Biology subjects

Cohen, L.

Publications and source records attributed to Cohen, L..

3 recordsLinked to original sources

bioRxiv2018

Distinctive interaction between cognitive networks and the visual cortex in early blind individuals

In early blind individuals, brain activation by a variety of non-perceptual cognitive tasks extends to the visual cortex, while in the sighted it is restricted to supramodal association areas. We hypothesized that such activation results from the integration of different sectors of the visual cortex into typical task-dependent networks. We tested this hypothesis with fMRI in blind and sighted subjects using tasks assessing speech comprehension, incidental long-term memory and both verbal and non-verbal executive control, in addition to collecting resting-state data. All tasks activated the visual cortex in blind relative to sighted subjects, which enabled its segmentation according to task sensitivity. We then assessed the unique brain-scale functional connectivity of the segmented areas during resting state. Language-related seeds were preferentially connected to frontal and temporal language areas; the seed derived from the executive task was connected to the right dorsal frontoparietal executive network; the memory-related seed was uniquely connected to mesial frontoparietal areas involved in episodic memory retrieval. Thus, using a broad set of language, executive, and memory tasks in the same subjects, combined with resting state connectivity, we demonstrate the selective integration of different patches of the visual cortex into brain-scale networks with distinct localization, lateralization, and functional roles.

neuroscience↗

bioRxiv2018

The AP-1 complex regulates AXL expression and determines sensitivity to PI3Kα inhibition in esophagus and head and neck squamous cell carcinoma

AXL overexpression is a common resistance mechanism to anti-cancer therapies, including the resistance to BYL719 (Alpelisib) - the p110 isoform specific inhibitor of phosphoinositide 3-kinase (PI3K) - in esophagus and head and neck squamous cell carcinoma (ESCC, HNSCC respectively). However, the mechanisms underlying AXL overexpression in resistance to BYL719 remain elusive. Here we demonstrated that the AP-1 transcription factors, c-JUN and c-FOS, regulate AXL overexpression in HNSCC and ESCC. The expression of AXL was correlated with that of c-JUN both in HNSCC patients and in HNSCC and ESCC cell lines. Silencing of c-JUN and c-FOS expression in tumor cells downregulated AXL expression and enhanced the sensitivity of human papilloma virus positive (HPVPos) and negative (HPVNeg) tumor cells to BYL719 in vitro. Blocking of the c-JUN N-terminal kinase (JNK) using SP600125 in combination with BYL719 showed a synergistic anti-proliferative effect in vitro, which was accompanied by AXL downregulation and potent inhibition of the mTOR pathway. In vivo, the BYL719-SP600125 drug combination led to the arrest of tumor growth in cell line-derived and patient-derived xenograft models, and in syngeneic head and neck murine cancer models. Collectively, our data suggests that JNK inhibition in combination with anti-PI3K therapy is a new therapeutic strategy that should be tested in HPVPos and HPVNeg HNSCC and ESCC patients.

cancer biology↗

bioRxiv2017

Distributed cortical structural properties contribute to motor cortical excitability and inhibition

The link between the local structure of the primary motor cortex and motor function has been well documented. However, motor function relies on a network of interconnected brain regions and the link between the structural properties characterizing these distributed brain networks and motor function remains poorly understood. Here, we examined whether distributed patterns of brain structure, extending beyond the primary motor cortex can help classify two forms of motor function: corticospinal excitability and intracortical inhibition. To this effect, we recorded high-resolution structural magnetic resonance imaging scans in 25 healthy volunteers. To measure corticospinal excitability and inhibition in the same volunteers we recorded motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) and short-interval intracortical inhibition (SICI) in a separate session. Support vector machine (SVM) pattern classification was used to identify distributed multivoxel gray matter areas, which distinguished subjects who had lower and higher MEPs and SICIs. We found that MEP and SICI classification could be predicted based on a widely distributed, largely non-overlapping pattern of voxels in the frontal, parietal, temporal, occipital and cerebellar regions. Thus, structural properties distributed over the brain beyond the primary motor cortex relate to motor function.

neuroscience↗