Linear CSD plots of the LFPs elicited by nociceptive, tactile, auditory, and visual stimuli delivered to the contralateral side.

<p>Upper left panel. CSD maps obtained from the right insula of a representative patient, expressing the recorded signals as a function of time (<i>x</i>-axis) and insular electrode contact location (<i>y</i>-axis). Note that polarity reversals are observed at the same insular locations for all four types of LFPs. One of these polarity reversals is shown by the horizontal arrows, between contacts 3 and 4. Lower left panel. CSD signals recorded from these two contacts. The signal shown for each insular contact corresponds to the signal measured from that contact, using the average of the two adjacent contacts as reference. Right panel. Total number of polarity reversals that occurred at the same contact locations across modalities and patients. In almost all cases, polarity reversals occurred at the same sites for all four modalities, indicating that, at least at the mesoscopic level of intracerebral EEG recordings, the locations of the sources generating nociceptive and non-nociceptive LFPs in the insula are largely identical. doi:<a href="http://dx.doi.org/10.17605/OSF.IO/4R7PM" target="_blank">10.17605/OSF.IO/4R7PM</a>.</p

Spatial distribution of the amplitudes of LFPs elicited by nociceptive, vibrotactile, auditory, and visual stimuli across the different insular contacts (normalized across subjects).

<p>The size of each electrode contact represents the peak-to-peak amplitude of the biphasic wave elicited by each type of stimulus delivered to the contralateral side. doi:<a href="http://dx.doi.org/10.17605/OSF.IO/4R7PM" target="_blank">10.17605/OSF.IO/4R7PM</a>.</p

LFPs elicited by nociceptive, tactile, auditory and visual stimuli in the contralateral anterior and posterior insula of two representative subjects.

<p>All four types of stimuli elicited responses at the same electrode contacts, both in the anterior insula and in the posterior insula (electrode contacts shown in red; reference electrode: A1A2). The greater part of the LFP appeared as a large biphasic wave. The evoked potentials recorded from the scalp vertex (Cz) and from intracerebral contacts located in the left temporoparietal cortex (LTP) and left mesial temporal cortex (LMT) are also shown for comparison. doi:<a href="http://dx.doi.org/10.17605/OSF.IO/4R7PM" target="_blank">10.17605/OSF.IO/4R7PM</a>.</p

Experimental procedure.

<p>Nociceptive stimuli (N) were brief pulses of radiant heat applied to the hand dorsum using a temperature-controlled CO₂ laser. This ensured that the elicited brain responses were exclusively related to the activation of heat-sensitive nociceptors. Tactile stimuli (T) were short-lasting mechanical vibrations delivered to the index fingertip, so as to selectively activate low-threshold mechanoreceptors of the medial lemniscal system. Auditory stimuli (A) were loud, lateralized short-lasting tones delivered through earphones. Visual stimuli (V) were brief, bright, and punctate flashes of light delivered using a light-emitting diode (LED) placed on the hand dorsum. The different stimuli were presented in blocks, using a long-lasting and variable interstimulus interval (5–10 s), so as to maximize their salience.</p

Image_1_DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma.tif

BackgroundGlioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors.MethodsWe analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient’s survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach.ResultsWe found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient’s survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region.ConclusionWe propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma.</p

Image_2_DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma.tif

BackgroundGlioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors.MethodsWe analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient’s survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach.ResultsWe found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient’s survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region.ConclusionWe propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma.</p