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S192 The role of the cerebellum in motion control
Abstracts / Clinical Neurophysiology 128 (2017) e178–e303
S188 The role of repetitive transcranial magnetic stimulation in treatment of diabetic polyneuropathic resistant pain—Ann Abd El Kader 1, Amira El Gohary 1, Husam Murad 2, Dina El Salmawy 1,* (1 Cairo University, Clinical Neurophysiology, Faculty of Medicine, Cairo, Egypt, 2 Cairo University, Neurology, Faculty of Medicine, Cairo, Egypt) Objective: The objective of our study is to reduce resistant diabetic polyneuropathic pain using repetitive transcranial magnetic stimulation (rTMS). Diabetes mellitus is a clinical syndrome characterized by hyperglycemia caused by relative or absolute deficiency of insulin in the body. Painful neuropathy is a common complication in chronic diabetes. Although painful neuropathy responds to antidepressants, anticonvulsants and opioid agonists, these drugs proved to have different side effects and are sometimes not effective. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, safe and effective mechanism used in relieving neuropathic pain. According to pulses given, it can modulate cortical plasticity, consequently causing excitability or inhibition according to the rate of stimulation. Methods: Twenty patients were randomly selected and divided into two groups: Insulin dependent (group A) and non-Insulin dependent (group B), each group contains10 patients. High frequency 10 Hz stimulation protocol is applied on both groups for 5 consecutive days, repetitive transcranial magnetic stimulation was applied over lower limbs’ motor cortex, VAS score and nerve conduction studies were compared before and after the sessions. Results and significance: Highly significant improvement of VAS score and nerve conduction studies (p-value < 0.01) were detected after the sessions. Discussion: To the best of our knowledge, this study is one of the first studies to apply rTMS over lower limb motor cortex in treating patients suffering from diabetic neuropathic pain by activating pain control systems as well as improving their nerve conduction studies. Improvement of nerve conduction studies is a result of pyramidal tract excitation, accordingly spinal synaptic plasticity. Conclusion: According to our study, we found that rTMS significantly reduced painful diabetic neuropathy. rTMS may produce its analgesic effects, inducing motor cortex plasticity and activating descending inhibitory pain control systems. Keywords: High frequency (rTMS), Painful diabetic neuropathy, Motor cortex, Nerve conduction studies doi:10.1016/j.clinph.2017.07.198
Symposium XXV. – The mystery of cerebellum S191 Cerebellar contributions to fear behaviour—Charlotte Lawrenson, Stella Koutsikou, Bridget Lumb, Richard Apps (University of Bristol, School of Physiology, Pharmacology and Neuroscience, Bristol, United Kingdom) Objectives: Various regions of the midbrain and cerebrum are known to play an important role in fear behaviour. This talk will present evidence that the cerebellum should also be added to this network. Methods: Electrophysiological, lesioning and behavioural techniques in rats were used to study interactions between the cerebellum and the midbrain periaqueductal grey (PAG). Freezing was used as a behavioural measure to quantify fear before and after localized cerebellar lesions and was initiated innately e.g. via the predator
e239
odour test, or learned via auditory cued aversive foot shock fear conditioning. Electrodes were also implanted into the PAG and cerebellar nuclei, and neuronal activity was recorded during these fear paradigms. Results: Our research has shown that a powerful physiological connection exists between the ventrolateral PAG and vermal lobule VIII (pyramis) of the cerebellum. Lesioning the pyramis disrupts innate and fear-conditioned freezing behaviour. In response to auditory cued fear conditioning there is an increase in beta and gamma local field potential activity in the cerebellar nuclei during presentation of the conditioned tone. Discussion: Further work is needed to understand how cerebellar computations play a role in the affective and motor aspects of fear evoked freezing behaviour. Conclusions: The cerebellar- PAG connection is a critical component of the neural network subserving emotionally related freezing behaviour. Significance: These results highlight a role for the cerebellum in the neural networks underlying fear behaviour, raising the possibility of a new therapeutic target for fear related disorders such as posttraumatic stress disorder. Keywords: Cerebellum, Periaqueductal grey, Fear doi:10.1016/j.clinph.2017.07.199
S192 The role of the cerebellum in motion control—Mario Manto (FNRS ULB Belgium, UEM GRIM, Brussels, Belgium) Objectives: To assess the roles of the cerebellum in motion control on the basis of clinical, anatomical, functional imaging and electrophysiological investigations. Methods: (a) Review of experimental findings starting from works of pioneers of the 19th century until 2017, (b) assessment of the theory of internal models. Results: Anatomically, the cerebellum has a modular organization. Parasagittal bands of Purkinje cells (PCs) project to specific areas of cerebellar nuclei (CN). Functionally, cerebellar cortex (CC) is composed of microzones gathering groups of about 1 PCs having the same somatotopic receptive field. The intrinsic connectivity networks (ICNs) derived from fMRI studies overlap with maps of structural connectivity. Transsynaptic tracer studies reveal disynaptic pathways linking the cerebellum and basal ganglia. Neurophysiologically, a very robust property of CN is their ability to fire rebound spike bursts following strong hyperpolarization, turning inhibition in CN output spiking. The timing of spiking is critical for the CC and is a pre-requisite for internal models. Anticipation of action is mandatory to plan the sequential movements on the basis of internal/external constraints. Cerebellar dysmetria can now be explained by biased internal models of limb dynamics. Similarly, in Schmahmann’s syndrome a mismatch between reality and perceived reality is suspected. Conclusions: The leading theory of forward models is now embracing not only the motor symptoms but also the cognitive deficits observed in cerebellar ataxias. Significance: The redundant architecture of the CC makes of the cerebellum an ideal structure to convey signals across microzones in a time-dependent fashion. Keywords: Cerebellum, Purkinje neurons, Internal models doi:10.1016/j.clinph.2017.07.200
S188 The role of repetitive transcranial magnetic stimulation in treatment of diabetic polyneuropathic resistant pain—Ann Abd El Kader 1, Amira El Gohary 1, Husam Murad 2, Dina El Salmawy 1,* (1 Cairo University, Clinical Neurophysiology, Faculty of Medicine, Cairo, Egypt, 2 Cairo University, Neurology, Faculty of Medicine, Cairo, Egypt) Objective: The objective of our study is to reduce resistant diabetic polyneuropathic pain using repetitive transcranial magnetic stimulation (rTMS). Diabetes mellitus is a clinical syndrome characterized by hyperglycemia caused by relative or absolute deficiency of insulin in the body. Painful neuropathy is a common complication in chronic diabetes. Although painful neuropathy responds to antidepressants, anticonvulsants and opioid agonists, these drugs proved to have different side effects and are sometimes not effective. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, safe and effective mechanism used in relieving neuropathic pain. According to pulses given, it can modulate cortical plasticity, consequently causing excitability or inhibition according to the rate of stimulation. Methods: Twenty patients were randomly selected and divided into two groups: Insulin dependent (group A) and non-Insulin dependent (group B), each group contains10 patients. High frequency 10 Hz stimulation protocol is applied on both groups for 5 consecutive days, repetitive transcranial magnetic stimulation was applied over lower limbs’ motor cortex, VAS score and nerve conduction studies were compared before and after the sessions. Results and significance: Highly significant improvement of VAS score and nerve conduction studies (p-value < 0.01) were detected after the sessions. Discussion: To the best of our knowledge, this study is one of the first studies to apply rTMS over lower limb motor cortex in treating patients suffering from diabetic neuropathic pain by activating pain control systems as well as improving their nerve conduction studies. Improvement of nerve conduction studies is a result of pyramidal tract excitation, accordingly spinal synaptic plasticity. Conclusion: According to our study, we found that rTMS significantly reduced painful diabetic neuropathy. rTMS may produce its analgesic effects, inducing motor cortex plasticity and activating descending inhibitory pain control systems. Keywords: High frequency (rTMS), Painful diabetic neuropathy, Motor cortex, Nerve conduction studies doi:10.1016/j.clinph.2017.07.198
Symposium XXV. – The mystery of cerebellum S191 Cerebellar contributions to fear behaviour—Charlotte Lawrenson, Stella Koutsikou, Bridget Lumb, Richard Apps (University of Bristol, School of Physiology, Pharmacology and Neuroscience, Bristol, United Kingdom) Objectives: Various regions of the midbrain and cerebrum are known to play an important role in fear behaviour. This talk will present evidence that the cerebellum should also be added to this network. Methods: Electrophysiological, lesioning and behavioural techniques in rats were used to study interactions between the cerebellum and the midbrain periaqueductal grey (PAG). Freezing was used as a behavioural measure to quantify fear before and after localized cerebellar lesions and was initiated innately e.g. via the predator
e239
odour test, or learned via auditory cued aversive foot shock fear conditioning. Electrodes were also implanted into the PAG and cerebellar nuclei, and neuronal activity was recorded during these fear paradigms. Results: Our research has shown that a powerful physiological connection exists between the ventrolateral PAG and vermal lobule VIII (pyramis) of the cerebellum. Lesioning the pyramis disrupts innate and fear-conditioned freezing behaviour. In response to auditory cued fear conditioning there is an increase in beta and gamma local field potential activity in the cerebellar nuclei during presentation of the conditioned tone. Discussion: Further work is needed to understand how cerebellar computations play a role in the affective and motor aspects of fear evoked freezing behaviour. Conclusions: The cerebellar- PAG connection is a critical component of the neural network subserving emotionally related freezing behaviour. Significance: These results highlight a role for the cerebellum in the neural networks underlying fear behaviour, raising the possibility of a new therapeutic target for fear related disorders such as posttraumatic stress disorder. Keywords: Cerebellum, Periaqueductal grey, Fear doi:10.1016/j.clinph.2017.07.199
S192 The role of the cerebellum in motion control—Mario Manto (FNRS ULB Belgium, UEM GRIM, Brussels, Belgium) Objectives: To assess the roles of the cerebellum in motion control on the basis of clinical, anatomical, functional imaging and electrophysiological investigations. Methods: (a) Review of experimental findings starting from works of pioneers of the 19th century until 2017, (b) assessment of the theory of internal models. Results: Anatomically, the cerebellum has a modular organization. Parasagittal bands of Purkinje cells (PCs) project to specific areas of cerebellar nuclei (CN). Functionally, cerebellar cortex (CC) is composed of microzones gathering groups of about 1 PCs having the same somatotopic receptive field. The intrinsic connectivity networks (ICNs) derived from fMRI studies overlap with maps of structural connectivity. Transsynaptic tracer studies reveal disynaptic pathways linking the cerebellum and basal ganglia. Neurophysiologically, a very robust property of CN is their ability to fire rebound spike bursts following strong hyperpolarization, turning inhibition in CN output spiking. The timing of spiking is critical for the CC and is a pre-requisite for internal models. Anticipation of action is mandatory to plan the sequential movements on the basis of internal/external constraints. Cerebellar dysmetria can now be explained by biased internal models of limb dynamics. Similarly, in Schmahmann’s syndrome a mismatch between reality and perceived reality is suspected. Conclusions: The leading theory of forward models is now embracing not only the motor symptoms but also the cognitive deficits observed in cerebellar ataxias. Significance: The redundant architecture of the CC makes of the cerebellum an ideal structure to convey signals across microzones in a time-dependent fashion. Keywords: Cerebellum, Purkinje neurons, Internal models doi:10.1016/j.clinph.2017.07.200