Abnormal thalamocortical network dynamics in migraine

Abstract

Objective: To investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity.

Methods: We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model.

Results: Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC.

Conclusion: Our results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.

Figure 1. Analysis flowchart to study dynamic functional network connectivity (dFNC) in migraine patients

Four major steps were included: (1) perform group independent component analysis (GICA) and select intrinsic connectivity networks (ICNs); (2) estimate dFNC; (3) perform clustering state analysis; and (4) perform dynamic topologic analysis.

Figure 2. Spatial maps of the 52 identified intrinsic connectivity networks (ICNs) sorted into 6 resting-state domains

Two thalamic nuclei were identified. Each color in the spatial maps corresponds to a different ICN.

Figure 3. Group difference of state occurrences and state-based transient dynamic functional network connectivity (dFNC) patterns

(A) Group difference in percentage of occurrences of 5 dFNC states. Bar represents the mean occurrence of each state, while error bar represents the standard error of mean of occurrence. Two out of 5 states have significant group difference. Asterisks indicate the significance (false discovery rate [FDR]–corrected, p < 0.05). (B) Cluster centroids of the 5 dFNC states. (C) Group difference of dFNC of 52 brain regions between migraine without aura patients (MIG) and healthy controls (HC) in the 5 states. (D) Group difference of dFNC of 6 selected brain networks between MIG and HC in 5 states. AUD = auditory domain; CC = cognitive control domain; DM = default mode domain; SC = subcortical; SM = sensorimotor domain; VS = visual domain.

Figure 4. Abnormal transient thalamus dynamic functional network connectivity (dFNC) and its association with migraine symptoms

In state 1, migraine patients had significantly stronger positive dFNC between the posterior thalamus (pTHA) and precuneus (PCUN) and stronger negative dFNC between the pTHA and middle occipital gyrus (MOG). The strength of dFNC was associated with headache frequency of migraine patients. The red rectangular box in the connectivity matrix highlights thalamus (medial and posterior) connectivity. Asterisks indicate significance (false discovery rate corrected, p < 0.05). AUD = auditory domain; CC = cognitive control domain; DM = default mode domain; HC = healthy controls; MIG = migraine without aura patients; mTHA = medial thalamus; SC = subcortical; SM = sensorimotor domain; VS = visual domain.

Figure 5. Topologic measures in dynamic functional connectivity

The global and local efficiencies in different dynamic states are shown using violin plots for the migraine patients (red) and healthy controls (blue). Horizontal lines indicate group means (black). Asterisks represent significant difference at p_FDR < 0.05. HC = healthy controls; MIG = migraine without aura patients.

Figure 6. Migraine-relevant multisensory networks

The posterior nucleus of the thalamus (pTHA) receives projections from the brainstem and relays to the primary and secondary somatosensory cortices (S1 and S2), insula (not shown in the figure), primary and secondary visual cortices (V1/V2), primary auditory cortex (A1), and anterior cingulate cortex (ACC). A detailed review of migraine-relevant networks can be found in reference 27. We found abnormal connections between the pTHA and visual cortex (blue line) and hyperconnectivity (red dashed lines) between the sensory cortices (visual, somatosensory, and auditory) in the migraine pathologic state.