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Brain Network Activation (BNA) Reveals Scopolamine-Induced Impairment of Visual Working Memory

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Abstract

The overarching goal of this event-related potential (ERP) study was to examine the effects of scopolamine on the dynamics of brain network activation using a novel ERP network analysis method known as Brain Network Activation (BNA). BNA was used for extracting group-common stimulus-activated network patterns elicited to matching probe stimuli in the context of a delayed matching-to-sample task following placebo and scopolamine treatments administered to healthy participants. The BNA extracted networks revealed the existence of two pathophysiological mechanisms following scopolamine, disconnection, and compensation. Specifically, weaker frontal theta and parietal alpha coupling was accompanied with enhanced fronto-centro-parietal theta activation relative to placebo. In addition, using the characteristic BNA network of each treatment as well as corresponding literature-guided selective subnetworks as combined biomarkers managed to differentiate between individual responses to each of the treatments. Behavioral effects associated with scopolamine included delayed response time and impaired response accuracy. These results indicate that the BNA method is sensitive to the effects of scopolamine on working memory and that it may potentially enable diagnosis and treatment assessment of dysfunctions associated with cholinergic deficiency.

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References

  • Aggelopoulos NC, Liebe S, Logothetis NK, Rainer G (2011) Cholinergic control of visual categorization in macaques. Front Behav Neurosci 5:73. doi:10.3389/fnbeh.2011.00073

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Araujo JA, Chan AD, Winka LL, Seymour PA, Milgram NW (2004) Dose-specific effects of scopolamine on canine cognition: impairment of visuospatial memory, but not visuospatial discrimination. Psychopharmacology (Berl) 175:92–98

    Article  CAS  Google Scholar 

  • Bankó EM, Vidnyánszky Z (2010) Retention interval affects visual short-term memory encoding. J Neurophysiol 103:1425–1430

    Article  PubMed  Google Scholar 

  • Başar E (2004) Macrodynamics of electrical activity in the whole brain. Int J Bifurcat Chaos 14:363–381

    Article  Google Scholar 

  • Bentin S, Allison T, Puce A, Perez E (1996) Electrophysiological studies of face perception in humans. J Cogn Neurosci 8:551–565

    Article  PubMed Central  PubMed  Google Scholar 

  • Bentin S, Deouell LY (2000) Structural encoding and identification in face processing: ERP evidence for separate mechanisms. Cogn Neuropsychol 15:35–54

    Article  Google Scholar 

  • Blokland A (2005) Scopolamine-induced deficits in cognitive performance: a review of animal studies. Scopolamine Rev 1–76

  • Brandeis D, Naylor H, Halliday R, Callaway E, Yano L (1992) Scopolamine effects on visual information processing, attention and event-related potential map latencies. Psychphysiology 29:315–336

    Article  CAS  Google Scholar 

  • Brandt J (1991) The Hopkins Verbal Learning Test: development of a new memory test with six equivalent forms. Clin Neurophysiol 5:125–142

    Google Scholar 

  • Buccafusco JJ, Terry AV Jr, Webster SJ et al (2008) The scopolamine-reversal paradigm in rats and monkeys: the importance of computer assisted operant-conditioning memory tasks for screening drug candidates. Psychopharmacology (Berl) 199:481–494

    Article  CAS  Google Scholar 

  • Buckner RL (2004) Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron 44:195–208

    Article  CAS  PubMed  Google Scholar 

  • Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Earlbaum Associates, Hillsdale, NJ

    Google Scholar 

  • Contestabile A (2011) The history of the cholinergic hypothesis. Behav Brain Res 221:334–340

    Article  CAS  PubMed  Google Scholar 

  • Dimitriadis SI, Laskaris NA, Tzelepi A, Economou G (2012) Analyzing functional brain connectivity by means of commute times: a new approach and its application to track event-related dynamics. IEEE Trans Biomed Eng 59:1302–1309

    Article  CAS  PubMed  Google Scholar 

  • Ebert U, Kirch W (1998) Scopolamine model of dementia: electroencephalogram findings and cognitive performance. Eur J Clin Invest 28:944–949

    Article  CAS  PubMed  Google Scholar 

  • Ebert U, Siepmann MD, Oertel R, Wesnes KA, Kirch W (1998) Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration. J Clin Pharmacol 38:720–726

    Article  CAS  PubMed  Google Scholar 

  • Fell J, Dietl T, Grunwald T et al (2004) Neural bases of cognitive ERPs: more than phase reset. J Cogn Neurosci 16:1595–1604

    Article  PubMed  Google Scholar 

  • Fell J, Ludowig E, Staresina BP et al (2011) Medial temporal theta/alpha power enhancement precedes successful memory encoding: evidence based on intracranial EEG. J Neurosci 31:5392–5397

    Article  CAS  PubMed  Google Scholar 

  • Finnigan S, O'Connell RG, Cummins TD, Broughton M, Robertson IH (2011) ERP measures indicate both attention and working memory encoding decrements in aging. Psychophysiology 48:601–611

    Article  PubMed  Google Scholar 

  • Fransén E, Alonso AA, Hasselmo ME (2002) Simulations of the role of the muscarinic-activated calcium-sensitive nonspecific cation current INCM in entorhinal neuronal activity during delayed matching tasks. J Neurosci 22:1081–1097

    PubMed  Google Scholar 

  • Fredrickson A, Snyder PJ, Cromer J, Thomas E, Lewis M, Maruff P (2008) The use of effect sizes to characterize the nature of cognitive change in psychopharmacological studies: an example with scopolamine. Hum Psychopharmacol 23:425–436

    Article  CAS  PubMed  Google Scholar 

  • Furey ML, Pietrini P, Haxby JV (2000) Cholinergic enhancement and increased selectivity of perceptual processing during working memory. Science 290:2315–2319

    Article  CAS  PubMed  Google Scholar 

  • Gazzaley A, Clapp W, Kelley J, McEvoy K, Knight RT, D'Esposito M (2008) Age-related top-down suppression deficit in the early stages of cortical visual memory processing. PNAS 105:13122–13126

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gevins A, Cutillo B (1993) Spatiotemporal dynamics of component processes in human working memory. Electroencephalogr Clin Neurophysiol 87:128–143

    Article  CAS  PubMed  Google Scholar 

  • Gevins AS, Doyle JC, Cutillo BA et al (1981) Electrical potentials in human brain during cognition: new method reveals dynamic patterns of correlation. Science 213:918–922

    Article  CAS  PubMed  Google Scholar 

  • Gevins A, Smith ME, McEvoy L, Yu D (1997) High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice. Cereb Cortex 7:374–835

    Article  CAS  PubMed  Google Scholar 

  • Giessing C, Thiel CM (2012) Pro-cognitive drug effects modulate functional brain network organization. Front Behav Neurosci 6:53. doi:10.3389/fnbeh.2012.00053

    Article  PubMed Central  PubMed  Google Scholar 

  • Grady CL, Furey ML, Pietrini P, Horwitz B, Rapoport SI (2001) Altered brain functional connectivity and impaired short-term memory in Alzheimer’s disease. Brain 124:739–756

    Article  CAS  PubMed  Google Scholar 

  • Harding GF, Daniels R, Panchal S, Drasdo N, Anderson SJ (1994) Visual evoked potentials to flash and pattern reversal stimulation after administration of systemic or topical scopolamine. Doc Ophthalmol 86:311–322

    Article  CAS  PubMed  Google Scholar 

  • Ioannides AA, Dimitriadis SI, Saridis GA (2012) Source space analysis of event-related dynamic reorganization of brain networks. Comput Math Methods Med 2012:452503. doi:10.1155/2012/452503

    Article  PubMed Central  PubMed  Google Scholar 

  • Itier RJ, Taylo MJ (2002) Inversion and contrast polarity reversal affect both encoding and recognition processes of unfamiliar faces: a repetition study using ERPs. Neuroimage 15:353–372

    Article  PubMed  Google Scholar 

  • Itier RJ, Taylor MJ (2004) N170 or N1? Spatiotemporal differences between object and face processing using ERPs. Cereb Cortex 14:132–142

    Article  PubMed  Google Scholar 

  • Jensen O, Lisman JE (1998) An oscillatory short-term memory buffer model can account for data on the Sternberg task. J Neurosc 18:10688–10699

    CAS  Google Scholar 

  • Kaufmann JM, Schweinberger SR, Burton AM (2009) N250 ERP correlates of the acquisition of face representations across different images. J Cogn Neurosci 21:625–641

    Article  PubMed  Google Scholar 

  • Kawasaki M, Kitajo K, Yamaguchi Y (2010) Dynamic links between theta executive functions and alpha storage buffers in auditory and visual working memory. Eur J Neurosci 31:1683–1689

    PubMed Central  PubMed  Google Scholar 

  • Kikuchi M, Wada Y, Nanbu Y et al (1999) EEG changes following scopolamine administration in healthy subjects. Quantitative analysis during rest and photic stimulation. Neuropsychobiology 39:219–226

    Article  CAS  PubMed  Google Scholar 

  • Klimesch W, Fellinger R, Freunberger R (2011) Alpha oscillations and early stages of visual encoding. Front Psychol 2:118. doi:10.3389/fpsyg.2011.00118

    Article  PubMed Central  PubMed  Google Scholar 

  • Koller G, Satzger W, Adam M et al (2003) Effects of scopolamine on matching to sample paradigm and related tests in human subjects. Neuropsychobiology 48:87–94

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Higuchi M, Marantz A, Kanwisher N (2000) The selectivity of the occipitotemporal M170 for faces. Neuroreport 11:337–341

    Article  CAS  PubMed  Google Scholar 

  • Luo W, Feng W, He W, Wang NY, Luo YJ (2010) Three stages of facial expression processing: ERP study with rapid serial visual presentation. Neuroimage 49:1857–1867

    Article  PubMed Central  PubMed  Google Scholar 

  • Makeig S, Bell AJ, Jung TP, Sejnowski TJ (1996) Independent component analysis of electroencephalographic data. Adv Neural Inf Process Syst 8:145–151

    Google Scholar 

  • Meador K, Loring DW, Hendrix N, Nichols ME, Oberzan R, Moore EE (1995) Synergistic anticholinergic and antiserotonergic effects in humans. J Clin Exp Neuropsychol 17:611–621

    Article  CAS  PubMed  Google Scholar 

  • Meador KJ, Loring DW, Adams RJ, Patel BR, Davis HC, Hammond EJ (1987) Central cholinergic systems and the P3 evoked potential. Int J Neurosci 33:199–205

    CAS  PubMed  Google Scholar 

  • Meador KJ, Loring DW, Davis HC et al (1989) Cholinergic and serotonergic effects on the P3 potential and recent memory. J Clin Exp Neuropsychol 11:252–260

    Article  CAS  PubMed  Google Scholar 

  • Miller BT, Deouell LY, Dam C, Knight RT, D'Esposito M (2008) Spatio-temporal dynamics of neural mechanisms underlying component operations in working memory. Brain Res 1206:61–75

    CAS  PubMed Central  PubMed  Google Scholar 

  • Montez T, Poil SS, Jones BF et al (2009) Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease. Proc Natl Acad Sci U S A 106:1614–1619

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Moran RJ, Campo P, Maestu F, Reilly RB, Dolan RJ, Strange BA (2010) Peak frequency in the theta and alpha bands correlates with human working memory capacity. Front Hum Neurosci 4:200. doi:10.3389/fnhum.2010.00200

    Article  PubMed Central  PubMed  Google Scholar 

  • Onton J, Delorme A, Makeig S (2005) Frontal midline EEG dynamics during working memory. Neuroimage 27:341–356

    Article  PubMed  Google Scholar 

  • Payne L, Kounios J (2009) Coherent oscillatory networks supporting short-term memory retention. Brain Res 1247:126–132

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pekkonen E, Hirvonen J, Jääskeläinen IP, Kaakkola S, Huttunen J (2001) Auditory sensory memory and the cholinergic system: implications for Alzheimer’s disease. Neuroimage 14:376–382

    Article  CAS  PubMed  Google Scholar 

  • Petrek J (2008) Pictorial cognitive task resolution and dynamics of event-related potentials. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 152:223–230

    Article  PubMed  Google Scholar 

  • Phillips PJ, Moon H, Rizvi SA, Rauss PJ (2000) The FERET evaluation methodology for face-recognition algorithms. IEEE Trans Pattern Anal Machine Intell 22:1090–1104

    Article  Google Scholar 

  • Plakke B, Ng CW, Poremba A (2008) Scopolamine impairs auditory delayed matching-to-sample performance in monkeys. Neurosci Lett 438:126–130

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Polikar R, Topalis A, Green D, Kounios J, Clark CM (2007) Comparative multiresolution wavelet analysis of ERP spectral bands using an ensemble of classifiers approach for early diagnosis of Alzheimer's disease. Comput Biol Med 37:542–558

    Article  PubMed Central  PubMed  Google Scholar 

  • Potter DD, Pickles CD, Roberts RC, Rugg MD (2000) Scopolamine impairs memory performance and reduces frontal but not parietal visual P3 amplitude. Biol Psychol 52:37–52

    Article  CAS  PubMed  Google Scholar 

  • Raghavachari S, Kahana M, Rizzuto DS et al (2001) Gating of human theta oscillations by a working memory task. Neurosciences 21:3175–3183

    CAS  Google Scholar 

  • Rebai M, Poiroux S, Bernard C, Lalonde R (2001) Event-related potentials for category-specific information during passive viewing of faces and objects. Int J Neurosci 106:209–226

    CAS  PubMed  Google Scholar 

  • Reches A, Kerem D, Gal N et al (2013a) A novel ERP pattern analysis method for revealing invariant reference brain network model. Funct Neurol Rehabil Ergon 3:295–317

    Google Scholar 

  • Reches A, Laufer I, Ziv K et al (2013b) Network dynamics predict improvement in working memory performance following donepezil administration in healthy young adults. NeuroImage. doi:10.1016/j.neuroimage.2013.11.020

    Google Scholar 

  • Robbins TW, Semple J, Kumar R et al (1997) Effects of scopolamine on delayed-matching-to-sample and paired associates tests of visual memory and learning in human subjects: comparison with diazepam and implications for dementia. Psychopharmacology 134:95–106

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez G, Arnaldi D, Picco A (2011) Brain functional network in Alzheimer's disease: diagnostic markers for diagnosis and monitoring. Int J Alzheimers Dis 2011:481903. doi:10.4061/2011/481903

    Article  PubMed Central  PubMed  Google Scholar 

  • Sams M, Hietanen JK, Hari R, Ilmoniemi RJ, Lounasmaa OV (1997) Face-specific responses from the human inferior occipito-temporal cortex. Neuroscience 77:49–55

    Article  CAS  PubMed  Google Scholar 

  • Sannita WG, Balestra V, DiBon G, Marotta V, Rosadini G (1993) Human flash-VEP and quantitative EEG are independently affected by acute scopolamine. Electroencephalogr Clin Neurophysiol 86:275–282

    Article  CAS  PubMed  Google Scholar 

  • Sauseng P, Klimesch W, Gruber W, Doppelmayr M, Stadler W, Schabus M (2002) The interplay between theta and alpha oscillations in the human electroencephalogram reflects the transfer of information between memory systems. Neurosci Lett 324:121–124

    Article  CAS  PubMed  Google Scholar 

  • Sauseng P, Klimesch W, Schabus M, Doppelmayr M (2005) Fronto-parietal EEG coherence in theta and upper alpha reflect central executive functions of working memory. Int J Psychophysiol 57:97–103

    Article  PubMed  Google Scholar 

  • Schack B, Klimesch W, Sauseng P (2005) Phase synchronization between theta and upper alpha oscillations in a working memory task. Int J Psychophysiol 57:105–114

    Article  CAS  PubMed  Google Scholar 

  • Schinkel S, Marwan N, Kurths J (2007) Order patterns recurrence plots in the analysis of ERP data. Cogn Neurodyn 1:317–325

    Article  PubMed Central  PubMed  Google Scholar 

  • Schon K, Atri A, Hasselmo ME, Tricarico MD, LoPresti ML, Stern CE (2005) Scopolamine reduces persistent activity related to long-term encoding in the parahippocampal gyrus during delayed matching in humans. J Neurosci 25:9112–9123

    Article  CAS  PubMed  Google Scholar 

  • Schweinberger SR, Huddy V, Burton AM (2004) N250r: a face-selective brain response to stimulus repetitions. Neuroreport 15:1501–1505

    Article  PubMed  Google Scholar 

  • Shahaf G, Reches A, Pinchuk N et al (2012) Introducing a novel approach of network oriented analysis of ERPs, demonstrated on adult attention deficit hyperactivity disorder. Clin Neurophysiol 123:1568–1580

    Article  CAS  PubMed  Google Scholar 

  • Shapiro AM, Benedict RH, Schretlen D, Brandt J (1999) Construct and concurrent validity of the Hopkins Verbal Learning Test-Revised. Clin Neuropsychol 13:348–358

    Article  CAS  PubMed  Google Scholar 

  • Skrandies W (2005) Brain mapping of visual evoked activity—topographical and functional components. Acta Neurol Taiwan 14:164–178

    PubMed  Google Scholar 

  • Snyder PJ, Bednar MM, Cromer JR, Maruff P (2005) Reversal of scopolamine-induced deficits with a single dose of donepezil, an acetylcholinesterase inhibitor. Alzheimers Dement 1:126–135

    Article  CAS  PubMed  Google Scholar 

  • Sperling R, Greve D, Dale A et al (2002) Functional MRI detection of pharmacologically induced memory impairment. Proc Natl Acad Sci U S A 99:455–460

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stam CJ, Reijneveld JC (2007) Graph theoretical analysis of complex networks in the brain. Nonlinear Biomed Phys 1:3

    Article  PubMed Central  PubMed  Google Scholar 

  • Sternberg S (1969) Memory-scanning: mental processes revealed by reaction-time experiments. Am Sci 57:421–457

    CAS  PubMed  Google Scholar 

  • Tanaka JW, Curran T, Porterfield AL, Collins D (2006) Activation of pre-existing and acquired face representations: the N250 ERP as an index of face familiarity. J Cogn Neurosci 18:1488–1497

    Article  PubMed  Google Scholar 

  • Terry AV Jr (2006) Muscarinic receptor antagonists in rats. In: Levin E.D. and Buccafusco JJ (eds) Animal Models of Cognitive Impairment, Chapter 2. CRC Press, Boca Raton, FL. Available from http://www.ncbi.nlm.nih.gov/books/NBK2525/

  • Terry AV Jr, Buccafusco JJ (2003) The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther 306:821–827

    Article  CAS  PubMed  Google Scholar 

  • Yener GG, Başar E (2010) Sensory evoked and event related oscillations in Alzheimer's disease: a short review. Cogn Neurodyn 4:263–274

    Article  PubMed Central  PubMed  Google Scholar 

  • Yener GG, Güntekin B, Tülay E, Başar E (2009) A comparative analysis of sensory visual evoked oscillations with visual cognitive event related oscillations in Alzheimer's disease. Neurosci Lett 462:193–197

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Prof. Leon Y. Deouell for his helpful comments and discussions. Amit Reches, Ilan Laufer, Revital Shani-Hershkovitch, Keren Ziv, Dani Kerem, Noga Gal, Yaki Stern, Guy Cukierman, and Amir B. Geva are employees of ElMindA Ltd., Herzliya, Israel. This study is part of ElMindA’s Brain Disorders Management and Imaging Technology program which is supported by the Office of the Chief Scientist (OCS), Israel.

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Authors and Affiliations

  1. ElMindA Ltd, Haminhara 16 St, Herzliya, Israel, 46586

    Amit Reches, Ilan Laufer, Revital Shani-Hershkovitch, Keren Ziv, Dani Kerem, Noga Gal, Yaki Stern, Guy Cukierman & Amir B. Geva

  2. INC Research, Toronto, Ontario, Canada

    Naama Levy-Cooperman

  3. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    Myroslava K. Romach & Edward M. Sellers

  4. DL Global Partners Inc, Toronto, Ontario, Canada

    Myroslava K. Romach & Edward M. Sellers

  5. Electrical and Computer Engineering, Ben Gurion University of the Negev, Beersheba, Israel

    Amir B. Geva

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  1. Amit Reches
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  2. Naama Levy-Cooperman
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  3. Ilan Laufer
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Reches, A., Levy-Cooperman, N., Laufer, I. et al. Brain Network Activation (BNA) Reveals Scopolamine-Induced Impairment of Visual Working Memory. J Mol Neurosci 54, 59–70 (2014). https://doi.org/10.1007/s12031-014-0250-6

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