Robert H. A. M. Reijntjes

EEG correlates in the spectrum of cognitive decline

OBJECTIVEnTo investigate relations between EEG measures and performance on tests of global cognition, memory, language and executive functioning.nnnMETHODSnTwenty-two controls, 18 patients with mild cognitive impairment (MCI) and 16 with probable Alzheimers disease (AD) underwent neuropsychological and EEG investigations. We used the following EEG measures: theta relative power during eyes closed, alpha reactivity during memory activation (i.e. the percentual decrease in alpha power as compared to eyes closed) and alpha coherence during eyes closed and memory activation.nnnRESULTSnTheta relative power was increased in AD patients as compared with controls (p<0.001) and MCI patients (p<0.01) and related to decreased performance in all cognitive domains. Alpha reactivity was decreased in AD patients as compared with controls (p<0.005) and related to decreased performance on tests of global cognition, memory and executive functioning. Alpha coherence did not differ between groups and was unrelated to cognition.nnnCONCLUSIONSnEEG power measures were associated with decreased performance on tests of global cognition, memory, language and executive functioning, while coherence measures were not.nnnSIGNIFICANCEnThe EEG yielded several power measures related to cognitive functions. These EEG power measures might prove useful in prospective studies aimed at predicting longitudinal cognitive decline and dementia.

The semiology of tilt-induced psychogenic pseudosyncope

Objectives: To provide a detailed semiology to aid the clinical recognition of psychogenic pseudosyncope (PPS), which concerns episodes of apparent transient loss of consciousness (TLOC) that mimic syncope. Methods: We analyzed all consecutive tilt-table tests from 2006 to 2012 showing proven PPS, i.e., apparent TLOC had occurred without EEG changes or a decrease in heart rate (HR) or blood pressure (BP). We analyzed baseline characteristics, video data, EEG, ECG, and continuous BP measurements on a 1-second time scale. Data were compared with those of 69 cases of tilt-induced vasovagal syncope (VVS). Results: Of 800 tilt-table tests, 43 (5.4%) resulted in PPS. The majority (74%) were women. The median duration of apparent TLOC was longer in PPS (44 seconds) than in VVS (20 seconds, p < 0.05). During the event, the eyes were closed in 97% in PPS but in only 7% in VVS (p < 0.0001). A sudden head drop or moving down the tilt table was more common in PPS than in VVS (p < 0.01), but jerking movements occurred more frequently in VVS (p < 0.0001). In PPS, both HR and BP increased before and during apparent TLOC (p < 0.0001). Conclusions: PPS is clinically distinct from VVS and can be diagnosed accurately with tilt-table testing and simultaneous EEG monitoring. Compared with VVS, eye closure during the event, long periods of apparent TLOC, and high HR and BP are highly specific for PPS. Improved understanding of the semiology of PPS as a clinical entity is vital to ensure accurate diagnosis.

Memory activation enhances EEG abnormality in mild cognitive impairment

This exploratory study investigated EEG power changes during memory activation in patients with amnestic mild cognitive impairment (MCI). Twelve MCI patients and 16 age-matched controls underwent EEG registration during two conventional EEG conditions (eyes closed and eyes open) and three memory conditions (word memory, picture memory and animal fluency). For all conditions, EEG power in the theta (4-8 Hz), lower alpha (8-10.5 Hz) and upper alpha (10.5-13 Hz) bands were expressed as percentile changes compared to eyes closed. MCI patients showed significantly less decrease in the lower alpha band than controls (p=0.04) during picture memory activation. The word memory task showed a trend towards a similar effect (p=0.09). This study suggests that memory activation reveals EEG differences between MCI patients and controls while conventional EEG conditions do not.

EEG markers of future cognitive performance in the elderly.

This exploratory follow-up study investigated whether EEG parameters can predict future cognitive performance. Forty elderly subjects, ranging from cognitively unimpaired to those with Alzheimer disease underwent EEG registration at baseline and neuropsychological examination at both baseline and follow-up. We assessed relations between EEG measures and future cognitive performance (i.e., global cognition, memory, language, and executive functioning) controlling for age, follow-up time, and baseline cognitive performance. Regression models were constructed to predict performance on the Cambridge Cognitive Examination, a widely used tool within dementia screenings. Baseline EEG measures, i.e., increased theta activity (4–8 Hz) during eyes closed and less alpha reactivity (8–13 Hz) during eyes open and memory activation, indicated lower global cognitive, language (trend significant), and executive performance at follow-up. A regression model combining baseline cognitive and EEG measures provided the best prediction of future Cambridge Cognitive Examination performance (93%). EEG and cognitive measures alone predicted, respectively, 43% and 92% of variance. EEG and cognitive measures combined provided the best prediction of future cognitive performance. Although the “cognition only” model showed similar predictive power, the EEG provided significant additional value. The added value of EEG registration in the diagnostic work-up of dementia should be further assessed in larger samples.

Corticospinal excitability during laughter: implications for cataplexy and the comparison with REM sleep atonia.

Cataplexy is usually seen as rapid eye movement (REM) sleep atonia occurring at an inopportune moment. REM sleep atonia is the result of postsynaptic inhibition, i.e. inhibition of alpha motor neurones. Although this may explain the suppression of H‐reflexes during REM sleep, cataplexy and laughter, it is not the only explanation. Presynaptic inhibition, in which afferent impulses are prevented from reaching motor neurones, is an alternative. Testing H‐reflexes and magnetic‐evoked potentials (MEPs) helps to tell them apart: in postsynaptic inhibition MEPs and H‐reflexes change in tandem, while H‐reflexes may decrease independent of MEPs with other inhibition modes. We studied motor inhibition during laughter, the strongest trigger for cataplexy. H‐reflexes were evoked every 2u2003s in the soleus muscle in 10 healthy subjects watching comical video fragments. MEPs were evoked when H‐reflexes decreased during laughter, and, as a control, when subjects did not laugh. Pairs of MEPs and the immediately preceding H‐reflexes were studied. Compared with the control condition, laughter caused mean MEP area to increase by 60% (Pu2003=u20030.006) and mean H‐reflex amplitude to decrease by 33% (Pu2003=u20030.008). This pattern proves that postsynaptic inhibition cannot have been the sole influence. The findings do not prove which mechanisms are involved; one possibility is that the decrease in H‐reflex amplitude was the result of presynaptic inhibition, and that cortical and/or spinal facilitation accounted for increased MEPs. Regardless, the pattern differs fundamentally from the reported mechanism of REM sleep atonia. Existing scanty data on cataplexy suggest a pattern of H‐reflexes and MEPs similar to that during laughter, but this needs further study.

Memory activation reveals abnormal EEG in preclinical Huntington's disease.

The EEG is potentially useful as a marker of early Huntingtons disease (HD). In dementia, the EEG during a memory activation challenge showed abnormalities where the resting EEG did not. We investigated whether memory activation also reveals EEG abnormalities in preclinical HD. Sixteen mutation carriers for HD and 13 nonmutation carriers underwent neurological, neuropsychological, MRI and EEG investigations. The EEG was registered during a rest condition, i.e. eyes closed, and a working memory task. In each condition we determined absolute power in the theta (4–8 Hz) and alpha (8–13 Hz) bands and subsequently calculated relative alpha power. The EEG during eyes closed did not differ between groups. The EEG during memory activation showed less relative alpha power in mutation carriers as compared to nonmutation carriers, even though memory performance was similar [F (1,27) = 10.87; P = 0.003]. Absolute powers also showed less alpha power [F (1,27) = 7.02; P = 0.013] but similar theta power. No correlations were found between absolute and relative alpha power on the one hand and neuropsychological scores, motor scores or number of CAG repeats on the other. In conclusion, memory activation reveals functional brain changes in Huntingtons disease before clinical signs become overt.

Microstructural brain abnormalities in Huntington's disease : A two-year follow-up

To investigate both cross‐sectional and time‐related changes of striatal and whole‐brain microstructural properties in different stages of Huntingtons disease (HD) using diffusion tensor imaging.

Time- and state-dependent analysis of autonomic control in narcolepsy: higher heart rate with normal heart rate variability independent of sleep fragmentation

Narcolepsy with hypocretin deficiency is known to alter cardiovascular control during sleep, but its aetiology is disputed. As cardiovascular control differs between sleep states, and narcolepsy affects sleep architecture, controlling for both duration and transitions of sleep states is necessary. This study therefore aimed to assess heart rate and its variability in narcolepsy during sleep taking these factors into account. The study included 12 medication‐naïve patients with narcolepsy with cataplexy and hypocretin deficiency (11 male, 16–53 years old), and 12 sex‐ and age‐matched healthy controls (11 male, 19–55 years). All subjects underwent 1‐night ambulatory polysomnography recording. Cardiovascular parameters were calculated for each 30‐s epoch. Heart rate was significantly higher in patients with narcolepsy than in controls in all sleep states and during wakefulness prior to sleep. Groups did not differ in heart rate variability measures. The effects of sleep state duration on heart rate and its variability were similar between patients and controls. In conclusion, heart rate was consistently higher in patients with narcolepsy than controls, independent of sleep stage and sleep fragmentation. A direct effect of hypocretin deficiency therefore seems probable.

Contrasting effects of isocapnic and hypocapnic hyperventilation on orthostatic circulatory control

The effects of hyperventilation (HV) on mean arterial pressure (MAP) are variable. To identify factors affecting the MAP response to HV, we dissected the effects of hypocapnic HV (HHV) and isocapnic HV (IHV) and evaluated the effects of acute vs. prolonged HHV. In 11 healthy subjects the cardio- and cerebrovascular effects of HHV and IHV vs. normal ventilation were examined for 15 min in the supine position and also for 15 min during 60 degrees head-up tilt. The end-tidal CO(2) of the HHV condition was set at 15-20 mmHg. With HHV in the supine position, mean cerebral blood flow velocity (mCBFV) declined [95% confidence interval (CI) -43 to -34%], heart rate (HR) increased (95% CI 7 to 16 beats/min), but MAP did not change (95% CI -1 to 6 mmHg). However, an augmentation of the supine MAP was observed in the last 10 min of HHV compared with the first 5 min of HHV (95% CI 2 to 12 mmHg). During HHV in the tilted position mCBFV declined (95% CI -28 to -12%) and MAP increased (95% CI 3 to 11 mmHg) without changes in HR. With supine IHV, mCBFV decreased (95% CI -14 to -4%) and MAP increased (95% CI 1 to 13 mmHg) without changes in HR. During IHV in the tilted position MAP was further augmented (95% CI 11 to 20 mmHg) without changes in CBFV or HR. Preventing hypocapnia during HV resulted in a higher MAP, suggesting two contrasting effects of HV on MAP: hypocapnia causing vasodepression and hyperpnea without hypocapnia acting as a vasopressor.

Deficient sustained attention to response task and P300 characteristics in early Huntington’s disease

Evidence for the extent and nature of attentional impairment in premanifest and manifest Huntington’s disease (HD) is inconsistent. Understanding such impairments may help to better understand early functional changes in HD and could have consequences concerning care for HD patients. We investigated attentional control in both early and premanifest HD. We studied 17 early HD subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years), and 15 healthy controls (mean age: 51 years), using the sustained attention to response task (SART), a simple Go/No-go test reflecting attentional and inhibitory processes through reaction time (RT) and error rates. Simultaneously recorded EEG yielded P300 amplitudes and latencies. The early HD group made more Go errors (pxa0<xa00.001) and reacted slower (pxa0<xa00.005) than the other groups. The RT pattern during the SART was remarkably different for early HD subjects compared to the other two groups (pxa0<xa00.005), apparent as significant post-error slowing. P300 data showed that for early HD the No-go amplitude was lower than for the other two groups (pxa0<xa00.05). Subjects with early HD showed a reduced capacity to effectively control attention. They proved unable to resume the task directly after having made an error, and need more time to return to pre-error performance levels. No attentional control deficits were found for the premanifest HD group.