Biomedical subjects

Henk J Groenewegen

Publications and source records attributed to Henk J Groenewegen.

12 recordsLinked to original sources

PubMed2005

Frontal-striatal dysfunction during planning in obsessive-compulsive disorder.

BACKGROUND: Dysfunction of frontal-striatal, particularly orbitofrontal-striatal, circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD), characterized by obsessions, ritualistic behavior, anxiety, and specific cognitive impairments. In addition, neuropsychological studies in OCD have reported impairments in visuospatial tasks and executive functions, such as planning. OBJECTIVE: To determine whether dorsal prefrontal-striatal dysfunction mediates planning impairment in patients with OCD. DESIGN: A parametric self-paced pseudorandomized event-related functional magnetic resonance imaging version of the Tower of London task was used in 22 medication-free patients with OCD and 22 healthy control subjects. This paradigm, allowing flexible responding and post hoc classification of correct responses, was developed to compare groups likely to differ in performance. RESULTS: Behavioral results showed significant planning impairments in OCD patients compared with control subjects. During planning, decreased frontal-striatal responsiveness was found in OCD patients, mainly in dorsolateral prefrontal cortex and caudate nucleus. In addition, OCD patients showed increased, presumably compensatory, involvement of brain areas known to play a role in performance monitoring and short-term memory processing, such as anterior cingulate, ventrolateral prefrontal, and parahippocampal cortices. CONCLUSIONS: These findings support the hypothesis that decreased dorsal prefrontal-striatal responsiveness is associated with impaired planning capacity in OCD patients. Because the described frontal-striatal dysfunction in OCD is independent of state anxiety and disease symptom severity, we conclude that executive impairment is a core feature in OCD.

Adult↗

PubMed2005

Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis.

CONTEXT: Attentional bias to disease-relevant emotional cues is considered to be pathogenetically relevant in anxiety disorders. OBJECTIVE: To investigate functional neural correlates and disease specificity of attentional bias across different anxiety disorders. DESIGN: A cognitive and emotional Stroop task, consisting of congruent and incongruent color words, obsessive-compulsive disorder (OCD)-related and panic-related negative words, and neutral words, was used in 3 patient groups and a control group during functional magnetic resonance imaging. SETTING: Academic outpatient department for anxiety disorders. PATIENTS AND PARTICIPANTS: Medication-free patients with OCD (n = 16), panic disorder (PD) (n = 15), and hypochondriasis (n = 13) and 19 controls. MAIN OUTCOME MEASURE: Voxel-wise analyses of cerebral blood flow changes for contrasts of interest (incongruent vs congruent color words, OCD-related vs neutral words, and panic-related vs neutral words) within and between groups. RESULTS: During incongruent vs congruent color naming, all patient groups recruited additional posterior brain regions relative to controls, but performance was impaired only in OCD. In OCD, color naming OCD-related, but not PD-related, words correlated with increased activation of frontal-striatal and temporal regions, although performance was unimpaired. In contrast, in PD, increased frontal-striatal involvement was found during color naming both OCD-related and panic-related words. In PD, color naming panic-related words was slowed and correlated with increased activation of the right amygdala and hippocampus. Patients with hypochondriasis showed a similar activation pattern to patients with PD. CONCLUSIONS: Our results support the hypothesis of increased distractibility for irrelevant information in patients with OCD, PD, and hypochondriasis associated with frontal-striatal and limbic involvement compared with controls. Although patients with OCD did not display an attentional bias in behavior relative to controls, there was a clear, specific neural response during color naming OCD-related words, involving mainly ventral brain regions. In contrast, generalized emotional interference effects were found in PD and hypochondriasis, involving ventral and widespread dorsal brain regions, reflecting not only unconscious emotional stimulus processing but also increased cognitive elaboration.

Adult↗

PubMed2004

Amygdala activity in obsessive-compulsive disorder with contamination fear: a study with oxygen-15 water positron emission tomography.

Previous imaging studies of obsessive-compulsive symptom states have implicated frontal-striatal and limbic regions in the pathophysiology of obsessive-compulsive disorder (OCD). Functional imaging studies, however, have yielded inconsistent results, presumably due to methodological differences (patient inclusion criteria, stimulus paradigm, imaging technique, and absence of control groups). In the present study, randomized presentation of contamination-related and neutral visual stimuli was used to investigate the neurophysiological correlates of contamination fear in a group of medication-free OCD patients with washing behaviors and healthy controls. A total of 21 subjects (11 OCD patients and 10 healthy controls) were scanned using H(2)(15)O positron emission tomography (PET). Subjects were presented with pictures of clean and dirty surroundings and were requested to make indoor/outdoor decisions to control for attention differences. State anxiety and obsessionality were rated after each scan using visual analogue scales. Main effects of stimulus type (contamination vs. neutral) were found in bilateral occipital cortex in both groups. A significant group interaction effect was observed in the left amygdala reflecting enhanced activity in response to contamination stimuli in OCD patients. Sensitization effects were observed in the right amygdala in the OCD group; these paralleled an increase in levels of distress and obsessionality as well as a decrease in dorsolateral prefrontal activity. The findings of the present study are consistent with the hypothesis of decreased frontal-striatal control of limbic structures, specifically the amygdala, resulting in an inadequate fear response in OCD patients with contamination fear.

Adult↗

PubMed2004

Putting a spin on the dorsal-ventral divide of the striatum.

Since its conception three decades ago, the idea that the striatum consists of a dorsal sensorimotor part and a ventral portion processing limbic information has sparked a quest for functional correlates and anatomical characteristics of the striatal divisions. But this classic dorsal-ventral distinction might not offer the best view of striatal function. Anatomy and neurophysiology show that the two striatal areas have the same basic structure and that sharp boundaries are absent. Behaviorally, a distinction between dorsolateral and ventromedial seems most valid, in accordance with a mediolateral functional zonation imposed on the striatum by its excitatory cortical, thalamic and amygdaloid inputs. Therefore, this review presents a synthesis between the dorsal-ventral distinction and the more mediolateral-oriented functional striatal gradient.

Animals↗

PubMed2003

Do rats have a prefrontal cortex?

The lack of a single anatomical or functional definition of 'prefrontal cortex' has led to different and, in some respects, controversial views on the existence of a prefrontal cortex in non-primate mammals, in particular in rats. Until the classic paper by Rose and Woolsey [Res. Publ. Assoc. Nerv. Ment. Dis. 27 (1948) 210], the general idea was that a prefrontal cortex is unique to primate species. Rose and Woolsey's 'prefrontal cortex' definition was based upon a single anatomical criterion, i.e. the cortical projection area of the mediodorsal thalamic nucleus. Single criteria, however, do not appear to be sufficient for defining the prefrontal cortex. Therefore, other anatomical and functional characteristics are currently used to identify the prefrontal cortex in different species. Yet, recently the debate about the nature of the prefrontal cortex in non-primate species has been resumed. In the present paper we will compare the structural and functional characteristics of the prefrontal cortex of nonhuman primates and rats. We will argue that rats have a functionally divided prefrontal cortex that includes not only features of the medial and orbital areas in primates, but also some features of the primate dorsolateral prefrontal cortex.

Animals↗

PubMed2003

Direct physiological evidence for synaptic connectivity between medium-sized spiny neurons in rat nucleus accumbens in situ.

Dual whole cell patch-clamp recordings in rat nucleus accumbens, the main component of the ventral striatum, were made to assess the presence of synaptic interconnections between medium-sized spiny neurons, a group of GABAergic and peptidergic neurons that constitute the principal cells of the striatum. Neurons were stained with biocytin for subsequent morphological analysis. Electrical activity of cells was recorded in current- and voltage-clamp mode; the characteristics of medium-sized spiny neurons were confirmed by electrophysiological and morphological properties. Thirteen of 38 medium-sized spiny neuron pairs (34%) showed a synaptic connection. In these pairs, suprathreshold stimulation with current injection evoked a train of action potentials in the presynaptic cell, which in turn elicited depolarizing postsynaptic potentials (dPSPs) in the postsynaptic cell. Twelve of these 13 pairs were connected unilaterally. The onset latency of the postsynaptic response was 1.7 +/- 0.7 ms. dPSPs were blocked by 12.5 microM bicuculline, suggesting they were mediated by GABA(A) receptors. A linear fit of the current-voltage relationship of GABAergic currents crossed the voltage axis near the value of -20 mV, in agreement with the Cl(-) equilibrium potential predicted from the composition of the artificial cerebrospinal fluid and pipette medium. No evidence for electrotonic coupling was found. Paired-pulse facilitation and depression were induced when the amplitude of the first IPSC of a pair was relatively small and large, respectively. No clear dependence of paired-pulse facilitation or depression was found on the width of the spike interval, which ranged between 100 and 380 ms. Conversely, 1- to 2-s trains of dPSPs showed marked frequency facilitation at low presynaptic frequencies, but frequency depression at high firing rates. These data show that intra-accumbens synaptic communication between medium-sized spiny neurons exists, is mediated by GABA(A) receptors, and exhibits spike train-dependent short-term dynamics.

Animals↗

PubMed2003

The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics.

The prefrontal cortex in rats can be distinguished anatomically from other frontal cortical areas both in terms of cytoarchitectonic characteristics and neural connectivity, and it can be further subdivided into subterritories on the basis of such criteria. Functionally, the prefrontal cortex of rats has been implicated in working memory, attention, response initiation and management of autonomic control and emotion. In humans, dysfunction of prefrontal cortical areas with which the medial prefrontal cortex of the rat is most likely comparable is related to psychopathology including schizophrenia, sociopathy, obsessive-compulsive disorder, depression, and drug abuse. Recent literature points to the relevance of conducting a functional analysis of prefrontal subregions and supports the idea that the area of the medial prefrontal cortex in rats is characterized by its own functional heterogeneity, which may be related to neuroanatomical and neurochemical dissociations. The present review covers recent findings with the intent of correlating these distinct functional differences in the dorso-ventral axis of the rat medial prefrontal cortex with anatomical and neurochemical patterns.

Animals↗

PubMed2003

Does an imbalance between the dorsal and ventral striatopallidal systems play a role in Tourette's syndrome? A neuronal circuit approach.

Tourette's syndrome is characterized by simple, involuntary muscle contractions and/or more complex movements or stereotyped behaviors, including vocalizations. There are strong indications that the basal ganglia play an important role in the pathophysiology of Tourette's syndrome. The present account reviews the functional anatomy of the basal ganglia, with an emphasis on the prefrontal cortex-ventral striatopallidal system. Different parts of the basal ganglia and thalamocortical system, with a focus on the premotor and prefrontal cortices, are connected with each other via parallel, functionally segregated basal ganglia-thalamocortical systems. These parallel circuits, representing sensorimotor, cognitive and emotional-motivational behavioral processes, are connected with each other through specific pathways that serve to integrate these various functions. In the context of the discussion on the pathophysiological mechanisms that lead to the expression of tics, emphasis is placed on the pathways that lead from the ventral striatum via the dopaminergic substantia nigra to the dorsal striatum. The dorsal striatum is crucial for habit formation. A conclusion of this overview of the anatomical organization of the basal ganglia is that via dopaminergic pathways limbic-relation information can influence the expression of (fragments of) motor and behavioral repertoires. Whether such mechanisms indeed play a role in the expression of tics in Tourette's syndrome remains to be established.

Animals↗

PubMed2003

Frontostriatal system in planning complexity: a parametric functional magnetic resonance version of Tower of London task.

In the present study, we sought to investigate which brain structures are recruited in planning tasks of increasing complexity. For this purpose, a parametric self-paced pseudo-randomized event-related functional MRI version of the Tower of London task was designed. We tested 22 healthy subjects, enabling assessment of imaging results at a second (random effects) level of analysis. Compared with baseline, planning activity was correlated with increased blood oxygenation level-dependent (BOLD) signal in the dorsolateral prefrontal cortex, striatum, premotor cortex, supplementary motor area, and visuospatial system (precuneus and inferior parietal cortex). Task load was associated with increased activity in these same regions. In addition, increasing task complexity was correlated with activity in the left anterior prefrontal cortex, a region supposed to be specifically involved in third-order higher cognitive functioning.

Adult↗

PubMed2003

The basal ganglia and motor control.

This paper briefly reviews the functional anatomy of the basal ganglia and their relationships with the thalamocortical system. The basal ganglia, including the striatum, pallidum, subthalamic nucleus, and substantia nigra, are involved in a number of parallel, functionally segregated cortical-subcortical circuits. These circuits support a wide range of sensorimotor, cognitive and emotional-motivational brain functions. A main role of the basal ganglia is the learning and selection of the most appropriate motor or behavioral programs. The internal functional organization of the basal ganglia is very well suited for such selection mechanisms, both in development and in adulthood. The question of whether clumsiness may be, at least in part, attributed to dysfunction of the basal ganglia is discussed in the context of the differential, complementary, or interactive roles of the basal ganglia and the cerebellum in the development of motor control.

Animals↗

PubMed2003

Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome. Report of three cases.

Based on the results of thalamotomies described by Hassler in 1970, the authors performed bilateral thalamic high-frequency stimulation (HFS) in three patients with intractable Tourette syndrome (TS). In this report they describe the long-term effects. Three male patients (42, 28, and 45 years of age) had manifested motor and vocal tics since early childhood. The diagnosis of TS was made according to the criteria of the Tourette Syndrome Classification Study Group. Any drug or alternative treatment had been either ineffective or only temporarily effective in all three patients. There was no serious comorbidity. The target for stimulation was chosen at the level of the centromedian nucleus, substantia periventricularis, and nucleus ventrooralis internus. After 2 weeks of test stimulation, the pulse generators were implanted. After a follow-up period of 5 years in the patient in Case 1, 1 year in the patient in Case 2, and 8 months in the patient in Case 3, all major motor and vocal tics had disappeared and no serious complications had occurred. When stimulation was applied at the voltage necessary to achieve an optimal result on the tics, a slight sedative effect was noted in all three patients. In the patients in Cases 1 and 3 there were stimulation-induced changes in sexual behavior. Chronic thalamic HFS may be an effective and safe treatment for medically intractable TS in adult patients. Unwanted stimulation-induced side effects may occur.

Adult↗

PubMed2002

The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness.

The thalamic midline and intralaminar nuclei, long thought to be a non-specific arousing system in the brain, have been shown to be involved in separate and specific brain functions, such as specific cognitive, sensory and motor functions. Fundamental to the participation of the midline and intralaminar nuclei in such diverse functions seems to be a role in awareness. It is unknown whether the midline and intralaminar nuclei, together often referred to as the 'non-specific' nuclei of the thalamus, act together or whether each nucleus is involved idiosyncratically in separate circuits underlying cortical processes. Detailed knowledge of the connectivity of each of these nuclei is needed to judge the nature of their contribution to cortical functioning. The present account provides an overview of the results of neuroanatomical tracing studies on the connections of the individual intralaminar and midline thalamic nuclei in the rat, that have been performed over the past decade in our laboratory. The results are discussed together with those reported by other laboratories, and with those obtained in other species. On the basis of the patterns of the afferent and efferent projections, we conclude that the midline and intralaminar thalamic nuclei can be clustered into four groups. Each of the groups can be shown to have its own set of target and input structures, both cortically and subcortically. These anatomical relationships, in combination with functional studies in animals and in humans, lead us to propose that the midline and intralaminar nuclei as a whole play a role in awareness, with each of the groups subserving a role in a different aspect of awareness. The following groups can be discerned: (1) a dorsal group, consisting of the paraventricular, parataenial and intermediodorsal nuclei, involved in viscero-limbic functions; (2) a lateral group, comprising the central lateral and paracentral nuclei and the anterior part of the central medial nucleus, involved in cognitive functions; (3) a ventral group, made up of the reuniens and rhomboid nucleus and the posterior part of the central medial nucleus, involved in multimodal sensory processing; (4) a posterior group, consisting of the centre médian and parafascicular nuclei, involved in limbic motor functions.

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