Author name cluster

Ysbrand D. van der Werf

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7 papers

1 author row

YNICL Journal 2025 Journal Article

Treatment outcome is associated with pre-treatment connectome measures across psychiatric disorders − evidence for connectomic reserve?

Chris Vriend
Sophie M.D.D. Fitzsimmons
Inga Aarts
Aniek Broekhuizen
Ysbrand D. van der Werf
Linda Douw
Henny A.D. Visser
Kathleen Thomaes

Predicting treatment efficacy in psychiatric disorders remains challenging, despite the availability of effective interventions. Previous studies suggest a link between pre-treatment brain network characteristics and treatment efficacy in individual disorders, but cross-disorder investigations are lacking. We analyzed pre-treatment MRI data from 177 individuals (113 females) with either obsessive-compulsive disorder (OCD) or post-traumatic stress disorder with comorbid personality disorders (PTSD) that received different non-pharmacological treatments. Using diffusion and resting-state MRI, we constructed structural, functional, and multilayer connectomes and calculated network measures for network integration (e.g. global efficiency, eccentricity), segregation (modularity) and their balance (small-worldness). We assessed the relationship between these pre-treatment network measures, and treatment improvement using mixed-model and Bayesian analyses. We also compared psychiatric cases with healthy controls and investigated associations between clinical response and treatment-induced changes in network measures. Across disorders and treatments, psychiatric cases showed a 41.6 ± 29.6 % symptom improvement (62 % response rate) after treatment. They also showed pre-treatment differences in functional and multilayer network topology compared to healthy controls. Symptom improvement was associated with pre-treatment functional (P = 0.04) and structural small-worldness (P = 0.01), and multilayer eccentricity (P = 0.01), while responders had higher functional modularity (P = 0.02). Results were robust across trials and treatments, when adjusting for medication status and showed high credibility in Bayesian analyses. Network change associations with treatment response were only modest. These results show that pre-treatment connectome characteristics are related to treatment response, regardless of treatment and psychiatric disorder, and suggest that individual differences in intrinsic features of the human connectome underlie amenability to treatment.

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YNICL Journal 2022 Journal Article

Eight-week multi-domain cognitive training does not impact large-scale resting-state brain networks in Parkinson’s disease

Tim D. van Balkom
Odile A. van den Heuvel
Henk W. Berendse
Ysbrand D. van der Werf
Chris Vriend

There is meta-analytic evidence for the efficacy of cognitive training (CT) in Parkinson’s disease (PD). We performed a randomized controlled trial where we found small positive effects of CT on executive function and processing speed in individuals with PD (ntotal = 140). In this study, we assessed the effects of CT on brain network connectivity and topology in a subsample of the full study population (nmri = 86). Participants were randomized into an online multi-domain CT and an active control condition and performed 24 sessions of either intervention in eight weeks. Resting-state functional MRI scans were acquired in addition to extensive clinical and neuropsychological assessments pre- and post-intervention. In line with our preregistered analysis plan (osf. io/3st82), we computed connectivity between ‘cognitive’ resting-state networks and computed topological outcomes at the whole-brain and sub-network level. We assessed group differences after the intervention with mixed-model analyses adjusting for baseline performance and analyzed the association between network and cognitive performance changes with repeated measures correlation analyses. The final analysis sample consisted of 71 participants (n CT = 37). After intervention there were no group differences on between-network connectivity and network topological outcomes. No associations between neural network and neuropsychological performance change were found. CT increased segregated network topology in a small sub-sample of cognitively intact participants. Post-hoc nodal analyses showed post-intervention enhanced connectivity of both the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex in the CT group. The results suggest no large-scale brain network effects of eight-week computerized CT, but rather localized connectivity changes of key regions in cognitive function, that potentially reflect the specific effects of the intervention.

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YNICL Journal 2020 Journal Article

Processing speed is related to striatal dopamine transporter availability in Parkinson's disease

Chris Vriend
Tim D. van Balkom
Corné van Druningen
Martin Klein
Ysbrand D. van der Werf
Henk W. Berendse
Odile A. van den Heuvel

BACKGROUND: Parkinson's disease (PD) affects the integrity of the dopamine and serotonin system, and is characterized by a plethora of different symptoms, including cognitive impairments of which the pathophysiology is not yet fully elucidated. OBJECTIVES: I-FP-CIT). METHODS: I-FP-CIT SPECT scan and a neuropsychological assessment. RESULTS: We showed a positive association between DAT availability in the head of the caudate nucleus and the Stroop Color Word Task - card I (reading words; β = 0.32, P = 0.001) and a positive association between DAT availability in the anterior putamen and the Trail Making Test part A (connecting consecutively numbered circles; β = 0.25, P = 0.02). These associations remained after adjusting for motor symptom severity or volume of the region-of-interest and were most pronounced in medication-naïve PD patients. There were no associations between cognitive performance and SERT availability in the thalamus or hippocampus. CONCLUSIONS: We interpret these results as a role for striatal dopamine - and its PD-related decline - in aspects of processing speed.

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YNICL Journal 2019 Journal Article

Widespread white matter connectivity abnormalities in narcolepsy type 1: A diffusion tensor imaging study

Jari K. Gool
Rolf Fronczek
Alexander Leemans
Dennis A. Kies
Gert Jan Lammers
Ysbrand D. van der Werf

Narcolepsy type 1 is caused by a selective loss of hypothalamic hypocretin-producing neurons, resulting in severely disturbed sleep-wake control and cataplexy. Hypocretin-producing neurons project widely throughout the brain, influencing different neural networks. We assessed the extent of microstructural white matter organization and brain-wide structural connectivity abnormalities in a homogeneous group of twelve drug-free patients with narcolepsy type 1 and eleven matched healthy controls using diffusion tensor imaging with multimodal analysis techniques. First, tract-based spatial statistics (TBSS) was carried out using fractional anisotropy (FA) and mean, axial and radial diffusivity (MD, AD, RD). Second, quantitative analyses of mean FA, MD, AD and RD were conducted in predefined regions-of-interest, including sleep-wake regulation-related, limbic and reward system areas. Third, we performed hypothalamus-seeded tractography towards the thalamus, amygdala and midbrain. TBSS analyses yielded brain-wide significantly lower FA and higher RD in patients. Localized significantly lower FA and higher RD in the left ventral diencephalon and lower AD in the midbrain, were seen in patients. Lower FA was also found in patients in left hypothalamic fibers connecting with the midbrain. No significant MD and AD differences nor a correlation with disease duration were found. The brain-wide, localized ventral diencephalon (comprising the hypothalamus and different sleep- and motor-related nuclei) and hypothalamic connectivity differences clearly show a heretofore underestimated direct and/or indirect effect of hypocretin deficiency on microstructural white matter composition, presumably resulting from a combination of lower axonal density, lower myelination and/or greater axon diameter.

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YNICL Journal 2018 Journal Article

Distinctive tics suppression network in Gilles de la Tourette syndrome distinguished from suppression of natural urges using multimodal imaging

Sandra M.A. van der Salm
Johan N. van der Meer
Daniëlle C. Cath
Paul F.C. Groot
Ysbrand D. van der Werf
Eelke Brouwers
Stella J. de Wit
Joris C. Coppens

BACKGROUND AND OBJECTIVES: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by tics. A hallmark of GTS is the ability to voluntarily suppress tics. Our aim was to distinguish the neural circuits involved in the voluntary suppression of ocular tics in GTS patients from blink suppression in healthy subjects. METHODS: Fifteen GTS patients and 22 healthy control subjects were included in a multimodal study using eye-tracker recordings during functional MRI (fMRI). The ability to suppress tics/blinks was compared both on subjective (self-rating) and objective (eye-tracker) performance. For fMRI analysis we used a novel designed performance-adapted block design analysis of tic/blink suppression and release based on eye-tracker monitoring. RESULTS: We found that the subjective self-reported ability to suppress tics or blinks showed no significant correlation with objective task performance. In GTS during successful suppression of tics, the dorsal anterior cingulate cortex and associated limbic areas showed increased activation. During successful suppression of eye blinks in healthy subjects, the right ventrolateral prefrontal cortex and supplementary and cingulate motor areas showed increased activation. CONCLUSIONS: These findings demonstrate that GTS patients use a characteristic limbic suppression strategy. In contrast, control subjects use the voluntary sensorimotor circuits and the classical 'stop' network to suppress natural urges. The employment of different neural suppression networks provides support for cognitive behavioral therapy in GTS.

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YNIMG Journal 2016 Journal Article

Carbon-wire loop based artifact correction outperforms post-processing EEG/fMRI corrections—A validation of a real-time simultaneous EEG/fMRI correction method

Johan N. van der Meer
André Pampel
Eus J.W. Van Someren
Jennifer R. Ramautar
Ysbrand D. van der Werf
German Gomez-Herrero
Jöran Lepsien
Lydia Hellrung

Simultaneous EEG-fMRI combines two powerful neuroimaging techniques, but the EEG signal suffers from severe artifacts in the MRI environment that are difficult to remove. These are the MR scanning artifact and the blood-pulsation artifact — strategies to remove them are a topic of ongoing research. Additionally large, unsystematic artifacts are produced across the full frequency spectrum by the magnet's helium pump (and ventilator) systems which are notoriously hard to remove. As a consequence, experimenters routinely deactivate the helium pump during simultaneous EEG-fMRI acquisitions which potentially risks damaging the MRI system and necessitates more frequent and expensive helium refills. We present a novel correction method addressing both helium pump and ballisto-cardiac (BCG) artifacts, consisting of carbon-wire loops (CWL) as additional sensors to accurately track unpredictable artifacts related to subtle movements in the scanner, and an EEGLAB plugin to perform artifact correction. We compare signal-to-noise metrics of EEG data, corrected with CWL and three conventional correction methods, for helium pump off and on measurements. Because the CWL setup records signals in real-time, it fits requirements of applications where immediate correction is necessary, such as neuro-feedback applications or stimulation time-locked to specific sleep oscillations. The comparison metrics in this paper relate to: (1) the EEG signal itself, (2) the “eyes open vs. eyes closed” effect, and (3) an assessment of how the artifact corrections impacts the ability to perform meaningful correlations between EEG alpha power and the BOLD signal. Results show that the CWL correction corrects for He pump artifact and also produces EEG data more comparable to EEG obtained outside the magnet than conventional post-processing methods.

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YNIMG Journal 2013 Journal Article

Disrupted directed connectivity along the cingulate cortex determines vigilance after sleep deprivation

Giovanni Piantoni
Bing Leung P. Cheung
Barry D. Van Veen
Nico Romeijn
Brady A. Riedner
Giulio Tononi
Ysbrand D. van der Werf
Eus J.W. Van Someren

The cingulate cortex is regarded as the backbone of structural and functional connectivity of the brain. While its functional connectivity has been intensively studied, little is known about its effective connectivity, its modulation by behavioral states, and its involvement in cognitive performance. Given the previously reported effects on cingulate functional connectivity, we investigated how eye-closure and sleep deprivation changed cingulate effective connectivity, estimated from resting-state high-density electroencephalography (EEG) using a novel method to calculate Granger Causality directly in source space. Effective connectivity along the cingulate cortex was dominant in the forward direction. Eyes-open connectivity in the forward direction was greater compared to eyes-closed, in well-rested participants. The difference between eyes-open and eyes-closed connectivity was attenuated and no longer significant after sleep deprivation. Individual variability in the forward connectivity after sleep deprivation predicted subsequent task performance, such that those subjects who showed a greater increase in forward connectivity between the eyes-open and the eyes-closed periods also performed better on a sustained attention task. Effective connectivity in the opposite, backward, direction was not affected by whether the eyes were open or closed or by sleep deprivation. These findings indicate that the effective connectivity from posterior to anterior cingulate regions is enhanced when a well-rested subject has his eyes open compared to when they are closed. Sleep deprivation impairs this directed information flow, proportional to its deleterious effect on vigilance. Therefore, sleep may play a role in the maintenance of waking effective connectivity.

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