Elsevier

Biological Psychiatry

Volume 62, Issue 5, 1 September 2007, Pages 373-380
Biological Psychiatry

Original Article
Long-Term Plasticity of Visually Evoked Potentials in Humans is Altered in Major Depression

https://doi.org/10.1016/j.biopsych.2006.10.006Get rights and content

Background

Long-term synaptic plasticity is a ubiquitous form of neuronal plasticity that regulates the strength of synaptic transmission in many brain areas. However, most data on long-term potentiation and long-term depression rely on research in animal brain slices. The role of synaptic plasticity in physiology and pathology of the functioning human brain remains obscure. Considering recent studies that provided evidence for a dysfunction of brain plasticity as the neurobiological basis of affective disorders, we assessed neural transmission and its plastic modulation in the visual pathway in healthy control subjects and patients with major depression.

Methods

Recordings of visually evoked potentials (VEPs) in humans.

Results

Prolonged visual presentation of checkerboard reversals resulted in a sustained amplitude modulation of early components of subsequent VEPs. After a 10-min block of visual stimulation (two checkerboard reversals per second), the C1 component was reduced, whereas P1 and N1 were both significantly increased for >30 min. Chronic application of the selective serotonin reuptake inhibitor sertraline in healthy control subjects augmented these effects, whereas the polarity of the modulation was inverted in patients with severe major depression. Moreover, early VEP amplitudes were decreased in depressed patients when compared with matched control subjects and increased in normal control subjects after chronic intake of an antidepressant.

Conclusions

Our results demonstrate that stimulus-induced response plasticity of VEPs can be induced in the human brain and is sharing properties with hebbian forms of synaptic plasticity. Major depression and antidepressant treatment of healthy control subjects differentially modulate amplitude and plasticity of evoked potentials. This study provides direct evidence in humans for a central role of synaptic plasticity in the pathophysiology of depression.

Section snippets

Subjects

Seventy-four healthy subjects and 40 depressed patients with normal or corrected-to-normal visual acuity participated in this study after providing written informed consent. The depressed subjects were inpatients at the Department of Psychiatry, University of Freiburg. All patients suffered from a severe depressive episode according to the diagnostic criteria of ICD-10 (World Health Organization 1992). Thirty-two of the 40 depressed patients presented with a recurrent depressive disorder and 8

Visual Stimulation Induces a Sustained Plastic Modulation of VEP Amplitudes

We aimed to modify the strength of cortical responses in the visual pathway by prolonged activation using distinct stimulation patterns and frequencies.

For this set of experiments, we used standard checkerboard reversal VEPs. We regularly identified two negative peaks at 64.9 ± .5 msec (C1) and 126.2 ± 1.7 msec (N1) after the reversal and one positive peak at 89.3 ± .6 msec (P1), with small interindividual variance. After baseline measurement of VEP amplitudes, a 2-rps checkerboard pattern was

Plasticity of Evoked Potentials in Humans

The present findings demonstrate that prolonged visual stimulation induces plastic changes of cortical responses in healthy humans. The amplitude of C1 did not change significantly, whereas P1 and N1 were increased after stimulation. The modulation of the VEP amplitudes was persistent for 20 min or more. Some control experiments showed a plastic modulation for up to 60 min. The induction of stimulus-induced response plasticity was frequency dependent; on the other hand, modulation using an

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