Neural Noise

Intracranial directed connectivity linking prefrontal subregions to major depression

2 min read

  • Intracranial directed connectivity links subregions of the prefrontal cortex to major depression.1
  • iEEG connectivity methods in PFC inform depression circuits and potential stimulation targets.1 1

Gardner updates

  • Intracranial directed connectivity links subregions of the prefrontal cortex to major depression; iEEG connectivity methods inform depression circuits and potential stimulation targets (Nature). 1

Weekly enrichment (2026-07-20)

  • The primary paper (Nature Communications, 2025) tested the hypothesis that major depression is a disorder of prefrontal cortical disinhibition using direct human intracranial recordings, which had not previously been possible at this spatiotemporal resolution.23
  • Cohort: six neurosurgical patients (3 male, 3 female) implanted with temporary stereo-EEG (sEEG) electrodes as part of a DBS clinical trial for treatment-resistant depression (trial UH3 NS103549).23
  • Electrodes sampled single grey-matter contacts in three prefrontal subregions — dorsolateral prefrontal cortex (Brodmann Areas 10/46), orbitofrontal cortex (Area 11), and anterior cingulate cortex (Areas 24/32) — during 5-minute resting-state fixation recordings.23
  • Over a roughly 10-day inpatient period the team collected n = 78 symptom-severity assessments (about 13 per patient) with the computerized adaptive depression inventory (CAT-DI), spanning scores from 27.0 (“normal”) to 86.0 (“severe”).3
  • Directed connectivity was quantified with Granger causality focused on the delta band (~1–3 Hz), an oscillation linked to GABAergic (parvalbumin- and somatostatin-positive) inhibitory control.23
  • In the left hemisphere, connectivity from left OFC to left dlPFC rose with symptom severity (z(74) = 3.82, p < 0.001) as did left dlPFC to left OFC (z(74) = 3.14, p = 0.002), and their bidirectional interaction was significant (z(74) = −4.97, p < 0.001), with symptoms worst when both regions exchanged information.3
  • Additional pathways included left dlPFC to left ACC (z(74) = 2.66, p = 0.008) and left ACC to left dlPFC (z(74) = 2.31, p = 0.020), plus a right-hemisphere OFC-to-ACC effect (p < 0.001), and symptom severity shifted as left-versus-right prefrontal connectivity became imbalanced.3
  • Clinical/BCI implication: resting-state prefrontal delta directed connectivity is proposed as a candidate closed-loop biomarker for adaptive DBS targeting, though the six-patient sample size limits generalizability and no decoder/stimulation-control results are reported.23

Footnotes

  1. https://news.google.com/rss/articles/CBMiX0FVX3lxTE9tMG1yOEJoVm5HdDNKMTJPeTNUQms3Qy1vem9vRzNJaExydGtPanNzUzJaclpoNjZVRDRVcFJWUDZ5aDlGcUVoc2dFZmd1Rl9FNHoyUjFrRWxiTXYwLUxV?oc=5 ↩ ↩2 ↩3 ↩4

  2. https://www.nature.com/articles/s41467-025-61487-6 ↩ ↩2 ↩3 ↩4 ↩5

  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC12238457/ ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8

Graph View