حافظه هیجانی در اسکیزوفرنی

Emotionally arousing scenes are better remembered than neutral ones. The biological basis of this emotional memory effect has been studied in lesion and neuro-imaging studies and depends upon an interaction between the amygdala and medial temporal lobe memory systems including the hippocampus. This study sought to investigate whether patients with schizophrenia had performance deficits on emotional memory tasks consistent with abnormal amygdala function. Patients with schizophrenia and matched control subjects were shown scenes with negative, positive and neutral emotional content. Subjects rated the slides according to how emotionally arousing they found them and then performed surprise memory tests at 10 min (recall) and 3 weeks (recall and recognition). Subjects with schizophrenia did not differ from control subjects in their ratings of the slides. However, patients showed a significant loss of the emotional enhancement of recognition memory for both negative and positive scenes. In addition, patients showed an overall deficit in recall memory, with a selective impairment in recall of the most arousing negative slides. These findings are consistent with the view that medial temporal lobe and in particular amygdala function is abnormal in schizophrenia.

Emotionally arousing events are better remembered than neutral events (Bradley, Greenwald, Petry, & Lang, 1992). This ability to enhance episodic memory for events of emotional significance is clearly of adaptive value. The memory modulation hypothesis proposes that the substrate for this emotional memory effect is an interaction between the amygdala and memory systems in the medial temporal lobe including the hippocampal complex, resulting in increased memory consolidation (McGaugh, 2004 and Phelps, 2004). Support for this hypothesis comes from animal studies which show that lesions of the amygdala or post-training intra-amygdala infusions of β-adrenaline-receptor antagonists block the enhancement of memory consolidation by stress hormones (McGaugh, 2000; McGaugh & Roozendaal, 2002; Roozendaal & McGaugh, 1996; Roozendaal, Portillo-Marquez, & McGaugh, 1996). In addition, electrophysiological studies have shown that stimulation of the amygdala increases induction of long-term potentiation (LTP) in the hippocampus, whilst amygdala lesions or intra-amygdala infusions of β-adrenaline-receptor antagonists block the induction of LTP (Akirav & Richter-Levin, 1999; Frey, Bergado-Rosado, Seidenbecher, Pape, & Frey, 2001; Ikegaya et al., 1994, Ikegaya et al., 1995a, Ikegaya et al., 1995b and Ikegaya et al., 1997). Human studies have provided further evidence for the memory-modulation hypothesis (LaBar & Cabeza, 2006; Phelps, 2004). Subjects with bilateral amygdala damage show a selective loss of the enhancement of memory for emotional events (Adolphs, Cahill, Schul, & Babinsky, 1997; Cahill, Babinsky, Markowitsch, & McGaugh, 1995). In addition, neuroimaging studies have demonstrated that increased amygdala activation during the viewing of emotional scenes is correlated with enhanced hippocampal activation and subsequent memory (Canli, Zhao, Brewer, Gabrieli, & Cahill, 2000; Dolcos et al., 2004a and Dolcos et al., 2004b; Hamann, Ely, Grafton, & Kilts, 1999). Activation of the amygdala is correlated with subsequent memory for emotionally arousing stimuli, independent of their valence (positive or negative) (Canli et al., 2000, Hamann et al., 1999 and Kensinger and Corkin, 2004). The involvement of the medial temporal lobe in emotional memory is not restricted to encoding, as studies have also shown amygdala and hippocampus activation during delayed recognition of emotional scenes (Dolcos, LaBar, & Cabeza, 2005). Evidence regarding the involvement of brain regions outside the medial temporal lobe in emotional memory is scarce, but functional neuroimaging studies have shown that activation of the lateral prefrontal cortex accompanies memory enhancement for affectively valenced stimuli even if these are of low arousal (Kensinger & Corkin, 2004), an effect that may be enhanced for emotionally arousing stimuli (Dolcos et al., 2004a). Abnormalities in medial temporal lobe structure, and in particular decreased volumes of the amygdala and hippocampus, are one of the most replicated findings in magnetic resonance imaging (MRI) studies of patients with schizophrenia (Lawrie & Abukmeil, 1998; Wright et al., 2000). Medial temporal lobe volume reductions are also seen in the relatives of patients with schizophrenia and have been considered to be a heritable vulnerability state for the disorder (Heckers, 2001, Lawrie et al., 2001, Steel et al., 2002 and van Rijn et al., 2005). Functional imaging studies of patients with schizophrenia have demonstrated reduced amygdala activation during the viewing of emotional faces or mood induction, and reduced hippocampal activation in episodic memory tasks (Achim & Lepage, 2005; Gur et al., 2002 and Schneider et al., 1998). Subjects with schizophrenia also have decreased amygdala activation when viewing scenes (Takahashi et al., 2004; Taylor, Liberzon, Decker, & Koeppe, 2002), although this has not been investigated in relation to subsequent memory. On the basis of these findings amygdala abnormalities have been argued to represent an intermediate phenotype in schizophrenia that may be related to the development of both positive and negative symptoms of the disorder (Aleman & Kahn, 2005; Shayegan & Stahl, 2005; van Rijn et al., 2005). In order to investigate the performance of patients with schizophrenia on a cognitive task known to be sensitive to damage to the amygdala we have studied the performance of patients and matched control subjects on tests of emotional memory for scenes. Previous studies of the modulatory effect of emotion on memory have used word stimuli (Calev & Edelist, 1993; Danion, Kazes, Huron, & Karchouni, 2003; Koh, Kayton, & Peterson, 1976; Mathews & Barch, 2004). Some of these studies have shown a relative preservation of emotional memory effects in schizophrenia in terms of both recall (Calev & Edelist 1993; Koh et al., 1976; Mathews & Barch, 2004) and recognition (Mathews & Barch, 2004) whilst others have shown selective deficits in recognition memory (Danion et al., 2003). The use of word stimuli in these previous studies may however have limited the degree of emotional arousal elicited by the stimuli. In addition, some earlier studies have examined memory at short recall intervals (Danion et al., 2003 and Koh et al., 1976; Mathews & Barch, 2004), although the effects of emotional arousal on memory consolidation are greatest after a delay (LaBar and Phelps, 1998). We, therefore, tested emotional memory using scenes from a well characterised battery that have been shown to include pictures that are highly emotionally arousing (Lang, Bradley, & Cuthbert, 1997; Lang, Greenwald, Bradley, & Hamm, 1993). Our primary outcome measure was delayed recognition memory, an objective measure which has previously been shown to be correlate with enhanced amygdala activation and amygdalo-hippocampal activation during the encoding of emotional scenes (Canli et al., 2000 and Hamann et al., 1999). We hypothesised that patients with schizophrenia would show an impairment in the emotional enhancement of recognition memory for scenes, reflecting abnormal amygdala function.