Abstract
In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37–51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders.
Similar content being viewed by others
References
Aman, M. G. (2004). Management of hyperactivity and other acting-out problems in patients with autism spectrum disorder. Seminars in Pediatric Neurology, 11(3), 225–228.
Aman, M. G., & Singh, N. N. (1994). Aberrant behavior checklist—Community. Supplementary manual. East Aurora, NY: Slosson Educational Publications.
American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (DSM-IV TR) (text revised) (4th ed.). D.C: Washington.
Barker, A. T. (1999). The history and basic principles of magnetic nerve stimulation. Electroencephalography and Clinical Neurophysiology, 51, 3–21.
Belmonte, M. K., Allen, G., Beckel-Mitchener, A., Boulanger, L., Carper, R., & Webb, S. J. (2004a). Autism and abnormal development of brain connectivity. Journal of Neuroscience, 24, 9228–9231.
Belmonte, M. K., Cook, E. H., Anderson, G. M., Rubenstein, J. L. R., Greenhough, W. T., Beckel-Mitchener, A., et al. (2004b). Autism as a disorder of neural information processing: Directions for research and targets for therapy. Molecular Psychiatry, 9, 646–663.
Belmonte, M. K., & Yurgelun-Todd, D. A. (2003a). Functional anatomy of impaired selective attention and compensatory processing in autism. Cognitive Brain Research, 17, 651–664.
Belmonte, M. K., & Yurgelun-Todd, D. A. (2003b). Anatomic dissociation of selective and suppressive processes in visual attention. Neuroimage, 19, 180–189.
Bertone, A., Mottron, L., Jelenic, P., & Faubert, J. (2005). Enhanced and diminished visuo-spatial information processing in autism depend on stimulus complexity. Brain, 128, 2430–2441.
Bodfish, J. W., Symons, F. J., & Lewis, M. H. (1999). Repetitive Behavior Scale. Western Carolina Center Research Reports.
Bodfish, J. W., Symons, F. S., Parker, D. E., & Lewis, M. H. (2000). Varieties of repetitive behavior in autism: Comparisons to mental retardation. Journal of Autism and Developmental Disorders, 30, 237–243.
Bomba, M. D., & Pang, E. W. (2004). Cortical auditory evoked potentials in autism: A review. International Journal of Psychophysiology, 53, 161–169.
Boutros, N. N., Korzyukov, O., Jansen, B., Feingold, A., & Bell, M. (2004). Sensory gating deficits during the mid-latency phase of information processing in medicated schizophrenia patients. Psychiatry Research, 126, 203–215.
Bruneau, N., Roux, S., Adrien, J. L., & Bathelemy, C. (1999). Auditory associative cortex dysfunction in children with autism: Evidence from late auditory evoked potentials (N 1 wave- T Complex). Clinical Neurophysiology, 110, 1927–1934.
Burack, J. A. (1994). Selective attention deficits in persons with autism: Preliminary evidence for inefficient attentional lens. Journal of Abnormal Psychology, 103, 515–543.
Casanova, M. F. (2005). Minicolumnar pathology in autism. In M. F. Casanova (Ed.), Recent developments in autism research (pp. 133–144). New York: Nova Biomedical Books.
Casanova, M. F. (2006). Neuropathological and genetic findings in autism: The significance of a putative minicolumnopathy. Neuroscientist, 12(5), 435–441.
Casanova, M. F., Buxhoeveden, D., & Gomez, J. (2003). Disruption in the inhibitory architecture of the cell minicolumn: Implications for autism. The Neuroscientist, 9, 496–507.
Casanova, M. F., Buxhoeveden, D. P., Switala, A. E., & Roy, E. (2002a). Minicolumnar pathology in autism. Neurology, 58, 428–432.
Casanova, M. F., Buxhoeveden, D. P., Switala, A. E., & Roy, E. (2002b). Neuronal density and architecture (gray level index) in the brains of autistic patients. Journal Child Neurology, 17, 515–521.
Casanova, M. F., van Kooten, I., Switala, A. E., van England, H., Heinsen, H., Steinbuch, H. W. M., et al. (2006a). Abnormalities of cortical minicolumnar organization in the prefrontal lobes of autistic patients. Clinical Neuroscience Research, 6(3–4), 127–133.
Casanova, M. F., van Kooten, I., van Engeland, H., Heinsen, H., Steinbursch, H. W. M., Hof, P. R., et al. (2006b). Minicolumnar abnormalities in autism II. Neuronal size and number. Acta Neuropathologica, 112, 287–303.
Chandana, S. R., Behen, M. E., Juhász, C., Muzik, O., Rothermel, R., Mangner, T. J., et al. (2005). Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism. International Journal of Developmental Neuroscience, 23, 171–182.
Childs, J. A., & Blair, J. L. (1997). Valproic acid treatment of epilepsy in autistic twins. Journal Neuroscience Nursing, 29, 244–248.
Ciesielski, K. T., Courchesne, E., & Elmasian, R. (1990). Effects of focused selective attention tasks on event-related potentials in autistic and normal individuals. Electroencephalography Clinical Neurophysiology, 75, 207–220.
Ciesielski, K. T., Knoght, J. E., Prince, R. J., Harris, R. J., & Handmaker, S. D. (1995). Event-related potentials in cross-modal divided attention in autism. Neuropsychologia, 33, 225–246.
Constantino, J. N., & Gruber, C. P. (2005). The Social Responsiveness Scale (SRS) manual. Los Angeles, CA: Western Psychological Services.
Courchesne, E., Lincoln, A. J., Yeung-Courchesne, R., Elmasian, R., & Grillon, C. (1989). Pathophysiologic findings in nonretarded autism and receptive developmental disorder. Journal of Autism and Developmental Disorders, 19, 1–17.
Courchesne, E., & Pierce, K. (2005). Brain overgrowth in autism during a critical time in development: Implications for frontal pyramidal neuron and interneuron development and connectivity. International Journal Developmental Neuroscience, 23, 153–170.
Daskalakis, Z. J., Christensen, B. K., Fitzgerald, P. B., & Chen, R. (2002). Transcranial magnetic stimulation: A new investigational and treatment tool in psychiatry. Journal of Neuropsychiatry and Clinical Neurosciences, 14, 406–415.
Dawson, G., Finley, C., Phillips, S., Galpert, L., & Lewy, A. (1988). Reduced P3 amplitude of the event-related brain potential: Its relationship to language ability in autism. Journal of Autism and Developmental Disorders, 18, 493–504.
DeFelipe, J. (1999). Chandelier cells and epilepsy. Brain, 122, 1807–1822.
DeFelipe, J. (2004). Cortical microanatomy and human brain disorders: Epilepsy. Cortex, 40, 232–233.
DeFelipe, J., Hendry, S. H. C., Hashikawa, T., Molinari, M., & Jones, E. G. (1990). A microcolumnar structure of monkey cerebral cortex revealed by immunocytochemical studies of double bouquet cell axons.
Favorov, O. V., & Kelly, D. G. (1994a). Minicolumnar organization within somatosensory cortical segregates, I: Development of afferent connections. Cerebral Cortex, 4, 408–427.
Favorov, O. V., & Kelly, D. G. (1994b). Minicolumnar organization within somatosensory cortical segregates, II: Emergent functional properties. Cerebral Cortex, 4, 428–442.
Ferree, T. C., Luu, P., Russell, G. S., & Tucker, D. M. (2001). Scalp electrode impedance, infection risk, and EEG data quality. Clinical Neurophysiology, 112, 444–536.
Ferri, R., Elia, M., Agarwal, N., Lanuzza, B., Musumeci, S. A., & Pennisi, G. (2003). The mismatch negativity and the P3a components of the auditory event-related potentials in autistic low-functioning subjects. Clinical Neurophysiology, 114, 1671–1680.
Fletcher, E. M., Kussmaul, C. L., & Mangun, G. R. (1996). Estimation of interpolation errors in scalp topographic mapping. Electroctoencephalography and Clinical Neuraphysiology, 98, 422–434.
Garvey, M. A., & Mall, V. (2008). Transcranial magnetic stimulation in children. Clinical Neurophysiology, 119, 973–984.
George, M. S., & Belmaker, R. H. (2007). Transcranial magnetic stimulation in clinical psychiatry. Arlington, VA: American Psychiatry Publishing Inc.
George, M. S., Nahas, J., Kozol, F. A., Li, X., Yamanaka, K., Mishory, A., et al. (2003). Mechanisms and the current state of transcranial magnetic stimulation. CNS Spectrums, 8(7), 496–514.
George, M. S., Nahas, Z., Molloy, M., Speer, A. M., Oliver, N. C., Li, X.-B., et al. (2000). A controlled trial of daily prefrontal cortex TMS for treating depression. Biological Psychiatry, 48, 962–970.
Gershon, A. A., Dannon, P. N., & Grunhaus, L. (2003). Transcranial magnetic stimulation in the treatment of depression. American Journal of Psychiatry, 160, 835–845.
Greenberg, B. D. (2007). Transcranial magnetic stimulation in anxiety disorders. In M. S. George & R. H. Belmaker (Eds.), Thanscranial magnetic stimulation in clinical psychiatry (pp. 165–178). Washington, DC: American Psychiatric Publishing Inc.
Griffith, E. M., Pennington, B. F., Wehner, E. A., & Rogers, S. J. (1999). Executive functions in young children with autism. Child Development, 70, 817–832.
Helmich, R. C., Siebner, H. R., Bakker, M., Munchau, A., & Bloem, B. R. (2006). Repetitive transcranial magnetic stimulation to improve mood and motor function in Parkinson’s disease. Journal of Neurological Sciences, 248, 84–96.
Hoffman, R. E., & Cavus, I. (2002). Slow transcranial magnetic stimulation, long-term depotentiation, and brain hyperexcitability disorders. American Journal of Psychiatry, 159, 1093–1102.
Holcomb, P. J., Ackerman, P. T., & Dykman, R. A. (1985). Cognitive event-related brain potentials in children with attention and reading deficits. Psychophysiology, 22, 656–667.
Hollander, E., Dolgoff-Kaspar, R., Cartwright, C., Rawitt, R., & Novotny, S. (2001). An open trial of divalproex sodium in autism spectrum disorders. Journal of Clinical Psychiatry, 62, 530–534.
Hruby, T., & Marsalek, P. (2003). Event-related potentials—The P3 wave. Acta Neurobiologiae Experimentalis (Wars), 63, 55–63.
Katayama, J., & Polich, J. (1998). Stimulus context determines P3a and P3b. Psychophysiology, 35, 23–33.
Kemner, C., van der Gaag, R. J., Verbaten, M., & van Engeland, H. (1999). ERP differences among subtypes of pervasive developmental disorders. Biological Psychiatry, 46, 781–789.
Kemner, C., Verbaten, M. N., Cuperus, J. M., Camfferman, G., & Van Engeland, H. (1994). Visual and somatosensory event-related brain potentials in autistic children and three different control groups. Electroencephalography and Clinical Neurophysiology, 92, 225–237.
Kemner, C., Verbaten, M. N., Cuperus, J. M., Camfferman, G., & Van Engeland, H. (1995). Auditory event-related potentials in autistic children and three different control groups. Biological Psychiatry, 38, 150–165.
Kisley, M. A., & Cornwell, Z. M. (2006). Gamma and beta neural activity evoked during a sensory gating paradigm: Effects of auditory, somatosensory and cross-modal stimulation. Clinical Neurophysiology, 11, 2549–2563.
Kisley, M. A., Noecker, T. L., & Guinther, P. M. (2004). Comparison of sensory gating to mismatch negativity and self-reported perceptual phenomena in healthy adults. Psychophysiology, 41, 604–612.
Le Couteur, A., Lord, C., & Rutter, M. (2003). The autism diagnostic interview—Revised (ADI-R). Los Angeles, CA: Western Psychological Services.
Lincoln, A. J., Courchesne, E., Harms, L., & Allen, M. (1993). Contextual probability evaluation in autistic, receptive developmental disorder and control children: Event-related potential evidence. Journal of Autism and Developmental Disorders, 23, 37–58.
Loo, C., & Mitchell, P. (2005). A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy. Journal of Affective Disorders, 88, 255–267.
Luu, P., Tucker, D. M. L., Englander, R., Lockfeld, A., Lutsep, H., & Oken, B. (2001). Localizing acute stroke-related EEC changes: Assessing the effects of spatial undersampling. Journal of Clinical Neurophysiology, 18, 302–317.
Mathalon, D. H., Fedor, M., Faustman, W. O., Gray, M., Askari, N., & Ford, J. M. (2002). Response-monitoring dysfunction in schizophrenia: An event-related brain potential study. Journal of Abnormal Psychology, 111, 22–41.
Mountcastle, V. B. (1997). The columnar organization of the neocortex. Brain, 120, 701–722.
Mountcastle, V. B. (2003). Introduction: Computation in cortical columns. Cerebral Cortex, 13, 2–4.
Nahas, Z., DeBrux, C., Chandler, V., Lorberbaum, J. P., Speer, A. M., et al. (2000). Lack of significant changes on magnetic resonance scans before and after 2 weeks of daily left prefrontal repetitive transcranial magnetic stimulation for depression. The Journal of ECT, 16(4), 380–390.
Oades, R. D., Walker, M. K., Geffen, L. B., & Stern, L. M. (1988). Event-related potentials in autistic and healthy children on an auditory choice reaction time task. International Journal of Psychophysiology, 6, 25–37.
Ogawa, A., Ukai, S., Shinosaki, K., Yamamoto, M., Kawaguchi, S., Ishii, R., et al. (2004). Slow repetitive transcranial magnetic stimulation increases somatosensory high-frequency oscillations in humans. Neuroscience Letters, 358, 193–196.
Pascual-Leone, A., Walsh, V., & Rothwell, J. (2000). Transcranial magnetic stimulation in cognitive neuroscience—Virtual lesion, chronometry, and functional connectivity. Current Opinions in Neurobiology, 10, 232–237.
Perrin, E., Pernier, J., Bertrand, O., Giard, M., & Echallier, J. F. (1987). Mapping of scalp potentials by surface spline interpolation. Electroencephalography and Clinical Neurophysiology, 66, 75–81.
Picton, T. W. (1992). The P300 wave of the human event-related potential. Journal Clinical Neurophysiology, 9, 456–479.
Plioplys, A. V. (1994). Autism: Electroencephalogram abnormalities and clinical improvement with valproic acid. Archives of Pediatrics and Adolescent Medicine, 148, 220–222.
Polich, J. (2003). Theoretical overview of P3a a nd P3b. In J. Polich (Ed.), Detection of change: Event-related potential and fMRI Findings (pp. 83–98). Boston: Kluwer Academic Press.
Potts, G. F., Patel, S. H., & Azzam, P. N. (2004). Impact of instructed relevance on the visual ERP. International Journal of Psychophysiology, 52, 197–209.
Quintana, H. (2005). Transcranial magnetic stimulation in persons younger than the age of 18. The Journal of ECT, 21, 88–95.
Roid, G. H. (2003). Stanford-Binet Intelligence Scales, fifth edition, technical manual. Itasca, IL: Riverside Publishing.
Rosenberg, P. B., Mehndiratta, R. B., Mehndiratta, Y. P., Wamer, A., Rosse, R. B., & Balish, M. (2002). Repetitive magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. Journal of Neuropsychiatry and Clinical Neurosciences, 14, 270–276.
Rossi, S., & Rossini, P. M. (2004). TMS in cognitive plasticity and the potential for rehabilitation. Trends in Cognitive Sciences, 86, 273–279.
Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: Increased ratio of excitation/inhibition in key neural systems. Genes Brain Behavior, 2, 255–267.
Seldon, H. L. (1981a). Structure of human auditory cortex, I: Cytoarchitectonics and dendritic distributions. Brain Research, 229, 277–294.
Seldon, H. L. (1981b). Structure of human auditory cortex, II: Axon distributions and morphological correlates of speech perception. Brain Research, 229, 295–310.
Seri, S., Cerquiglini, A., Pisani, F., & Curatolo, P. (1999). Autism in tuberous sclerosis: Evoked potential evidence for a deficit in auditory sensory processing. Clinical Neurophysiology, 110, 1825–1830.
Sokhadze, E., Baruth, J., Tasman, A., Sears, L., Mathai, G., El-Baz, A., et al. (2009a). Event-related potential study of novelty processing abnormalities in autism. Applied Psychophysiology and Biofeedback, 34, 37–51.
Sokhadze, E. M., Singh, S., El-Baz, A., Baruth, J., Mathai, G., Sears, L., et al. (2009b). Effect of a low-frequency repetitive transcranial magnetic stimulation (rTMS) on induced gamma frequency oscillations and event-related potentials during processing of illusory figures in autism spectrum disorders. Journal of Autism and Developmental Disorders, 39, 619–634.
Srinivasan, R., Tucker, D. M., & Murias, M. (1998). Estimating the spatial Nyquist of the human EEC. Behavior Research Methods, Instruments, and Computers, 30, 8–19.
Townsend, J., Westerfield, M., Leaver, E., Makeig, S., Jung, T., et al. (2001). Event-related brain response abnormalities in autism: Evidence for impaired cerebello-frontal spatial attention networks. Brain Research: Cognitive Brain Research, 11, 127–145.
Uvebrant, P., & Bauzienè, R. (1994). Intractable epilepsy in children: The efficacy of lamotrigine treatment, including non-seizure-related benefits. Neuropediatrics, 25, 284–289.
Verbaten, M. N., Roelofs, J. W., van Engeland, H., Kenemans, J. K., & Slangen, J. L. (1991). Abnormal visual event-related potentials of autistic children. Journal of Autism and Developmental Disorders, 21(4), 449–470.
Volkmar, F. R., & Nelson, D. S. (1995). Seizure disorders in autism. Journal of American Academy of Child Adolescent Psychiatry, 29, 127–129.
Walsh, V., & Pascual-Leone, A. (2003). Transcranial magnetic stimulation: A neurochronometrics of mind. Cambridge, Massachusetts: MIT Press.
Wassermann, E. M., Grafman, J., Berry, C., Hollnagel, C., Wild, K., Clark, K., et al. (1996). Use and safety of a new repetitive transcranial magnetic stimulator. Electroencephalography Clinical Neurophysiology, 101, 412–417.
Wassermann, E. M., & Lisanby, S. H. (2001). Therapeutic application of repetitive transcranial magnetic stimulation: A review. Clinical Neurophysiology, 112, 1367–1377.
Wechsler, D. (2003). Wechsler Intelligence Scale for children (4th ed.). San Antonio, TX: Harcourt Assessment Inc.
Wechsler, D. (2004). Wechsler Abbreviated Scale for intelligence. San Antonio, TX: Harcourt Assessment Inc.
Welchew, D. E., Ashwin, C., Berkouk, K., Salvador, R., Suckling, J., Baron-Cohen, S., et al. (2005). Functional disconnectivity of the medial temporal lobe in Asperger’s syndrome. Biological Psychiatry, 57, 991–998.
Wijers, A. A., Mulder, G., Gunter, T. C., & Smid, H. G. O. M. (1996). Brain potential analysis of selective attention. In O. Neumann & A. F. Sanders (Eds.), Handbook of perception and action. Vol. 3: Attention (pp. 333–387). Tullamore, Ireland: Academic Press.
Ziemann, U. (2004). TMS induced plasticity in human cortex. Reviews Neuroscience, 15(4), 253–266.
Acknowledgments
The project was partially supported by R01 Eureka grant from the National Institutes of Health to Manuel Casanova.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sokhadze, E., Baruth, J., Tasman, A. et al. Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Affects Event-Related Potential Measures of Novelty Processing in Autism. Appl Psychophysiol Biofeedback 35, 147–161 (2010). https://doi.org/10.1007/s10484-009-9121-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10484-009-9121-2