Pharmacopsychiatry 2007; 40: S54-S61
DOI: 10.1055/s-2007-990302
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Synchronous Oscillatory Activity and Working Memory in Schizophrenia

C. Haenschel 1 , 2 , P. J. Uhlhaas 1 , 2 , W. Singer 1 , 3
  • 1MPI for Brain Research, Frankfurt am Main
  • 2Department of Psychiatry, Johann Wolfgang Goethe Universität, Frankfurt am Main
  • 3Frankfurt Institute for Advanced Studies, Johann Wolfgang Goethe Universität, Frankfurt am Main
Further Information

Publication History

Publication Date:
17 December 2007 (online)

Abstract

Impairments in working memory (WM) are a core cognitive deficit in schizophrenia. Recent models of cognitive deficits have emphasized the potential role of neural synchrony as a pathophysiological mechanism underlying impaired WM performance in the disorder, suggesting that impaired maintenance as well as encoding of information may be related to deficits in sustaining precisely timed synchronized activity patterns. In the present paper, we will first summarise the role of synchronous oscillatory activity for working memory in normal brain functioning. Then we will examine the existing data on abnormal neural synchrony in schizophrenia, suggesting that neural synchrony may be critically involved in WM deficits. Neuropharmacological hypotheses will be discussed that have attempted to relate dysfunctional neural synchrony in schizophrenia to abnormalities in dopaminergic and GABAergic neurotransmission. Finally, computational neuropsychiatry may offer a framework for understanding neural synchrony within a complex dynamic nonlinear system and may provide new vistas for modelling WM deficits in schizophrenia.

References

  • 1 Adler CM, Goldberg TE, Malhotra AK, Pickar D, Breier A. Effects of ketamine on thought disorder, working memory, and semantic memory in healthy volunteers.  Biological psychiatry. 1998;  43 811-816
  • 2 Heiden U an der. Schizophrenia as a dynamical disease.  Pharmacopsychiatry. 2006;  39 ((Suppl 1)) S36-42
  • 3 Andrew C, Pfurtscheller G. Event-related coherence as a tool for studying dynamic interaction of brain regions.  Electroencephalography and clinical neurophysiology. 1996;  98 144-148
  • 4 Awh E, Barton B, Vogel EK. Visual working memory represents a fixed number of items regardless of complexity.  Psychol Sci. 2007;  18 622-628
  • 5 Barch DM, Carter CS, Braver TS, Sabb FW, MacDonald 3rd A, Noll DC, Cohen JD. Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia.  Archives of general psychiatry. 2001;  58 280-288
  • 6 Basar-Eroglu C, Brand A, Hildebrandt H, Karolina Kedzior K, Mathes B, Schmiedt C. Working memory related gamma oscillations in schizophrenia patients.  Int J Psychophysiol. 2007;  64 39-45
  • 7 Bender W, Albus M, Moller HJ, Tretter F. Towards systemic theories in biological psychiatry.  Pharmacopsychiatry. 2006;  39 ((Suppl 1)) S4-S9
  • 8 Brozoski TJ, Brown RM, Rosvold HE, Goldman PS. Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey.  Science (New York, NY). 1979;  205 929-932
  • 9 Callicott JH, Egan MF, Mattay VS, Bertolino A, Bone AD, Verchinksi B, Weinberger DR. Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia.  The American journal of psychiatry. 2003;  160 709-719
  • 10 Callicott JH, Bertolino A, Mattay VS, Langheim FJ, Duyn J, Coppola R, Goldberg TE, Weinberger DR. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited.  Cereb Cortex. 2000;  10 1078-1092
  • 11 Canolty RT, Edwards E, Dalal SS, Soltani M, Nagarajan SS, Kirsch HE, Berger MS, Barbaro NM, Knight RT. High gamma power is phase-locked to theta oscillations in human neocortex.  Science (New York, NY. 2006;  313 1626-1628
  • 12 Cho RY, Konecky RO, Carter CS. Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia.  Proceedings of the National Academy of Sciences of the United States of America. 2006;  103 19878-19883
  • 13 Deco G. A dynamical model of event-related FMRI signals in prefrontal cortex: predictions for schizophrenia.  Pharmacopsychiatry. 2006;  39 ((Suppl 1)) S65-S67
  • 14 Deiber MP, Missonnier P, Bertrand O, Gold G, Fazio-Costa L, Ibanez V, Giannakopoulos P. Distinction between perceptual and attentional processing in working memory tasks: a study of phase-locked and induced oscillatory brain dynamics.  Journal of cognitive neuroscience. 2007;  19 158-172
  • 15 Demiralp T, Herrmann CS, Erdal ME, Ergenoglu T, Keskin YH, Ergen M, Beydagi H. DRD4 and DAT1 polymorphisms modulate human gamma band responses.  Cereb Cortex. 2007;  17 1007-1019
  • 16 Demiralp T, Bayraktaroglu Z, Lenz D, Junge S, Busch NA, Maess B, Ergen M, Herrmann CS. Gamma amplitudes are coupled to theta phase in human EEG during visual perception.  Int J Psychophysiol. 2007;  64 24-30
  • 17 Doheny HC, Faulkner HJ, Gruzelier JH, Baldeweg T, Whittington MA. Pathway-specific habituation of induced gamma oscillations in the hippocampal slice.  Neuroreport. 2000;  11 2629-2633
  • 18 Engel AK, Konig P, Kreiter AK, Singer W. Interhemispheric synchronization of oscillatory neuronal responses in cat visual cortex.  Science (New York, NY). 1991;  252 1177-1179
  • 19 Fries P. A mechanism for cognitive dynamics: neuronal communication through neuronal coherence.  Trends in cognitive sciences. 2005;  9 474-480
  • 20 Fries P, Nikolic D, Singer W. The gamma cycle.  Trends in neurosciences. 2007;  30 309-316
  • 21 Fries P, Reynolds JH, Rorie AE, Desimone R. Modulation of oscillatory neuronal synchronization by selective visual attention.  Science (New York, NY). 2001;  291 1560-1563
  • 22 Gallinat J, Winterer G, Herrmann CS, Senkowski D. Reduced oscillatory gamma-band responses in unmedicated schizophrenic patients indicate impaired frontal network processing.  Clin Neurophysiol. 2004;  115 1863-1874
  • 23 Gevins A, Smith ME, MacEvoy L, Yu D. High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice.  Cereb Cortex. 1997;  7 374-385
  • 24 Goldman-Rakic P. Working memory dysfunction in schizophrenia. In: Salloway SP MP, Duffy JD ed, The frontal lobes and neuropsychiatric illness. Washington DC: American Psychiatric Publishing, Inc. 2001: 71-82
  • 25 Goldman-Rakic PS, Muly 3rd EC, Williams GV. D(1) receptors in prefrontal cells and circuits.  Brain Res Brain Res Rev. 2000;  31 295-301
  • 26 Gray CM, Singer W. Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex.  Proceedings of the National Academy of Sciences of the United States of America. 1989;  86 1698-1702
  • 27 Gray CM, Konig P, Engel AK, Singer W. Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties.  Nature. 1989;  338 334-337
  • 28 Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”?.  Schizophrenia bulletin. 2000;  26 119-136
  • 29 Green MF, Mintz J, Salveson D, Nuechterlein KH, Breitmeyer B, Light GA, Braff DL. Visual masking as a probe for abnormal gamma range activity in schizophrenia.  Biological psychiatry. 2003;  53 1113-1119
  • 30 Haenschel C, Bittner RA, Haertling F, Rotarska-Jagiela A, Maurer K, Singer W, Linden DEJ. Contribution of impaired early-stage visual processing to working memory dysfunction in adolescents with schizophrenia - a study with event-related potentials and functional magnetic resonance imaging.  , Archives of general psychiatry in press;i
  • 31 Haig AR, Gordon E, De Pascalis V, Meares RA, Bahramali H, Harris A. Gamma activity in schizophrenia: evidence of impaired network binding?.  Clin Neurophysiol. 2000;  111 1461-1468
  • 32 Herrmann CS, Munk MH, Engel AK. Cognitive functions of gamma-band activity: memory match and utilization.  Trends in cognitive sciences. 2004;  8 347-355
  • 33 Honey RA, Honey GD, O'Loughlin C, Sharar SR, Kumaran D, Bullmore ET, Menon DK, Donovan T, Lupson VC, Bisbrown-Chippendale R, Fletcher PC. Acute ketamine administration alters the brain responses to executive demands in a verbal working memory task: an FMRI study.  Neuropsychopharmacology. 2004;  29 1203-1214
  • 34 Howard MW, Rizzuto DS, Caplan JB, Madsen JR, Lisman J, Aschenbrenner-Scheibe R, Schulze-Bonhage A, Kahana MJ. Gamma oscillations correlate with working memory load in humans.  Cereb Cortex. 2003;  13 1369-1374
  • 35 Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia.  The American journal of psychiatry. 1991;  148 1301-1308
  • 36 Jensen O, Tesche CD. Frontal theta activity in humans increases with memory load in a working memory task.  The European journal of neuroscience. 2002;  15 1395-1399
  • 37 Jensen O, Kaiser J, Lachaux JP. Human gamma-frequency oscillations associated with attention and memory.  Trends in neurosciences. 2007;  30 317-324
  • 38 Jokisch D, Jensen O. Modulation of gamma and alpha activity during a working memory task engaging the dorsal or ventral stream.  J Neurosci. 2007;  27 3244-3251
  • 39 Kaiser J, Ripper B, Birbaumer N, Lutzenberger W. Dynamics of gamma-band activity in human magnetoencephalogram during auditory pattern working memory.  NeuroImage. 2003;  20 816-827
  • 40 Klimesch W, Sauseng P, Hanslmayr S. EEG alpha oscillations: the inhibition-timing hypothesis.  Brain research reviews. 2007;  53 63-88
  • 41 Kopell N, Ermentrout GB, Whittington MA, Traub RD. Gamma rhythms and beta rhythms have different synchronization properties.  Proceedings of the National Academy of Sciences of the United States of America. 2000;  97 1867-1872
  • 42 Krishnan GP, Vohs JL, Hetrick WP, Carroll CA, Shekhar A, Bockbrader MA, O'Donnell BF. Steady state visual evoked potential abnormalities in schizophrenia.  Clin Neurophysiol. 2005;  116 614-624
  • 43 Kwon JS, O'Donnell BF, Wallenstein GV, Greene RW, Hirayasu Y, Nestor PG, Hasselmo ME, Potts GF, Shenton ME, MacCarley RW. Gamma frequency-range abnormalities to auditory stimulation in schizophrenia.  Archives of general psychiatry. 1999;  56 1001-1005
  • 44 Lachaux JP, Rodriguez E, Martinerie J, Varela FJ. Measuring phase synchrony in brain signals.  Human brain mapping. 1999;  8 194-208
  • 45 Lee J, Park S. Working memory impairments in schizophrenia: a meta-analysis.  Journal of abnormal psychology. 2005;  114 599-611
  • 46 Lewis DA, Volk DW, Hashimoto T. Selective alterations in prefrontal cortical GABA neurotransmission in schizophrenia: a novel target for the treatment of working memory dysfunction.  Psychopharmacology. 2004;  174 143-150
  • 47 Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia.  Nature reviews. 2005;  6 312-324
  • 48 Light GA, Hsu JL, Hsieh MH, Meyer-Gomes K, Sprock J, Swerdlow NR, Braff DL. Gamma band oscillations reveal neural network cortical coherence dysfunction in schizophrenia patients.  Biological psychiatry. 2006;  60 1231-1240
  • 49 Linden DE, Bittner RA, Muckli L, Waltz JA, Kriegeskorte N, Goebel R, Singer W, Munk MH. Cortical capacity constraints for visual working memory: dissociation of fMRI load effects in a fronto-parietal network.  NeuroImage. 2003;  20 1518-1530
  • 50 Lisman JE, Idiart MA. Storage of 7±2 short-term memories in oscillatory subcycles.  Science (New York, NY). 1995;  267 1512-1515
  • 51 Lutzenberger W, Ripper B, Busse L, Birbaumer N, Kaiser J. Dynamics of gamma-band activity during an audiospatial working memory task in humans.  J Neurosci. 2002;  22 5630-5638
  • 52 Mainy N, Kahane P, Minotti L, Hoffmann D, Bertrand O, Lachaux JP. Neural correlates of consolidation in working memory.  Human brain mapping. 2007;  28 183-193
  • 53 Manoach DS. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings.  Schizophrenia research. 2003;  60 285-298
  • 54 Menzies L, Ooi C, Kamath S, Suckling J, MacKenna P, Fletcher P, Bullmore E, Stephenson C. Effects of gamma-aminobutyric acid-modulating drugs on working memory and brain function in patients with schizophrenia.  Archives of general psychiatry. 2007;  64 156-167
  • 55 Meyer-Lindenberg A, Poline JB, Kohn PD, Holt JL, Egan MF, Weinberger DR, Berman KF. Evidence for abnormal cortical functional connectivity during working memory in schizophrenia.  The American journal of psychiatry. 2001;  158 1809-1817
  • 56 Micheloyannis S, Pachou E, Stam CJ, Breakspear M, Bitsios P, Vourkas M, Erimaki S, Zervakis M. Small-world networks and disturbed functional connectivity in schizophrenia.  Schizophrenia research. 2006;  87 60-66
  • 57 Miller EK, Erickson CA, Desimone R. Neural mechanisms of visual working memory in prefrontal cortex of the macaque.  J Neurosci. 1996;  16 5154-5167
  • 58 Morgan CJ, Curran HV. Acute and chronic effects of ketamine upon human memory: a review.  Psychopharmacology. 2006;  188 408-424
  • 59 Morgan CJ, Mofeez A, Brandner B, Bromley L, Curran HV. Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers.  Neuropsychopharmacology. 2004;  29 208-218
  • 60 Niessing J, Ebisch B, Schmidt KE, Niessing M, Singer W, Galuske RA. Hemodynamic signals correlate tightly with synchronized gamma oscillations.  Science (New York, NY). 2005;  309 948-951
  • 61 Peled A, Geva AB, Kremen WS, Blankfeld HM, Esfandiarfard R, Nordahl TE. Functional connectivity and working memory in schizophrenia: an EEG study.  The International journal of neuroscience. 2001;  106 47-61
  • 62 Rodriguez E, George N, Lachaux JP, Martinerie J, Renault B, Varela FJ. Perception's shadow: long-distance synchronization of human brain activity.  Nature. 1999;  397 430-433
  • 63 Roelfsema PR, Engel AK, Konig P, Singer W. Visuomotor integration is associated with zero time-lag synchronization among cortical areas.  Nature. 1997;  385 157-161
  • 64 Sarnthein J, Petsche H, Rappelsberger P, Shaw GL, Stein A von. Synchronization between prefrontal and posterior association cortex during human working memory.  Proceedings of the National Academy of Sciences of the United States of America. 1998;  95 7092-7096
  • 65 Sawaguchi T, Goldman-Rakic PS. D1 dopamine receptors in prefrontal cortex: involvement in working memory.  Science (New York, NY). 1991;  251 947-950
  • 66 Sawaguchi T, Goldman-Rakic PS. The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task.  Journal of neurophysiology. 1994;  71 515-528
  • 67 Schack B, Vath N, Petsche H, Geissler HG, Moller E. Phase-coupling of theta-gamma EEG rhythms during short-term memory processing.  Int J Psychophysiol. 2002;  44 143-163
  • 68 Schlosser R, Gesierich T, Kaufmann B, Vucurevic G, Hunsche S, Gawehn J, Stoeter P. Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling.  NeuroImage. 2003;  19 751-763
  • 69 Schmiedt C, Brand A, Hildebrandt H, Basar-Eroglu C. Event-related theta oscillations during working memory tasks in patients with schizophrenia and healthy controls.  Brain research. 2005;  25 936-947
  • 70 Schnitzler A, Gross J. Normal and pathological oscillatory communication in the brain.  Nature reviews. 2005;  6 285-296
  • 71 Sederberg PB, Kahana MJ, Howard MW, Donner EJ, Madsen JR. Theta and gamma oscillations during encoding predict subsequent recall.  J Neurosci. 2003;  23 10809-10814
  • 72 Silver H, Feldman P, Bilker W, Gur RC. Working memory deficit as a core neuropsychological dysfunction in schizophrenia.  The American journal of psychiatry. 2003;  160 1809-1816
  • 73 Singer W. Neuronal synchrony: a versatile code for the definition of relations?.  Neuron. 1999;  24 49-65 , 111-125
  • 74 Singer W, Gray CM. Visual feature integration and the temporal correlation hypothesis.  Annual review of neuroscience. 1995;  18 555-586
  • 75 Slewa-Younan S, Gordon E, Harris AW, Haig AR, Brown KJ, Flor-Henry P, Williams LM. Sex differences in functional connectivity in first-episode and chronic schizophrenia patients.  The American journal of psychiatry. 2004;  161 1595-1602
  • 76 Spencer KM, Nestor PG, Niznikiewicz MA, Salisbury DF, Shenton ME, MacCarley RW. Abnormal neural synchrony in schizophrenia.  J Neurosci. 2003;  23 7407-7411
  • 77 Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, Shenton ME, MacCarley RW. Neural synchrony indexes disordered perception and cognition in schizophrenia.  Proceedings of the National Academy of Sciences of the United States of America. 2004;  101 17288-17293
  • 78 Symond MP, Harris AW, Gordon E, Williams LM. “Gamma synchrony” in first-episode schizophrenia: a disorder of temporal connectivity?.  The American journal of psychiatry. 2005;  162 459-465
  • 79 Tallon-Baudry C, Bertrand O. Oscillatory gamma activity in humans and its role in object representation.  Trends in cognitive sciences. 1999;  3 151-162
  • 80 Tallon-Baudry C, Bertrand O, Peronnet F, Pernier J. Induced gamma-band activity during the delay of a visual short-term memory task in humans.  J Neurosci. 1998;  18 4244-4254
  • 81 Tallon-Baudry C, Mandon S, Freiwald WA, Kreiter AK. Oscillatory synchrony in the monkey temporal lobe correlates with performance in a visual short-term memory task.  Cereb Cortex. 2004;  14 713-720
  • 82 Tiitinen H, Sinkkonen J, Reinikainen K, Alho K, Lavikainen J, Naatanen R. Selective attention enhances the auditory 40-Hz transient response in humans.  Nature. 1993;  364 59-60
  • 83 Towers SK, Gloveli T, Traub RD, Driver JE, Engel D, Fradley R, Rosahl TW, Maubach K, Buhl EH, Whittington MA. Alpha 5 subunit-containing GABAA receptors affect the dynamic range of mouse hippocampal kainate-induced gamma frequency oscillations in vitro.  The Journal of physiology. 2004;  559 721-728
  • 84 Tretter F, Scherer J. Schizophrenia, neurobiology and the methodology of systemic modeling.  Pharmacopsychiatry. 2006;  39 ((Suppl 1)) S26-S35
  • 85 Uhlhaas PJ, Singer W. Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology.  Neuron. 2006;  52 155-168
  • 86 Uhlhaas PJ, Linden DE, Singer W, Haenschel C, Lindner M, Maurer K, Rodriguez E. Dysfunctional long-range coordination of neural activity during Gestalt perception in schizophrenia.  J Neurosci. 2006;  26 8168-8175
  • 87 Stelt O van der, Belger A, Lieberman JA. Macroscopic fast neuronal oscillations and synchrony in schizophrenia.  Proceedings of the National Academy of Sciences of the United States of America. 2004;  101 17567-17568
  • 88 Varela F, Lachaux JP, Rodriguez E, Martinerie J. The brainweb: phase synchronization and large-scale integration.  Nature reviews. 2001;  2 229-239
  • 89 Stein A von, Sarnthein J. Different frequencies for different scales of cortical integration: from local gamma to long range alpha/theta synchronization.  Int J Psychophysiol. 2000;  38 301-313
  • 90 Wang XJ. Toward a prefrontal microcircuit model for cognitive deficits in schizophrenia.  Pharmacopsychiatry. 2006;  39 ((Suppl 1)) S80-S87
  • 91 Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia.  Archives of general psychiatry. 1987;  44 660-669
  • 92 Whittington MA, Traub RD, Jefferys JG. Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation.  Nature. 1995;  373 612-615
  • 93 Whittington MA, Faulkner HJ, Doheny HC, Traub RD. Neuronal fast oscillations as a target site for psychoactive drugs.  Pharmacology & therapeutics. 2000;  86 171-190
  • 94 Winterer G. Cortical microcircuits in schizophrenia-the dopamine hypothesis revisited.  Pharmacopsychiatry. 2006;  39 ((Suppl 1)) S68-S71
  • 95 Winterer G, Weinberger DR. Genes, dopamine and cortical signal-to-noise ratio in schizophrenia.  Trends in neurosciences. 2004;  27 683-690
  • 96 Winterer G, Egan MF, Kolachana BS, Goldberg TE, Coppola R, Weinberger DR. Prefrontal electrophysiologic “noise” and catechol-O-methyltransferase genotype in schizophrenia.  Biological psychiatry. 2006;  60 578-584
  • 97 Winterer G, Coppola R, Goldberg TE, Egan MF, Jones DW, Sanchez CE, Weinberger DR. Prefrontal broadband noise, working memory, and genetic risk for schizophrenia.  The American journal of psychiatry. 2004;  161 490-500
  • 98 Wynn JK, Light GA, Breitmeyer B, Nuechterlein KH, Green MF. Event-related gamma activity in schizophrenia patients during a visual backward-masking task.  The American journal of psychiatry. 2005;  162 2330-2336
  • 99 Yoon JH, Curtis CE, D'Esposito M. Differential effects of distraction during working memory on delay-period activity in the prefrontal cortex and the visual association cortex.  NeuroImage. 2006;  29 1117-1126
  • 100 Yuval-Greenberg S, Deouell LY. What you see is not (always) what you hear: induced gamma band responses reflect cross-modal interactions in familiar object recognition.  J Neurosci. 2007;  27 1090-1096

Correspondence

Dr. C. Haenschel

MPI for Brain Research

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60528 Frankfurt am Main

Germany

Phone: 069/6301 71 81

Fax: 069/6301 38 33

Email: haenschel@mpih-frankfurt.mpg.de

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