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Biomedical subjects

Dick J Veltman

Publications and source records attributed to Dick J Veltman.

At least 19 recordsLinked to original sources

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. METHODS: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). RESULTS: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected  = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected  = .001). CONCLUSIONS: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Humans↗

Intrapair differences in hippocampal volume in monozygotic twins discordant for the risk for anxiety and depression.

BACKGROUND: Current biological psychiatric models assume that genetic and environmental risk factors for anxiety and depression act on the same brain structures. METHODS: To test this assumption, we assessed brain anatomy by using optimized voxel-based morphometry on magnetic resonance images obtained in monozygotic twin pairs who were discordant for the risk of anxiety and depression (n = 10 pairs) and in monozygotic twin pairs who were concordant for high (n = 7 pairs) or low (n = 15 pairs) risk for anxiety and depression. RESULTS: We observed volume reductions in the temporal lobe, most notably in the left posterior hippocampal region in subjects at high risk for anxiety and depression, but exclusively in the intrapair comparison of discordant monozygotic twins. Because monozygotic twins are genetically identical, any discordance in their risk for anxiety and depression and hippocampal volume must arise from differential exposure to environmental influences. A group comparison between pairs concordant for low or high risk, which is more likely to reflect differences in genetic vulnerability, did not show reduced temporal-lobe and posterior hippocampal volumes in the pairs at high risk for anxiety and depression. CONCLUSIONS: This pattern of results suggests that damage to temporal-lobe structures may be specific to an environmentally driven etiology of anxiety and depression.

Adolescent↗

Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulators.

OBJECTIVE: To compare changes in regional cerebral blood flow (rCBF), using positron emission tomography (PET), during chronic and acute sacral neuromodulation (SN). SN is an effective long-term treatment for chronic urge incontinence due to urinary bladder hyperactivity, as sensory nerves, spinal and supraspinal structures are probably responsible for the action of SN. It is not known which brain areas are involved, and the optimum benefit of SN is not immediate, suggesting that induced plasticity of the brain is necessary. PATIENTS AND METHODS: Brain activity was measured in two groups: 12 urge incontinent patients (11 women and one man; mean age 52 years) in whom an implanted unilateral S3 nerve neurostimulator had been effective for >6 months (mean time after implantation 4.5 years); and eight urge incontinent patients (seven women and one man; mean age 49 years) in whom the neurostimulator was activated for the first time in the PET scanner. RESULTS: During SN in chronically implanted patients, there were significant decreases in rCBF in the middle part of the cingulate gyrus, the ventromedial orbitofrontal cortex, midbrain and adjacent midline thalamus, and rCBF increases in the dorsolateral prefrontal cortex. During acute SN in newly implanted patients, there were significant decreases in rCBF the medial cerebellum, and increases in the right postcentral gyrus cortex, the right insular cortex and the ventromedial orbitofrontal cortex. Group analysis between chronic and newly implanted patients showed significant differences in the associative sensory cortex, premotor cortex and the cerebellum, all three involved in learning behaviour. CONCLUSIONS: These findings suggests that chronic SN influences, presumably via the spinal cord, brain areas previously implicated in detrusor hyperactivity, awareness of bladder filling, the urge to void and the timing of micturition. Furthermore, SN affects areas involved in alertness and awareness. Acute SN modulates predominantly areas involved in sensorimotor learning, which might become less active during the course of chronic SN.

Acute Disease↗

Neural correlates of enhanced working-memory performance in dissociative disorder: a functional MRI study.

BACKGROUND: Memory functioning has been highlighted as a central issue in pathological dissociation. In non-pathological dissociation, evidence for enhanced working memory has been found, together with greater task-load related activity. So far, no imaging studies have investigated working memory in dissociative patients. METHOD: To assess working memory in dissociative patients functional magnetic resonance imaging was used during performance of a parametric, verbal working-memory task in patients with a dissociative disorder (n=16) and healthy controls (n=16). RESULTS: Imaging data showed that both groups activated brain regions typically involved in working memory, i.e. anterior, dorsolateral and ventrolateral prefrontal cortex (PFC), and parietal cortex. Dissociative patients showed more activation in these areas, particularly in the left anterior PFC, dorsolateral PFC and parietal cortex. In line with these findings, patients made fewer errors with increasing task load compared to controls, despite the fact that they felt more anxious and less concentrated during task performance. CONCLUSIONS: These results extend findings in non-pathological high dissociative individuals, suggesting that trait dissociation is associated with enhanced working-memory capacities. This may distinguish dissociative patients from patients with post-traumatic stress disorder, who are generally characterized by impaired working memory.

Adult↗

Effects of growth hormone substitution therapy on cognitive functioning in growth hormone deficient patients: a functional MRI study.

Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 +/- 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging.

Adolescent↗

Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder.

CONTEXT: The orbitofrontal cortex (OFC)-striatal circuit, which is important for motivational behavior, is assumed to be involved in the pathophysiology of obsessive-compulsive disorder (OCD) according to current neurobiological models of this disorder. However, the engagement of this neural loop in OCD has not been tested directly in a cognitive activation imaging paradigm so far. OBJECTIVE: To determine whether the OFC and the ventral striatum show abnormal neural activity in OCD during cognitive challenge. DESIGN: A reversal learning task was employed in 20 patients with OCD who were not receiving medication and 27 healthy controls during an event-related functional magnetic resonance imaging experiment using a scanning sequence sensitive to OFC signal. This design allowed investigation of the neural correlates of reward and punishment receipt as well as of "affective switching," ie, altering behavior on reversing reinforcement contingencies. RESULTS: Patients with OCD exhibited an impaired task end result reflected by a reduced number of correct responses relative to control subjects but showed adequate behavior on receipt of punishment and with regard to affective switching. On reward outcome, patients showed decreased responsiveness in right medial and lateral OFC as well as in the right caudate nucleus (border zone ventral striatum) when compared with controls. During affective switching, patients recruited the left posterior OFC, bilateral insular cortex, bilateral dorsolateral, and bilateral anterior prefrontal cortex to a lesser extent than control subjects. No areas were found for which patients exhibited increased activity relative to controls, and no differential activations were observed for punishment in a direct group comparison. CONCLUSIONS: These data show behavioral impairments accompanied by aberrant OFC-striatal and dorsal prefrontal activity in OCD on a reversal learning task that addresses this circuit's function. These findings not only confirm previous reports of dorsal prefrontal dysfunction in OCD but also provide evidence for the involvement of the OFC-striatal loop in the pathophysiology of OCD.

Adult↗

Growth hormone deficiency and memory functioning in adults visualized by functional magnetic resonance imaging.

Cognitive functioning, especially memory performance, is known to be impaired in patients with childhood-onset growth hormone deficiency (CO-GHD), and growth hormone substitution has been found to counteract this memory impairment. Neuropsychological and functional magnetic resonance imagining (fMRI) data acquired during a working memory task in 13 childhood-onset GH-deficient patients were compared with 13 age, sex and education level matched healthy controls. Results demonstrated that there is no difference in the quality of the performance in the working memory task between GH-deficient patients and control subjects. However, memory speed was found to be subnormal in patients. Concerning mood, patients reported more complaints of fatigue, and less vigor. Imaging data showed that patients had increased activity in dorsolateral/ventrolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, supplementary motor and motor cortex, as well as in the thalamus and precuneus area. Increasing task load was also associated with an increase in brain activity in similar areas in patients compared to control subjects. In conclusion, this fMRI study shows that GH-deficient patients have a subnormal memory speed, but no impaired quality of memory performance, which may be due to compensatory recruitment of dorsal prefrontal brain regions. These findings indicate that the GH-IGF-1 axis contributes to prefrontal functioning in patients with CO-GHD.

Adolescent↗

Performance monitoring in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is associated with hyperactivity of brain structures involved in performance monitoring. It has been proposed that this pathophysiology results in the generation of inappropriate or excessive internal error signals, giving rise to the characteristic symptoms of OCD. We measured an electrophysiological correlate of performance monitoring, error-related negativity (ERN), to study whether OCD patients exhibit enhanced brain activity associated with errors and negative performance feedback. We found that OCD patients (n=16) and healthy control participants (n=16) did not differ in the amplitude of the ERN associated with errors and negative feedback in a probabilistic learning task. The discrepancy between these results and the results from previous studies is discussed.

Adult↗

Memory performance and the growth hormone/insulin-like growth factor axis in elderly: a positron emission tomography study.

The relationship between the growth hormone/insulin-like growth factor (GH-IGF)-I status and memory performance is studied in 24 elderly males and females, aged 75-85 years. Positron emission tomography (PET) was used to measure differences in regional cerebral blood flow during the performance of a delayed-non-match-to-sample (DNMTS) working memory task. Quality and speed of performance on the DNMTS task were measured separately for the easy items (3, 4 and 5 letters) and difficult items (6, 7 and 8 letters). Results were analyzed in two different groups based on the IGF-I level of the subjects (low or high IGF-I). Error rates on the working memory task were not different, but the high IGF-I group had shorter reaction times on the easy items. The high IGF-I group showed a significantly greater increase in cerebral blood flow in the left premotor cortex (easy items) and left dorsolateral prefrontal cortex (difficult items) compared to the low IGF-I group. It is concluded that elderly with high IGF-I levels are capable of faster working memory performance and increased recruitment of task-associated prefrontal regions.

Aged↗

Neural correlates of a reversal learning task with an affectively neutral baseline: an event-related fMRI study.

Reversal learning may conceptually be dissected into acquiring stimulus-reinforcement associations and subsequently altering behavior by switching to new associations as stimulus-reinforcement contingencies reverse (i.e., affective switching). Previous imaging studies have found regions of the ventrolateral and orbitofrontal cortex (OFC) to be involved in both subprocesses. However, these studies did not contain an affectively neutral baseline, which precluded adequate assessment of main effects of reward, punishment, and affective switching. We aimed to determine the neural substrate of these main effects, and of common and dissociable regions for reward and punishment. Furthermore, we aimed to discriminate between stimulus-punishment association and affective switching, i.e., to assess affective switching proper. To this end, we implemented a reversal learning task with an affectively neutral baseline condition that matched the experimental task in visual complexity and motor demands. Interestingly, we found dorsolateral prefrontal cortex (DLPFC) and anterior PFC to be engaged in affective switching, a finding that has not been reported before to our knowledge. Enhanced responses in these areas may represent their involvement in cognitive set shifting per se unrelated to the affective context in a reversal learning design. In addition, OFC, insular and medial prefrontal cortex regions were involved in affective switching. Left medial and lateral OFC were shown to be common areas for feedback processing, whereas left ventral striatum and left lateral OFC were specifically activated by reward and punishment, respectively. These results extend our understanding of the neural substrate of reversal learning in humans.

Adult↗

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↗

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↗

Aging affects both perceptual and lexical/semantic components of word stem priming: An event-related fMRI study.

In this event-related fMRI study, brain activity patterns were compared in extensive groups of young (N=25) and older (N=38) adults, while they were performing a word stem completion priming task. Based on behavioral findings, we tested the hypothesis that aging affects only the lexical/semantic, but not the perceptual component of word stem priming. To this end, we distinguished between priming-related activity reductions in posterior regions involved in visual processing, and regions associated with lexical/semantic retrieval processes, i.e., left lateral temporal and left prefrontal regions. Both groups revealed significant priming-related response time reductions. However, in accordance with earlier findings, a larger priming effect was found in the group of young participants. In line with previous imaging studies, the groups showed common priming-related activity reductions in the anterior cingulate, and the left inferior prefrontal cortex extending into the anterior portion of the left superior temporal gyrus, and at lower thresholds also in the right occipital lobe. However, when directly comparing the groups, greater priming-related reductions were found for the young group in the left anterior superior temporal gyrus and the right posterior occipital lobe. These findings suggest that, converse to current psychological views, aging affects both perceptual and lexical/semantic components of repetition priming.

Adult↗

Neurophysiological correlates of increased verbal working memory in high-dissociative participants: a functional MRI study.

BACKGROUND: Dissociation, defined as a disruption in usually integrated mental functions, is found not only in DSM-IV dissociative disorders, but also in post-traumatic stress disorder and eating disorders. Dissociative phenomena are also common in the general population, and may reflect a constitutionally determined cognitive style rather than a pathological trait acquired through experiencing adverse life events. In pathological dissociation, evidence has been presented for episodic memory dysfunction. In contrast, in high-dissociative subjects increased performance has been found for episodic memory and dual task performance. These findings have been linked to changes in working memory capacity. METHOD: In the present study, the authors sought to extend these findings by using functional magnetic resonance imaging during performance of two parametric working memory tasks. We tested 21 healthy low- and high-dissociative participants. RESULTS: High-dissociative participants performed slightly better during both tasks. Imaging data showed that both groups activated similar networks for both tasks, i.e. (bilateral) dorsolateral (DL) and ventrolateral prefrontal cortex (PFC), parietal cortex, and supplementary motor area. Group x task interactions were found in the high-dissociative group in L DLPFC and L parietal cortex; in the low-dissociative group in R fusiform gyrus. The differences in the high-dissociative group were independent from performance differences, implying that high-dissociative subjects generally recruit this network to a greater extent. CONCLUSIONS: These results confirm earlier findings using a verbal WM task in high-dissociative participants, and are compatible with the conceptualization of non-pathological dissociation as an information-processing style, characterized by distinct attentional and mnemonic abilities.

Adult↗

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↗

Neurophysiological correlates of habituation during exposure in spider phobia.

Imaging studies using symptom-provocation paradigms in specific phobia have yielded contradictory results, possibly reflecting a failure to account for habituation processes. Given that a single session of exposure in vivo can result in significant improvement in specific phobia, we used prolonged exposure to phobic stimuli to identify CNS regions showing habituation. Eighteen subjects (12 with spider phobia, 6 healthy controls) underwent H(2)(15)O-positron emission tomography while being continuously presented with pictures of spiders or butterflies. Results showed main effects (spiders>butterflies) in the phobia group in the left fusiform gyrus (FG) and the right parahippocampal gyrus (PHG), with bilateral perirhinal cortex and right limbic areas approaching significance. Group x condition effects were found in the right amygdala and PHG. During spider scans, large habituation effects were observed in the anterior medial temporal lobe (MTL) bilaterally. Regression analyses demonstrated that state anxiety was correlated with activity in left amygdala, bilateral perirhinal cortex, right FG, and periaquaductal grey; by contrast, phobic fear was only associated with right-sided hippocampal activity. We conclude that prolonged exposure to phobic stimuli is associated with a significant decrease in bilateral anterior MTL regional cerebral blood flow. Right anterior MTL, identified when comparing phobic vs. neutral stimuli and habituation to phobic vs. neutral stimuli in the phobia group, implicates this region in phobic fear. Analyses of covariance suggest a further functional segregation with state anxiety being linked to enhanced activity in amygdala, perirhinal cortex, and tegmentum, and phobic fear with enhanced right hippocampal activity, suggesting a neuroanatomical differentiation between emotional-vegetative and cognitive aspects of (phobic) fear.

Adult↗

Common pathway in the medial temporal lobe for storage and recovery of words as revealed by event-related functional MRI.

Lesion studies have provided compelling evidence that episodic memory is dependent on the integrity of the medial temporal lobe (MTL). This role of the MTL in episodic memory has been supported by several neuroimaging studies during both episodic encoding and retrieval. After two meta-analyses of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies, we investigated a possible dissociation within the MTL memory system in relation to encoding and retrieval processes. Based on previous reports that specifically related the function of the MTL in episodic memory to successful encoding and actual recovery of information, we applied event-related fMRI to compare successful encoding of words (ES) directly with successful recognition of those same words (RS). Our results did not indicate a clear dissociation between encoding and retrieval activations in the MTL. Instead, a region in the left MTL, covering the parahippocampal cortex and hippocampal formation, which was activated during ES almost completely overlapped with the area that was activated during RS. An additional region in the left anterior MTL, including the entorhinal cortex, was found to be activated exclusively during ES. Research has indicated that a large percentage of cells in this region are particularly sensitive to the relative novelty of stimuli. Our results, therefore, suggest that the parahippocampal/hippocampal region is involved in the formation and subsequent reactivation of memory traces, whereas the activity observed in the entorhinal cortex may reflect elementary memory processes related to novelty detection.

Adult↗

Similar network activated by young and old adults during the acquisition of a motor sequence.

In this functional MRI (fMRI) study, we investigated ageing effects on motor skill learning. We applied an adapted version of the serial reaction time (SRT) task to extensive groups of young (N=26) and elderly (N=40) subjects. Since indications have been provided for age-related shrinkage of brain regions assumed to be critical to motor skill learning, we tested the hypothesis that age effects on implicit sequence learning are larger on a neurofunctional level than on a behavioural level. The SRT task consisted of two identical scan sessions, in which subjects had to manually trail an asterisk appearing serially in one of four spatial positions by means of button-pressing. Reliable response time reductions were already found in the first session for both the young and the elderly groups, when comparing a fixed sequence condition to a random sequence, but the learning effect was greater for the young subjects. In the second session, though, both groups showed a similar degree of learning. This indicates that implicit sequence learning is still intact in elderly adults, but that the rate of learning is somewhat slower. Reliable learning-related changes in brain activity were also observed. A similar network of brain regions was recruited by both groups during the fixed compared to the random sequence, involving several regions that have been previously associated with implicit sequence learning, including bilateral parietal, and frontal regions, the supplementary motor area (SMA), cerebellum and the basal ganglia. The direct group comparison did not reveal any differences in brain activity. In addition, we did not observe any significant differences in activity when comparing the different sessions either, neither for the young nor for the elderly subjects. Hence, we did not find indications for an age-related functional reorganisation of neural networks involved in motor sequence learning. In view of earlier reports of pronounced ageing effects on the performance on declarative memory tasks, our finding of age-related sparing of processes that sustain motor skill learning, provides further support for the proposition of different memory systems relying on different brain substrates.

Adult↗