PMC5715395_01
Timeline of case history of the patient since the stroke event. The patient suffered a brainstem ischemic stroke in July 2008 (55 years of age). Several physical rehabilitation regimes were implemented since 2009 to improve motor functions, swallowing difficulties and phonation disorders. In August 2012, the patient experienced auditory hallucinations (AHs) for the first time, which disappeared spontaneously after 3 months. AHs reappeared almost 1 year later in September 2013. After failure of a pharmacological therapy, 1 Hz repetitive transcranial magnetic stimulation (rTMS) sessions applied over the left temporoparietal junction were administered from April to May 2014 consisted in 17 blocks of 2 consecutive sessions (34 sessions, first period), which induced a complete remission of AHs. After 10 weeks, the patient suffered a hallucinatory relapse so additional 11 blocks of 2 consecutive sessions (22 sessions, second period) were performed, led again a complete abolition of AHs. Unexpectedly, the patient and his relatives reported an unproved voluntary motor control of his right hand after 14 rTMS sessions during the first period.
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Localization on our patient's T1 magnetic resonance imaging (MRI) sequence of the left temporoparietal junction region targeted in the treatment of auditory hallucinations in schizophrenia patients as the one we report. This region corresponds to the MNI coordinates x = -55, y = -41, z = 11. As it can be observed in this figure, it is located at the posteriori end of the sylvian fissure, ventral to the supramarginal gyrus. See coronal (A), sagittal (B), and axial (C) MRI views of the location for the transcranial magnetic stimulation target.
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The TMS coil was oriented with the handle oriented in an anterior-to-posterior and medial-to-lateral direction. The TPJ target was identified according to the patient's brain surface anatomical features in the posterior end of the sylvian/lateral fissure (where the temporal and parietal lobes meet; see Figure 2) and labeled on a 3D rendering of the patient's individual T1 MRI sequence. The neuronavigation system recorded the location and after daily spatial calibration taking into account specific head fiducial points, allowing the stimulation of the exact same brain area on any new visit.
Changes of the Auditory Hallucinations Rating Scale (AHRS) score for the first period of 1 Hz repetitive transcranial magnetic stimulation (rTMS) treatment. Before rTMS (baseline), the patient scored 29 in the AHRS. At week 2 (after 14 rTMS sessions), the score achieved a level of 18 (38% decrease) and at week 5 (after 34 rTMS sessions), the patient scored a value of 0 in the AHRS corresponding to a complete remission of auditory hallucinations.
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By the end of the 26th daily rTMS session, 5 weeks after the rTMS treatment onset, AHs had completely disappeared, and the patient scored a value of 0 in the AHRS (see Figure 3).
Structural magnetic resonance imaging images (T1-weighted isovoxel) of the patient presented in the current case obtained at the end of his repetitive transcranial magnetic stimulation treatment for auditory hallucinations, hence 4 years after suffering his brainstem stroke. Ischemic stroke lesions reveal areas of damage (outlined in red) in (A) the lateral aspect of the left bulbo-pontine junction, (B) the left cerebral peduncle, and (C) the left capsulo-thalamic region.
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A three-dimensional, high-resolution T1-weighted acquisition was performed to characterize the stroke ischemic lesions [field of view (FoV) = 256 mm, voxel size = 1 mm, slice thickness = 1 mm, repetition time (TR) = 2,300 ms, echo time (TE) = 2.98 ms, flip angle (FA) = 9 , inversion time = 900 ms] (see Figure 4).
Brain activations as measured from functional magnetic resonance imaging BOLD responses (EPI-BOLD sequence, uncollected threshold, p < 0.01, 30 voxels minimum) during blocks of hand grasping performed with the right hand as compared with blocks of rest and visualized on a 3D structural MR image. This figure shows activations in the right middle temporal gyms (1; x = 54, y = -62, z = 8; p = 0.003), right postcentral gyms (2; x = 34, y = -38, z = 62; p = 0.044), left superior parietal gyms (3; x = -36, y = -44, z = 60, p = 0.037), left precentral gyms (4; x = -24, y = -24, z = 68; p = 0.050), and left middle temporal gyms (5; x = -54, y = -68, z = 0; p = 0.019). Abbreviations: A, anterior; P, posterior.
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During the grasping performed with the right hand, fMRI recordings showed bilateral activations of the middle temporal gyrus, and also unilateral activations of the left fusiform gyrus, the right postcentral gyrus, the left superior parietal gyrus, the left precentral gyrus and finally, the left superior occipital gyrus, and the right middle occipital gyrus (see Figure 5; Table 1).
(Top panel) Deterministic tracking of white matter tract fibers from the repetitive transcranial magnetic stimulation (rTMS) stimulated target in the left temporoparietal junction (TPJ) of the patient estimated from diffusion imaging data obtained at the end of his rTMS treatment for auditory hallucinations, hence 4 years after suffering his brainstem stroke. Note that a few fibers reached the cerebral peduncles in the left side of the midbrain (cerebral peduncles) and the medulla. (Bottom panel) Deterministic tracking of cortico-spinal projections from bilateral frontal regions passing through the cerebral peduncles and reaching the medulla oblongata. These images show white matter connectivity linking the left TPJ and the brainstem (across the pontine lesion; top panel) and between the left and right motor cortex and the brainstem (bottom panel), which hence could drive cortico-spinal signals recovery. Abbreviations: A, anterior; P, posterior; R, right; L, left.
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Analysis revealed white matter bundles from the left TPJ (631 fibers, volume of tract = 29.21 ml, length = 41.30 +- 22.32 mm) (see Figure 6). Finally, the cortico-spinal tract was also reconstructed (271 fibers, volume of tract = 30.62 ml, length = 87.87 +- 34.92 mm) (see Figure 6).