Activation in the anterior left auditory cortex associated with phonological analysis of speech input: localization of the phonological mismatch negativity response with MEG

The spatio-temporal dynamics of cortical activation underlying auditory word recognition, particularly its phonological stage, was studied with whole-head magnetoencephalography (MEG). Subjects performed a visuo-auditory priming task known to evoke the phonological mismatch negativity (PMN) response that is elicited by violations of phonological expectancies. Words and non-words were presented in separate conditions. In each of the 318 trials, the subjects first saw a word/non-word (e.g., 'cat') that was soon followed by a prime letter (e.g., 'h'). Their task was to replace mentally the sound of the first letter of the word/non-word with the prime letter, thus resulting in a new word/non-word (e.g., 'hat'). Finally, an auditory word/non-word either matching or mismatching with the anticipated item was presented. In most subjects, a PMNm followed by a later, N400m-like negativity was obtained in the left hemisphere to the mismatching auditory stimuli. A similar response pattern was obtained in the right hemisphere only in a few subjects. Source localization of the N1m, an index of acoustic analysis, and the PMNm and N400m-like responses was performed using L1 minimum-norm estimation. In the left hemisphere, the PMNm source for the words was significantly more anterior than the source of the N400m-like response; for the non-words, the PMNm source was significantly more anterior than the sources of the N1m and the N400m-like response. These results suggest that the left-hemisphere neuronal networks involved in sub-lexical phonological analysis are at least partly different from those responsible for the earlier (acoustic) and later (whole item) processing of speech input.     

Life satisfaction and depression in a 15-year follow-up of healthy adults

OBJECTIVE: The aim of this study was to investigate the cross-sectional and longitudinal relationship between life satisfaction and depressive symptoms in healthy adults. METHOD: This is a 15-year prospective cohort study with a nationwide sample of healthy Finnish adults (N = 9679), aged 18-45, who responded to postal questionnaires in 1975, 1981 and 1990 including a 4-item life satisfaction (LS) scale (range 4-20) and, in 1990, the 21-item Beck Depression Inventory (BDI). RESULTS: A strong linear association was found between concurrent LS and BDI scales (r = 0.6). With an LS cut-off point of 11/12, moderate/severe depression (BDI > or = 19) was detected with 87% sensitivity, 88 % specificity and a 94% area under the ROC curve. Longitudinally, a strongly increased risk of moderate/severe depression in 1990 was observed among the dissatisfied (LS 12-20) compared with the satisfied (LS 4-6) in 1975 (OR = 6.7; 95 %CI 4.2-10.9) and in 1981 (OR = 10.4; 6.1-17.6). CONCLUSION: The 4-item LS scale can identify a group of healthy people from the general population with a high risk of having or developing depressive symptoms. Since low life satisfaction also indicates an elevated risk of other adverse health outcomes, the assessment of subjective well-being should be encouraged both in surveys and in clinical practice.     

Newborn human brain identifies repeated auditory feature conjunctions of low sequential probability

Natural environments are usually composed of multiple sources for sounds. The sounds might physically differ from one another only as feature conjunctions, and several of them might occur repeatedly in the short term. Nevertheless, the detection of rare sounds requires the identification of the repeated ones. Adults have some limited ability to effortlessly identify repeated sounds in such acoustically complex environments, but the developmental onset of this finite ability is unknown. Sleeping newborn infants were presented with a repeated tone carrying six frequent (P = 0.15 each) and six rare (P approximately 0.017 each) conjunctions of its frequency, intensity and duration. Event-related potentials recorded from the infants' scalp were found to shift in amplitude towards positive polarity selectively in response to rare conjunctions. This finding suggests that humans are relatively hard-wired to preattentively identify repeated auditory feature conjunctions even when such conjunctions occur rarely among other similar ones.     

Do stressful life-events or sociodemographic variables associate with depression and alexithymia among a general population?--A 3-year follow-up study

This 3-year follow-up study examined background factors, stressful life-events, and changes in alexithymia and depression scores in four groups of subjects from a general population (N = 1,339): alexithymic (A), depressed (D), simultaneously alexithymic/depressed (AD), and non-alexithymic/non-depressed (O). Alexithymia was assessed using the 20-item version of the Toronto Alexithymia Scale (TAS) and depression using the 21-item Beck Depression Inventory (BDI). A questionnaire screening sociodemography and stressful life-events was also used. The results showed that alexithymia was associated with male gender and blue-collar working, whereas depressive symptoms associated with female gender, older age, poor subjective health, poor financial situation, and low life satisfaction. During the follow-up the sum of stressful life-events was higher among groups AD and D than in groups A and O. The most common stressful life-events were the death of a close relative or friend, a negative change in the health of a family member, and financial problems. The TAS scores decreased only in groups A and AD. The BDI scores decreased in group AD but remained relatively unchanged in group D. Interestingly, if only those without depressive symptoms are considered, alexithymia appears to be a rarer phenomenon than has been reported previously. Furthermore, it seems that depressive symptoms were chronic and long-lasting among the general population.     

Alexithymia and suicidal ideation: a 12-month follow-up study in a general population

Alexithymic features are often associated with depression, which is the most important risk factor for suicidal behaviors. Nevertheless, little is known about the associations between alexithymia and suicidality. In this 12-month follow-up study we investigated the relationship between alexithymia and suicidal ideation in a sample of the general population (N = 1,563) using the 20-item Toronto Alexithymia Scale (TAS-20) and the 21-item Beck Depression Inventory (BDI). Suicidal ideation was more common among subjects with alexithymia than among nonalexithymic subjects (32% v 9% at baseline and 36% v 9% after 12 months). In cross-sectional analyses, alexithymia associated with the presence of suicidal ideation even after adjustment for sex, age, and several psychosocial and socioeconomic factors and the presence of depression. Moreover, after adjustment for depression at baseline, the decrease and increase in alexithymic features during the study period associated independently with recovery from and the occurrence of suicidal ideation, respectively. Nevertheless, these associations were no longer independent when adjusted for concomitant changes in the level of depressive symptoms. In conclusion, if depression presents alexithymic features the subject has an additive impact on the risk of suicidal ideation.     

Progression of brain damage after status epilepticus and its association with epileptogenesis: a quantitative MRI study in a rat model of temporal lobe epilepsy

PURPOSE: This study examined the hypothesis that neurodegeneration continues after status epilepticus (SE) ends and that the severity of damage at the early phase of the epileptogenic process predicts the outcome of epilepsy in a long-term follow-up. METHODS: SE was induced in rats by electrical stimulation of the amygdala, and the progression of structural alterations was monitored with multiparametric magnetic resonance imaging (MRI). Absolute T2, T1rho, and diffusion (Dav) images were acquired from amygdala, piriform cortex, thalamus, and hippocampus for < or = 4.5 months after SE. Frequency and type of spontaneous seizures were monitored with video-electroencephalography recordings. Histologic damage was assessed from Nissl, Timm, and Fluoro-Jade B preparations at 8 months. RESULTS: At the acute phase (2 days after SE induction), quantitative MRI revealed increased T2, T1rho, and Dav values in the primary focal area (amygdala), reflecting disturbed water homeostasis and possible early structural damage. Pathologic T2 and T1rho were observed in mono- or polysynaptically connected regions, including the piriform cortex, midline thalamus, and hippocampus. The majority of acute MRI abnormalities were reversed by 9 days after SE. In later time points (> 20 days after induction), both the T1rho and diffusion MRI revealed secondarily affected areas, most predominantly in the amygdala and hippocampus. At this time, animals began to have spontaneous seizures. The initial pathology revealed by MRI had a low predictive value for the subsequent severity of epilepsy and tissue damage. CONCLUSIONS: The results demonstrate progressive neurodegeneration after SE in the amygdala and the hippocampus and stress the need for continued administration of neuroprotectants in the treatment of SE even after electrographic seizure activity has ceased.     

Lack of increased oxidative stress in catechol-<Emphasis Type="Italic">O</Emphasis>-methyltransferase (COMT)-deficient mice

The effect of catechol-O-methyltransferase (COMT) deficiency on methamphetamine-induced hydroxyl radical production in the brain was assessed by the salicylate trapping method. Methamphetamine-induced hyperthermia was also studied. Furthermore, the effect of COMT deficiency on the activities of glutathione S-transferase, quinone reductase and liver mono-oxygenases was assessed with and without l-dopa challenge. Finally, two alternative pathways of l-dopa metabolism were evaluated. Methamphetamine increased 2,3-dihydroxybenzoic acid levels only slightly (n.s.) at the lowest dose level (2.5 mg/kg × 4 i.p.). This was accompanied by a simultaneous increase in salicylate levels so that the 2,3-dihydroxybenzoic acid/salicylate ratio decreased correspondingly. Most importantly, no COMT genotype-dependent changes were observed. However, hyperthermia was induced even at the lowest methamphetamine dose, the COMT-deficient mice being most sensitive. COMT deficiency did not significantly change the activities of liver glutathione S-transferase, quinone reductase or 7-ethoxyresorufin and 7-pentoxyresorufin O-dealkylation. In COMT-deficient female mice, l-dopa (30–80 mg/kg b.i.d. for 2 days) did not induce any significant changes in liver or brain glutathione S-transferase and quinone reductase activity or liver 7-ethoxyresorufin O-deethylation activity. The levels of l-dopa conjugates in urine were also negligible in COMT-deficient mice. Skin tyrosinase activity was increased in 7- to 8-day-old hairless COMT-deficient pups. The present results suggest that despite the increased hyperthermic response, COMT deficiency does not increase methamphetamine-induced hydroxyl radical production or change significantly the activity of certain enzymes involved in defense against reactive oxygen species. In conclusion, we found no evidence of increased oxidative stress in the liver or brain of adult mice lacking COMT activity.     

Blinding decreased recruitment in a prevention trial of postmenopausal hormone therapy

PURPOSE: To compare the effect of blind design (active drug and placebo) and nonblind design (active drug and no treatment) on recruitment. SETTING: A primary prevention trial with postmenopausal hormone therapy in Estonia. METHODS: Women who were eligible and willing to participate on the basis of the questionnaire survey were randomized into blind and nonblind groups. Recruitment rates are based on record keeping, and reasons for participating were requested in the first-year follow-up. RESULTS: The recruitment was 30% higher in the nonblind group: of the 4,295 women invited, 37% (95% confidence interval CI=35-39%) in the blind group and 48% (95% CI=46-49%) in the nonblind group were recruited. In both groups, once randomized, most of the losses were women who did not attend the first clinical examination: 49% (blind; 95% CI=47-51%) and 40% (nonblind; 95% CI=38-42%). The rest were found ineligible or lost their interest during clinical examinations. The reasons for joining the trial were relatively similar in the two groups. CONCLUSIONS: Blinding decreased women's interest in joining a long-term preventive trial. Women's reasons for joining the trial were not influenced by blinding.