Biology subjects

Cohen, L.

Publications and source records attributed to Cohen, L..

42 records · Page 3Linked to original sources

bioRxiv2019

Voluntary movement initiation is not coupled to optimal sensorimotor oscillatory phases

Voluntary movement requires motor commands to be released from motor cortex (M1) and transmitted to spinal motoneurons and effector muscles. M1 activity oscillates between brief excitatory and inhibitory states that correlate with single neuron spiking rates. Here, we asked if the motor commands needed to produce voluntary, self-paced finger movements are preferentially released from M1 during restricted phases of this ongoing sensorimotor oscillatory activity. 21 healthy adults performed a self-paced finger movement task while EEG and EMG signals were recorded. For each finger movement, we identified the individual sensorimotor mu (8-12 Hz) and beta (13-35 Hz) oscillatory phase at the estimated time of motor command release from M1 by subtracting individually-defined MEP latencies from EMG-determined movement onset times. We report that motor commands were preferentially released at ~120{degrees} along the beta cycle but were released uniformly across the mu cycle. These results suggest that motor commands are preferentially released from M1 near optimal peak phases of endogenous beta rhythms.

neuroscience↗

bioRxiv2019

TrackUSF, a novel methodology for automated analysis of ultrasonic vocalizations, reveals modified social communication in a rat model of autism

Rodents emit various social ultrasonic vocalizations (USVs), which reflect their emotional state and mediate social interaction. USVs are usually analyzed by manual or semi-automated methodologies categorizing discrete USVs according to their structure in the frequency-time domains. This laborious analysis hinders effective use of USVs for screening animal models of human pathologies associated with modified social behavior, such as autism spectrum disorder (ASD). Here we present a novel, automated methodology for analyzing USVs, termed TrackUSF. To validate TrackUSF, we analyzed a dataset of mouse mating calls and compared the results with a manual analysis by a trained observer. We found that TrackUSF was capable of detecting most USVs, with less than 1% of false-positive detections. We then employed TrackUSF to social vocalizations in Shank3-deficient rats, a rat model of ASD and found, for the first time, that these vocalizations exhibit a spectrum of deviations from pro-social calls towards aggressive calls.

animal behavior and cognition↗

bioRxiv2019

Semantic coding in the occipital cortex of early blind individuals

The visual cortex of early blind individuals is reorganized to support cognitive functions distinct from vision. Research suggests that one such prominent function is language. However, it is unknown whether the visual cortex of blind individuals codes for word meaning. We addressed this question by comparing neuronal activity evoked by a semantic decision task, using magnetoencephalography (MEG), between 12 early blind and 14 sighted participants otherwise comparable with regard to gender, age and education. We found that average brain responses to thousands of auditory word stimuli followed similar time courses in blind and sighted participants. However, in blind participants only, we found a sustained enhancement of activity in the visual cortex. Moreover, across the whole brain, we found an effect of semantic category from about 400 ms after word onset. Strikingly, in blind participants, semantic categories were discriminable starting 580 ms after word onset from signal captured by sensors sensitive to the visual cortex. We replicated the analyses in time windows locked to stimulus onset and behavioral response, using both classical hypothesis testing and machine learning for single-trial classification. Semantic decisions were well classified in all participants (AUC [~] 0.60), but generalization capacity across participants was found reduced in the blind group due to a larger variability of discriminative patterns. In conclusion, our findings suggest that brain plasticity reorganizes the semantic system of blind individuals, and extends semantic computation into the visual cortex.

neuroscience↗

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↗