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P295 APOE polymorphism and cortical plasticity are independently associated with cognitive decline in Alzheimer’s disease
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Abstracts / Clinical Neurophysiology 128 (2017) e1–e163
anthropomorphic prosthesis connected to the peripheral nervous system via bidirectional neural interfaces. Transcranial magnetic stimulation (TMS) is a non-invasive technique commonly used to assess topographical reorganization of motor brain areas. Objective: The aim of this study is to evaluate the motor cortical reorganization of primary motor cortex with the TMS mapping technique in a left trans-radial amputee patient following the use of a novel prosthetic system able to provide somatosensory feed-back from the lost hand of the user. Materials and methods: Cortical motor output was mapped via TMS (intensity 10% above standardized excitability motor Threshold) for each hemisphere at the beginning, after 1 month and 2 month of training with the new prosthetic system. Peripheral responses were recorded from forearm flexor and extensor carpi ulnaris muscles of both limbs. Resting and Active motor threshold were also collected during separate mapping of right and left hemispheres. Results: No significant differences were found in the motor thresholds between the two hemispheres before and after implantation. Pre-surgical TMS motor maps showed a slight abnormal interhemispheric asymmetry of motor cortex topography, resulted in a smaller area of representation of muscles governing the stump compared to the area for the intact limb. Following training, post-surgical maps, showed a reduction and a partial reversal of this asymmetry because of an enlargement of the excitable area on the right hemisphere contralateral to the stump, leading towards a more symmetrical muscle representation in the two hemispheres, as in control subjects. Conclusions: Our experiment provides a direct and unique evidence of brain plasticity changes occurring in the motor cortex following the use of a prosthetic system able to restore a somatosensory feedback from the missing limb after amputation.
doi:10.1016/j.clinph.2016.10.401
P294 Developmental profile of interhemispheric inhibition in children—P. Ciechanski *, E. Zewdie, A. Kirton (University of Calgary, Calgary, Canada) ⇑
Corresponding author.
Question: Interhemispheric inhibition (IHI) is a crossed, transcallosal inhibitory relationship between the left and right motor cortex (M1). This can be assessed in vivo using transcranial magnetic stimulation (TMS). Interhemispheric interactions may be altered in disease such as stroke where IHI imbalance is a potential target for therapeutic neuromodulation. IHI is well defined in adults, but its properties in the developing brain are poorly defined. Methods: 24 typically developing, right-handed children aged 6– 18 years completed a TMS-evaluation of transcallosal inhibition. Bilateral ipsilateral silent period (iSP) measures delivered suprathreshold (120% resting motor threshold, RMT) stimulation during 50% maximum contraction of the ipsilateral first dorsal interosseous. Bidirectional paired-pulse IHI (LtoR and RtoL) delivered a 120%RMT conditioning stimulus prior to contralateral 120%RMT test stimulus at interstimulus intervals (ISI) of 8, 10, 40 or 50 ms. Results: Left iSP latency (r = 0.38) and suppression (r = 0.48) correlated with age and degree of handedness (r = 0.49). Right iSP was not associated with age or handedness. Children exhibited IHI in both LtoR and RtoL directions with maximal reduction of 70% in RtoL at a 40 ms ISI. RtoL IHI was greater than LtoR at ISI of 10, 40
and 50 ms. IHI was positively correlated with handedness in both directions (r = 0.47): more ‘‘right-handed” subjects had less IHI. iSP suppression and LtoR IHI were negatively correlated (r = 0.53), whereas iSP suppression and RtoL IHI displayed a positive correlation (r = 0.52). Conclusions: Interhemispheric inhibition is measureable in children with TMS. iSP and IHI demonstrate developmental effects of age and laterality. In contrast to some adult descriptions, elements of iSP and IHI appear to be associated. Understanding the developmental profile of IHI and iSP may inform the study of interhemispheric neurophysiology in pediatric disease states. doi:10.1016/j.clinph.2016.10.402
P295 APOE polymorphism and cortical plasticity are independently associated with cognitive decline in Alzheimer’s disease—F.Di Lorenzo *, C. Motta, V. Ponzo, S. Bonnı`, A. Martorana, G. Koch (Non Invasive Stimulation Unit, Fondazione Santa Lucia, Roma, Italy) ⇑
Corresponding author.
Introduction: APOE E4 allele associates not only with AD risk and a lower age onset, but also with faster cognitive decline and greater cerebral atrophy, suggesting a key role of this polymorphism in modulating both disease risk and clinical outcome. Objectives: In this study we investigated the correlation between cognitive decline, motor cortical plasticity and cerebrospinal fluid (CSF) biomarkers profile of AD patients divided by APOE polymorphism in E4 allele carriers (E4) and homozygous E3 carriers. Materials and methods: A monophasic Magstim 200 device was used to deliver intermitted/continuous theta burst stimulation (iTBS/cTBS) protocols. ELISA was used for determination of CSF biomarkers level. Forty-one AD patients underwent lumbar puncture for CSF withdrawal, blood screening for APOE polymorphism, stimulation protocols applied over the primary motor cortex and mini mental state examination (MMSE) at baseline and at 6-, 12- and 18-months. Results: No difference was found in CSF biomarkers profile within the APOE variants group. I-TBS after-effects were significantly reduced in E3 in comparison with E4 AD patients. Correlation analyses revealed that the individual amount of iTBS induced plasticity correlated with delta-MMSE and total Tau showing that a less pronounced LTP-like plasticity and higher total-Tau CSF levels were associated with a higher delta-MMSE. Only in apoE4 patients Tau pathology correlates with cortical plasticity impairment and cognitive decline. A multivariate analysis showed that APOE polymorphism and LTP-like plasticity, but not t-Tau levels, are independently able to predict delta-MMSE in AD patients. Conclusions: APOE variants show different level of cortical plasticity and are independently associated with clinical progression in AD patients. Tau pathology is specific for ApoE4 group driving cortical plasticity impairment and cognitive decline. ApoE4 patients represent a pure model of TAU-driven AD pathology. ApoE3 patients are characterized by different mechanisms of cortical plasticity impairment and clinical symptoms. LTP impairment is a marker of pathophysiological dysfunction in AD and, as such, it should be taken in account also for the adoption of new pharmacological strategies, considering AD as a disorder of synaptic plasticity. doi:10.1016/j.clinph.2016.10.403
Abstracts / Clinical Neurophysiology 128 (2017) e1–e163
anthropomorphic prosthesis connected to the peripheral nervous system via bidirectional neural interfaces. Transcranial magnetic stimulation (TMS) is a non-invasive technique commonly used to assess topographical reorganization of motor brain areas. Objective: The aim of this study is to evaluate the motor cortical reorganization of primary motor cortex with the TMS mapping technique in a left trans-radial amputee patient following the use of a novel prosthetic system able to provide somatosensory feed-back from the lost hand of the user. Materials and methods: Cortical motor output was mapped via TMS (intensity 10% above standardized excitability motor Threshold) for each hemisphere at the beginning, after 1 month and 2 month of training with the new prosthetic system. Peripheral responses were recorded from forearm flexor and extensor carpi ulnaris muscles of both limbs. Resting and Active motor threshold were also collected during separate mapping of right and left hemispheres. Results: No significant differences were found in the motor thresholds between the two hemispheres before and after implantation. Pre-surgical TMS motor maps showed a slight abnormal interhemispheric asymmetry of motor cortex topography, resulted in a smaller area of representation of muscles governing the stump compared to the area for the intact limb. Following training, post-surgical maps, showed a reduction and a partial reversal of this asymmetry because of an enlargement of the excitable area on the right hemisphere contralateral to the stump, leading towards a more symmetrical muscle representation in the two hemispheres, as in control subjects. Conclusions: Our experiment provides a direct and unique evidence of brain plasticity changes occurring in the motor cortex following the use of a prosthetic system able to restore a somatosensory feedback from the missing limb after amputation.
doi:10.1016/j.clinph.2016.10.401
P294 Developmental profile of interhemispheric inhibition in children—P. Ciechanski *, E. Zewdie, A. Kirton (University of Calgary, Calgary, Canada) ⇑
Corresponding author.
Question: Interhemispheric inhibition (IHI) is a crossed, transcallosal inhibitory relationship between the left and right motor cortex (M1). This can be assessed in vivo using transcranial magnetic stimulation (TMS). Interhemispheric interactions may be altered in disease such as stroke where IHI imbalance is a potential target for therapeutic neuromodulation. IHI is well defined in adults, but its properties in the developing brain are poorly defined. Methods: 24 typically developing, right-handed children aged 6– 18 years completed a TMS-evaluation of transcallosal inhibition. Bilateral ipsilateral silent period (iSP) measures delivered suprathreshold (120% resting motor threshold, RMT) stimulation during 50% maximum contraction of the ipsilateral first dorsal interosseous. Bidirectional paired-pulse IHI (LtoR and RtoL) delivered a 120%RMT conditioning stimulus prior to contralateral 120%RMT test stimulus at interstimulus intervals (ISI) of 8, 10, 40 or 50 ms. Results: Left iSP latency (r = 0.38) and suppression (r = 0.48) correlated with age and degree of handedness (r = 0.49). Right iSP was not associated with age or handedness. Children exhibited IHI in both LtoR and RtoL directions with maximal reduction of 70% in RtoL at a 40 ms ISI. RtoL IHI was greater than LtoR at ISI of 10, 40
and 50 ms. IHI was positively correlated with handedness in both directions (r = 0.47): more ‘‘right-handed” subjects had less IHI. iSP suppression and LtoR IHI were negatively correlated (r = 0.53), whereas iSP suppression and RtoL IHI displayed a positive correlation (r = 0.52). Conclusions: Interhemispheric inhibition is measureable in children with TMS. iSP and IHI demonstrate developmental effects of age and laterality. In contrast to some adult descriptions, elements of iSP and IHI appear to be associated. Understanding the developmental profile of IHI and iSP may inform the study of interhemispheric neurophysiology in pediatric disease states. doi:10.1016/j.clinph.2016.10.402
P295 APOE polymorphism and cortical plasticity are independently associated with cognitive decline in Alzheimer’s disease—F.Di Lorenzo *, C. Motta, V. Ponzo, S. Bonnı`, A. Martorana, G. Koch (Non Invasive Stimulation Unit, Fondazione Santa Lucia, Roma, Italy) ⇑
Corresponding author.
Introduction: APOE E4 allele associates not only with AD risk and a lower age onset, but also with faster cognitive decline and greater cerebral atrophy, suggesting a key role of this polymorphism in modulating both disease risk and clinical outcome. Objectives: In this study we investigated the correlation between cognitive decline, motor cortical plasticity and cerebrospinal fluid (CSF) biomarkers profile of AD patients divided by APOE polymorphism in E4 allele carriers (E4) and homozygous E3 carriers. Materials and methods: A monophasic Magstim 200 device was used to deliver intermitted/continuous theta burst stimulation (iTBS/cTBS) protocols. ELISA was used for determination of CSF biomarkers level. Forty-one AD patients underwent lumbar puncture for CSF withdrawal, blood screening for APOE polymorphism, stimulation protocols applied over the primary motor cortex and mini mental state examination (MMSE) at baseline and at 6-, 12- and 18-months. Results: No difference was found in CSF biomarkers profile within the APOE variants group. I-TBS after-effects were significantly reduced in E3 in comparison with E4 AD patients. Correlation analyses revealed that the individual amount of iTBS induced plasticity correlated with delta-MMSE and total Tau showing that a less pronounced LTP-like plasticity and higher total-Tau CSF levels were associated with a higher delta-MMSE. Only in apoE4 patients Tau pathology correlates with cortical plasticity impairment and cognitive decline. A multivariate analysis showed that APOE polymorphism and LTP-like plasticity, but not t-Tau levels, are independently able to predict delta-MMSE in AD patients. Conclusions: APOE variants show different level of cortical plasticity and are independently associated with clinical progression in AD patients. Tau pathology is specific for ApoE4 group driving cortical plasticity impairment and cognitive decline. ApoE4 patients represent a pure model of TAU-driven AD pathology. ApoE3 patients are characterized by different mechanisms of cortical plasticity impairment and clinical symptoms. LTP impairment is a marker of pathophysiological dysfunction in AD and, as such, it should be taken in account also for the adoption of new pharmacological strategies, considering AD as a disorder of synaptic plasticity. doi:10.1016/j.clinph.2016.10.403