Y.D. van der Werf

Neuropsychological correlates of a right unilateral lacunar thalamic infarction

OBJECTIVES To report on a patient with a lacunar infarction in the right intralaminar nuclei of the thalamus. The role of the thalamic intralaminar nuclei in cognitive function is as yet insufficiently known. The patient described has shown signs of apathy and loss of initiative, in combination with cognitive deficits, which have persisted essentially unaltered up to the present day since an abrupt onset 17 years ago. METHODS High resolution MRI was performed to show the extent of the lesion; a combination of published and experimental neuropsychological techniques was administered to show the nature of the cognitive defects; Single photon emission computed tomography (SPECT) was employed to obtain a measure of cortical perfusion. RESULTS Brain MRI disclosed an isolated lacunar infarction in the dorsal caudal intralaminar nuclei of the thalamus. Neuropsychological evaluation indicated problems with attention and concentration, executive disturbances, and memory deficits both in the visual and verbal domains. The memory deficits could not be attributed to problems in the early stages of information processing, and are hence regarded as resulting from a failure of retrieval rather than encoding or storage. Brain SPECT disclosed a hypoperfusion of the right frontal cortex. CONCLUSION The data indicate that the cognitive profile is the result of a dysfunction of executive functions. This is corroborated by the finding of decreased blood flow in the right frontal cortex, and by evidence from the neuroanatomical literature. Thus the dysexecutive symptoms are thought to be caused by disconnection of the prefrontal cortex from the brainstem activating nuclei through the strategic localisation of the right thalamic infarction.

Brain correlates of memory dysfunction in alcoholic Korsakoff's syndrome

OBJECTIVES To investigate the relation between anterograde amnesia and atrophy of brain structures involved in memory processing in alcoholic Korsakoffs syndrome. METHODS The volume of brain structures involved in memory processing was measured with MRI from 13 subjects with Korsakoffs syndrome, 13 subjects with chronic alcoholism without Korsakoffs syndrome, and 13 control subjects. The brain structures analysed were the hippocampus, the parahippocampal gyrus, the mamillary bodies, the third ventricle, and the thalamus. Brain volumes were correlated with the delayed recall of a verbal learning test. RESULTS Compared with subjects with chronic alcoholism and control subjects, subjects with Korsakoffs syndrome had a reduced volume of the hippocampus, the mamillary bodies, and the thalamus, and enlargement of the third ventricle. The impairment of delayed recall correlated with the volume of the third ventricle (r=−0.55, p=0.05) in the Korsakoff group. CONCLUSIONS Anterograde amnesia in alcoholic Korsakoffs syndrome is associated with atrophy of the nuclei in the midline of the thalamus, but not with atrophy of the mamillary bodies, the hippocampus, or the parahippocampal gyrus.

Slow brain oscillations of sleep, resting state, and vigilance

The most important quest of cognitive neuroscience may be to unravel the mechanisms by which the brain selects, links, consolidates, and integrates new information into its neuronal network, while preventing saturation to occur. During the past decade, neuroscientists working within several disciplines have observed an important involvement of the specific types of brain oscillations that occur during sleep--the cortical slow oscillations; during the resting state--the fMRI resting state networks including the default-mode network (DMN); and during task performance--the performance modulations that link as well to modulations in electroencephalography or magnetoencephalography frequency content. Understanding the role of these slow oscillations thus appears to be essential for our fundamental understanding of brain function. Brain activity is characterized by oscillations occurring in spike frequency, field potentials or blood oxygen level-dependent functional magnetic resonance imaging signals. Environmental stimuli, reaching the brain through our senses, activate or inactivate neuronal populations and modulate ongoing activity. The effect they sort is to a large extent determined by the momentary state of the slow endogenous oscillations of the brain. In the absence of sensory input, as is the case during rest or sleep, brain activity does not cease. Rather, its oscillations continue and change with respect to their dominant frequencies and coupling topography. This chapter briefly introduces the topics that will be addressed in this dedicated volume of Progress in Brain Research on slow oscillations and sets the stage for excellent papers discussing their molecular, cellular, network physiological and cognitive performance aspects. Getting to know about slow oscillations is essential for our understanding of plasticity, memory, brain structure from synapse to DMN, cognition, consciousness, and ultimately for our understanding of the mechanisms and functions of sleep and vigilance.

Emotion regulation before and after transcranial magnetic stimulation in obsessive compulsive disorder

BACKGROUND Impaired emotion regulation may underlie exaggerated emotional reactivity in patients with obsessive compulsive disorder (OCD), yet instructed emotion regulation has never been studied in the disorder. METHOD This study aimed to assess the neural correlates of emotion processing and regulation in 43 medication-free OCD patients and 38 matched healthy controls, and additionally test if these can be modulated by stimulatory (patients) and inhibitory (controls) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (dlPFC). Participants performed an emotion regulation task during functional magnetic resonance imaging before and after a single session of randomly assigned real or sham rTMS. Effect of group and rTMS were assessed on self-reported distress ratings and brain activity in frontal-limbic regions of interest. RESULTS Patients had higher distress ratings than controls during emotion provocation, but similar rates of distress reduction after voluntary emotion regulation. OCD patients compared with controls showed altered amygdala responsiveness during symptom provocation and diminished left dlPFC activity and frontal-amygdala connectivity during emotion regulation. Real v. sham dlPFC stimulation differentially modulated frontal-amygdala connectivity during emotion regulation in OCD patients. CONCLUSIONS We propose that the increased emotional reactivity in OCD may be due to a deficit in emotion regulation caused by a failure of cognitive control exerted by the dorsal frontal cortex. Modulatory rTMS over the left dlPFC may influence automatic emotion regulation capabilities by influencing frontal-limbic connectivity.

Cold Hands, Warm Feet: Sleep Deprivation Disrupts Thermoregulation and Its Association with Vigilance

STUDY OBJECTIVES Vigilance is affected by induced and spontaneous skin temperature fluctuations. Whereas sleep deprivation strongly affects vigilance, no previous study examined in detail its effect on human skin temperature fluctuations and their association with vigilance. DESIGN In a repeated-measures constant routine design, skin temperatures were assessed continuously from 14 locations while performance was assessed using a reaction time task, including eyes-open video monitoring, performed five times a day for 2 days, after a normal sleep or sleep deprivation night. SETTING Participants were seated in a dimly lit, temperature-controlled laboratory. PATIENTS OR PARTICIPANTS Eight healthy young adults (five males, age 22.0 ± 1.8 yr (mean ± standard deviation)). INTERVENTION One night of sleep deprivation. MEASUREMENTS AND RESULTS Mixed-effect regression models were used to evaluate the effect of sleep deprivation on skin temperature gradients of the upper (ear-mastoid), middle (hand-arm), and lower (foot-leg) body, and on the association between fluctuations in performance and in temperature gradients. Sleep deprivation induced a marked dissociation of thermoregulatory skin temperature gradients, indicative of attenuated heat loss from the hands co-occurring with enhanced heat loss from the feet. Sleep deprivation moreover attenuated the association between fluctuations in performance and temperature gradients; the association was best preserved for the upper body gradient. CONCLUSIONS Sleep deprivation disrupts coordination of fluctuations in thermoregulatory skin temperature gradients. The dissociation of middle and lower body temperature gradients may therefore be evaluated as a marker for sleep debt, and the upper body gradient as a possible aid in vigilance assessment when sleep debt is unknown. Importantly, our findings suggest that sleep deprivation affects the coordination between skin blood flow fluctuations and the baroreceptor-mediated cardiovascular regulation that prevents venous pooling of blood in the lower limbs when there is the orthostatic challenge of an upright posture.

rTMS affects working memory performance, brain activation and functional connectivity in patients with multiple sclerosis.

Objective To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) on working memory performance, while measuring task-related brain activation and task-related brain connectivity in patients with multiple sclerosis (MS). Methods 17 patients with MS and 11 healthy controls (HCs) underwent 3 experimental sessions (baseline, real-rTMS, sham-rTMS), all including an N-back task (3 task loads: N1, N2, N3; control condition: N0) inside the MR scanner. Prior to imaging, real-rTMS (10 Hz) was applied to the right DLPFC. The stimulation site was defined based on individually assessed N-back task activation at baseline and located using neuronavigation. Changes in whole brain functional activation and functional connectivity with the right DLPFC were calculated. Results N-back task accuracy (N2 and N3) improved after real-rTMS (and not after sham-rTMS) compared with baseline (p=0.029 and p=0.015, respectively), only in patients. At baseline, patients with MS, compared with HCs, showed higher task-related frontal activation (left DLPFC, N2>N0), which disappeared after real-rTMS. Task-related (N1>N0) functional connectivity between the right DLPFC and the right caudate nucleus and bilateral (para)cingulate gyrus increased in patients after real-rTMS when compared with sham stimulation. Conclusions In patients with MS, N-back accuracy improved while frontal hyperactivation (seen at baseline relative to HCs) disappeared after real-rTMS. Together with the changes in functional connectivity after real-rTMS in patients, these findings may represent an rTMS-induced change in network efficiency in patients with MS, shifting patients’ brain function towards the healthy situation. This implicates a potentially relevant role for rTMS in cognitive rehabilitation in MS.

Dynamics underlying spontaneous human alpha oscillations: A data-driven approach

Although the cognitive and clinical correlates of spontaneous human alpha oscillations as recorded with electroencephalography (EEG) or magnetoencephalography (MEG) are well documented, the dynamics underlying these oscillations is still a matter of debate. This study proposes a data-driven method to reveal the dynamics of these oscillations. It demonstrates that spontaneous human alpha oscillations as recorded with MEG can be viewed as noise-perturbed damped harmonic oscillations. This provides evidence for the hypothesis that these oscillations reflect filtered noise and hence do not possess limit-cycle dynamics. To illustrate the use of the model, we apply it to two data-sets in which a decrease in alpha power can be observed across conditions. The associated differences in the estimated model parameters show that observed decreases in alpha power are associated with different kinds of changes in the dynamics. Thus, the model parameters are useful dynamical biomarkers for spontaneous human alpha oscillations.

Gray matter differences contribute to variation in cognitive performance in Parkinson's disease

A substantial proportion of patients with Parkinsons disease (PD) suffer from cognitive deficits, although there is a large variability in the severity of these impairments. Whilst the cognitive deficits are often attributed to monoaminergic changes, there is evidence that alterations in structural brain volume also play a role. The aim of our study was to gain more insight into the variability of cognitive performance amongst PD patients by examining the relation between regional gray matter (GM) volume and cognitive performance.

The role of sleep on cognition and functional connectivity in patients with multiple sclerosis

Sleep disturbances are common in multiple sclerosis (MS), but its impact on cognition and functional connectivity (FC) of the hippocampus and thalamus is unknown. Therefore, we investigated the relationship between sleep disturbances, cognitive functioning and resting-state (RS) FC of the hippocampus and thalamus in MS. 71 MS patients and 40 healthy controls underwent neuropsychological testing and filled out self-report questionnaires (anxiety, depression, fatigue, and subjective cognitive problems). Sleep disturbances were assed with the five-item version of the Athens Insomnia Scale. Hippocampal and thalamic volume and RS FC of these regions were determined. Twenty-three patients were categorized as sleep disturbed and 48 as normal sleeping. No differences were found between disturbed and normal sleeping patients concerning cognition and structural MRI. Sleep disturbed patients reported more subjective cognitive problems, and displayed decreased FC between the thalamus and middle and superior frontal gyrus, inferior frontal operculum, anterior cingulate cortex, inferior parietal gyrus, precuneus, and angular gyrus compared to normal sleeping patients. We conclude that sleep disturbances in MS are not (directly) related to objective cognitive functioning, but rather to subjective cognitive problems. In addition, sleep disturbances in MS seem to coincide with a specific pattern of decreased thalamic FC.

Observations on the cortical silent period in Parkinson's disease

Transcranial magnetic stimulation is a tool in the neurosciences to study motor functions and nervous disorders, amongst others. Single pulses of TMS applied over the primary motor cortex lead to a so-called cortical silent period in the recording from the corresponding muscle, i.e. a period of approximately 100ms with no muscle activity. We here show that in Parkinsons disease (PD), this cortical silent period in some cases is interrupted by short bursts of EMG activity. We describe in detail these interruptions in two patients with PD. These interruptions may number up to 3 per cortical silent period and show a consistent frequency across trials and hemispheres within a given patient; the two patients described here do differ, however, in the time-delay of the interruptions and hence the induced frequency. For one patient, the frequency of the interruptions proved to be around 13 Hz, the other patient showed a frequency of around 17 Hz. The results corroborate earlier findings of cortical oscillations elicited by pulses of TMS and may be related to abnormal oscillatory activity found in the cortical-subcortical motor system in PD.