Dynamic spectral signatures of mirror movements in the sensorimotor functional connectivity network of patients with Kallmann syndrome

In Kallmann syndrome (KS), the peculiar phenomenon of bimanual synkinesis or mirror movement (MM) has been associated with a spectral shift, from lower to higher frequencies, of the resting-state fMRI signal of the large-scale sensorimotor brain network (SMN). To possibly determine whether a similar frequency specificity exists across different functional connectivity SMN states, and to capture spontaneous transitions between them, we investigated the dynamic spectral changes of the SMN functional connectivity in KS patients with and without MM symptom. Brain MRI data were acquired at 3 Tesla in 39 KS patients (32 without MM, KSMM-, seven with MM, KSMM+) and 26 age- and sex-matched healthy control (HC) individuals. The imaging protocol included 20-min rs-fMRI scans enabling detailed spectro-temporal analyses of large-scale functional connectivity brain networks. Group independent component analysis was used to extract the SMN. A sliding window approach was used to extract the dynamic spectral power of the SMN functional connectivity within the canonical physiological frequency range of slow rs-fMRI signal fluctuations (0.01-0.25 Hz). K-means clustering was used to determine (and count) the most recurrent dynamic states of the SMN and detect the number of transitions between them. Two most recurrent states were identified, for which the spectral power peaked at a relatively lower (state 1) and higher (state 2) frequency. Compared to KS patients without MM and HC subjects, the SMN of KS patients with MM displayed significantly larger spectral power changes in the slow 3 canonical sub-band (0.073-0.198 Hz) and significantly fewer transitions between state 1 (less recurrent) and state 2 (more recurrent). These findings demonstrate that the presence of MM in KS patients is associated with reduced spontaneous transitions of the SMN between dynamic functional connectivity states and a higher recurrence and an increased spectral power change of the high-frequency state. These results provide novel information about the large-scale brain functional dynamics that could help to understand the pathologic mechanisms of bimanual synkinesis in KS syndrome and, potentially, other neurological disorders where MM may also occur.