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Background: Multiple studies have documented deficits in verbal declarative memory function in depression that improve with resolution of symptoms; imaging studies show deficits in anterior cingulate function in depression, a brain area that mediates memory. No studies to date have examined neural correlates of emotionally valenced declarative memory using affectively negative (sad) verbal material that is clinically relevant to understanding depression. Also no studies have examined the effects of treatment on neural correlates of verbal declarative memory. The purpose of this study was to examine the effects of treatment with antidepressants on verbal declarative memory in patients with depression., Methods: Subjects with (N=18) and without (N=9) mid-life major depression underwent positron emission tomography (PET) imaging during verbal declarative memory tasks with both neutral paragraph encoding compared to a control condition, and emotional (sad) word pair retrieval compared to a control condition. Imaging was repeated in 13 subjects with depression after treatment with antidepressants., Results: Patients with untreated depression had a failure of anterior cingulate activation relative to controls during retrieval of emotional word pairs. Antidepressant treatment resulted in increased anterior cingulate function compared to the untreated baseline for both neutral and emotional declarative memory., Limitations: Limitations include a small sample size and variety of antidepressants used., Conclusions: These results are consistent with alterations in anterior cingulate function that are reversible with treatment in patients with depression. These findings may have implications for understanding the mechanism of action of antidepressants in the treatment of depression.

Disturbed comprehension of complex noncanonical sentences in Parkinson's disease (PD) has been linked to dopamine depletion and delayed lexical retrieval. The aim of the present study was to replicate findings of delayed lexical activation in PD patients with noncanonical sentence processing difficulties, and investigate the influence of dopamine depletion on these changes to lexical access. In the first experiment, 20 patients with PD (tested whilst 'on' dopaminergic medication) and 23 controls participated in a list priming experiment. In this paradigm, stimuli are presented as a continuous list of words/nonwords, and semantic priming effects were measured across inter-stimulus intervals (ISIs) of 500 ms, 1000 ms and 1500 ms, with data analyzed using multivariate analyses of variance. The results revealed longer delays in lexical activation for PD patients with poor comprehension of noncanonical sentences, suggesting that the speed of lexical access may be compromised in PD, and that this feature may contribute to certain sentencecomprehension difficulties. In the second experiment, 7 patients with PD who participated in the first experiment, performed the same lexical decision task while 'off' their dopaminergic medication. Semantic priming effects were measured across ISIs of 500 ms and 1500 ms. Within group comparisons revealed a different pattern of semantic priming for the PD patients when 'on' compared to 'off' medication, providing further support for a dopaminergic influence on the speed of information processing and lexical activation.

Background: Semantic priming is a function related to prefrontal cortical (PFC) networks and is lateralized. There is evidence that semantic priming underlies dopaminergic modulation. It is known that the D1-receptor is more abundant in prefrontal networks; however, until now there have been no studies investigating the selective modulation of semantic priming with dopamine agonists. Furthermore, D1 receptor dysfunction has been described in schizophrenia, and patients with formal thought disorder seem to have disturbed focusing of associations and increased indirect priming., Methods: With a subtraction design, we compared the influence of pergolide (D1/D2 agonist) with bromocriptine (D2 agonist) and placebo, in a randomized, double-blind, crossover design in 40 healthy male volunteers. Subjects performed a lateralized lexical decision task including direct and indirect related prime-target pairs (stimulus onset asynchrony = 750 msec)., Results: Only on pergolide a decrease of the indirect priming in the left hemisphere presentations was found., Conclusions: These findings point to a potential selective modulation of agonists with a D1 component on the focusing of semantic associations. The clinical relevance of this study is that it might help the development of therapeutic strategies for treating cognitive deficits in schizophrenia and Parkinson's disease, which are highly relevant to the functional outcome.

Research has suggested that semantic processing deficits in Parkinson's disease (PD) are related to striatal dopamine deficiency. As an investigation of the influence of dopamine on semantic activation in PD, 7 participants with PD performed a lexical-decision task when on and off levodopa medication. Seven healthy controls matched to the participants with PD in terms of sex, age, and education also participated in the study. By use of a multipriming paradigm, whereby 2 prime words were presented prior to the target word, semantic priming effects were measured across stimulus onset asynchronies (SOAs) of 250 ms and 1,200 ms. The results revealed a similar pattern of priming across SOAs for the control group and the PD participants on medication. In contrast, within-group comparisons revealed that automatic semantic activation was compromised in PD participants when off medication. The implications of these results for the neuromodulatory influence of dopamine on semantic processing in PD are discussed., (Copyright (c) 2006 APA, all rights reserved.)

Background: While some cognitive accounts of disorganized speech, or thought disorder, in schizophrenia have emphasized failures in working memory/discourse planning or selective attention, we have suggested that thought disorder resides in the semantic system. In this study we assessed the effect of neuroleptic medication on thought disorder and semantic processing., Methods: Seventeen patients with schizophrenia were assessed while receiving neuroleptic medications and in crossover fashion, placebo. A number of measures were obtained: clinically rated thought disorder (using the Thought, Language and Communication Scale); working memory letter number span); lexical integrity (naming and receptive vocabulary); and, semantic priming of intracategorical word pairs., Results: Semantic priming measures improved with neuroleptic medication, as did clinically rated thought disorder. No other measure changed significantly. Priming selectively covaried with changes in thought disorder., Conclusion: Changes in spreading semantic activation, measured in a semantic priming paradigm and presumably brought about by neuroleptics' influence on dopaminergic neuromodulatory systems, might reflect changes in the biases of pre-existing associative networks that favour or increase the accessibility of representations related by shared features. This study also has implications for the architecture of normal language in that a dissociation between the lexical and semantic levels was observed, due to the selective compromise of tasks demanding semantic processing.

Semantic priming in word pronunciation was examined at 5 stimulus onset asynchronies (SOAs) in 75 medicated and 25 unmedicated people with schizophrenia (SCZ) and in 10 depressed and 28 normal controls. At SOAs < 950 ms, SCZ displayed priming similar to that of normal and depressed controls. At the 950-ms SOA, SCZ displayed less priming than controls. Medication dosage, but not conceptual disorganization scores, was positively associated with priming at SOAs < 950 ms. These results suggest that prior reports of enhanced priming in schizophrenia may have been confounded by methodological problems and that automatic priming processes operate normally in SCZ. The failure of SCZ to display significant priming at the 950-ms SOA is consistent with a hypothesized disturbance in higher level processes.

In order to examine the effect of dopamine on semantic processing, we performed a double-blind, placebo-controlled study. Healthy volunteers (n = 31) were tested in a lexical decision paradigm after ingestion of either L-dopa 100 mg with benserazide 25 mg or placebo. While direct semantic priming was influenced only marginally by L-dopa, the indirect priming effects was reduced significantly. These data support the hypothesis that dopamine increases the signal-to-noise ratio in semantic networks by reducing the spread of semantic processing, thereby leading to a focussing of activation.