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The contribution of various brain areas to the overall progression of Parkinson's disease remains to be determined. In this study, we apply MRI diffusion tensor imaging to investigate how alterations in diffusion relate to phenotype and symptoms measured by clinical rating scales. Sixty-four patients were investigated at baseline and three follow-ups (1, 3 and 5 years). Thirty-six patients remained in the last follow-up. Regions of interests included frontal white matter, basal ganglia, thalamus, and cerebellum. Scoring on the Unified Parkinson's Disease Rating Scale (UPDRS) I, II, III, Hoehn and Yahr (HY) scale and the Schwab and England scale (SE) was determined. Mean, radial, and axial diffusion and fractional anisotropy were modeled with phenotype and clinical scales in a multivariate/univariate analysis correcting for other covariates. Significance was set at 0.05 Bonferroni corrected. All rating scales except UPDRS III significantly correlated to the diffusion measures, as did clinical phenotype. Specifically, putamen, globus pallidus, and thalamus demonstrated higher diffusion with worsening scores. Diffusion in thalamus was higher in the tremor dominant phenotype than in postural imbalance and gait disturbance. Decline in overall functionality (UPDRS II and SE scale), including mental status (UPDRS I) and stage of the disease (HY scale), in Parkinson's disease is related to altered diffusion in the lentiform nucleus and thalamus. Motor function is not mirrored in diffusion changes, possibly due to medication. Tremor dominant PD patients show diffusion alterations in the thalamus, but the significance of this for tremor generation remains to be determined.

The contribution of various brain areas to the overall progression of Parkinson's disease remains to be determined. In this study, we apply MRI diffusion tensor imaging to investigate how alterations in diffusion relate to phenotype and symptoms measured by clinical rating scales. Sixty-four patients were investigated at baseline and three follow-ups (1, 3 and 5 years). Thirty-six patients remained in the last follow-up. Regions of interests included frontal white matter, basal ganglia, thalamus, and cerebellum. Scoring on the Unified Parkinson's Disease Rating Scale (UPDRS) I, II, III, Hoehn and Yahr (HY) scale and the Schwab and England scale (SE) was determined. Mean, radial, and axial diffusion and fractional anisotropy were modeled with phenotype and clinical scales in a multivariate/univariate analysis correcting for other covariates. Significance was set at 0.05 Bonferroni corrected. All rating scales except UPDRS III significantly correlated to the diffusion measures, as did clinical phenotype. Specifically, putamen, globus pallidus, and thalamus demonstrated higher diffusion with worsening scores. Diffusion in thalamus was higher in the tremor dominant phenotype than in postural imbalance and gait disturbance. Decline in overall functionality (UPDRS II and SE scale), including mental status (UPDRS I) and stage of the disease (HY scale), in Parkinson's disease is related to altered diffusion in the lentiform nucleus and thalamus. Motor function is not mirrored in diffusion changes, possibly due to medication. Tremor dominant PD patients show diffusion alterations in the thalamus, but the significance of this for tremor generation remains to be determined.

Deficits in executive and working-memory functioning associated with frontal lobe dysfunction are prominent in depression and work-related long-term sick leave (LTSL). This study used functional magnetic resonance imaging (fMRI) to investigate potential differences in brain activation patterns in these conditions. In addition, the function of the hypothalamic-pituitary-adrenal (HPA)-axis was examined and compared between groups. Since there is a clear overrepresentation of women in these diagnostic groups, and to ensure a more homogenous sample population, only women were included. To examine the neural correlates of relevant cognitive processes in patients on sick-leave > 90 days due to work-related LTSL, recently diagnosed patients with major depression (DSM-IV criteria, untreated), and healthy controls (n=10 each group), a 2-back working memory task and a visual long-term memory task were administered during fMRI scanning. HPA-axis functioning was investigated using a diurnal curve of saliva cortisol and a dexamethasone suppression test. Task performance was comparable among the three groups. Multivariate image analysis revealed that both memory tasks engaged a similar brain network in all three groups, including the prefrontal and parietal cortex. During the 2-back task, LTSL patients had significant frontal hypoactivation compared to controls and patients with depression. Saliva cortisol measurements showed a flattening of the diurnal rythmicity in LTSL patients compared to patients with depression and healthy contols. Taken together, these findings indicate that work stress-related LTSL and major depression are dissociable in terms of frontal activation and diurnal cortisol rhythmicity.

Recent studies implicate regions in the frontal, temporal and occipital cortices of the brain in audio-visual (AV) integration of familiar objects. It remains unclear, however, which brain regions contribute to the creation of object-related AV memories, and whether activation of these regions is affected by crossmodal congruency. Here we used event-related functional MRI in a subsequent memory paradigm to investigate the neural substrates of successful encoding of semantically congruent and incongruent AV memories. Creation of both types of memories activated a region in the left inferior frontal gyrus (IFG). In addition, successful encoding of semantically related and unrelated AV pairs was correlated with increased activity in regions within the right lateral occipital cortex and bilateral lateral temporal cortex, respectively. These results may highlight a common role of IFG in retrieval of semantic information during encoding and suggest that the occipital and temporal cortices differentially process perceptual versus conceptual associations of AV memories.

BACKGROUND:: Idiopathic normal pressure hydrocephalus (INPH) is associated with white matter lesions, but the extent and severity of the lesions do not cohere with symptoms or improvement after shunting, implying the presence of further, yet undisclosed, injuries to white matter in INPH. OBJECTIVE:: To apply diffusion tensor imaging (DTI) to explore white matter lesions in patients with INPH before and after drainage of cerebrospinal fluid (CSF). METHODS:: Eighteen patients and ten controls were included. DTI was performed in a 1.5T MRI scanner before and after three-day drainage of 400 ml of CSF. Regions of interest included corpus callosum, capsula interna, frontal and lateral periventricular white matter, and centrum semiovale. White matter integrity was quantified by assessing fractional anisotropies (FA) and apparent diffusion coefficients (ADC), comparing them between patients and controls and between patients before and after drainage. The significance level corresponded to 0.05 (Bonferroni corrected). RESULTS:: Decreased FA in patients was found in three regions (p<0.002, p<0.001 and p<0.0001) in anterior frontal white matter, whereas elevated ADC was found in genu corpus callosum (p<0.0001) and areas of centrum semiovale associated to the precentral gyri (p<0.002). Diffusion patterns in these areas did not change after drainage. CONCLUSION:: DTI reveals subtle injuries - interpreted as axonal loss and gliosis - to anterior frontal white matter where high-order motor systems between frontal cortex and basal ganglia travel, further supporting the notion that motor symptoms in INPH are caused by a chronic ischemia to the neuronal systems involved in the planning processes of movements.

Background: Few previous studies have described other than age- and gender related changes in regional cerebral blood flow (rCBF) in healthy elderly. What is the influence of other common clinically relevant variables such as ache, education, MMSE, and smoking history? Purpose: To study rCBF in Swedish healthy elderly by single-photon emission computed tomography (SPECT) and evaluate the influence on rCBF of age, gender, education, MMSE, ache, and smoking with a focus on education in relation to the ‘cognitive reserve’. Methods: Healthy subjects (n = 45, 50 -75 y), sampled from a large longitudinal aging study took part in an extensive examination of health and memory, including cognitive testing and socio-economic survey. After injection of 99 mTc-hexamethylpropylene amine oxime (HMPAO) followed by SPECT the rCBF-SPECT images were analyzed using statistical parametric mapping (SPM). Results: Age-related decreases in uptake were seen in interhemispheric and interlobar regions. There was a positive rCBF correlation with education in the inferior frontal lobe and a higher uptake in the left temporal lobe in an age-gender-matched high education subgroup. Conclusion: The localization of the age related findings except for the medial temporal lobe differs markedly from typical dementia related findings. A reduction close to interhemispheric or interlobar space should always be related to chronological age. Education seems to have an influence on basal brain function at a resting-state condition. Knowledge of normal rCBF variations for variables such as age and education should be considered when making clinical diagnosis. The findings could be interpreted as further support for the theory of cognitive reserve.

The catechol O-methyltransferase (COMT) gene--encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)--contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme-activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.

Using hybrid-blocked/event-related fMRI and the 2-back task we aimed to decompose tonic and phasic temporal dynamics of basal ganglia response abnormalities in working memory associated with early untreated Parkinson's disease. In view of the tonic/phasic dopamine hypothesis, which posits a functional division between phasic D(2)-dependent striatal updating processes and tonic D(1)-dependent prefrontal context-maintenance processes, we predicted that newly diagnosed, drug-naïve Parkinson's disease patients, with selective striatal dopamine deprivation, would demonstrate transient rather than sustained activation changes in the basal ganglia during 2-back performance. Task-related activation patterns within discrete basal ganglia structures were directly compared between patients and healthy elderly controls. The obtained results yielded uniquely transient underactivation foci in caudate nuclei, putamen and globus pallidus in Parkinson's disease patients, which indicates suboptimal phasic implementation of striatal D(2)-dependent gating mechanisms during updating. Sustained underactivation was only seen in the anterior putamen, which may reflect initial signs of tonic control impairment. No significant changes were exhibited in prefrontal cortex. The present findings resonate well with the tonic/phasic dopamine account and suggest that basal ganglia under-recruitment associated with executive dysfunction in early Parkinson's disease might predominantly stem from deficiencies in phasic executive components subserved by striatum.

It has been suggested that episodic and semantic long-term memory systems interact during retrieval. Here we examined the flexibility of memory retrieval in an associative task taxing memories of different strength, assumed to differentially engage episodic and semantic memory. Healthy volunteers were pre-trained on a set of 36 face-name pairs over a 6-week period. Another set of 36 items was shown only once during the same time period. About 3 months after the training period all items were presented in a randomly intermixed order in an event-related fMRI study of face-name memory. Once presented items differentially activated anterior cingulate cortex and a right prefrontal region that previously have been associated with episodic retrieval mode. High-familiar items were associated with stronger activation of posterior cortices and a left frontal region. These findings fit a model of memory retrieval by which early processes determine, on a trial-by-trial basis, if the task can be solved by the default semantic system. If not, there is a dynamic shift to cognitive control processes that guide retrieval from episodic memory.

Multi-modal brain imaging was used to examine the relation between individual differences in resting-state striatal dopamine D2 binding and the magnitude of prefrontal BOLD activation during updating of long-term memory (LTM) representations. Increased activity in the left prefrontal cortex was observed when LTM updating was required, and there was a positive correlation between striatal D2 activity and the magnitude of left prefrontal activity during updating. These findings support predictions from neurocomputational models of a relation of dopaminergic neurotransmission to transient cognitive operations and related brain activity.

This study used functional magnetic resonance imaging (fMRI) to investigate differences in brain activity between one group of active high jumpers and one group of high jumping novices (controls) when performing motor imagery of a high jump. It was also investigated how internal imagery training affects neural activity. The results showed that active high jumpers primarily activated motor areas, e.g. pre-motor cortex and cerebellum. Novices activated visual areas, e.g. superior occipital cortex. Imagery training resulted in a reduction of activity in parietal cortex. These results indicate that in order to use an internal perspective during motor imagery of a complex skill, one must have well established motor representations of the skill which then translates into a motor/internal pattern of brain activity. If not, an external perspective will be used and the corresponding brain activation will be a visual/external pattern. Moreover, the findings imply that imagery training reduces the activity in parietal cortex suggesting that imagery is performed more automatic and results in a more efficient motor representation more easily accessed during motor performance.

Previous studies on the neural correlates of perceptual awareness implicate sensory-specific regions and higher cortical regions such as the prefrontal cortex (PFC) in this process. The specific role of PFC regions is, however, unknown. PFC activity could be bottom-up driven, integrating signals from sensory regions. Alternatively, PFC regions could serve more active top-down processes that help to define the content of consciousness. To compare these alternative views of PFC function, we used functional magnetic resonance imaging and measured brain activity specifically related to conscious perception of items that varied in ease of identification (by being presented 0, 12, or 60 times previously). A bottom-up account predicts that PFC activity would be largely insensitive to stimulus difficulty, whereas a top-down account predicts reduced PFC activity as identification becomes easier. The results supported the latter prediction by showing reduced activity for previously presented compared to novel items in the PFC and several other regions. This was further confirmed by a functional connectivity analysis showing that the interaction between frontal and visual sensory regions declined as a function of ease of identification. Given the attribution of top-down processing to PFC regions in combination with the marked decline in PFC activity for easy items, these findings challenge the prevailing notion that the PFC is necessary for consciousness.

In patients with idiopathic normal pressure hydrocephalus (INPH), the changes in brain function that take place in conjunction with improved behavioural performance after CSF drainage is still unknown. In this study, we use functional MRI (fMRI) to investigate the changes in cortical activity that accompany improved motor and cognitive performance after long-term external lumbar drainage (ELD) of CSF in patients with INPH. Eighteen INPH patients were initially included together with age- and sex-matched controls. Data from 11 INPH patients were analysed both before and after ELD. The average drain volume for these 11 patients was 400 ml/3 days. Brain activation was investigated by fMRI before and after the procedure on a 1.5T Philips scanner using protocols taxing motor performance (finger tapping and reaction time) and cognitive functioning (memory and attention). Behavioural data were compared using non-parametric tests at a significance level of 0.05, whereas fMRI data were analysed by statistical parametric mapping including conjunction analysis of areas with enhanced activity after drainage in patients and areas activated in controls (P < 0.005, uncorrected). Improved regions were defined as areas in the INPH brain that increased in activity after ELD with the requirement that the same areas were activated in control subjects. Following ELD, right-hand finger tapping improved from 104 +/- 38 to 117 +/- 25 (mean +/- SD) (P = 0.02). Left-hand finger tapping showed a tendency to improve, the number of keystrokes increasing from 91 +/- 40 to 105 +/- 20 (P = 0.12). Right-hand reaction time improved from 1630 +/- 566 ms to 1409 +/- 442 ms, whereas left-hand reaction time improved from 1760 +/- 600 ms to 1467 +/- 420 ms (both P-values = 0.01). Significant improvements in motor performance were accompanied by bilateral increased activation in the supplementary motor area. No improvement was found in cognitive functioning. The results suggest that motor function reco

This study used functional magnetic resonance imaging (fMRI) to investigate differences in brain activity between one group of active high jumpers and one group of high jumping novices (controls) when performing motor imagery of a high jump. It was also investigated how internal imagery training affects neural activity. The results showed that active high jumpers primarily activated motor areas, e.g. pre-motor cortex and cerebellum. Novices activated visual areas, e.g. superior occipital cortex. Imagery training resulted in a reduction of activity in parietal cortex. These results indicate that in order to use an internal perspective during motor imagery of a complex skill, one must have well established motor representations of the skill which then translates into a motor/internal pattern of brain activity. If not, an external perspective will be used and the corresponding brain activation will be a visual/external pattern. Moreover, the findings imply that imagery training reduces the activity in parietal cortex suggesting that imagery is performed more automatic and results in a more efficient motor representation more easily accessed during motor performance.

This study used functional magnetic resonance imaging (fMRI) to investigate differences in brain activity between one group of active high jumpers and one group of high jumping novices (controls) when performing motor imagery of a high jump. It was also investigated how internal imagery training affects neural activity. The results showed that active high jumpers primarily activated motor areas, e.g. pre-motor cortex and cerebellum. Novices activated visual areas, e.g. superior occipital cortex. Imagery training resulted in a reduction of activity in parietal cortex. These results indicate that in order to use an internal perspective during motor imagery of a complex skill, one must have well established motor representations of the skill which then translates into a motor/internal pattern of brain activity. If not, an external perspective will be used and the corresponding brain activation will be a visual/external pattern. Moreover, the findings imply that imagery training reduces the activity in parietal cortex suggesting that imagery is performed more automatic and results in a more efficient motor representation more easily accessed during motor performance.

This study used functional magnetic resonance imaging (fMRI) to investigate differences in brain activity between one group of active high jumpers and one group of high jumping novices (controls) when performing motor imagery of a high jump. It was also investigated how internal imagery training affects neural activity. The results showed that active high jumpers primarily activated motor areas, e.g. pre-motor cortex and cerebellum. Novices activated visual areas, e.g. superior occipital cortex. Imagery training resulted in a reduction of activity in parietal cortex. These results indicate that in order to use an internal perspective during motor imagery of a complex skill, one must have well established motor representations of the skill which then translates into a motor/internal pattern of brain activity. If not, an external perspective will be used and the corresponding brain activation will be a visual/external pattern. Moreover, the findings imply that imagery training reduces the activity in parietal cortex suggesting that imagery is performed more automatic and results in a more efficient motor representation more easily accessed during motor performance.

This study used functional magnetic resonance imaging (fMRI) to investigate differences in brain activity between one group of active high jumpers and one group of high jumping novices (controls) when performing motor imagery of a high jump. It was also investigated how internal imagery training affects neural activity. The results showed that active high jumpers primarily activated motor areas, e.g. pre-motor cortex and cerebellum. Novices activated visual areas, e.g. superior occipital cortex. Imagery training resulted in a reduction of activity in parietal cortex. These results indicate that in order to use an internal perspective during motor imagery of a complex skill, one must have well established motor representations of the skill which then translates into a motor/internal pattern of brain activity. If not, an external perspective will be used and the corresponding brain activation will be a visual/external pattern. Moreover, the findings imply that imagery training reduces the activity in parietal cortex suggesting that imagery is performed more automatic and results in a more efficient motor representation more easily accessed during motor performance.

This study used functional magnetic resonance imaging (fMRI) to investigate differences in brain activity between one group of active high jumpers and one group of high jumping novices (controls) when performing motor imagery of a high jump. It was also investigated how internal imagery training affects neural activity. The results showed that active high jumpers primarily activated motor areas, e.g. pre-motor cortex and cerebellum. Novices activated visual areas, e.g. superior occipital cortex. Imagery training resulted in a reduction of activity in parietal cortex. These results indicate that in order to use an internal perspective during motor imagery of a complex skill, one must have well established motor representations of the skill which then translates into a motor/internal pattern of brain activity. If not, an external perspective will be used and the corresponding brain activation will be a visual/external pattern. Moreover, the findings imply that imagery training reduces the activity in parietal cortex suggesting that imagery is performed more automatic and results in a more efficient motor representation more easily accessed during motor performance.

The brain is able to create coherent percepts from multisensory input. This phenomenon, known as multisensory integration (MSI), is a ubiquitous feature of everyday life and has been found to be essential for a reliable interaction with the environment. Recent functional neuroimaging studies suggest that several different networks are engaged in various forms of MSI depending on the nature of information being integrated. However, little is known about the neural basis of a fundamental form of MSI in natural conditions; integration of common auditory and visual objects which are conceptually related, such as when we look at a cat and hear a meowing sound. Here we used event-related fMRI to compare the brain response to conceptually related and unrelated pairs of audio-visual stimuli denoting common objects. Our protocol was designed to preclude contamination of the results by cognitive processes additional to those needed for MSI. The results indicate that higher-order temporal and occipital areas respond to coincident sounds and pictures regardless of their semantic relationship; whereas, the right claustrum/insula region is differentially activated in association with multisensory integration of conceptually related common objects. This observation has important implications for understanding how multimodal information about common objects is represented in the brain.

The present study aimed to delineate the extent to which unitary executive functions might be shared across the separate domains of episodic and working memory. A mixed blocked/event-related functional magnetic resonance imaging (fMRI) design was employed to assess sustained (tonic control) and transient (phasic control) brain responses arising from incrementing executive demand (source versus item episodic memory - vis-à-vis - two-back versus one-back working memory) using load-dependent activation overlaps as indices of common components. Although an extensive portion of the regional load effects constituted differential control modulations in both sustained and transient responses, commonalities were also found implicating a subset of executive core mechanisms consistent with unitary or domain general control. 'Unitary' control modulations were temporally dissociated into (1) shared tonic components involving medial and lateral prefrontal cortex, striatum, cerebellum and superior parietal cortex, assumed to govern enhanced top-down context processing, monitoring and sustained attention throughout task periods and (2) stimulus-synchronous phasic components encompassing posterior intraparietal sulcus, hypothesized to support dynamic shifting of the 'focus of attention' among internal representations. Taken together, these results converge with theoretical models advocating both unity and diversity among executive control processes.

It has been suggested that fMRI at 3T yields stronger and more extensive BOLD activations than fMRI at 1.5T, and that imaging at higher field strengths can reveal unique activations. In the present study we compared, within-subjects, activation patterns during a finger-tapping task at 1.5 and 3T. The data were analyzed with a random-effects model in SPM2. At a strict statistical level (p<0.05, FWE correction for multiple comparisons), ipsilateral cerebellar activation was revealed at 1.5T. At 3T, activation in sensory-motor regions in the contra-lateral cerebrum was identified in addition to the activation in cerebellum. At a less stringent statistical threshold, imaging at 1.5T and 3T revealed overlapping cortical regions with more extensive clusters at 3T. A similar pattern was seen in a comparison of familiar and novel sequences. However, subcortical activations of thalamus and parts of the basal ganglia were uniquely identified at 3T. Analyses at the individual level substantiated the group results by showing that the higher sensitivity of the 3T resulted in images with higher between-individual consistency in activation patterns.

The present study aimed to delineate the extent to which unitary executive functions might be shared across the separate domains of episodic and working memory. A mixed blocked/event-related functional magnetic resonance imaging (fMRI) design was employed to assess sustained (tonic control) and transient (phasic control) brain responses arising from incrementing executive demand (source versus item episodic memory - vis-à-vis - two-back versus one-back working memory) using load-dependent activation overlaps as indices of common components. Although an extensive portion of the regional load effects constituted differential control modulations in both sustained and transient responses, commonalities were also found implicating a subset of executive core mechanisms consistent with unitary or domain general control. 'Unitary' control modulations were temporally dissociated into (1) shared tonic components involving medial and lateral prefrontal cortex, striatum, cerebellum and superior parietal cortex, assumed to govern enhanced top-down context processing, monitoring and sustained attention throughout task periods and (2) stimulus-synchronous phasic components encompassing posterior intraparietal sulcus, hypothesized to support dynamic shifting of the 'focus of attention' among internal representations. Taken together, these results converge with theoretical models advocating both unity and diversity among executive control processes.