Abstract：
BACKGROUND:Comparing prefrontal cortical activity during particular phases of working memory in healthy subjects and individuals diagnosed with schizophrenia might help to define the phase-specific deficits in cortical function that contribute to cognitive impairments associated with schizophrenia. This study featured a spatial working memory task, similar to that used in nonhuman primates, that was designed to facilitate separating brain activation into encoding, maintenance, and response phases. METHODS:Fourteen patients with schizophrenia (4 medication-free) and 12 healthy comparison participants completed functional magnetic resonance imaging while performing a spatial working memory task with two levels of memory load. RESULTS:Task accuracy was similar in patients and healthy participants. However, patients showed reductions in brain activation during maintenance and response phases but not during the encoding phase. The reduced prefrontal activity during the maintenance phase of working memory was attributed to a greater rate of decay of prefrontal activity over time in patients. Cortical deficits in patients did not appear to be related to antipsychotic treatment. In patients and in healthy subjects, the time-dependent reduction in prefrontal activity during working memory maintenance correlated with poorer performance on the memory task. CONCLUSIONS:Overall, these data highlight that basic research insights into the distinct neurobiologies of the maintenance and response phases of working memory are of potential importance for understanding the neurobiology of cognitive impairment in schizophrenia and advancing its treatment.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Driesen NR,Leung HC,Calhoun VD,Constable RT,Gueorguieva R,Hoffman R,Skudlarski P,Goldman-Rakic PS,Krystal JHdoi
10.1016/j.biopsych.2008.07.029subject
Has Abstractpub_date
2008-12-15 00:00:00pages
1026-34issue
12eissn
0006-3223issn
1873-2402pii
S0006-3223(08)00970-0journal_volume
64pub_type
杂志文章abstract：BACKGROUND:A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H3 receptor inverse agonists upregulate histamine relea...
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