Faculty Bibliography

We have recently introduced a set of sequence learning tasks that emphasize explicit learning and target anticipation and involve the activation of frontal lobes. This type of learning is impaired even in the early stages of Parkinson's disease (PD). Studies on the effects of L-Dopa on cognitive symptoms of PD have yielded controversial results. To verify whether L-Dopa acutely improves explicit sequence learning, we tested six normal subjects and seven PD patients both off-drug and during L-Dopa infusion with two tasks: SEQ, a motor task with multiple demands, where a sequence had to be learned while reaching for a targets; VSEQ, a visual task where a sequence had to be learned by attending to a visual display without moving. Motor performance was assessed with simple motor tasks. L-Dopa improved motor scores and movement speed, but had no beneficial effect on either type of sequence learning

BACKGROUND: The aim of this study was to determine whether neocortical long-term potentiation (LTP) is deficient in patients with Alzheimer's disease (AD) and in amyloid precursor protein (APP)/presenilin-1 (PS1) mice, an AD animal model. We then ascertained whether this deficit might be paralleled by functional abnormalities of N-methyl-D-aspartate (NMDAR) glutamate receptors. METHODS: We studied neocortical LTP-like plasticity in 10 patients with mild-to-moderate AD and 10 age-matched normal controls using paired associative stimulation (PAS). We assessed neocortical (medial prefrontal cortex and primary motor cortex) and hippocampal LTP in brain slices of symptomatic APP/PS1 mice. NMDAR composition and signaling as well as synaptic calcium influx were determined in motor, prefrontal and hippocampal cortices of APP/PS1 mice. RESULTS: Both AD patients and transgenic animals showed a deficit in NMDAR-dependent forms of neocortical plasticity. Biochemical analysis showed impaired NMDAR function in symptomatic APP/PS1 mice. CONCLUSIONS: Neocortical plasticity is impaired in both patients with AD and APP/PS1 mice. The results of our biochemical studies point to impaired NMDAR function as the most likely cause for the neocortical plasticity deficit in AD

We studied the effects of movement rate and sequence complexity on the execution of externally paced finger movements. Simple thumb-index opposition movements (SEQ1), oppositions of thumb to index, medium, ring and little fingers (SEQ2), and oppositions of thumb to index, ring, medium and little fingers (SEQ3) were paced by a metronome at rates that ranged from 0.5 to 5 Hz. At rates higher than 2.5 Hz touch duration, as well as spatial and timing accuracy changed, although with a different pattern, for the sequences. Delayed movements were mostly present at lowest rates in SEQ1; at 0.5 Hz and at frequencies higher than 3.5 Hz in SEQ2; at rates higher than 3.5 Hz in SEQ3. Syncopation occurred at rates higher than 3 Hz but only for SEQ2 and SEQ3 when movements are delayed. Power spectrum analysis of timing error series indicated that SEQ1 performance is influenced by memory-related processes at all movement rates. On the other hand, for the other two sequences, at rates higher than 4 Hz the timing error series exhibit a slight but significant reduction of its long-range correlation characteristics. These findings suggest that different strategies are used for sensorimotor processing when the movement rate and sequence complexity are increased