Time-locked association between rapid cerebral blood flow modulation and attentional performance.

OBJECTIVE: The study investigated relationships between rapid cerebral hemodynamic modulation and attentional performance. Based on former results on complex cognitive functioning, a specific association between the first seconds of the hemodynamic response and performance was hypothesized. METHODS: Using transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 48 healthy subjects. The applied task comprised motor reactions on a visual stimulus which was preceded by an acoustic warning signal (interstimulus interval 5s). Task-induced hemodynamic changes were assessed second-by-second, and related to reaction time using analysis of variance and linear regression. RESULTS: A right dominant blood flow response was observed. Flow velocity increase in the middle fraction of the interstimulus interval, i.e. seconds 2 and 3 after the cuing signal, significantly correlated with reaction time. This was not the case for the very early and late components of the response. CONCLUSIONS: The results suggest a time-locked association between cerebral blood flow increase and attentional performance. This is in accordance with neurophysiological studies that revealed the closest relationship between brain perfusion and cortical activity during a similar time window. SIGNIFICANCE: The study supports the assumption of a specific, relatively early time interval in which relationships between cerebral blood flow and behavior become apparent.

Determinants of voluntary vs. involuntary admission in bipolar disorder and the impact of adherence.

INTRODUCTION: Treatment adherence plays a pivotal role in hospitalisation in bipolar disorder (BD). We examined the impact of adherence and pharmacological variables on involuntary vs. voluntary admission on a sample of inpatients from the European Mania in Bipolar Longitudinal Evaluation of Medication study (EMBLEM). METHODS: 1374 inpatients with an acute manic or mixed episode of BD participated in this observational study on clinical, functional and economic outcomes of pharmacological treatment. We analysed data at the time of study inclusion, and the primary outcome measure was admission status (voluntary vs. involuntary admission). RESULTS: The strongest baseline factor of admission status was adherence whereby patients' adherence was significantly associated with admission when treated with atypical antipsychotics or lithium as monotherapy. Adherence with typical antipsychotics was not significantly associated with admission status. DISCUSSION: These results emphasise the crucial role of treatment adherence for admission status and, within the context of a naturalistic study, some advantage of atypical over typical antipsychotics on admission in acute mania of BD.

Specific alterations of cerebral hemodynamics during a planning task: a transcranial Doppler sonography study.

Planning plays an important role in daily activities, and several experimental paradigms have been investigated with brain imaging methods showing activity in putative brain regions such as dorsolateral prefrontal cortex and other frontal and non-frontal regions. The Stockings of Cambridge (SOC), a related procedure to the Tower of London task, was introduced to 21 healthy subjects while they underwent bilateral transcranial Doppler sonography (TCD) of the middle (MCA) and anterior (ACA) cerebral arteries. Different levels of difficulty were applied during continuous registration of peak mean cerebral blood flow velocity (CBFV). A specific test procedure allowed separating the actual planning from the execution phase. There was also a similar control task, which did not involve planning. CBFV differed among the planning, execution, and control conditions (MCA: P < 0.01; ACA: P < 0.001), but did not show a significant difference between the MCA and ACA (P > 0.1). Easy tasks yielded a more rapid increase of CBFV in the MCA compared to difficult problems during planning (P < 0.05). In conclusion, our findings of specific CBFV patterns support the idea of different cognitive challenges for planning and control and between easy and difficult conditions.

Cerebral hemodynamic response induced by the Tower of Hanoi puzzle and the Wisconsin Card Sorting test.

Transcranial Doppler sonography (TCD) was applied in normal subjects to investigate the effect of prefrontal functions like the Tower of Hanoi (TOH) task and the Wisconsin Card Sorting test (WCST) on cerebral hemodynamics. In 20 healthy volunteers, left and right middle cerebral artery (MCA) and anterior cerebral artery (ACA) were insonated. The TOH task and the WCST were administered while cerebral blood flow velocity (CBFV) was registered. Each test was repeated once per artery pair. There was a visuomotor test to control the motor and visual stimulations. Three phases of CBFV time course were detected: an initial peak within 5 s, a following decrease within 25 s and a steady state beginning at 40 s. The TOH task, WCST and visuomotor tests had different mean CBFV during the initial peak (MCA: P<0.05; ACA: P<0.05) as well as for the decrease (ACA: P<0.01) and the steady state (MCA: P<0.01; ACA: P<0.01). The TOH showed an increased mean CBFV as compared with the WCST during the steady state (MCA: P<0.01; ACA: P<0.05). However, temporal modulation of mean CBFV during category shift of the WCST resulted in significantly increased values after category shift (MCA: P<0.001; ACA: P<0.01) as compared with CBFV before the category shift. These findings showed a different CBFV pattern during the TOH task and WCST than during the visuomotor test. In conclusion, TCD was able to assess CBFV in prefrontal functions, using a high resolution in time.

Successful challenge with clozapine in a history of eosinophilia.

Eosinophilia has been encountered from 0.2 to 61.7% in clozapine-treated patients, mostly with a transient course and spontaneous remission. There have been few reports, however, which have investigated a challenge with clozapine in patients previously showing eosinophilia. Two case reports are presented: the first with clozapine challenge after eosinophilia, the second under clozapine treatment and no previous haematological side effects. The challenge case showed eosinophilia with 1.2 10(9)/l (z = 1.79, p = 0.04) being followed by normalization despite clozapine continuation, whereas the maximum value reached 2.1 10(9)/l in the single episode case, with consecutive normalization and uninterrupted treatment. Eosinophilia caused by clozapine was observed in challenge, preceded by a faster neutrophil production and consecutive decrease (z = 2.27, p = 0.01). A challenge with clozapine was feasible and showed no clinical symptoms of eosinophilia.