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The Journal of Neuroscience, November 2, 2005, 25(44):10131-10137; doi:10.1523/JNEUROSCI.3244-05.2005

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Behavioral/Systems/Cognitive
Breakdown of Long-Range Temporal Correlations in Theta Oscillations in Patients with Major Depressive Disorder

Klaus Linkenkaer-Hansen,^1,3 Simo Monto,¹ Heikki Rytsälä,⁵ Kirsi Suominen,⁶ Erkki Isometsä,² and Seppo Kähkönen^1,4

¹BioMag Laboratory, Engineering Centre, and ²Department of Psychiatry, Helsinki University Central Hospital, FIN-00029 HUS, Finland, ³Center for Neurogenomics and Cognitive Research, Department of Experimental Neurophysiology, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands, ⁴Cognitive Brain Research Unit, Department of Psychology, University of Helsinki, FIN-00014, Finland, ⁵Department of Psychiatry, Peijas Hospital, Helsinki University Central Hospital, FIN-01400 Vantaa, Finland, and ⁶Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, FIN-02740 Espoo, Finland

Neuroimaging has revealed robust large-scale patterns of high neuronal activity in the human brain in the classical eyes-closed wakeful rest condition, pointing to the presence of a baseline of sustained endogenous processing in the absence of stimulus-driven neuronal activity. This baseline state has been shown to differ in major depressive disorder. More recently, several studies have documented that despite having a complex temporal structure, baseline oscillatory activity is characterized by persistent autocorrelations for tens of seconds that are highly replicable within and across subjects. The functional significance of these long-range temporal correlations has remained unknown.

We recorded neuromagnetic activity in patients with a major depressive disorder and in healthy control subjects during eyes-closed wakeful rest and quantified the long-range temporal correlations in the amplitude fluctuations of different frequency bands. We found that temporal correlations in the theta-frequency band (3-7 Hz) were almost absent in the 5-100 s time range in the patients but prominent in the control subjects. The magnitude of temporal correlations over the left temporocentral region predicted the severity of depression in the patients.

These data indicate that long-range temporal correlations in theta oscillations are a salient characteristic of the healthy human brain and may have diagnostic potential in psychiatric disorders. We propose a link between the abnormal temporal structure of theta oscillations in the depressive patients and the systems-level impairments of limbic-cortical networks that have been identified in recent anatomical and functional studies of patients with major depressive disorder.

Key words: major depressive disorder; ongoing oscillations; long-range temporal correlations; magnetoencephalography; theta oscillations; fractal physiology

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Received April 20, 2005; revised August 2, 2005; accepted September 17, 2005.

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