Healthy Control Subjects Subjects Research Articles

Altered Impulse Control in Alcohol Dependence: Neural Measures of Stop Signal Performance

Altered impulse control has been implicated in the shaping of habitual alcohol use and eventual alcohol dependence. We sought to identify the neural correlates of altered impulse control in 24 abstinent patients with alcohol dependence (PAD), as compared to 24 demographics matched healthy control subjects (HC). In particular, we examined the processes of risk taking and cognitive control as the neural endophenotypes of alcohol dependence. To this end, functional magnetic resonance imaging (fMRI) was conducted during a stop signal task (SST), in which a procedure was used to elicit errors in the participants. The paradigm allowed trial-by-trial evaluation of response inhibition, error processing, and post-error behavioral adjustment. Furthermore, by imposing on the subjects to be both fast and accurate, the SST also introduced a distinct element of risk, which participants may or may not avert during the task. Brain imaging data were analyzed with Statistical Parametric Mapping in covariance analyses accounting for group disparity in general performance. The results showed that, compared to HC, PAD demonstrated longer go trial reaction time (RT) and higher stop success rate (SS%). HC and PAD were indistinguishable in stop signal reaction time (SSRT) and post-error slowing (PES). In a covariance analysis accounting for go trial RT and SS%, HC showed greater activity in the left dorsolateral prefrontal cortex than PAD, when subjects with short and long SSRT were contrasted. By comparing PAD and HC directly during stop errors (SE), as contrasted with SS, we observed greater activity in PAD in bilateral visual and frontal cortices. Compared to HC, PAD showed less activation of the right dorsolateral prefrontal cortex during PES, an index of post-error behavioral adjustment. Furthermore, PAD who showed higher alcohol urge at the time of the fMRI were particularly impaired in dorsolateral prefrontal activation, as compared to those with lower alcohol urge. Finally, compared to HC subjects, PAD showed less activity in cortical and subcortical structures including putamen, insula, and amygdala during risk-taking decisions in the SST. These preliminary results provided evidence for altered neural processing during impulse control in PAD. These findings may provide a useful neural signature in the evaluation of treatment outcomes and development of novel pharmacotherapy for alcohol dependence.

Disturbance of automatic auditory change detection in dementia associated with Parkinson's disease: A mismatch negativity study

Objective To investigate whether automatic auditory change detection, as measured by the mismatch negativity (MMN) event-related potential waveform, differs in dementia associated with Parkinson's disease (PDD) and dementia with Lewy-bodies (DLB) as compared to Alzheimer's disease (AD), Parkinson's disease without dementia (PD) and healthy control subjects (HC). Method Seventeen DLB, 15 PDD, 16 PD, 16 AD patients and 18 HC subjects participated. A passive MMN event-related potential paradigm and an oddball-distractor reaction time paradigm were presented. Results The PDD patients had reduced MMN area and amplitude compared to the DLB, PD, and the HC groups. The MMN area correlated significantly with number of missed target stimuli in the oddball-distractor task, and the PDD group missed targets significantly more often than the DLB group. Conclusion The results indicate that PDD patients to a larger degree than patients with DLB have a deficit of automatic auditory change detection that contributes to impairment in their ability to selectively attend and respond to deviant auditory stimuli.

Pain Thresholds as a Putative Functional Test for Cerebral Laterality in Major Depressive Disorder and Panic Disorder1

Objective: Both major depressive disorder (MDD) and panic disorder (PD) exhibit an illness-related functional cerebral laterality with a frontal right/left asymmetry. Using experimental pain lateralization as a putative indicator of functional cerebral laterality, we assessed body side differences in pressure, cold and heat pain thresholds in patients with MDD and PD as well as in healthy control subjects (HC). To control for an attentional bias in perception, reaction times for selective attention were also measured for both visual fields. Method: 21 inpatients with MDD, 21 inpatients with PD (DSM-IV diagnosis) and 20 HC subjects, all right-handed, were investigated drug free. Pain thresholds for pressure, cold and heat were assessed at the right and left forearm or hand. A neuropsychological standard test was used to measure selective attention (signal detection, Wiener Testsystem), which allows for the discrimination between left and right visual field stimulus processing. Results: In all participants, a left-sided increased pain sensitivity could be verified by using pressure pain, but not by thermal pain (cold, heat). The diagnosis of MDD or PD had no influence on pain threshold lateralization. There were no differences in reaction times of selective attention between the groups of patients and the HC. Neither did stimulus presentation in the left or right visual field affect reaction time differently. Conclusion: Body side asymmetry of pain perception was only found for pressure pain targeting mainly deep tissue (muscle) nociception. This asymmetry, however, cannot be regarded as an indicator of a pathological functional cerebral laterality in MDD and PD.

Interleukin-6 is not altered in cerebrospinal fluid of first-degree relatives and patients with Alzheimer's disease

We investigated interleukin-6 (IL-6) levels in cerebrospinal fluid (CSF) of 25 patients with clinically diagnosed sporadic Alzheimer's disease (AD) and 19 healthy control subjects (HC). For comparison 19 clinically healthy subjects with at least one first-degree relative with clinical or autopsy confirmed AD (CF/AD) were examined. CSF levels of IL-6 did not show statistically significant differences between AD patients, CF/AD and HC subjects. There was no correlation between age, gender, age of onset, degree of cognitive impairment, blood–brain barrier dysfunction and IL-6 values. We could not demonstrate altered CSF concentrations of IL-6 that may indicate an inflammatory response or capability to support neuronal survival in the central nervous system (CNS) of first-degree relatives and patients with AD. We suggest that combined measurement of all parameters of the IL-6-receptor complex could yield more insight in a probably altered IL-6 function.

Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals

Background Chronic fatigue syndrome (CFS) is a condition that may be associated with substantial disability. The Medical Outcomes Study Short-Form General Health Survey (SF-36) is an instrument that has been widely used in outpatient populations to determine functional status. Our objectives were to describe the usefulness of the SF-36 in CFS patients and to determine if subscale scores could distinguish patients with CFS from subjects with unexplained chronic fatigue (CF), major depression (MD), or acute infectious mononucleosis (AIM), and from healthy control subjects (HC). An additional goal was to ascertain if subscale scores correlated with the signs and symptoms of CFS or the presence of psychiatric disorders and fibromyalgia. Design Prospectively collected case series. setting Patients with CFS and CF were seen in a university-based referral clinic and had undergone a complete medical and psychiatric evaluation. Other study subjects were recruited from the community to participate in research studies. Participants The study included 185 patients with CFS, 246 with CF, 111 with AIM, and 25 with MD. There were 99 HC subjects. Measures The SF-36 and a structured psychiatric interview were used. The SF-36 contains 8 subscales: physical, emotional, social, and role functioning, body pain, mental health, vitality, and general health—and a structured psychiatric interview. Results Performance characteristics (internal reliability coefficients, convergent validity) of the SF-36 were excellent. A strikingly consistent pattern was found for the physical functioning, role functioning, social functioning, general health, and body pain subscales, with the lowest scores in CFS patients, intermediate scores in AIM patients, and the highest scores in the HC subjects. The CFS patients had significantly lower scores than patients with CF alone on the physical functioning ( P ≤0.01), role functioning ( P ≤0.01), and body pain ( P ≤0.001) subscales. The emotional functioning and mental health scores were worst among those with MD. The presence of fibromyalgia, being unemployed, and increasing fatigue severity all were associated with additional functional limitations across multiple functional domains, with increasing fatigue appearing to have the greatest effect. Conclusions The SF-36 is useful in assessing functional status in patients with fatiguing illnesses. Patients with CFS and CF have marked impairment of their functional status. The severity and pattern of impairment as documented by the SF-36 distinguishes patients with CFS and CF from those with MD and AIM, and from HC, but does not discriminate between CF and CFS.