Publications by authors named "Sebastiaan Koekkoek"

Introduction: Physical exercise has repeatedly been reported to have advantageous effects on brain functions, including learning and memory formation. However, objective tools to measure such effects are often lacking. Eyeblink conditioning is a well-characterized method for studying the neural basis of associative learning.

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Gait ataxia is one of the most common and impactful consequences of cerebellar dysfunction. Purkinje cells, the sole output neurons of the cerebellar cortex, are often involved in the underlying pathology, but their specific functions during locomotor control in health and disease remain obfuscated. We aimed to describe the effect of gradual adult-onset Purkinje cell degeneration on gaiting patterns in mice, and to determine whether two different mechanisms that both lead to Purkinje cell degeneration cause different patterns in the development of gait ataxia.

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Article Synopsis
  • Four-dimensional ultrasound imaging of complex biological systems, like the brain, faces challenges due to the need for precise spatial and temporal data collection.
  • The introduced method, computational ultrasound imaging (cUSi), utilizes sophisticated ultrasound fields generated by basic hardware and a wave prediction model to overcome these limitations.
  • cUSi enables high-resolution, four-dimensional imaging of blood flow in the brains of both awake and anesthetized mice.
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Functional ultrasound (fUS) using a 1-D-array transducer normally is insufficient to capture volumetric functional activity due to being restricted to imaging a single brain slice at a time. Typically, for volumetric fUS, functional recordings are repeated many times as the transducer is moved to a new location after each recording, resulting in a nonunique average mapping of the brain response and long scan times. Our objective was to perform volumetric 3-D fUS in an efficient and cost-effective manner.

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  • Volumetric 3-D Doppler ultrasound imaging offers improved insight into blood flow dynamics compared to the limitations of conventional 2-D power Doppler images, using advanced imaging techniques and equipment.
  • The study aims to enhance 3-D imaging sensitivity and affordability by utilizing a 1-D-array transducer mounted on a motorized linear stage to scan the mouse brain, thus reducing scan times.
  • Part I of the study focuses on optimizing the combination of different ultrasound frames to improve vascular image quality, while Part II examines how the speed of the transducer's movement affects imaging quality and overall Doppler spectrum resolution.
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  • Surgical resection of spinal cord hemangioblastomas poses a challenge, as achieving total tumor removal risks causing neurological deficits.
  • Current imaging tools like MRI are limited to pre-operative assessments and do not adapt to real-time changes during surgery.
  • µDoppler-imaging is a new high-resolution technique that allows for continuous and detailed blood flow visualization, and this study explores its first application in spinal cord surgeries, potentially improving outcomes for complex vascular tumors.
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Delay eyeblink conditioning has been extensively used to study associative learning and the cerebellar circuits underlying this task have been largely identified. However, there is a little knowledge on how factors such as strain, sex and innate behaviour influence performance during this type of learning. In this study, we used male and female mice of C57BL/6J (B6) and B6CBAF1 strains to investigate the effect of sex, strain and locomotion in delay eyeblink conditioning.

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When the brain is exposed, such as after a craniotomy in neurosurgical procedures, we are provided with the unique opportunity for real-time imaging of brain functionality. Real-time functional maps of the exposed brain are vital to ensuring safe and effective navigation during these neurosurgical procedures. However, current neurosurgical practice has yet to fully harness this potential as it pre-dominantly relies on inherently limited techniques such as electrical stimulation to provide functional feedback to guide surgical decision-making.

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Functional ultrasound (fUS) indirectly measures brain activity by detecting changes in cerebral blood volume following neural activation. Conventional approaches model such functional neuroimaging data as the convolution between an impulse response, known as the hemodynamic response function (HRF), and a binarized representation of the input signal based on the stimulus onsets, the so-called experimental paradigm (EP). However, the EP may not characterize the whole complexity of the activity-inducing signals that evoke the hemodynamic changes.

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  • The study discusses the necessity of precise imaging techniques for the surgical removal of arteriovenous malformations (AVMs), highlighting that current methods primarily focus on preoperative imaging and are not adaptable during surgery.
  • The authors introduced intraoperative micro-Doppler imaging, which is capable of high-resolution visualization of vascular structures and blood flow in real-time, allowing for better identification of crucial anatomical details during AVM resections.
  • The findings suggest that micro-Doppler imaging could serve as an effective supplementary tool to traditional imaging methods, enhancing the understanding of cerebrovascular conditions and improving surgical outcomes.
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: Pigs have been an increasingly popular preclinical model in nutritional neuroscience, as their anatomy, physiology, and nutrition requirements are highly comparable to those of humans. Eyeblink conditioning is one of the most well-validated behavioral paradigms in neuroscience to study underlying mechanisms of learning and memory formation in the cerebellum. Eyeblink conditioning has been performed in many species but has never been done on young pigs.

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Background And Purpose: Oncological neurosurgery relies heavily on making continuous, intra-operative tumor-brain delineations based on image-guidance. Limitations of currently available imaging techniques call for the development of real-time image-guided resection tools, which allow for reliable functional and anatomical information in an intra-operative setting. Functional ultrasound (fUS), is a new mobile neuro-imaging tool with unprecedented spatiotemporal resolution, which allows for the detection of small changes in blood dynamics that reflect changes in metabolic activity of activated neurons through neurovascular coupling.

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Pavlovian eyeblink conditioning has been used extensively to study the neural mechanisms underlying associative and motor learning. During this simple learning task, memory formation takes place at Purkinje cells in defined areas of the cerebellar cortex, which acquire a strong temporary suppression of their activity during conditioning. Yet, it is unknown which neuronal plasticity mechanisms mediate this suppression.

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A growing body of evidence suggests that the cerebellum is involved in both cognition and language. Abnormal cerebellar development may contribute to neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD), autism, fetal alcohol syndrome, dyslexia, and specific language impairment. Performance in eyeblink conditioning, which depends on the cerebellum, can potentially be used to clarify the neural mechanisms underlying the cerebellar dysfunction in disorders like these.

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Classical delay eyeblink conditioning is likely the most commonly used paradigm to study cerebellar learning. As yet, few studies have focused on extinction and savings of conditioned eyeblink responses (CRs). Saving effects, which are reflected in a reacquisition after extinction that is faster than the initial acquisition, suggest that learned associations are at least partly preserved during extinction.

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Three decades of electrophysiological research on cerebellar cortical activity underlying Pavlovian conditioning have expanded our understanding of motor learning in the brain. Purkinje cell simple spike suppression is considered to be crucial in the expression of conditional blink responses (CRs). However, trial-by-trial quantification of this link in awake behaving animals is lacking, and current hypotheses regarding the underlying plasticity mechanisms have diverged from the classical parallel fiber one to the Purkinje cell synapse LTD hypothesis.

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Spinocerebellar ataxia type 6 (SCA6) is linked to poly-glutamine (polyQ) within the C terminus (CT) of the pore-forming subunits of P/Q-type Ca(2+) channels (Cav2.1) and is characterized by CT protein aggregates found in cerebellar Purkinje cells (PCs). One hypothesis regarding SCA6 disease is that a CT fragment of the Cav2.

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There are controversies whether learning of conditioned eyeblink responses primarily takes place within the cerebellar cortex, the interposed nuclei, or both. It has also been suggested that the cerebellar cortex may be important during early stages of learning, and that there is a shift to the cerebellar nuclei during later stages. As yet, human studies have provided little to resolve this question.

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Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI) to study changes in spinal dorsal horn metabolic activity.

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Article Synopsis
  • The study examines how specific types of brain cells in the cerebellar cortex contribute to basic and complex motor skills, like walking and obstacle crossing.
  • Using various mouse mutant lines with impaired cerebellar functions, researchers found significant deficiencies in locomotion and coordination, especially in mice with Purkinje cell issues.
  • Despite these physical impairments, motivation and basic avoidance behaviors remained intact, suggesting that the cerebellum plays a crucial role in coordinating complex movements rather than general motivation.
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  • Whisker-based object localization relies on the activation and adaptability of the somatosensory and motor cortex, which are influenced by the cerebellum through the thalamus.
  • Knock-out mice with impaired cerebellar function (L7-PP2B) struggled significantly more than wild-type mice in learning a whisker localization task, despite showing normal basic motor abilities.
  • The study suggests that cerebellar processing, particularly the ability to enhance synaptic connections (potentiation), plays a critical role in the successful learning of complex tasks that require precise timing.
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Background: To investigate the pathophysiology of temperature hypersensitivity in neuropathic pain rodent models, it is essential to be able to quantify the phenotype as objective as possible. Current temperature sensitivity measuring paradigms are performed during exposure to external factors, i.e.

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Plastic changes in the efficacy of synapses are widely regarded to represent mechanisms underlying memory formation. So far, evidence for learning-dependent, new neuronal wiring is limited. In this study, we demonstrate that pavlovian eyeblink conditioning in adult mice can induce robust axonal growth and synapse formation in the cerebellar nuclei.

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Background: The notion that cerebellar deficits may underlie clinical symptoms in people with schizophrenia is tested by evaluating 2 forms of cerebellar learning in patients with recent-onset schizophrenia. A potential medication effect is evaluated by including patients with or without antipsychotics.

Methods: We assessed saccadic eye movement adaptation and eyeblink conditioning in men with recent-onset schizophrenia who were taking antipsychotic medication or who were antipsychotic-free and in age-matched controls.

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