Table_3_Neuroimaging markers of Alice in Wonderland syndrome in patients with migraine with aura.docx

BackgroundThe Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs.MethodsWe conducted a case–control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups.ResultsWe found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC.ConclusionThe posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas.</p

Table_1_Neuroimaging markers of Alice in Wonderland syndrome in patients with migraine with aura.docx

BackgroundThe Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs.MethodsWe conducted a case–control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups.ResultsWe found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC.ConclusionThe posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas.</p

Z-statistic images showing clusters of significantly increased RSFC (p < 0.05, cluster-level FWE corrected) after one session of effective AMPS of the primary sensory motor cortex (a), the nuclei striati (c) and the cerebellum (d), overlaid onto a MNI-registered anatomical 3D-T1 volume.

<p>Seed regions of interest are red-coloured in the panels on the left. MNI coordinates (x, y, z) of the maximal Z-scores are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137977#pone.0137977.t002" target="_blank">Table 2</a>. Coronal and axial views follow the neurological convention.</p

Demographic and clinical parameters of patients with Parkinson’s disease before and after effective AMPS and sham stimulation.

<p>Acronyms: M: male; F: female; DD: disease duration; H&Y: Hoehn and Yahr; MMSE: Mini-Mental State Examination; Side: Symtom-dominant side; LEDD: L-dopa equivalent daily dose; UPDRS: Unified Parkinson’s Disease Rating Scale; PIGD: Postural Instability Gait Disturbances</p><p>^# Data from the total group of patients (n = 11)</p><p>* Data from the group of patients eligible for fMRI analysis (n = 7).</p><p>^a Tremor sub score represents the sum of the UPDRS items in OFF condition: 3.15, 3.16, 3.17 e 3.18.</p><p>^b PIGD subscore represents the sum of the UPDRS items in OFF condition: 3.9, 3.10, 3.11, 3.12, 3.13, 3.14.</p><p>^c Rigidity subscore represents the sum of the UPDRS items in OFF condition: 3.3.</p><p>Statistically significant P-values (p < 0.05) are presented in bold.</p><p>Demographic and clinical parameters of patients with Parkinson’s disease before and after effective AMPS and sham stimulation.</p

The device used for the AMPS treatment (a), the sites of feet stimulation (b), the effective AMPS (c), and the sham stimulation (d).

<p>The device used for the AMPS treatment (a), the sites of feet stimulation (b), the effective AMPS (c), and the sham stimulation (d).</p

Z-statistic images showing clusters of significantly increased RSFC (p < 0.05, cluster-level FWE corrected) in the effective AMPS vs. sham stimulation for the nuclei striati (a) and the cerebellum (b).

<p>Seed regions of interest are red-coloured in the panels on the left. MNI coordinates (x, y, z) of the maximal Z-scores are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137977#pone.0137977.t003" target="_blank">Table 3</a>. Coronal and axial views follow the neurological convention.</p

AMPS_Pilot_MRI data

AMPS_Pilot_MRI dat

Flowchart of the experimental protocol of the pilot interventional study as approved by the local ethical committee.

<p>Flowchart of the experimental protocol of the pilot interventional study as approved by the local ethical committee.</p