Transcranial magnetic stimulation paired with electroencephalography (TMS–EEG) can measure local

excitability and functional connectivity. To address trial-to-trial variability, responses to multiple TMS
pulses are recorded to obtain an average TMS evoked potential (TEP). Balancing adequate data
acquisition to establish stable TEPs with feasible experimental duration is critical when applying TMS–
EEG to clinical populations. Here we aim to investigate the minimum number of pulses (MNP) required
to achieve stable TEPs in children with epilepsy. Eighteen children with Self-Limited Epilepsy with
Centrotemporal Spikes, a common epilepsy arising from the motor cortices, underwent multiple 100-
pulse blocks of TMS to both motor cortices over two days. TMS was applied at 120% of resting motor
threshold (rMT) up to a maximum of 100% maximum stimulator output. The average of all 100 pulses
was used as a “gold-standard” TEP to which we compared “candidate” TEPs obtained by averaging
subsets of pulses. We defined TEP stability as the MNP needed to achieve a concordance correlation
coefficient of 80% between the candidate and “gold-standard” TEP. We additionally assessed whether
experimental or clinical factors affected TEP stability. Results show that stable TEPs can be derived from
fewer than 100 pulses, a number typically used for designing TMS-EEG experiments. The early segment
(15–80 ms) of the TEP was less stable than the later segment (80–350 ms). Global mean field amplitude
derived from all channels was less stable than local TEP derived from channels overlying the stimulated
site. TEP stability did not differ depending on stimulated hemisphere, block order, or antiseizure
medication use, but was greater in older children. Stimulation administered with an intensity above the
rMT yielded more stable local TEPs. Studies of TMS-EEG in pediatrics have been limited by the
complexity of experimental set-up and time course. This study serves as a critical starting point,
demonstrating the feasibility of designing efficient TMS–EEG studies that use a relatively small number
of pulses to study pediatric epilepsy and potentially other pediatric groups

o create proteins, DNA is transcribed into RNA, and that RNA is then “translated” into protein. Between
the creation of the RNA and the translation to protein is often a step called splicing. During splicing,
segments called introns are removed, and the remaining pieces, called exons, are joined together to
form the blueprint for translation. By splicing together different exons, the cell can create different
proteins from the same section of genetic code. When splicing goes awry, it can lead to diseases and
cancers.

New research recently published in Disease Models & Mechanisms from the Calo Lab in the Department
of Biology at MIT has identified the mechanism for how cells respond to disruptions in splicing, which
involves activating a cellular stress response. The stress response, once activated, causes widespread
effects, including changes to cell metabolism.

Researchers have discovered cellular stress responses for other core cellular processes, such as ribosome
biogenesis. However, this is the first time researchers have identified how cells respond to perturbing the
splicing process.

A particular protein acts as a kind of canary in a coal mine: Mdm2, which responds to a broad range of
splicing disruptions. Mdm2 does not cause a stress response by itself. Rather, Mdm2 is itself spliced
differently in response to splicing disruptions. Downstream, the alternative splicing of Mdm2 leads to the
activation of a protein called p53, which is known to orchestrate a cascade of responses to stress.