Depotentiation of associative plasticity is intact in Parkinson's disease with mild dyskinesia.

OBJECTIVE: Depotentiation of homosynaptic plasticity of the primary motor cortex (M1) is impaired in patients with Parkinson's disease (PD) who have developed dyskinesias. In this exploratory study, we tested whether this holds true for heterosynaptic plasticity induced by paired associative stimulation (PAS). METHODS: Dyskinetic (n=11) and Non-dyskinetic (n=11), levodopa-treated PD patients were tested in M1 with PAS25ms alone, PAS25ms preceded by continuous theta-burst stimulation of the cerebellum (cTBSCB-PAS) as a method to evoke a larger plastic response in M1, and each of these two interventions followed by a depotentiation protocol (cTBS150pulses) to M1. RESULTS: PAS25ms and cTBSCB-PAS25ms induced long-term potentiation (LTP)-like responses in both groups of PD patients, with cTBSCB significantly boosting the plastic response. Both these LTP-like responses could be depotentiated by cTBS150, in both groups of patients. CONCLUSIONS: Cerebellar stimulation enhances heterosynaptic plasticity in PD irrespective of dyskinesias. Depotentiation mechanisms of heterosynaptic plasticity are preserved in PD patients, including those with dyskinesias. The lack of depotentiation of LTP-like plasticity as a hallmark of dyskinesia in PD patients is not absolute. The ability to depotentiate LTP-like plasticity may potentially depend on the type of plasticity induced (homosynaptic or heterosynaptic), the circuits involved in these responses and the adequacy of dopaminergic stimulation.

Plastic responsiveness of motor cortex to paired associative stimulation depends on cerebellar input.

OBJECTIVE: The extent of plastic responses of motor cortex (M1) to paired associative stimulation (PAS) varies among healthy subjects. Continuous theta-burst stimulation (cTBS) of cerebellum enhances the mean PAS-induced plasticity in groups of healthy subjects. We tested whether the initial status of Responder or Non -Responder to PAS, influenced the effect of cerebellar stimulation on PAS-induced plasticity. METHODS: We assessed in 19 young healthy volunteers (8 Responders, 11 Non-Responders to PAS), how cTBS and iTBS (intermittent TBS) applied to the cerebellum before a PAS protocol influenced the plastic responsiveness of M1 to PAS. We tested whether the PAS-induced plastic effects could be depotentiated by a short cTBS protocol applied to M1 shortly after PAS and whether cerebellar stimulation influenced GABA-ergic intracortical inhibition and M1 plasticity in parallel. RESULTS: Cerebellar cTBS restored the M1 response to PAS in Non-Responders while cerebellar iTBS turned the potentiating response to PAS to a depressive response in both groups. The depotentiation protocol abolished both responses. CONCLUSION: Non-Responder status to PAS is a state of M1 amenable to bidirectional plastic modulation when primed by a change in cerebello-thalamic drive. SIGNIFICANCE: The meaning of lack of responsiveness to certain protocols probing plasticity should be reconsidered.

Expression of CK 19 as a biomarker in early detection of oral squamous cell carcinoma.

BACKGROUND: Increased mortality in oral squamous cell carcinoma (OSCC) had been attributed to delay in diagnosis. Lack of a specific marker to assess the malignant potential of premalignant lesions is thought to be one of the reasons for late detection. Expression of Cytokeratin 19, which is widely used as an odontogenic epithelial marker had been reported in OSCC. Downregulation of CK 19 expression plays an important role in terminal differentiation of superficial squamous cell and increased expression in various epithelial malignancies has been suggested to be an indicator of malignant change. AIMS AND OBJECTIVES: To assess the role of CK19 as a potential marker in predicting malignant transformation in oral precancerous lesions and as a prognostic marker in OSCC. MATERIALS AND METHODS: Study population consisted of ten samples each of normal oral mucosa, epithelial hyperplasia, varying grades of both oral epithelial dysplasias and OSCC. The tissue sections were subjected to immunohistochemical staining for the marker cytokeratin 19. RESULTS: An increased expression of CK19 was noted in oral epithelial hyperplasia, severe dysplasia and in superficial epithelium at the invading front in OSCC. In mild and moderate dysplasias, CK19 expression was lower than the normal mucosa. In oral squamous cell carcinoma, the expression of CK19 was restricted to either a few islands or a few cells within the islands, resulting in a lesser expression than the normal epithelium. The malignant epithelial islands in the superficial connective tissue stroma were showing greater expression than the deeper islands. The epithelial cells associated with formation of keratin pearls were found to be showing more expression than those with infrequent keratin pearls. CONCLUSION: The study suggests that malignant transformation of epithelium can be predicted based on the increased expression of CK19. But it should be done with caution as a similar increased expression may also be noticed in presence of inflammation.