Corticosteroids (cortisol in man and corticosterone in rodents) act on the brain inducing alterations in mood, emotion and neurocognitive functions. Many studies have investigated the effects of cortisol administration in healthy humans on episodic memory, memory for previously encountered events, with some demonstrating impaired memory (Newcomer et al., 1999 and McAllister-Williams and Rugg, 2002). Episodic memory has also been shown to be impaired in patients with depression, a disorder that is frequently associated with increased cortisol concentration. Therefore, studies of the effects of cortisol on episodic memory are essential in full understanding the underlying mechanisms involved in the pathology associated with depressive illness. The effects of corticosteroids on neurocognitive processes have been demonstrated to be dose- and time-dependent (Lupien and McEwen, 1997). In rodents, hippocampal long-term potentiation (LTP), which may be a neurobiological correlate of memory, has been shown to have an inverted-U shape correlation with corticosteroids (Diamond et al., 1992). Similarly, some human studies have also indicated inverted-U shape correlation between exogenous cortisol dose and memory performance. Lupien and colleagues found that while a high dose of cortisol impaired working memory, a low dose actually improved memory performance (Lupien et al., 1999).
Cortical activity, as assessed using EEG and fMRI methodology, in general shows asymmetry during the performance of cognitive task, with this presumably reflecting the cerebral localisation of cortical networks involved in cognition. Changes in asymmetry occur in states of emotional disturbance, such as stress, anxiety and depression. Relative greater right frontal activity, demonstrated by less frontal alpha electroencephalography (EEG) frequency, has been found in fearful and distressed children (Calkins et al., 1996, Fox, 1994 and Schmidt and Fox, 1998) and anxious and depressed adults (Coan and Allen, 2004, Allen et al., 2004, Davidson, 1998 and Henriques and Davidson, 1991). Corticosteroids may play a part in the EEG asymmetry seen in stressful conditions. Indeed, it has been shown that 4 days of administration of 160 mg of the synthetic glucocorticoid prednisone to healthy subjects alters the laterality of alpha EEG, increasing right frontal activation (Schmidt et al., 1999). Similar findings have also been shown following acute treatment with cortisol in healthy subjects (Tops et al., 2005).
Asymmetry in the electrophysiological correlates underlying episodic memory has been shown in healthy humans (Tulving et al., 1994 and Baddeley, 2001). Asymmetrical frontal and prefrontal cortex (PFC) activity, with relatively higher right hemisphere activity, has been reported in many (Tulving et al., 1994, Ragland et al., 2000 and Bernard et al., 2001) but not all studies of episodic retrieval (Cabeza and Nyberg, 2000 and Mayes and Montaldi, 2001). Event-related potential (ERP) data have shown differences in waveforms associated with accurate memory recollection when subjects are presented with a previously studied item compared to correct identification of new non-studied items (Wilding and Rugg, 1997, McAllister-Williams and Rugg, 2002 and Alhaj et al., 2006). This “old/new” effect comprises two components: a left parietal activity, which is believed to reflect hippocampal-modulated cortical activation underlying episodic memory retrieval (Alvarez and Squire, 1994 and McClelland et al., 1995) and right frontal activity, which is believed to originate from PFC and may reflect evaluation and monitoring processes that operate upon the products of memory retrieval (Rugg et al., 1996 and Rugg et al., 2002).
We have previously shown that endogenous cortisol concentrations correlate with the laterality specific to episodic memory retrieval in depressed patients and healthy subjects (Alhaj et al., 2007). In particular, cortisol concentrations were demonstrated to correlate negatively with the early left parietal and positively with the late right frontal ERP “old/new” effect components (Alhaj et al., 2007). We hypothesise that the correlation between endogenous cortisol and cortical asymmetric activity is due to a causal effect of cortisol. To test this hypothesis, we utilised a four-day exogenous cortisol administration paradigm in healthy subject who underwent an episodic memory task. The neural correlates of retrieval were assessed using ERPs and low-resolution brain electromagnetic tomography (LORETA) (Pascual-Marqui et al., 1999 and Pascual-Marqui et al., 1994).
