Cellular and Circuit Models of Increased Resting State Network Gamma Activity in Schizophrenia

AbstractHigh-frequency gamma activity of verbal-memory encoding using invasive-electroencephalogram coupled has laid the foundation for numerous studies testing the integrity of memory in diseased populations. Yet, the functional connectivity characteristics of networks subserving these HFA-memory linkages remains uncertain. By integrating this electrophysiological biomarker of memory encoding from IEEG with resting-state BOLD fluctuations, we estimated the segregation and hubness of HFA-memory regions in drug-resistant epilepsy patients and matched healthy controls. HFA-memory regions express distinctly different hubness compared to neighboring regions in health and in epilepsy, and this hubness was more relevant than segregation in predicting verbal memory encoding. The HFA-memory network comprised regions from both the cognitive control and primary processing networks, validating that effective verbal-memory encoding requires multiple functions, and is not dominated by a central cognitive core. Our results demonstrate a tonic intrinsic set of functional connectivity, which provides the necessary conditions for effective, phasic, task-dependent memory encoding.HighlightsHigh frequency memory activity in IEEG corresponds to specific BOLD changes in resting-state data.HFA-memory regions had lower hubness relative to control brain nodes in both epilepsy patients and healthy controls.HFA-memory network displayed hubness and participation (interaction) values distinct from other cognitive networks.HFA-memory network shared regional membership and interacted with other cognitive networks for successful memory encoding.HFA-memory network hubness predicted both concurrent task (phasic) and baseline (tonic) verbal-memory encoding success.

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Abstract W P29: Tissue Plasminogen Activator Mediated Reperfusion, and Subsequent Improvement in Resting State Connectivity Correlates with Functional Outcome in Acute Ischemic Stroke Patients

Stroke ◽

10.1161/str.46.suppl_1.wp29 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Souvik Sen ◽

Johann Fridriksson ◽

Taylor Hanayik ◽

Christopher Rorden ◽

Isabel Hubbard ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Connectivity ◽

Functional Outcome ◽

Resting State ◽

Network Connectivity ◽

Stroke Patients ◽

Post Stroke ◽

Resting State Network ◽

Tissue Plasminogen

Background: Intravenous Tissue Plasminogen Activator (TPA) is the only FDA approved medical therapy for acute ischemic stroke (AIS). Prior study suggests that early recanalization is associated with better stroke outcome. Our aim was to correlate task-negative and task-positive (TN/TP) resting state network activity with tissue perfusion and functional outcome, in stroke patients who received TPA. Method: AIS patients were consented and underwent NIH stroke scale (NIHSS) assessment and magnetic resonance imaging (MRI) scans during TPA infusion (baseline) and six hours post stroke. The MRI sequences include contrast-enhanced perfusion weighted image (PWI) and resting state Blood Oxygen Level-Dependent or BOLD (RSB) images acquired using a Siemens Treo 3T MRI scanner. Additionally, the RSB scan and the NIHSS were obtained at a 30-day follow up visit. Results: Fourteen patients (mean age ± SD=63 ±14, 50% male, 50% white, 43% black and 7% others) who qualified for TPA completed the study at baseline and 6 hours post stroke. Of these, 6 patients had valid follow up data at 30 days. Three patients without cerebral ischemia were excluded. A paired samples t-test comparing baseline and 6h post stroke showed a significantly improved TP network t(10)= -4.24 p< 0.05. The resting network connectivity improved from 6 hours post stroke to 30-days follow up, t(5)= -5.35 p< 0.01. Similarly, NIHSS, at 6h post stroke t(10)= 3.62 p< 0.01 and at 30-days follow up t(5)= -3.4 p< 0.01 were significantly better than the NIHSS at baseline. The 6-hours post-stroke perfusion correlated with the resting network connectivity in both the damaged (r=-0.56 p= 0.07) and intact hemispheres (r= -0.57 p= 0.06). Differences in functional connectivity and NIHSS scores from baseline to 6 h were positively correlated (r= 0.56 p=0.07). Conclusion: In this pilot study we found that TPA led to changes in MRI based resting state networks and associated functional outcome. Correlations were found between perfusion, functional connectivity and NIHSS. This suggests that the improvement of resting state network means improved efficiency of brain activity indicated by functional outcome and may be a potential predictive MRI biomarker for TPA response. A larger study is needed to verify this finding.

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