Knowledge Vault 3/96 - G.TEC BCI & Neurotechnology Spring School 2024 - Day 10
Probing physiology and pathology of the human brain connectome by CCEP
Riki Matsumoto, Kobe University Hospital (JP)
<Resume Image >

Concept Graph & Resume using Claude 3 Opus | Chat GPT4 | Llama 3:

graph LR classDef probing fill:#f9d4d4, font-weight:bold, font-size:14px; classDef ccep fill:#d4f9d4, font-weight:bold, font-size:14px; classDef surgery fill:#d4d4f9, font-weight:bold, font-size:14px; classDef connectivity fill:#f9f9d4, font-weight:bold, font-size:14px; classDef future fill:#f9d4f9, font-weight:bold, font-size:14px; A[Riki Matsumoto] --> B[CCEP probes connectivity by
stimulating and recording. 1] A --> C[CCEP has early N1
and late N2 peaks. 2] C --> D[N1 reflects short
cortical-cortical connectivity. 2] A --> E[CCEP maps functional networks
intraoperatively by stimulation. 3] A --> F[Key steps: preop imaging,
stimulation, finding best match. 4] A --> G[CCEP monitors arcuate fasciculus
during tumor resection. 5] G --> H[Stimulation changes alter
CCEP connectivity pattern. 6] H --> I[Broca's stimulation elicits
robust temporal CCEP. 6] A --> J[CCEP probes connectivity when
tractography fails due to edema. 7] J --> K[N1 amplitude increases after
tumor resection relieves edema. 7] A --> L[No clear N1 cutoff yet
for predicting language deficits. 8] A --> M[Broca's and Wernicke's show
reciprocal bidirectional CCEP connectivity. 9] A --> N[CCEP recordable under general
anesthesia without significant changes. 10] A --> O[2023 review: CCEP has potential
but needs more research, standardization. 11] A --> P[CCEP decline during clipping may
indicate ischemia, predict deficits. 12] P --> Q[Decline reversibility may
predict outcomes. 12] A --> R[DTI-CCEP allows calculating
N1 velocity for tracts. 13] R --> S[Velocity faster in tracts
with higher anisotropy. 13] A --> T[Subcortical-cortical EP has
fast onset, suggests direct excitation. 14] T --> U[Later N1 may reflect
fiber diameter differences. 14] A --> V[Intraoperative subcortical-cortical EP maps
tracts and connections, needs refinement. 15] A --> W[N1 and N2 mechanisms:
excitation, delay, cortical circuits. 16] A --> X[CCEP waveform classification may
provide connectivity insights. 17] A --> Y[Connectivity probing concept
dates back decades. 18] A --> Z[CCEP is effective connectivity,
differs from functional connectivity. 19] A --> AA[N1 depends on cytoarchitecture
and fiber properties. 20] A --> AB[N2 may involve reverberating
circuits or subcortical structures. 21] A --> AC[Establishing N1 cutoffs requires
careful multicenter studies. 22] A --> AD[Fast early CCEP components
have small amplitude. 23] AD --> AE[N1 peak easier to quantify,
correlates with functional outcomes. 23] A --> AF[Intraoperative CCEP mapping of
Broca's takes 16 min. 24] A --> AG[CCEP may probe other tracts,
arcuate fasciculus most robust. 25] A --> AH[Low-frequency stimulation neuromodulation
needs translational research. 26] class B,E,F,J,O,Y probing; class C,D,G,H,I,K,L,M,N,P,Q,R,S,T,U,V,W,X,Z,AA,AB,AC,AD,AE,AF,AG ccep; class F,G,V,AF surgery; class D,H,I,J,K,M,R,S,T,U,Z,AA connectivity; class AH future;


1.- CCEP (cortico-cortical evoked potential) is a method to probe connectivity by stimulating one cortical area and recording responses in other areas.

2.- CCEP consists of early negative N1 and late negative N2 peaks. N1 reflects connectivity conveyed through short cortical-cortical fibers.

3.- CCEP can map functional networks intraoperatively by stimulating various cortical sites. Literature on clinical and research applications is growing.

4.- Key steps: Using preop imaging to guide electrodes, stimulating frontal sites, finding best CCEP match to arcuate fasciculus connectivity.

5.- During tumor resection near arcuate fasciculus, CCEP is monitored by stimulating Broca's area and recording from temporal sites.

6.- Moving stimulation 1 cm changes CCEP connectivity pattern, showing differences in cortical wiring. Broca's stimulation elicits robust temporal CCEP.

7.- CCEP can probe physiological connectivity when tractography fails due to edema. N1 amplitude increases after tumor resection relieves edema.

8.- No clear CCEP N1 amplitude cutoff value is established yet for predicting language deficits. More research is needed.

9.- Broca's and Wernicke's areas show reciprocal bidirectional CCEP connectivity, but Broca's stimulation yields more robust temporal responses.

10.- CCEP can be recorded under general anesthesia like propofol without significant changes in waveform, distribution or amplitude.

11.- A 2023 review concludes CCEP has potential to guide surgical decisions and minimize deficits, but needs more research and standardization.

12.- CCEP decline during aneurysm clipping may indicate ischemia and predict deficits better than MEP/SEP. Decline reversibility may predict outcomes.

13.- DTI-CCEP combination allows calculating N1 velocity for different tracts. Velocity is faster in tracts with higher fractional anisotropy.

14.- Subcortical-cortical EP from arcuate fasciculus shows fast (~12 ms) onset, suggesting direct excitation. Later N1 may reflect fiber diameter differences.

15.- Intraoperative subcortical-cortical EP can map white matter tracts and their cortical connections to guide surgery, but needs methodological refinements.

16.- N1 and N2 genesis mechanisms: N1 onset indicates fastest direct excitation, later N1 has synaptic/conduction delay, N2 involves cortical circuits.

17.- Classification of CCEP waveforms based on N1 and N2 peak latencies and amplitudes may provide insights into connectivity.

18.- Concept of probing connectivity with electrical stimulation dates back decades. Recent years see growing interest in clinical applications.

19.- CCEP is effective connectivity reflecting direct cortico-cortical pathways. It differs from functional connectivity measured by resting-state fMRI correlations.

20.- N1 latency and waveform depend on cortical cytoarchitecture at stimulation and recording sites as well as white matter fiber properties.

21.- N2 may reflect cortico-cortical reverberating circuits or involve subcortical structures. Its significance needs more research.

22.- Establishing CCEP N1 amplitude cutoff values for intraoperative tract monitoring requires careful determination through large multicenter patient cohorts.

23.- Fast early CCEP components have small amplitude. N1 peak is easier to quantify and correlates better with functional outcomes.

24.- Intraoperative CCEP mapping of Broca's area takes about 16 min (2 min/site) and can be done under general anesthesia.

25.- CCEP may also probe other tracts like inferior longitudinal fasciculus, but arcuate fasciculus responses are most robust and reproducible.

26.- How low-frequency stimulation induces neuromodulation and plasticity needs more translational research in animals and humans using EP and oscillations.

27.- CCEP requires live brain tissue and axons, so cannot be evoked in formalin-fixed deceased brains.

28.- Next steps include using CCEP and connectomics to study epilepsy networks to guide treatment and understand pathological connectivity changes.

29.- Kobe is known for delicious Kobe beef, sweets, and magnificent views of Osaka Bay from the mountains.

30.- The talk ended with an invitation to continue the discussion and visit Kobe to enjoy the food and sights.

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