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Alpha-pyrrolidinovalerophenone (α-PVP) is a designer drug, the mechanism of action of which resembles that of cocaine and amphetamine. New data about the side effects of α-PVP are emerging. We present a case report of an acute ischemic stroke following the recreational use of α-PVP. The ischemic lesions were located in the middle cerebral artery and deep watershed areas of the left cerebral hemisphere. Occupational therapy and physiotherapy were initiated, and the patient was discharged with only a mild right hemiparesis. [ABSTRACT FROM AUTHOR]

Abstract: Functional magnetic resonance imaging has been widely used to study brain activation induced either by specific sensory stimulation or motor or cognitive task performance. We demonstrate that functional magnetic resonance imaging can provide information of brain regions involved in opioid-induced central nervous system effects. The reproducibility of the responses in the predefined regions of interest was confirmed by repeated boluses of ultra-short acting mu-opioid receptor agonist remifentanil and saline. We report spatially and temporally detailed information after remifentanil administration. Areas rich in mu-opioid receptors showed strong activations, whereas primary somatosensory cortex that has the lowest density of mu-opioid receptors showed negligible activation. The cingulate, orbitofrontal, posterior parietal and insular cortices, and amygdala showed activation, which was temporally closely related to most subjective sensations that were strongest at 80 to 90 s after drug administration. These areas belong to a circuitry that modulates the affective experience of sensory stimuli. [Copyright &y& Elsevier]

Objectives: Neuropsychiatric symptoms are related to disease progression and cognitive decline over time in cerebral small vessel disease (SVD) but their significance is poorly understood in covert SVD. We investigated neuropsychiatric symptoms and their relationships between cognitive and functional abilities in subjects with varying degrees of white matter hyperintensities (WMH), but without clinical diagnosis of stroke, dementia or significant disability. Methods: The Helsinki Small Vessel Disease Study consisted of 152 subjects, who underwent brain magnetic resonance imaging (MRI) and comprehensive neuropsychological evaluation of global cognition, processing speed, executive functions, and memory. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory Questionnaire (NPI-Q, n = 134) and functional abilities with the Amsterdam Instrumental Activities of Daily Living questionnaire (A-IADL, n = 132), both filled in by a close informant. Results: NPI-Q total score correlated significantly with WMH volume (r s = 0.20, p = 0.019) and inversely with A-IADL score (r s = −0.41, p < 0.001). In total, 38% of the subjects had one or more informant-evaluated neuropsychiatric symptom. Linear regressions adjusted for age, sex, and education revealed no direct associations between neuropsychiatric symptoms and cognitive performance. However, there were significant synergistic interactions between neuropsychiatric symptoms and WMH volume on cognitive outcomes. Neuropsychiatric symptoms were also associated with A-IADL score irrespective of WMH volume. Conclusions: Neuropsychiatric symptoms are associated with an accelerated relationship between WMH and cognitive impairment. Furthermore, the presence of neuropsychiatric symptoms is related to worse functional abilities. Neuropsychiatric symptoms should be routinely assessed in covert SVD as they are related to worse cognitive and functional outcomes. [ABSTRACT FROM AUTHOR]

Background: Return to work (RTW) might be delayed in patients with complicated mild traumatic brain injury (MTBI), i.e., MTBI patients with associated traumatic intracranial lesions. However, the effect of different types of lesions on RTW has not studied before. We investigated whether traumatic intracranial lesions detected by CT and MRI are associated with return to work and post-concussion symptoms in patients with MTBI. Methods: We prospectively followed up 113 adult patients with MTBI that underwent a brain MRI within 3–17 days after injury. Return to work was assessed with one-day accuracy up to one year after injury. Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and Glasgow Outcome Scale Extended (GOS-E) were conducted one month after injury. A Kaplan–Meier log-rank analysis was performed to analyze the differences in RTW. Results: Full RTW-% one year after injury was 98%. There were 38 patients with complicated MTBI, who had delayed median RTW compared to uncomplicated MTBI group (17 vs. 6 days), and more post-concussion symptoms (median RPQ 12.0 vs. 6.5). Further, RTW was more delayed in patients with multiple types of traumatic intracranial lesions visible in MRI (31 days, n = 19) and when lesions were detected in the primary CT (31 days, n = 24). There were no significant differences in GOS-E. Conclusions: The imaging results that were most clearly associated with delayed RTW were positive primary CT and multiple types of lesions in MRI. RTW-% of patients with MTBI was excellent and a single intracranial lesion does not seem to be a predictive factor of disability to work. [ABSTRACT FROM AUTHOR]

Background: Post-traumatic headache (PTH) is a common symptom following mild traumatic brain injury (mTBI). Patients at risk to develop acute PTH (aPTH) and further persistent PTH (pPTH) need to be recognized. Methods: This is a one-year follow-up of 127 patients with mTBI, aged 18 to 68, referred to outpatient clinic in the Helsinki University Hospital. Symptoms were assessed at the emergency department (ED), with structured interview at outpatient clinic visit and with Rivermead post-concussion symptom questionnaire at one, three, and 12 months after injury. Psychiatric disorders were assessed with Structured Clinical Interview for DSM-IV Axis I disorders at 3-4 months and return to work (RTW) from patient records. Results: At one month, 77/127 patients (61%) had aPTH. According to multiple logistic regression analysis, risk factors for aPTH were headache at the emergency department (ED) (OR 5.43), other pain (OR 3.19), insomnia (OR 3.23), and vertigo (OR 5.98). At three months, 17 patients (22% of aPTH patients) had developed pPTH, and at one year, 4 patients (24% of pPTH patients) still presented with pPTH. Risk factors for pPTH at three months were older age (OR 1.06) and current insomnia (OR 12.3). The frequency of psychiatric disorders did not differ between the groups. pPTH patients performed worse on their RTW. Conclusions: Risk factors for aPTH were insomnia, headache at ED, other pain, and vertigo and for pPTH, insomnia and older age. RTW rate was lower among pPTH patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Slow evoked responses have been extensively studied using electrophysiological and neuroimaging methods, but there is no consensus regarding their generators. We investigated the generators of the P3 and positive slow wave (PSW) in the evoked responses to probes recorded during auditory working memory tasks to find out whether there is dissociation between functional networks involved in the generation of the P3 and PSW and between spatial and nonspatial auditory processing within this time window. Methods: Whole-head magneto-(MEG) and electroencephalography (EEG); analysis of MEG data using minimum-norm current estimates. Results: The associative temporal, occipito-temporal and parietal areas contributed to the generation of the slow evoked responses. The temporal source increased while the occipito-temporal source diminished activity during transition from the P3 to PSW. The occipito-temporal generator of the P3 was activated more during the spatial than nonspatial task, and the left temporal generator of the PSW tended to be more strongly activated during the nonspatial task. Conclusions: These findings indicate that partially distinct functional networks generate the P3 and PSW and provide evidence for segregation of spatial and nonspatial auditory information processing in associative areas beyond the supratemporal auditory cortex. Significance: The present results support the dual-stream model for auditory information processing. [Copyright &y& Elsevier]

Background: Cognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH). Methods: Participants of the Helsinki Small Vessel Disease Study (n = 152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation. Results: Cognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single‐leg stance, timed up‐and‐go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant‐evaluated IADL, but not on self‐evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up‐and‐go performance. Conclusion: The results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment. [ABSTRACT FROM AUTHOR]

Results from several recent studies suggest that neuronal processing of sound content and its spatial location may be dissociated. The use of modern neuroimaging techniques has allowed for the determination that different brain structures may be specifically activated during working memory processing of pitch and location of sound. The time course of these task-related differences, however, remains uncertain. In the present study, we performed simultaneous whole-head electroencephalogram and magnetoencephalogram recordings, using a new behavioral paradigm, to investigate the dynamics of differences between “what” and “where” evoked responses in the auditory system as a function of memory load. In the location task the latency of the N1m was shorter and its generator was situated more inferiorly than in the pitch task. Working memory processing of the tonal frequency enhanced the amplitude of the N2 component, as well as the negative-going deflection at a latency around 400 ms. A memory-load-dependent task-related difference was found in the positive slow wave which was higher during the location than pitch task at the low load. Late slow waves were affected by memory load but not type of task. These results suggest that separate neuronal networks are involved in the attribute-specific analysis of auditory stimuli and their encoding into working memory, whereas the maintenance of auditory information is accomplished by a common, nonspecific neuronal network. [Copyright &y& Elsevier]

The main objective of this prospective cohort study was to evaluate whether traumatic microbleeds (TMBs) are a significant prognostic factor of return to work (RTW), post-traumatic symptoms, and overall recovery in patients with mild traumatic brain injury (mTBI). One hundred and thirteen patients with mTBI were recruited from the Helsinki University Hospital emergency units. All patients underwent multi-contrast 3T magnetic resonance imaging (MRI) 3–17 days after mTBI. Patients were evaluated in the Traumatic Brain Injury Outpatient Clinic of Helsinki University Hospital 1 month after injury. Post-concussion symptoms were assessed with the Post-Concussion Symptom Questionnaire (RPQ) and overall recovery was assessed with the Glasgow Outcome Scale Extended (GOS-E). Their time to RTW was continuously measured up to 1 year after TBI. Median RTW was 9 days (interquartile range [IQR] 4–30) after mTBI and full RTW rate after 1 year was 98%. Patients with TMBs (n = 22) did not have more post-concussion symptoms (median RPQ 10.0 vs. 7.0, p = 0.217) or worse overall recovery (58% vs. 56% with GOS-E = 8, p = 0.853) than patients without TMBs (n = 91). There was no significant difference in time to RTW (13.5 vs. 7.0 days, p = 0.063). In this study, patients with TMBs did not have delayed RTW or more post-concussion symptoms than other patients with mTBI. TMBs in mTBI do not seem to be a significant prognostic factor of RTW. [ABSTRACT FROM AUTHOR]

Background and purpose: Cerebral small vessel disease is characterized by progressive white matter hyperintensities (WMH) and cognitive decline. However, variability exists in how individuals maintain cognitive capabilities despite significant neuropathology. The relationships between individual cognitive reserve, psychological resilience and cognitive functioning were examined in subjects with varying degrees of WMH. Methods: In the Helsinki Small Vessel Disease Study, 152 subjects (aged 65–75 years) underwent a comprehensive neuropsychological assessment, evaluation of subjective cognitive complaints and brain magnetic resonance imaging with volumetric WMH evaluation. Cognitive reserve was determined by education (years) and the modified Cognitive Reserve Scale (mCRS). Psychological resilience was evaluated with the Resilience Scale 14. Results: The mCRS total score correlated significantly with years of education (r = 0.23, p < 0.01), but it was not related to age, sex or WMH volume. Together, mCRS score and education were associated with performance in a wide range of cognitive domains including processing speed, executive functions, working memory, verbal memory, visuospatial perception and verbal reasoning. Independently of education, the mCRS score had incremental predictive value on delayed verbal recall and subjective cognitive complaints. Psychological resilience was not significantly related to age, education, sex, WMH severity or cognitive test scores, but it was associated with subjective cognitive complaints. Conclusions: Cognitive reserve has strong and consistent associations with cognitive functioning in subjects with WMH. Education is widely associated with objective cognitive functioning, whereas lifetime engagement in cognitively stimulating leisure activities (mCRS) has independent predictive value on memory performance and subjective cognitive complaints. Psychological resilience is strongly associated with subjective, but not objective, cognitive functioning. [ABSTRACT FROM AUTHOR]

Purpose: Severity of white matter lesion (WML) is typically evaluated on magnetic resonance images (MRI), yet the more accessible, faster, and less expensive method is computed tomography (CT). Our objective was to study whether WML can be automatically segmented from CT images using a convolutional neural network (CNN). The second aim was to compare CT segmentation with MRI segmentation. Methods: The brain images from the Helsinki University Hospital clinical image archive were systematically screened to make CT-MRI image pairs. Selection criteria for the study were that both CT and MRI images were acquired within 6 weeks. In total, 147 image pairs were included. We used CNN to segment WML from CT images. Training and testing of CNN for CT was performed using 10-fold cross-validation, and the segmentation results were compared with the corresponding segmentations from MRI. Results: A Pearson correlation of 0.94 was obtained between the automatic WML volumes of MRI and CT segmentations. The average Dice similarity index validating the overlap between CT and FLAIR segmentations was 0.68 for the Fazekas 3 group. Conclusion: CNN-based segmentation of CT images may provide a means to evaluate the severity of WML and establish a link between CT WML patterns and the current standard MRI-based visual rating scale. [ABSTRACT FROM AUTHOR]

We applied fMRI and diffusion-weighted MRI to study the segregation of cognitive and motor functions in the human cerebrocerebellar system. Our fMRI results show that a load increase in a nonverbal auditory working memory task is associated with enhanced brain activity in the parietal, dorsal premotor, and lateral prefrontal cortices and in lobules VII-VIII of the posterior cerebellum, whereas a sensory-motor control task activated the motor/somatosensory, medial prefrontal, and posterior cingulate cortices and lobules V/ VI of the anterior cerebellum. The load-dependent activity in the crus I/ II had a specific relationship with cognitive performance: This activity correlated negatively with load-dependent increase in RTs. This correlation between brain activity and RTs was not observed in the sensory-motor task in the activated cerebellar regions. Furthermore, probabilistic tractography analysis of the diffusion-weighted MRI data suggests that the tracts between the cerebral and the cerebellar areas exhibiting cognitive loaddependent and sensory-motor activity are mainly projected via separated pontine (feed-forward tracts) and thalamic (feedback tracts) nuclei. The tractography results also indicate that the crus I/II in the posterior cerebellum is linked with the lateral prefrontal areas activated by cognitive load increase, whereas the anterior cerebellar lobe is not. The current results support the view that cognitive and motor functions are segregated in the cerebellum. On the basis of these results and theories of the function of the cerebellum, we suggest that the posterior cerebellar activity during a demanding cognitive task is involved with optimization of the response speed. [ABSTRACT FROM AUTHOR]

Musical competence may confer cognitive advantages that extend beyond processing of familiar musical sounds. Behavioural evidence indicates a general enhancement of both working memory and attention in musicians. It is possible that musicians, due to their training, are better able to maintain focus on task-relevant stimuli, a skill which is crucial to working memory. We measured the blood oxygenation-level dependent (BOLD) activation signal in musicians and nonmusicians during working memory of musical sounds to determine the relation among performance, musical competence and generally enhanced cognition. All participants easily distinguished the stimuli. We tested the hypothesis that musicians nonetheless would perform better, and that differential brain activity would mainly be present in cortical areas involved in cognitive control such as the lateral prefrontal cortex. The musicians performed better as reflected in reaction times and error rates. Musicians also had larger BOLD responses than non-musicians in neuronal networks that sustain attention and cognitive control, including regions of the lateral prefrontal cortex, lateral parietal cortex, insula, and putamen in the right hemisphere, and bilaterally in the posterior dorsal prefrontal cortex and anterior cingulate gyrus. The relationship between the task performance and the magnitude of the BOLD response was more positive in musicians than in non-musicians, particularly during the most difficult working memory task. The results confirm previous findings that neural activity increases during enhanced working memory performance. The results also suggest that superior working memory task performance in musicians rely on an enhanced ability to exert sustained cognitive control. This cognitive benefit in musicians may be a consequence of focused musical training. [ABSTRACT FROM AUTHOR]

Goal-directed behavior lowers activity in brain areas that include the medial frontal cortex, the medial and lateral parietal cortex, and limbic and paralimbic brain regions, commonly referred to as the ''default network.'' These activity decreases are believed to reflect the interruption of processes that are ongoing when the mind is in a restful state. Previously, the nature of these processes was probed by varying cognitive task parameters, but the presence of emotional processes, while often assumed, was little investigated. With fMRI, we studied the effect of systematic variations of both cognitive load and emotional stimulus connotation on task-related decreases in the default network by employing an auditory working memory (WM) task with musical sounds. The performance of the WM task, compared to passive listening, lowered the activity in medial and lateral, prefrontal, parietal, temporal, and limbic regions. In a subset of these regions, the magnitude of decrease depended on the memory load; the greater the cognitive load, the larger the magnitude of the observed decrease. Furthermore, in the right amygdala and the left precuneus, areas previously associated with processing of unpleasant dissonant musical sounds, there was an interaction between the experimental condition and the stimulus type. The current results are consistent with the previously reported effect of task difficulty on task-related brain activation decreases. The results also indicate that task-related decreases may be further modulated by the emotional stimulus connotation. [ABSTRACT FROM AUTHOR]

Abstract: Using functional magnetic resonance imaging (fMRI) and n-back tasks we investigated whether, in 11–13-year-old children, spatial (location) and nonspatial (color) information is differentially processed during visual attention (0-back) and working memory (WM) (2-back) tasks and whether such cognitive task performance, compared to a resting state, results in regional deactivation. The location 0-back task, compared to the color 0-back task, activated segregated areas in the frontal, parietal and occipital cortices whereas no differentially activated voxels were obtained when location and color 2-back tasks were directly contrasted. Several midline cortical areas were less active during 0- and 2-back task performance than resting state. The task-induced deactivation increased with task difficulty as demonstrated by larger deactivation during 2-back than 0-back tasks. The results suggest that, in 11–13-year-old children, the visual attentional network is differently recruited by spatial and nonspatial information processing, but the functional organization of cortical activation in WM in this age group is not based on the type of information processed. Furthermore, 11–13-year-old children exhibited a similar pattern of cortical deactivation that has been reported in adults during cognitive task performance compared to a resting state. [Copyright &y& Elsevier]

Visuospatial working memory mechanisms have been studied extensively at single cell level in the dorsolateral prefrontal cortex (PFCd) in nonhuman primates. Despite the importance of short-term memory of sound location for behavioral orientation, there are only a few studies on auditory spatial working memory. The purpose of this study was to investigate neuronal mechanisms underlying working memory processing of auditory and visual location information at single cell level in the PFCd. Neuronal activity was recorded in monkeys performing a delayed matching-to-sample task (DMTS). The location of a visual or auditory stimulus was used as a memorandum. The majority of the neurons that were activated during presentation of the cue memorandum were selective either for visual or auditory spatial information. A small group of cue related bimodal neurons were sensitive to the location of the cue regardless of whether the stimulus was visual or auditory, suggesting modality independent processing of spatial information at cellular level in the PFCd. Most neurons that were activated during the delay period were modality specific, responding either during visual or auditory trials. All bimodal delay related neurons that responded during both visual and auditory trials were spatially nonselective. The results of the present study suggest that in addition to the modality specific parallel mechanism, working memory of auditory and visual space also involves modality independent processing at cellular level in the PFCd. [ABSTRACT FROM AUTHOR]

We demonstrate that spatially accurate and selective stimulation is crucial when cortical functions are studied by the creation of temporary lesions with transcranial magnetic stimulation (TMS). Previously, the interpretation of the TMS results has been hampered by inaccurate knowledge of the site and strength of the induced electric current in the brain. With a Navigated Brain Stimulation (NBS) system, which provides real-time magnetic resonance image (MRI)-guided targeting of the TMS-induced electric field, we found that TMS of a spatially restricted cortical S1 thenar area is sufficient to abolish sensation from a weak electric stimulation of the corresponding skin area. We demonstrate that with real-time navigation, TMS can be repeatably directed at millimeter-level precision to a target area defined on the MRI. The stimulation effect was temporally and spatially specific: the greatest inhibition of sensation occurred when TMS was applied 20 ms after the cutaneous test stimulus and the TMS effect was sensitive to 8-13 mm displacements of the induced electric field pattern. The results also indicate that TMS selectively to S1 is sufficient to abolish perception of cutaneous stimulation of the corresponding skin area. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Somatosensory point localization is a clinical test evaluating spatial accuracy of the somatosensory system. Possible effects of the interstimulus interval (ISI) on point localization threshold have not been previously examined. In the present set of experiments the effect of time delay on somatosensory point localization was studied using ISIs of 1, 3, 5, 7, and 9 s, and applying a newly developed computer-controlled application method of a Semmes-Weinstein monofilament. It was found that the point localization threshold was not significantly affected by the ISI length. However, the response time was shorter and response accuracy better at the shorter (1 and 3 s) than at the longer (5, 7, and 9 s) ISIs, suggesting a change in the mechanism underlying point localization decision criteria in ISIs longer than 3 s. [ABSTRACT FROM AUTHOR]

Deals with a study which presented a contextual clustering procedure for statistical parametric maps calculated from time varying three-dimensional images for the analysis of functional magnetic resonance imaging. Computation of a statistical parametric map; Experiments; Discussion and conclusion.

Background: We evaluated the prevalence of psychiatric disorders in mild traumatic brain injury (MTBI) patients and investigated psychiatric comorbidity in relation to subjective symptoms and return to work (RTW). Methods: We recruited 103 MTBI patients (mean age 40.8 years, SD 3.1) prospectively from University Hospital. The patients were followed up for one year. The Rivermead Post-Concussion Symptom Questionnaire (RPQ) and Extended Glasgow Outcome Scale (GOSE) were administered one month after MTBI. Three months after MTBI, any psychiatric disorders were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders. Results: Psychiatric disorders were diagnosed in 26 patients (25.2%). The most common disorders were previous/current depression. At three months, there was no difference between patients with psychiatric disorders versus those without them in RTW (95.7% vs. 87.3%, p = 0.260) or at least in part-time work (100% vs. 94.4%, p = 0.245). In Kaplan–Meier analysis, the median time to RTW was 10 days for both groups. The median RPQ score was 13.0 (Interquartile range (IQR) 6.5–19.0) in patients with a psychiatric disorder compared to 8.5 (IQR 2.3–14.0) in those without one (p = 0.021); respectively, the median GOSE was 7.0 (IQR 7.0–8.0) compared to 8.0 (IQR 7.0–8.0, p = 0.003). Conclusions: Approximately every fourth patient with MTBI had a psychiatric disorder. These patients reported more symptoms, and their functional outcome measured with GOSE at one month after MTBI was worse. However, presence of any psychiatric disorder did not affect RTW. Early contact and adequate follow-up are important when supporting the patient's return to work. [ABSTRACT FROM AUTHOR]