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ORIGINAL ARTICLE
Year : 2018  |  Volume : 21  |  Issue : 4  |  Page : 280-284
 

Evaluating the effect of repetitive transcranial magnetic stimulation in cerebral palsy children by employing electroencephalogram signals


Department of Biomedical Engineering, North Eastern Hill University, Shillong, Meghalaya, India

Date of Web Publication2-Nov-2018

Correspondence Address:
Dr. Dinesh Bhatia
Department of Biomedical Engineering, North Eastern Hill University, Shillong - 793 022, Meghalaya
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aian.AIAN_413_17

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   Abstract 


Introduction: Transcranial magnetic stimulation is a new tool that has been employed to modulate the neuronal activity of brain by its excitatory and inhibitory property. In cerebral palsy (CP) learning of any new task is an extremely slow process due to damage in sensory and motor areas of brain affecting the cognitive ability of the child and putting constraints in achieving timely developmental milestones. For such patients the electroencephalogram (EEG) is one of the most cost effective diagnostic tools used that minimizes hospital stay. Its analysis helps to identify various neurological disorders determining the role of brain waves outlining the present status of mind. Materials and Methods: This study evaluated the EEG power spectrum density (PSD) of CP children both pre and post rTMS intervention to identify significance changes in signal patterns arising from different brain regions. thirty CP children participated in this study. Fifteen individuals underwent repetitive TMS (rTMS) therapy for 20 session comprising of 10 Hz frequency for 5 days a week for 4 weeks and another fifteen individual participated in activities of daily living for 20 sessions where they were administered mandatory standard therapy only. pre- EEG versus post EEG data recorded and analyzed employing the standard montage configuration. PSD was extracted employing fast fourier transform post acquisition of artifact free signal to undermine changes in signal pattern. Discussion and Conclusion: The results revealed that rTMS improves learning ability in CP children and it shows higher power peak at frequency of 50 Hz and lower power peak frequency at 100 Hz. The power intensity in gamma wave region shows significant reduction post-rTMS therapy between 38-24 power peak frequency and 7-4 range in 100 Hz power peak frequency. In future, it will be used as effective tool as memory enhancers, especially for children with neurological disorders.


Keywords: Cerebral palsy, cognitive ability, electroencephalograph, transcranial magnetic stimulation


How to cite this article:
Gupta M, Bhatia D. Evaluating the effect of repetitive transcranial magnetic stimulation in cerebral palsy children by employing electroencephalogram signals. Ann Indian Acad Neurol 2018;21:280-4

How to cite this URL:
Gupta M, Bhatia D. Evaluating the effect of repetitive transcranial magnetic stimulation in cerebral palsy children by employing electroencephalogram signals. Ann Indian Acad Neurol [serial online] 2018 [cited 2018 Dec 15];21:280-4. Available from: http://www.annalsofian.org/text.asp?2018/21/4/280/244867





   Introduction Top


Transcranial magnetic stimulation (TMS) is one of the upcoming noninvasive techniques for brain stimulation. In 1985, Barker et al. discovered the use of transcranial magnetic stimulator for brain as well as for peripheral nerve stimulation.[1] In the USA, TMS is employed in many clinical setups for therapeutic as well as in diagnostic purpose approved by Food and Drug Administration, USA.[2] In many psychiatric as well as neurological cases such as depression, 10 Hz frequency, with 120% Motor threshold (MT) and 3000 pulses up to 26 s duration were used for therapeutic purpose.[3] TMS is widely used research tool to study various functional organizations and physiology of human brain. Due to its clinical utility, its use in therapeutic purposes in different psychiatric and neurological conditions has been well established. Rajak et al. (2016) in their study on CP children suggested that repetitive TMS (rTMS) therapy shows more significant results with rTMS therapy as compared with only standard therapy. Forty-five individuals were recruited in the study and were randomly divided into three groups. Each group received standard therapy, Group 2 received rTMS at 5 Hz frequency and Group 3 received rTMS at 10 Hz frequency. During the analysis, it was observed that P values were significant in case of 10 Hz frequency in rTMS group. They found that 10 Hz frequency at 80% MT shows better results as compared with 5 Hz frequency. In similar study on spastic CP children by Gupta et al., they suggested that rTMS in combination with standard therapy decreases the spasticity significantly in these children when compared with standard therapy only. The rate of progress or improvement shows more than double improvement with rTMS therapy as compared with standard therapy alone which has been used since past several years in treatment of such cases. One more study by Valle et al., 2007 suggested rTMS with either low (5 Hz) or high (10 Hz) frequency did not result in any adverse effects.

The cerebral palsy (CP) is one of the most common neurodevelopmental disorder seen in pediatric population. It occurs due to insult in brain, premature birth, or any traumatic head injury during birth or after delivery. It is associated with many problems related to speech, vision, fine and gross motor function, oromotor, and cognitive impairment.[4] As rTMS is one of the latest technologies being employed for deep brain stimulation,[5] the aim of our study was to determine the effect of rTMS (within safety range) in the improvement of understanding and cognitive abilities by employing magnetic stimulation in patients and analyzing changes in recorded electroencephalogram (EEG) data post-rTMS intervention. For data analysis, fast Fourier Transform (FFT) technique and power spectrum density (PSD) were calculated from the EEG signals.


   Materials and Methods Top


Study design

This study was conducted after approval from the Institutional Ethics Committee for human samples or participants, from North Eastern Hill University, Shillong, Meghalaya. Before start of the procedure, written informed consent was obtained from parent or guardian of each participating child. During this study, 20-min rTMS therapy for 20 sessions (5 days a week for 4r weeks) of 10 Hz frequency[3] was administered to children recruited for treatment in experimental group (EG), and activities of daily living (ADL) were performed by the control group (CG). During this study, pre- and post-assessment were performed using outcome measures employing raw EEG signals for analysis of different brain regions. After the completion of TMS intervention again, the recorded EEG signals were analyzed using statistical tools.

Subjects

Thirty children with diagnosed cases of CP through pediatrician or pediatric neurologist were recruited in the study with age group 5–18 years.[6] Their mean age, weight, and height were 2.1 + 5.05, 10 + 5.44, and 18 + 45.39, respectively. All the recruited individuals were divided into two groups named as CG and EG. All the individuals in EG received 20 min of repetitive TMS therapy for 20 days (5 days in a week for four weeks) by using M/s Neurosoft system, Canada. The individuals in the CG did not receive any TMS therapy but they underwent routine exercises (standard therapy) for ADL tasks. Inclusion criteria comprised of CP children with the age group 5–18 years, willingness to participate in the study, both gender either male or female, seizure under antiepileptic control medicine, only spastic diplegic, and hemiplegic type of SCP, adhering to Gross Motor Function Classification System for CP Level II and III.[7] Children with any metallic implant, not willing to participate in the study, development of unstable medical condition or severe behavioral disturbance, refusal of therapy by caregivers, and TMS therapy in the past three months before study onset were excluded from the study.

Stimulation protocol

In case of all the EG patients for r-TMS therapy, the MT was checked first to set the intensity for the 5 days' interval (day 1, 6, 11, and 16) at which the treatment was provided as shown in [Figure 1]. During this process, the patient received single pulse TMS at left dorsolateral prefrontal cortex (DLPFC)[8] with frequency of 10 Hz to check the MT. DLFPC is an area in the prefrontal cortex of the brain of humans and nonhuman primates. It is one of the most recently evolved parts of the human brain. It undergoes a prolonged period of maturation which lasts until adulthood. The DLPFC is not an anatomical structure, but rather a functional one that is why DLFPC was chosen for evaluating as well as for rTMS treatment. When twitching of right side abductor pollicis brevis muscle was observed in the individual's hand, the stimulation intensity was fixed for the next 5 days as it denotes MT, and the same process is continued till the completion of 20 consecutive days. The targeted area for r-TMS stimulation was same as DLPFC where we provided 20-min magnetic stimulation (total 2500 pulse with resting interval of 50 s) every day for 20 days (5 days/week for four weeks).
Figure 1: Repetitive transcranial magnetic stimulation stimulation protocol

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Transcranial magnetic stimulation system

In this study, Neuro-MS. NET software and therapeutic magnetic stimulator (Neurosoft-MS/D Variant-2, Neurosoft, Russia) comprising of angulated coil in figure of eight shape (AFEC-02-100-C) was employed for providing repetitive TMS. The eight-shaped magnetic coil generates the magnetic field of 4 Tesla that penetrates the cranium up to 6 cm thereby stimulating the neurons in the underlying brain region. Before starting, the magnetic stimulation MT is determined as described in Section 2.3, to set the intensity at which the magnetic stimulation is given to the individual. MT is tested by using single TMS pulse, where in the magnetic coil is placed on respective dermatome to induce twitching sensation in the desired region. After identifying the intensity at which muscle twitches, the MT is fixed for the entire therapy duration. For setting the MT, certain essential preparations are required to be done on the individual such as the patient should be comfortable and relaxed and hair should be cleaned and washed prior the TMS therapy so that the TMS penetrates the targeted stimulation area effectively.

Electroencephalogram data recording

EEG data were recorded by using the BioTrace software for Nexus-10 (Human Karigar, Canada) which has two-channel EEG recording setup and inbuilt bioamplifiers and filters. Before EEG signal recording, all participants were instructed to wash their head to remove oil and dust from the hair and again targeted area of the scalp was cleaned by using alcohol swabs to reduce the risk of increased skin impedance. In bipolar manner, button electrode was placed, namely on the F3-F4, C3-C4, P3-P4, and O3-O4 brain regions,[9] and reference electrode was placed on right mastoid according to 10–20 system for EEG recoding. After the preparation, EEG was recorded for 15-min duration without use of any sedative in awake condition of the participants as shown in [Figure 2].
Figure 2: (a) Montage 10–20 showing electroencephalogram recording area. (b) Electroencephalogram recording of spastic cerebral palsy child

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Electroencephalogram data analysis

The recorded EEG raw signal was first imported in an ANSI text format using Biotrace Nexus Mark II, neurofeedback system. Before converting the signal in ANSI text format, any noise artifact in the recorded signal was removed by employing 0.1 Hz low pass filter, 70 Hz high pass filter, and 50 Hz notch filter. In this study, the sample rate of 256[10] per se cond was selected. The imported ANSI text format file was used for analysis of collected data in MATLAB. The PSD values shows the strength of the variations as a function of frequency that was calculated by employing FFT technique. It was calculated by applying a 2 s epochs of 15 minutes duration of recorded EEG signal which yields 2880 epochs during the total recoding time. We used Welch method to obtain the PSD which was plotted as power versus frequency. Welch method is a nonparametric method that calculates the periodogram by computing the squared magnitude on the result of its discrete Fourier transform. In this method, the data sequences xi (n) can be represented as

xi (n) = x (n + iD) here n = 0, 1, 2., M– 1 and I = 0, 1, 2. L– 1

Where iD is the beginning of i th sequence. This will lead to formation of L data segments each of length 2M. The modified periodogram is given as in equation-1:



Where U is the normalization factor for the power in the window function given as: and ω(n) is the window function. Finally, the Welch power spectrum which is the average of these periodogram is given as in equation 2:




   Results Top


PSD analysis of pre-EEG versus post-EEG signals was calculated by using FFT. The imported ANSI text format file was used for analysis of collected data in MATLAB for different brain wave patterns. The result shows that alpha wave has power peaks at same frequency 15 Hz in both the cases (pre vs. post), but power intensity (PI) shows 200 PI in pre-rTMS therapy and 175 PI in post-rTMS therapy. Similarly, in case of beta waves, power peak frequency was seen at 30 Hz but no significant changes in their peaks power values was seen as compared to alpha wave. In case of theta wave, power peak frequency shows 15 Hz, but there is not much difference in their powers. Gamma wave shows drastic change in their power peak frequency. It shows highest power peak at frequency 50 Hz and lowest power peak frequency at 100 Hz and intensity of power in gamma wave drops down after rTMS therapy, that is, 38–24 in 50 Hz power peak frequency and 7–4 in 100 Hz power peak frequency as shown in [Figure 3].
Figure 3: Power spectrum density of central brain area of spastic cerebral palsy children (C3 C4) in Experimental group. (a) Prerepetitive transcranial magnetic stimulation alpha wave. (b) Postrepetitive transcranial magnetic stimulation alpha wave. (c) Prerepetitive transcranial magnetic stimulation beta wave. (d) Postrepetitive transcranial magnetic stimulation beta wave. (e) Prerepetitive transcranial magnetic stimulation theta wave. (f) Postrepetitive transcranial magnetic stimulation theta wave. (g) Prerepetitive transcranial magnetic stimulation gamma wave. (h) Postrepetitive transcranial magnetic stimulation gamma wave

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In case of CG results, where we asked individuals to perform ADL tasks, their EEG patterns did not show much changes after the completion of 20 days. In pre versus post rTMS data analysis of alpha and beta waves, it is observed that alpha peak value comes at 15 Hz and beta peak value at 30 Hz although there is no change in their power intensity. It is suggested that ADL tasks are a part of routine activity which is learned due to practice, but it does not help in enhancement of cognitive skills in SCP children. In pre- versus post rTMS data, it is observed that in the theta wave the level of PI decreases after completion ADLs from peak power of 600 to 50. It suggested that theta waves have closed relationship in encoding the new information. It also suggested that ADL helps in reliving the mental stress of children who have difficulty in performing ADLs in particular time period which is quite challenging job for them. Similarly, we analyzed the gamma waves, but it again did not show any significant changes in their peak value as well as PI as shown in [Figure 4]. In one of our previous studies, Gupta et al., 2017,[5] the assessment of all pre- and posttest data was performed by employing Vineland social maturity scale (VSMS), which is one of the important psychometric tests having several domains related to cognition and social activities. It was found that the rTMS helps in improving various cognitive domains such as socialization and understanding in such population. The results from the present study can be validated with our previous work in which we used VSMS for measure of the cognitive domains.
Figure 4: Power spectrum density of central brain area of spastic cerebral palsy children (C3 C4) in control group without repetitive transcranial magnetic stimulation therapy and only with activities of daily living. (a) Prealpha wave. (b) Postalpha wave. (c) Prebeta wave. (d) Postbeta wave. (e) Pretheta wave. (f) Posttheta wave. (g) Pregamma wave. (h) Postgamma wave

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Data were also analyzed using BioTrace software Nexus-10 available in the Neurfeedback system. Pre- versus postcomparison results for EG as well as CG are shown in [Table 1] and [Table 2]. The results suggested that EG has more significant P value than CG for theta wave, that is, P < 0.04 as compared to P < 0.05, respectively. It was also observed that the alpha, beta, and gamma wave for EG have significant results, P < 0.02, P < 0.05, and P < 0.04, respectively, but in CG, only theta waves show significant changes.
Table 1: Pre v/s post results of experimental group

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Table 2: Pre v/s post results of control group

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   Discussion and Conclusion Top


In CP, major factor that limits the social and intellectual development is impairment in cognition. The amount of EEG power in the theta and alpha frequency range is related to cognitive and memory performance.[11] According to Klimesch, 1996, small theta power but large alpha power in EEG indicates good performance.[12] It suggested that theta waves have closed relationship in encoding the new information.[13] In one study, Givens and Olton, 1995 suggested that pharmacological manipulations decreases the theta wave activity which blocks the learning.[14] One more study by Gray et al., 1987 suggested that gamma waves are responsible for visual encoding process and it results in helping through visual learning.[15] This study suggested that rTMS is a powerful tool which have capacity to neuromodulate brain signals. Excitatory property of rTMS helps to activate neurons which generated new pathways in cerebral cortex by increasing mental activity. The excitatory property of rTMS helps to activate neurons which generated new pathways in cerebral cortex by increasing mental activity. These increased mental activities activate the dormant neural structures forming a brief connection by communicating through gaps called synapses and ultimately strengthening the overall neural connection thereby enhancing cognitive ability in CP children.

In one of our previous studies of Gupta et al., 2017[5] on CP patients, we found significant improvement in cognitive domain with the use of rTMS in EG as compared to CG with significant P values for the EG. In another study by Guse et al., 2010,[3] they found selective cognitive improvement after employing high-frequency TMS stimulation specifically over the left DLPFC.[3] They analyzed cognitive effects with regard to the impact of clinical status in patients as well as on healthy volunteers. The result of this study suggested that patients tend to reach a greater improvement than healthy volunteers. In the present study, thirty spastic CP individuals were recruited. Out of these individuals, fifteen individuals underwent only ADLs (CG) with the rest (EG) being provided rTMS stimulation at fixed frequency of 10 Hz. We observed definite changes in their brainwave patterns and its physiology. The temporal relationship between EEG recording and TMS reveals no epileptic discharge during the TMS stimulation in each patient although epileptic discharge could be considered as one of the associated clinical features observed in CP patients. It shows decreased power peak values in theta waves and increased power peak values in alpha waves which are correlated with enhancement of learning and acquisition of new skills in CP children. The statistical analysis in case of theta wave peak frequency values shows 15 Hz, but there is no much difference in their powers. Gamma wave shows drastic change in the power peak frequency values. It shows highest power peak at frequency 50 Hz and lowest power peak frequency at 100 Hz and intensity of power in gamma wave drops down after rTMS therapy that is 38–24 in 50 Hz power peak frequency and 7–4 in 100 Hz power peak frequency. The results suggested that rTMS improves learning ability in CP children, and in future, it will be effective tool as memory enhancers, especially for treating neurodegenerative diseases in children and adults, slow learners, Alzheimer and cognitively impaired patients. In field of rehabilitation, there is hope of better results with rTMS in future for cognitive impaired cases. On the other hand, CG result shows that daily living activities help in reliving the mental stress of children who have difficulty in performing ADLs in particular time period which is quite challenging job for them, but it is not effective in cognitive improvement as they are routine tasks and practiced regularly.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex. Lancet 1985;1:1106-7.  Back to cited text no. 1
    
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Guse B, Falkai P, Wobrock T. Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: A systematic review. J Neural Transm (Vienna) 2010;117:105-22.  Back to cited text no. 3
    
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Gupta M, Bhatia D, Rajak BL. Study of available intervention technique to improve cognitive function in cerebral palsy patients. Curr Neurobiol 2017;8:51-9.  Back to cited text no. 4
    
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Gupta M, Bhatia D. Effect of repetitive transcranial magnetic stimulation on cognition in spastic cerebral palsy children. J Neurol Disord 2017;5:1-2.  Back to cited text no. 5
    
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Sumnima K, Reddy KJ. Cognitive function deficits in cerebral palsy: Comprehensive review and update. Int J Curr Res 2013;59:2931-3.  Back to cited text no. 6
    
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Palisano RJ, Rosenbaum P, Bartlett D, Livingston MH. Content validity of the expanded and revised gross motor function classification system. Dev Med Child Neurol 2008;50:744-50.  Back to cited text no. 7
    
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Naro A, Russo M, Leo A, Bramanti P, Quartarone A, Calabrò RS, et al. A single session of repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex in patients with unresponsive wakefulness syndrome: Preliminary results. Neurorehabil Neural Repair 2015;29:603-13.  Back to cited text no. 8
    
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Walker JE, Kozlowski GP, Lawson R. A modular activation/coherence approach to evaluating clinical/QEEG correlations. J Neurother 2007;11:25-44.  Back to cited text no. 9
    
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Teplan M. Fundamentals of EEG measurement. Meas Sci Rev 2002;2:1-11.  Back to cited text no. 10
    
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Klimesch W. EEG alpha and theta oscillations reflect cognitive and memory performance: A review and analysis. Brain Res Brain Res Rev 1999;29:169-95.  Back to cited text no. 11
    
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Klimesch W. Memory processes brain oscillation and EEG synchronization. Int J Psychophysiol 1996;24:61-100.  Back to cited text no. 12
    
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Miller R. Cortico-Hippocampal Interplay and the Representation of Contexts in the Brain. Berlin: Springer; 1991.  Back to cited text no. 13
    
14.
Givens B, Olton D. Bidirectional modulation of scopolamine in duced working memory impaired by muscarinic by muscarinic activation of the medical Septal area. Neurobiol Learn Mem 1995;63:269-76.  Back to cited text no. 14
    
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Grey C, Singer W. Stimulus dependent neuronal oscillations in the cat visual cortex area 17. Neuroscience 1987;22 Suppl: 434.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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