*: Apr 15, 2026 08:00 AM Eastern Time (US and Canada, EDT)
> > *Place*:
> >
> https://urldefense.com/v3/__https://ucsd.zoom.us/j/3026035468?pwd=bQg61iUIe0AHfDQ5QSipOSEXi4FzCs.1&omn=97531862557__;!!Mih3wA!FZmTaWWKaDH-9ElW5sUmquTyS4E1TAy3KcNOWuur9efjaocNW7F7lNBCzhmS1d1FL9tA6L-gHGo2EbexRI-rf5m6dcE$
> > *Meeting ID*: 302 603 5468
> > *Password*: 1overF
> >
> > To provide a bit of background, since the publication of the original
> FOOOF
> > paper, the idea that a flatter or steeper 1/f slope in the EEG power
> > spectral density reflects excitatory/inhibitory states appears to have
> been
> > overgeneralized. However, the 1/f-like behavior of EEG is an intrinsic
> > property predicted by cable theory. If there are two contributors (at
> > least) to 1/f-ness, they should be compared quantitatively to determine
> > which contributes more.
> >
> > Makoto
> > _______________________________________________
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-- 
李景明