Abnormal neural oscillations and synchrony in schizophrenia

Key Points

  • Schizophrenia is a severe psychotic disorder with prominent cognitive dysfunctions. The pathophysiological mechanisms that give rise to the signs and symptoms of the disorder are still unclear, however.

  • Neural oscillations and their synchronization may be core pathophysiological mechanisms in schizophrenia, as neural oscillations are fundamental for coordinated neural activity during normal brain functioning.

  • Recent evidence shows that schizophrenia is associated with deficits in neural oscillations, especially in the beta- and gamma-band frequencies. These impairments closely correlate with cognitive dysfunctions and the core symptoms of the disorder.

  • Dysfunctions in neural synchrony could result from deficits in GABA (γ-aminobutyric acid)-ergic neurotransmission and the reduced integrity of cortico-cortical connections, which are crucially involved in the generation of synchronized, oscillatory activity.

  • Developmentally, neural oscillations are involved in the maturation of cortical networks during early and late critical periods that have been implicated in the pathophysiology of schizophrenia.

Abstract

Converging evidence from electrophysiological, physiological and anatomical studies suggests that abnormalities in the synchronized oscillatory activity of neurons may have a central role in the pathophysiology of schizophrenia. Neural oscillations are a fundamental mechanism for the establishment of precise temporal relationships between neuronal responses that are in turn relevant for memory, perception and consciousness. In patients with schizophrenia, the synchronization of beta- and gamma-band activity is abnormal, suggesting a crucial role for dysfunctional oscillations in the generation of the cognitive deficits and other symptoms of the disorder. Dysfunctional oscillations may arise owing to anomalies in the brain's rhythm-generating networks of GABA (γ-aminobutyric acid) interneurons and in cortico-cortical connections.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Neural oscillations and synchrony in cortical networks.
Figure 2: Neural oscillations and synchrony in schizophrenia.
Figure 3: Mechanisms underlying the generation of gamma oscillations and synchrony.
Figure 4: Neurobiological correlates of deficits in neural oscillations and synchrony in schizophrenia.
Figure 5: Emergence of high-frequency oscillations and synchrony during the transition from adolescence to adulthood.

References

  1. 1

    Phillips, W. A. & Silverstein, S. M. Convergence of biological and psychological perspectives on cognitive coordination in schizophrenia. Behav. Brain Sci. 26, 65–82 (2003).

    PubMed  Google Scholar 

  2. 2

    Friston, K. J. Schizophrenia and the disconnection hypothesis. Acta Psychiatr. Scand. Suppl. 395, 68–79 (1999).

    CAS  PubMed  Google Scholar 

  3. 3

    Buzsaki, G. & Draguhn, A. Neuronal oscillations in cortical networks. Science 304, 1926–1929 (2004).

    CAS  PubMed  Google Scholar 

  4. 4

    Fries, P. Neuronal gamma-band synchronization as a fundamental process in cortical computation. Annu. Rev. Neurosci. 32, 209–224 (2009).

    CAS  PubMed  Google Scholar 

  5. 5

    Buzsaki, G. Rhythms of the Brain (Oxford Univ. Press, New York, 2006). A brilliant and comprehensive overview of the role of neural oscillations in cortical processing.

    Google Scholar 

  6. 6

    Singer, W. Neuronal synchrony: a versatile code for the definition of relations? Neuron 24, 49–65, 111–125 (1999).

    CAS  PubMed  Google Scholar 

  7. 7

    Gray, C. M., Konig, P., Engel, A. K. & Singer, W. Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties. Nature 338, 334–337 (1989). The first study to show a close correspondence between synchronized gamma-band oscillations and Gestalt properties of visual stimuli in the primary visual cortex of anaesthetized cats.

    CAS  PubMed  Google Scholar 

  8. 8

    Womelsdorf, T. et al. Modulation of neuronal interactions through neuronal synchronization. Science 316, 1609–1612 (2007).

    CAS  PubMed  Google Scholar 

  9. 9

    von Stein, A., Chiang, C. & Konig, P. Top-down processing mediated by interareal synchronization. Proc. Natl Acad. Sci. USA 97, 14748–14753 (2000).

    CAS  PubMed  Google Scholar 

  10. 10

    Uhlhaas, P. J. et al. Neural synchrony in cortical networks: history, concept and current status. Front. Integr. Neurosci. 3, 17 (2009).

    PubMed  PubMed Central  Google Scholar 

  11. 11

    Park, S. & Holzman, P. S. Schizophrenics show spatial working memory deficits. Arch. Gen. Psychiatry 49, 975–982 (1992).

    CAS  PubMed  Google Scholar 

  12. 12

    Frith, C. D. Neuropsychology of Schizophrenia (Taylor and Francis, Hove, 1992).

    Google Scholar 

  13. 13

    Uhlhaas, P. J. & Silverstein, S. M. Perceptual organization in schizophrenia spectrum disorders: empirical research and theoretical implications. Psychol. Bull. 131, 618–632 (2005).

    PubMed  Google Scholar 

  14. 14

    Green, M. F. What are the functional consequences of neurocognitive deficits in schizophrenia? Am. J. Psychiatry 153, 321–330 (1996).

    CAS  PubMed  Google Scholar 

  15. 15

    Singer, W. & Gray, C. M. Visual feature integration and the temporal correlation hypothesis. Annu. Rev. Neurosci. 18, 555–586 (1995).

    CAS  PubMed  Google Scholar 

  16. 16

    Wespatat, V., Tennigkeit, F. & Singer, W. Phase sensitivity of synaptic modifications in oscillating cells of rat visual cortex. J. Neurosci. 24, 9067–9075 (2004).

    CAS  PubMed  Google Scholar 

  17. 17

    Pavlides, C., Greenstein, Y. J., Grudman, M. & Winson, J. Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of theta-rhythm. Brain Res. 439, 383–387 (1988).

    CAS  PubMed  Google Scholar 

  18. 18

    Huerta, P. T. & Lisman, J. E. Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. Nature 364, 723–725 (1993).

    CAS  PubMed  Google Scholar 

  19. 19

    Daskalakis, Z. J., Christensen, B. K., Fitzgerald, P. B. & Chen, R. Dysfunctional neural plasticity in patients with schizophrenia. Arch. Gen. Psychiatry 65, 378–385 (2008).

    PubMed  Google Scholar 

  20. 20

    Shelley, A. M. et al. Mismatch negativity: an index of a preattentive processing deficit in schizophrenia. Biol. Psychiatry 30, 1059–1062 (1991).

    CAS  PubMed  Google Scholar 

  21. 21

    Stephan, K. E., Friston, K. J. & Frith, C. D. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr. Bull. 35, 509–527 (2009).

    PubMed  PubMed Central  Google Scholar 

  22. 22

    Light, G. A. et al. Gamma band oscillations reveal neural network cortical coherence dysfunction in schizophrenia patients. Biol. Psychiatry 60, 1231–1240 (2006).

    PubMed  Google Scholar 

  23. 23

    Vierling-Claassen, D., Siekmeier, P., Stufflebeam, S. & Kopell, N. Modeling GABA alterations in schizophrenia: a link between impaired inhibition and altered gamma and beta range auditory entrainment. J. Neurophysiol. 99, 2656–2671 (2008).

    PubMed  PubMed Central  Google Scholar 

  24. 24

    Kwon, J. S. et al. Gamma frequency-range abnormalities to auditory stimulation in schizophrenia. Arch. Gen. Psychiatry 56, 1001–1005 (1999). The first demonstration of a deficit in the entrainment of gamma-band oscillations to click trains presented at 40 Hz in the auditory cortex in patients with schizophrenia.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Krishnan, G. P. et al. Steady state and induced auditory gamma deficits in schizophrenia. Neuroimage 47, 1711–1719 (2009).

    CAS  PubMed  Google Scholar 

  26. 26

    Brenner, C. A., Sporns, O., Lysaker, P. H. & O'Donnell, B. F. EEG synchronization to modulated auditory tones in schizophrenia, schizoaffective disorder, and schizotypal personality disorder. Am. J. Psychiatry 160, 2238–2240 (2003).

    PubMed  Google Scholar 

  27. 27

    Spencer, K. M., Salisbury, D. F., Shenton, M. E. & McCarley, R. W. Gamma-band auditory steady-state responses are impaired in first episode psychosis. Biol. Psychiatry 64, 369–375 (2008).

    PubMed  PubMed Central  Google Scholar 

  28. 28

    Spencer, K. M., Niznikiewicz, M. A., Nestor, P. G., Shenton, M. E. & McCarley, R. W. Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia. BMC Neurosci. 10, 85 (2009).

    PubMed  PubMed Central  Google Scholar 

  29. 29

    Wilson, T. W. et al. Cortical gamma generators suggest abnormal auditory circuitry in early-onset psychosis. Cereb. Cortex 18, 371–378 (2008).

    PubMed  Google Scholar 

  30. 30

    Hong, L. E. et al. Evoked gamma band synchronization and the liability for schizophrenia. Schizophr. Res. 70, 293–302 (2004).

    PubMed  Google Scholar 

  31. 31

    Krishnan, G. P. et al. Steady state visual evoked potential abnormalities in schizophrenia. Clin. Neurophysiol. 116, 614–624 (2005).

    PubMed  Google Scholar 

  32. 32

    Galambos, R., Makeig, S. & Talmachoff, P. J. A 40-Hz auditory potential recorded from the human scalp. Proc. Natl Acad. Sci. USA 78, 2643–2647 (1981).

    CAS  PubMed  Google Scholar 

  33. 33

    Ross, B., Herdman, A. T. & Pantev, C. Stimulus induced desynchronization of human auditory 40-Hz steady-state responses. J. Neurophysiol. 94, 4082–4093 (2005).

    CAS  PubMed  Google Scholar 

  34. 34

    Ross, B., Picton, T. W. & Pantev, C. Temporal integration in the human auditory cortex as represented by the development of the steady-state magnetic field. Hear. Res. 165, 68–84 (2002).

    PubMed  Google Scholar 

  35. 35

    Skosnik, P. D., Krishnan, G. P. & O'Donnell, B. F. The effect of selective attention on the gamma-band auditory steady-state response. Neurosci. Lett. 420, 223–228 (2007).

    CAS  PubMed  Google Scholar 

  36. 36

    Johannesen, J. K., Bodkins, M., O'Donnell, B. F., Shekhar, A. & Hetrick, W. P. Perceptual anomalies in schizophrenia co-occur with selective impairments in the gamma frequency component of midlatency auditory ERPs. J. Abnorm. Psychol. 117, 106–118 (2008).

    PubMed  Google Scholar 

  37. 37

    Spencer, K. M. et al. Neural synchrony indexes disordered perception and cognition in schizophrenia. Proc. Natl. Acad. Sci. USA 101, 17288–17293 (2004).

    CAS  PubMed  Google Scholar 

  38. 38

    Hirano, S. et al. Abnormal neural oscillatory activity to speech sounds in schizophrenia: a magnetoencephalography study. J. Neurosci. 28, 4897–4903 (2008).

    CAS  PubMed  Google Scholar 

  39. 39

    Roach, B. J. & Mathalon, D. H. Event-related EEG time-frequency analysis: an overview of measures and an analysis of early gamma band phase locking in schizophrenia. Schizophr. Bull. 34, 907–926 (2008).

    PubMed  PubMed Central  Google Scholar 

  40. 40

    Spencer, K. M., Niznikiewicz, M. A., Shenton, M. E. & McCarley, R. W. Sensory-evoked gamma oscillations in chronic schizophrenia. Biol. Psychiatry 63, 744–747 (2008).

    PubMed  PubMed Central  Google Scholar 

  41. 41

    Gallinat, J., Winterer, G., Herrmann, C. S. & Senkowski, D. Reduced oscillatory gamma-band responses in unmedicated schizophrenic patients indicate impaired frontal network processing. Clin. Neurophysiol. 115, 1863–1874 (2004).

    PubMed  Google Scholar 

  42. 42

    Ferrarelli, F. et al. Reduced evoked gamma oscillations in the frontal cortex in schizophrenia patients: a TMS/EEG study. Am. J. Psychiatry 165, 996–1005 (2008).

    PubMed  Google Scholar 

  43. 43

    Tillmann, C. et al. Source localization of high-frequency oscillations reveals widespread reductions in gamma-band activity during perceptual organisation in chronic and first-episode schizophrenia. Soc. Neurosci. Abstr. 54.2 (2008).

  44. 44

    Haenschel, C. et al. Cortical oscillatory activity is critical for working memory as revealed by deficits in early onset schizophrenia J. Neurosci. 29, 9481–9489 (2009).

    CAS  PubMed  Google Scholar 

  45. 45

    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 Res. Cogn. Brain Res. 25, 936–947 (2005).

    CAS  PubMed  Google Scholar 

  46. 46

    Cho, R. Y., Konecky, R. O. & Carter, C. S. Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia. Proc. Natl Acad. Sci. USA 103, 19878–19883 (2006).

    CAS  PubMed  Google Scholar 

  47. 47

    Winterer, G. et al. Schizophrenia: reduced signal-to-noise ratio and impaired phase-locking during information processing. Clin. Neurophysiol. 111, 837–849 (2000).

    CAS  PubMed  Google Scholar 

  48. 48

    Varela, F., Lachaux, J. P., Rodriguez, E. & Martinerie, J. The brainweb: phase synchronization and large-scale integration. Nature Rev. Neurosci. 2, 229–239 (2001).

    CAS  Google Scholar 

  49. 49

    Uhlhaas, P. J. et al. Dysfunctional long-range coordination of neural activity during Gestalt perception in schizophrenia. J. Neurosci. 26, 8168–8175 (2006).

    CAS  PubMed  Google Scholar 

  50. 50

    Spencer, K. M. et al. Abnormal neural synchrony in schizophrenia. J. Neurosci. 23, 7407–7411 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Symond, M. P., Harris, A. W., Gordon, E. & Williams, L. M. “Gamma synchrony” in first-episode schizophrenia: a disorder of temporal connectivity? Am. J. Psychiatry 162, 459–465 (2005).

    PubMed  Google Scholar 

  52. 52

    Boutros, N. N. et al. The status of spectral EEG abnormality as a diagnostic test for schizophrenia. Schizophr. Res. 99, 225–237 (2008).

    PubMed  Google Scholar 

  53. 53

    Rutter, L. et al. Magnetoencephalographic gamma power reduction in patients with schizophrenia during resting condition. Hum. Brain Mapp. 30, 3254–3264 (2009).

    PubMed  PubMed Central  Google Scholar 

  54. 54

    Koenig, T. et al. Decreased functional connectivity of EEG theta-frequency activity in first-episode, neuroleptic-naive patients with schizophrenia: preliminary results. Schizophr. Res. 50, 55–60 (2001).

    CAS  PubMed  Google Scholar 

  55. 55

    Linkenkaer-Hansen, K. et al. Genetic contributions to long-range temporal correlations in ongoing oscillations. J. Neurosci. 27, 13882–13889 (2007).

    CAS  PubMed  Google Scholar 

  56. 56

    Hong, L. E. et al. Sensory gating endophenotype based on its neural oscillatory pattern and heritability estimate. Arch. Gen. Psychiatry 65, 1008–1016 (2008). An important study that examined auditory sensory gating in patients with schizophrenia and their first-degree relatives, highlighting the utility of neural oscillations as an endophenotype in schizophrenia research.

    PubMed  PubMed Central  Google Scholar 

  57. 57

    Lee, K. H., Williams, L. M., Haig, A. & Gordon, E. “Gamma (40 Hz) phase synchronicity” and symptom dimensions in schizophrenia. Cogn. Neuropsychiatry 8, 57–71 (2003).

    PubMed  Google Scholar 

  58. 58

    Lee, S. H. et al. Quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging of patients with persistent auditory hallucinations. Schizophr. Res. 83, 111–119 (2006).

    PubMed  Google Scholar 

  59. 59

    Dierks, T. et al. Activation of Heschl's gyrus during auditory hallucinations. Neuron 22, 615–621 (1999).

    CAS  PubMed  Google Scholar 

  60. 60

    Ford, J. M. & Mathalon, D. H. Corollary discharge dysfunction in schizophrenia: can it explain auditory hallucinations? Int. J. Psychophysiol. 58, 179–189 (2005).

    PubMed  Google Scholar 

  61. 61

    Feinberg, I. Efference copy and corollary discharge: implications for thinking and its disorders. Schizophr. Bull. 4, 636–640 (1978).

    CAS  PubMed  Google Scholar 

  62. 62

    Ford, J. M., Mathalon, D. H., Whitfield, S., Faustman, W. O. & Roth, W. T. Reduced communication between frontal and temporal lobes during talking in schizophrenia. Biol. Psychiatry 51, 485–492 (2002).

    PubMed  Google Scholar 

  63. 63

    Ford, J. M., Roach, B. J., Faustman, W. O. & Mathalon, D. H. Out-of-synch and out-of-sorts: dysfunction of motor-sensory communication in schizophrenia. Biol. Psychiatry 63, 736–743 (2007).

    PubMed  PubMed Central  Google Scholar 

  64. 64

    Gross, J., Schnitzler, A., Timmermann, L. & Ploner, M. Gamma oscillations in human primary somatosensory cortex reflect pain perception. PLoS Biol. 5, e133 (2007).

    PubMed  PubMed Central  Google Scholar 

  65. 65

    Shenton, M. E., Dickey, C. C., Frumin, M. & McCarley, R. W. A review of MRI findings in schizophrenia. Schizophr. Res. 49, 1–52 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Selemon, L. D. & Goldman-Rakic, P. S. The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol. Psychiatry 45, 17–25 (1999).

    CAS  PubMed  Google Scholar 

  67. 67

    Onitsuka, T. et al. Functional and structural deficits in brain regions subserving face perception in schizophrenia. Am. J. Psychiatry 163, 455–462 (2006).

    PubMed  PubMed Central  Google Scholar 

  68. 68

    McCarley, R. W. et al. Association between smaller left posterior superior temporal gyrus volume on magnetic resonance imaging and smaller left temporal P300 amplitude in first-episode schizophrenia. Arch. Gen. Psychiatry 59, 321–331 (2002).

    PubMed  Google Scholar 

  69. 69

    Salisbury, D. F., Kuroki, N., Kasai, K., Shenton, M. E. & McCarley, R. W. Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia. Arch. Gen. Psychiatry 64, 521–529 (2007).

    PubMed  PubMed Central  Google Scholar 

  70. 70

    Engel, A. K., Konig, P., Kreiter, A. K. & Singer, W. Interhemispheric synchronization of oscillatory neuronal responses in cat visual cortex. Science 252, 1177–1179 (1991).

    CAS  PubMed  Google Scholar 

  71. 71

    Löwel, S. & Singer, W. Selection of intrinsic horizontal connections in the visual cortex by correlated neuronal activity. Science 255, 209–212 (1992).

    PubMed  Google Scholar 

  72. 72

    Kubicki, M. et al. A review of diffusion tensor imaging studies in schizophrenia. J. Psychiatr. Res. 41, 15–30 (2007).

    PubMed  Google Scholar 

  73. 73

    Rotarska-Jagiela, A. et al. The corpus callosum in schizophrenia-volume and connectivity changes affect specific regions. Neuroimage 39, 1522–1532 (2008).

    PubMed  Google Scholar 

  74. 74

    Lim, K. O. et al. Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging. Arch. Gen. Psychiatry 56, 367–374 (1999).

    CAS  PubMed  Google Scholar 

  75. 75

    Cobb, S. R., Buhl, E. H., Halasy, K., Paulsen, O. & Somogyi, P. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 378, 75–78 (1995).

    CAS  Google Scholar 

  76. 76

    Wang, X. J. & Buzsaki, G. Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model. J. Neurosci. 16, 6402–6413 (1996).

    CAS  PubMed  Google Scholar 

  77. 77

    Sohal, V. S., Zhang, F., Yizhar, O. & Deisseroth, K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459, 698–702 (2009). An elegant demonstration of the functional significance of parvalbumin-containing interneurons in the generation of gamma-band oscillations that used a novel combination of optogenetic technologies in mice to selectively modulate multiple distinct circuit elements in the neocortex.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Lewis, D. A., Hashimoto, T. & Volk, D. W. Cortical inhibitory neurons and schizophrenia. Nature Rev. Neurosci. 6, 312–324 (2005). An excellent review that highlights the role of inhibitory neurons in the pathophysiology of schizophrenia.

    CAS  Google Scholar 

  79. 79

    Akbarian, S. et al. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch. Gen. Psychiatry 52, 258–266 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80

    Volk, D. W., Austin, M. C., Pierri, J. N., Sampson, A. R. & Lewis, D. A. Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch. Gen. Psychiatry 57, 237–245 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Volk, D. W., Austin, M. C., Pierri, J. N., Sampson, A. R. & Lewis, D. A. GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons. Am. J. Psychiatry 158, 256–265 (2001).

    CAS  PubMed  Google Scholar 

  82. 82

    Hashimoto, T. et al. Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J. Neurosci. 23, 6315–6326 (2003).

    CAS  PubMed  Google Scholar 

  83. 83

    Lodge, D. J., Behrens, M. M. & Grace, A. A. A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J. Neurosci. 29, 2344–2354 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Cunningham, M. O. et al. Region-specific reduction in entorhinal gamma oscillations and parvalbumin-immunoreactive neurons in animal models of psychiatric illness. J. Neurosci. 26, 2767–2776 (2006).

    CAS  PubMed  Google Scholar 

  85. 85

    Kinney, J. W. et al. A specific role for NR2A-containing NMDA receptors in the maintenance of parvalbumin and GAD67 immunoreactivity in cultured interneurons. J. Neurosci. 26, 1604–1615 (2006).

    CAS  PubMed  Google Scholar 

  86. 86

    Krystal, J. H. et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch. Gen. Psychiatry 51, 199–214 (1994).

    CAS  PubMed  Google Scholar 

  87. 87

    Zhang, Y., Behrens, M. M. & Lisman, J. E. Prolonged exposure to NMDAR antagonist suppresses inhibitory synaptic transmission in prefrontal cortex. J. Neurophysiol. 2, 959–965 (2008).

    Google Scholar 

  88. 88

    Behrens, M. M. et al. Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase. Science 318, 1645–1647 (2007).

    CAS  PubMed  Google Scholar 

  89. 89

    Do, K. Q., Cabungcal, J. H., Frank, A., Steullet, P. & Cuenod, M. Redox dysregulation, neurodevelopment, and schizophrenia. Curr. Opin. Neurobiol. 19, 220–230 (2009).

    CAS  PubMed  Google Scholar 

  90. 90

    Roopun, A. K. et al. Region-specific changes in gamma and beta2 rhythms in NDMA receptor dysfunction models of schizophrenia. Schizophr. Bull. 34, 962–973 (2008).

    PubMed  PubMed Central  Google Scholar 

  91. 91

    Plourde, G., Baribeau, J. & Bonhomme, V. Ketamine increases the amplitude of the 40-Hz auditory steady-state response in humans. Br. J. Anaesth. 78, 524–529 (1997).

    CAS  PubMed  Google Scholar 

  92. 92

    Pinault, D. N-methyl D-aspartate receptor antagonists ketamine and MK-801 induce wake-related aberrant gamma oscillations in the rat neocortex. Biol. Psychiatry 63, 730–735 (2008).

    CAS  PubMed  Google Scholar 

  93. 93

    Homayoun, H. & Moghaddam, B. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J. Neurosci. 27, 11496–11500 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94

    Lisman, J. E. et al. Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci. 31, 234–242 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Rodriguez, R., Kallenbach, U., Singer, W. & Munk, M. H. Short- and long-term effects of cholinergic modulation on gamma oscillations and response synchronization in the visual cortex. J. Neurosci. 24, 10369–10378 (2004).

    CAS  PubMed  Google Scholar 

  96. 96

    Steriade, M., Dossi, R. C., Pare, D. & Oakson, G. Fast oscillations (20–40 Hz) in thalamocortical systems and their potentiation by mesopontine cholinergic nuclei in the cat. Proc. Natl Acad. Sci. USA 88, 4396–4400 (1991).

    CAS  PubMed  Google Scholar 

  97. 97

    Sarter, M., Nelson, C. L. & Bruno, J. P. Cortical cholinergic transmission and cortical information processing in schizophrenia. Schizophr. Bull. 31, 117–138 (2005).

    PubMed  Google Scholar 

  98. 98

    Krenz, I. et al. Parvalbumin-containing interneurons of the human cerebral cortex express nicotinic acetylcholine receptor proteins. J. Chem. Neuroanat. 21, 239–246 (2001).

    CAS  PubMed  Google Scholar 

  99. 99

    Martin, L. F. & Freedman, R. Schizophrenia and the α7 nicotinic acetylcholine receptor. Int. Rev. Neurobiol. 78, 225–246 (2007).

    CAS  PubMed  Google Scholar 

  100. 100

    Guan, Z. Z., Zhang, X., Blennow, K. & Nordberg, A. Decreased protein level of nicotinic receptor α7 subunit in the frontal cortex from schizophrenic brain. Neuroreport 10, 1779–1782 (1999).

    CAS  PubMed  Google Scholar 

  101. 101

    Brown, P. et al. Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson's disease. J. Neurosci. 21, 1033–1038 (2001).

    CAS  PubMed  Google Scholar 

  102. 102

    Ito, H. T. & Schuman, E. M. Frequency-dependent gating of synaptic transmission and plasticity by dopamine. Front. Neural Circuits 1, 1 (2007).

    PubMed  PubMed Central  Google Scholar 

  103. 103

    Lewis, D. A. & Levitt, P. Schizophrenia as a disorder of neurodevelopment. Annu. Rev. Neurosci. 25, 409–432 (2002).

    CAS  PubMed  Google Scholar 

  104. 104

    Walker, E. F., Savoie, T. & Davis, D. Neuromotor precursors of schizophrenia. Schizophr. Bull. 20, 441–451 (1994).

    CAS  PubMed  Google Scholar 

  105. 105

    Feinberg, I. Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J. Psychiatr. Res. 17, 319–334 (1982).

    PubMed  Google Scholar 

  106. 106

    Khazipov, R. & Luhmann, H. J. Early patterns of electrical activity in the developing cerebral cortex of humans and rodents. Trends Neurosci. 29, 414–418 (2006).

    CAS  PubMed  Google Scholar 

  107. 107

    Ben-Ari, Y. Developing networks play a similar melody. Trends Neurosci. 24, 353–360 (2001).

    CAS  PubMed  Google Scholar 

  108. 108

    Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996).

    CAS  PubMed  Google Scholar 

  109. 109

    Khazipov, R. et al. Early motor activity drives spindle bursts in the developing somatosensory cortex. Nature 432, 758–761 (2004).

    CAS  PubMed  Google Scholar 

  110. 110

    Hanganu, I.L., Ben-Ari, Y. & Khazipor, R. Retinal waves trigger spindle bursts in the neonatal rat visual cortex. J. Neurosci. 26, 6728–6736 (2006)

    CAS  PubMed  Google Scholar 

  111. 111

    Chiu, C. & Weliky, M. Spontaneous activity in developing ferret visual cortex in vivo. J. Neurosci. 21, 8906–8914 (2001).

    CAS  PubMed  Google Scholar 

  112. 112

    Stellwagen, D. & Shatz, C. J. An instructive role for retinal waves in the development of retinogeniculate connectivity. Neuron 33, 357–367 (2002).

    CAS  PubMed  Google Scholar 

  113. 113

    Cang, J. et al. Development of precise maps in visual cortex requires patterned spontaneous activity in the retina. Neuron 48, 797–809 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. 114

    Yang, J. W., Hanganu-Opatz, I. L., Sun, J. J. & Luhmann, H. J. Three patterns of oscillatory activity differentially synchronize developing neocortical networks in vivo. J. Neurosci. 29, 9011–9025 (2009).

    CAS  PubMed  Google Scholar 

  115. 115

    Hebb, D. O. The Organization of Behavior: A Neuropsychological Theory (Wiley, New York, 1949).

    Google Scholar 

  116. 116

    Markram, H., Lubke, J., Frotscher, M. & Sakmann, B. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275, 213–215 (1997). An important paper showing that modifications in synaptic connections between neurons in the neocortex are dependent on the precise temporal relation between postsynaptic action potentials and unitary excitatory postsynaptic potentials.

    CAS  PubMed  Google Scholar 

  117. 117

    Uhlhaas, P. J. et al. The development of neural synchrony reflects late maturation and restructuring functional networks in humans. Proc. Natl Acad. Sci. USA 106, 9866–9871 (2009). The first study to comprehensively examine the development of task-related neural synchrony in humans, highlighting the role of late brain maturation for the shaping and reorganization of functional networks.

    CAS  PubMed  Google Scholar 

  118. 118

    Yakovlev, P. I. & Lecours, A. R. in In Regional Development of the Brain in Early Life (ed. Minkowski, A.) 3–70 (Blackwell Scientific, Oxford, 1967).

    Google Scholar 

  119. 119

    Perrin, J. S. et al. Sex differences in the growth of white matter during adolescence. Neuroimage 45, 1055–1066 (2009).

    CAS  PubMed  Google Scholar 

  120. 120

    Salami, M., Itami, C., Tsumoto, T. & Kimura, F. Change of conduction velocity by regional myelination yields constant latency irrespective of distance between thalamus and cortex. Proc. Natl Acad. Sci. USA 100, 6174–6179 (2003).

    CAS  PubMed  Google Scholar 

  121. 121

    Takahashi, T. et al. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch. Gen. Psychiatry 66, 366–376 (2009).

    PubMed  Google Scholar 

  122. 122

    Vidal, C. N. et al. Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia. Arch. Gen. Psychiatry 63, 25–34 (2006).

    PubMed  Google Scholar 

  123. 123

    Hashimoto, T. et al. Protracted developmental trajectories of GABAA receptor α1 and α2 subunit expression in primate prefrontal cortex. Biol. Psychiatry 65, 1015–1023 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124

    Klausberger, T., Roberts, J. D. & Somogyi, P. Cell type- and input-specific differences in the number and subtypes of synaptic GABAA receptors in the hippocampus. J. Neurosci. 22, 2513–2521 (2002).

    CAS  PubMed  Google Scholar 

  125. 125

    Doischer, D. et al. Postnatal differentiation of basket cells from slow to fast signaling devices. J. Neurosci. 28, 12956–12968 (2008).

    CAS  PubMed  Google Scholar 

  126. 126

    Fisahn, A., Neddens, J., Yan, L. & Buonanno, A. Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia. Cereb. Cortex 19, 612–618 (2009).

    PubMed  Google Scholar 

  127. 127

    Demiralp, T. et al. DRD4 and DAT1 polymorphisms modulate human gamma band responses. Cereb. Cortex 17, 1007–1019 (2007).

    PubMed  Google Scholar 

  128. 128

    Schoffelen, J. M. & Gross, J. Source connectivity analysis with MEG and EEG. Hum. Brain. Mapp. 30, 1857–1865 (2009).

    PubMed  Google Scholar 

  129. 129

    Meyer-Lindenberg, A. & Weinberger, D. R. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nature Rev. Neurosci. 7, 818–827 (2006).

    CAS  Google Scholar 

  130. 130

    Uhlhaas, P. J. & Singer, W. Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology. Neuron 52, 155–168 (2006).

    CAS  PubMed  Google Scholar 

  131. 131

    O'Donnell, B. F. et al. Neural synchronization deficits to auditory stimulation in bipolar disorder. Neuroreport 15, 1369–1372 (2004).

    PubMed  Google Scholar 

  132. 132

    Uhlhaas, P. J. et al. Gamma-band oscillations during perceptual integration in autism spectrum disorders. Soc. Neurosci. Abstr. 411.8 (2008).

  133. 133

    Lakatos, P. et al. An oscillatory hierarchy controlling neuronal excitability and stimulus processing in the auditory cortex. J. Neurophysiol. 94, 1904–1911 (2005).

    PubMed  Google Scholar 

  134. 134

    Sirota, A. et al. Entrainment of neocortical neurons and gamma oscillations by the hippocampal theta rhythm. Neuron 60, 683–697 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. 135

    Tognoli, E. & Kelso, J. A. Brain coordination dynamics: true and false faces of phase synchrony and metastability. Prog. Neurobiol. 87, 31–40 (2009).

    PubMed  Google Scholar 

  136. 136

    van Vugt, M. K., Sederberg, P. B. & Kahana, M. J. Comparison of spectral analysis methods for characterizing brain oscillations. J. Neurosci. Methods 162, 49–63 (2007).

    PubMed  Google Scholar 

  137. 137

    Fries, P. A mechanism for cognitive dynamics: neuronal communication through neuronal coherence. Trends Cogn. Sci. 9, 474–480 (2005).

    PubMed  Google Scholar 

  138. 138

    Woo, T. U., Miller, J. L. & Lewis, D. A. Schizophrenia and the parvalbumin-containing class of cortical local circuit neurons. Am. J. Psychiatry 154, 1013–1015 (1997).

    CAS  PubMed  Google Scholar 

  139. 139

    Lodge, D. J. & Grace, A. A. Gestational methylazoxymethanol acetate administration: a developmental disruption model of schizophrenia. Behav. Brain Res. 204, 306–312 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. 140

    Raghavachari, S. et al. Theta oscillations in human cortex during a working-memory task: evidence for local generators. J. Neurophysiol. 95, 1630–1638 (2006).

    CAS  PubMed  Google Scholar 

  141. 141

    Tsujimoto, T., Shimazu, H. & Isomura, Y. Direct recording of theta oscillations in primate prefrontal and anterior cingulate cortices. J. Neurophysiol. 95, 2987–3000 (2006).

    PubMed  Google Scholar 

  142. 142

    Vertes, R. P. Hippocampal theta rhythm: a tag for short-term memory. Hippocampus 15, 923–935 (2005).

    CAS  PubMed  Google Scholar 

  143. 143

    Gevins, A., Smith, M. E., McEvoy, 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 7, 374–385 (1997).

    CAS  PubMed  Google Scholar 

  144. 144

    Andersen, P. & Andersson, S. A. Physiological Basis of the Alpha Rhythm (Appelton Century Crofts, New York, 1968).

    Google Scholar 

  145. 145

    Schürmann, M., Bas¸ar-Eroglu, C. & Bas¸ar, E. A possible role of evoked alpha in primary sensory processing: common properties of cat intracranial recordings and human EEG and MEG. Int. J. Psychophysiol. 26, 149–170 (1997).

    PubMed  Google Scholar 

  146. 146

    Berger, H. Über das elektrenkephalogramm des menschen. Arch. Psychiatr. Nervenkr. 87, 527–570 (1929).

    Google Scholar 

  147. 147

    Pfurtscheller, G., Neuper, C., Andrew, C. & Edlinger, G. Foot and hand area mu rhythms. Int. J. Psychophysiol. 26, 121–135 (1997).

    CAS  PubMed  Google Scholar 

  148. 148

    Klimesch, W., Sauseng, P. & Hanslmayr, S. EEG alpha oscillations: the inhibition-timing hypothesis. Brain Res. Rev. 53, 63–88 (2007).

    PubMed  Google Scholar 

  149. 149

    Thut, G., Nietzel, A., Brandt, S. A. & Pascual-Leone, A. Alpha-band electroencephalographic activity over occipital cortex indexes visuospatial attention bias and predicts visual target detection. J. Neurosci. 26, 9494–9502 (2006).

    CAS  PubMed  Google Scholar 

  150. 150

    Palva, S., Linkenkaer-Hansen, K., Naatanen, R. & Palva, J. M. Early neural correlates of conscious somatosensory perception. J. Neurosci. 25, 5248–5258 (2005).

    CAS  PubMed  Google Scholar 

  151. 151

    Doesburg, S. M., Green, J. J., McDonald, J. J. & Ward, L. M. From local inhibition to long- range integration: a functional dissociation of alpha-band synchronization across cortical scales in visuospatial attention. Brain Res. 1303, 97–110 (2009).

    CAS  PubMed  Google Scholar 

  152. 152

    Marco-Pallares, J. et al. Human oscillatory activity associated to reward processing in a gambling task. Neuropsychologia 46, 241–248 (2008).

    PubMed  Google Scholar 

  153. 153

    Martin, C., Gervais, R., Hugues, E., Messaoudi, B. & Ravel, N. Learning modulation of odor-induced oscillatory responses in the rat olfactory bulb: a correlate of odor recognition? J. Neurosci. 24, 389–397 (2004).

    CAS  PubMed  Google Scholar 

  154. 154

    Hong, L. E., Buchanan, R. W., Thaker, G. K., Shepard, P. D. & Summerfelt, A. Beta (16 Hz) frequency neural oscillations mediate auditory sensory gating in humans. Psychophysiology 45, 197–204 (2008).

    PubMed  Google Scholar 

  155. 155

    Gross, J. et al. Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans. Proc. Natl Acad. Sci. USA 101, 13050–13055 (2004).

    CAS  PubMed  Google Scholar 

  156. 156

    Kilner, J. M., Baker, S. N., Salenius, S., Hari, R. & Lemon, R. N. Human cortical muscle coherence is directly related to specific motor parameters. J. Neurosci. 20, 8838–8845 (2000).

    CAS  PubMed  Google Scholar 

  157. 157

    Kopell, N., Ermentrout, G. B., Whittington, M. A. & Traub, R. D. Gamma and beta rhythms have different synchronization properties. Proc. Natl Acad. Sci. USA 97, 1867–1872 (2000).

    CAS  PubMed  Google Scholar 

  158. 158

    Neuenschwander, S. & Singer, W. Long-range synchronization of oscillatory light responses in the cat retina and lateral geniculate nucleus. Nature 379, 728–732 (1996).

    CAS  PubMed  Google Scholar 

  159. 159

    Stopfer, M., Bhagavan, S., Smith, B. H. & Laurent, G. Impaired odour discrimination on desynchronization of odour-encoding neural assemblies. Nature 390, 70–74 (1997).

    CAS  PubMed  Google Scholar 

  160. 160

    Fries, P., Reynolds, J. H., Rorie, A. E. & Desimone, R. Modulation of oscillatory neuronal synchronization by selective visual attention. Science 291, 1560–1563 (2001).

    CAS  PubMed  Google Scholar 

  161. 161

    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. 18, 4244–4254 (1998).

    CAS  PubMed  Google Scholar 

  162. 162

    Melloni, L. et al. Synchronization of neural activity across cortical areas correlates with conscious perception. J. Neurosci. 27, 2858–2865 (2007).

    CAS  PubMed  Google Scholar 

  163. 163

    Berlucchi, G. Anatomical and physiological aspects of visual fuctions of corpus callosum. Brain Res. 37, 371–392 (1972).

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Peter J. Uhlhaas.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information S1 (table)

Abnormal Neural Oscillations and Synchrony in Schizophrenia (PDF 254 kb)

Supplementary information S2 (figure)

Measuring neural synchrony in EEG/MEG Signals. (PDF 285 kb)

Related links

Related links

FURTHER INFORMATION

Peter J. Uhlhaas's homepage

Wolf Singer's homepage

Glossary

Negative symptoms

An absence of behaviour, characterized by flat or blunted affect and emotion, poverty of speech (alogia), inability to experience pleasure (anhedonia) and lack of motivation (avolition).

Perceptual grouping

The ability of perceptual systems to organize sensory information into coherent representations that can serve as the basis of our phenomenal experience of the world.

Transcranial magnetic stimulation

(TMS). A non-invasive method to excite neurons in the brain by inducing weak electric currents in the tissue using rapidly changing magnetic fields.

Mismatch negativity

An event-related potential that is elicited when a sequence of repeated stimuli (standards) is interrupted by stimuli that deviate in sensory characteristics such as intensity, frequency or duration (deviants).

Endophenotype

A neurophysiological, neuroanatomical, cognitive or neuropsychological marker that points to the genetic underpinnings of a clinical syndrome. An endophenotype must be heritable and state independent, and within families the endophenotype and illness must co-segregate.

Positive symptoms

A range of psychotic symptoms that most individuals do not normally experience. Typical symptoms are hallucinations in various modalities (auditory, visual and tactile) and delusions (paranoid delusions and delusions of reference).

Phase synchrony

Phase synchrony and coherence are estimates of the synchrony of brain oscillations. Phase synchrony provides an estimate of synchrony independent of the amplitude of oscillations. This contrasts with measures of coherence, in which synchrony and amplitude are intertwined.

Corollary discharge

The estimate of sensory feedback that is derived from the internal copy of the motor signal (the efference copy).

Diffusion tensor imaging

(DTI). An MRI technique used to map three-dimensional diffusion of water in brain tissue. It provides information about the microstructural integrity of the white matter, including axonal density and thickness, myelinationand axonal fibre direction.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Uhlhaas, P., Singer, W. Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci 11, 100–113 (2010). https://doi.org/10.1038/nrn2774

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing