اختلال آموزش معکوس زمینه ای، اما نه آموزش معکوس نشانه ای در بیماران مبتلا به اختلال شناختی خفیف

It has been proposed that reversal learning is impaired following damage to the orbitofrontal and ventromedial frontal cortex (OFC/VMFC) and to the medial temporal lobe (MTL), including the hippocampal formation. However, the exact characteristics of the MTL-associated reversal learning deficit are not known. To investigate this issue, we assessed 30 newly diagnosed patients with amnestic mild cognitive impairment (aMCI) and 30 matched healthy controls. All patients fulfilled the aMCI criteria of the Mayo Clinic Alzheimer's Disease Research Center and underwent head magnetic resonance imaging that confirmed MTL atrophy. Reversal learning was assessed using a novel reinforcement learning task. Participants first acquired and then reversed stimulus–outcome associations based on negative and positive feedback (losing and gaining points). Stimuli consisted of a cue (geometric shapes) and a spatial context (background color or pattern). Neuropsychological assessment included tasks related to the MTL (paired associates learning), dorsolateral prefrontal cortex (DLPFC) (extradimensional shift, One-touch Stockings of Cambridge), and OFC/VMFC (Holiday Apartment Task). Results revealed that, relative to controls, patients with aMCI exhibited a marked reversal learning deficit, which was highly selective for the reversal of context. The acquisition of stimulus–outcome associations and cue reversal learning were spared. Performance on the context reversal learning task significantly correlated with the right hippocampal volume. In addition, patients with aMCI had deficits on tests related to DLPFC but not to OFC/VMFC. However, DLPFC dysfunctions were not associated with context reversal learning. These results suggest that MTL deficits in aMCI selectively affect context reversal learning when OFC/VMFC functions are spared. This deficit is not influenced by the valence of the outcome (positive or negative feedback) and by executive dysfunctions.

Adapting to environmental changes is one of the most fundamental challenges for every organism. Conditions that once were rewarding may become disadvantageous and non-adaptive and vice versa. Cognitive flexibility, including attentional set-shifting and reversal learning, is a crucial element of adaptation (Frank and Claus, 2006 and Robbins and Arnsten, 2009). Clinical studies and animal models have shown that frontal lobe lesions cause marked cognitive rigidity (Chudasama & Robbins, 2006). Specifically, lesion to the dorsolateral prefrontal cortex (DLPFC) and its rodent analogues results in deficits on tasks requiring the shifting of attentional sets, whereas damage to the orbitofrontal and ventromedial frontal cortex (OFC/VMFC) is associated with reversal learning impairment (Birrell and Brown, 2000 and Dias et al., 1996). Additional brain regions implicated in reversal learning are the cortico-striatal system and the medial temporal lobe (MTL), including the hippocampal formation (e.g., Cools et al., 2002, Marston et al., 1993, Myers et al., 2006, Shohamy et al., 2009 and Swainson et al., 2000). However, the potential difference between the roles of these brain regions is not fully understood.