Neuroprotective Effects of Inhaled Xenon Gas on Brain Structural Gray Matter Changes After Out-of-Hospital Cardiac Arrest Evaluated by Morphometric Analysis: A Substudy of the Randomized Xe-Hypotheca Trial.

BACKGROUND: We have earlier reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). A predefined secondary objective was to assess the effect of inhaled xenon on the structural changes in gray matter in comatose survivors after OHCA. METHODS: Patients were randomly assigned to receive either inhaled xenon combined with target temperature management (33 °C) for 24 h (n = 55, xenon group) or target temperature management alone (n = 55, control group). A change of brain gray matter volume was assessed with a voxel-based morphometry evaluation of high-resolution structural brain magnetic resonance imaging (MRI) data with Statistical Parametric Mapping. Patients were scheduled to undergo the first MRI between 36 and 52 h and a second MRI 10 days after OHCA. RESULTS: Of the 110 randomly assigned patients in the Xe-Hypotheca trial, 66 patients completed both MRI scans. After all imaging-based exclusions, 21 patients in the control group and 24 patients in the xenon group had both scan 1 and scan 2 available for analyses with scans that fulfilled the quality criteria. Compared with the xenon group, the control group had a significant decrease in brain gray matter volume in several clusters in the second scan compared with the first. In a between-group analysis, significant reductions were found in the right amygdala/entorhinal cortex (p = 0.025), left amygdala (p = 0.043), left middle temporal gyrus (p = 0.042), left inferior temporal gyrus (p = 0.008), left parahippocampal gyrus (p = 0.042), left temporal pole (p = 0.042), and left cerebellar cortex (p = 0.005). In the remaining gray matter areas, there were no significant changes between the groups. CONCLUSIONS: In comatose survivors of OHCA, inhaled xenon combined with targeted temperature management preserved gray matter better than hypothermia alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT00879892.

Frontal white and gray matter abnormality in gambling disorder: A multimodal MRI study.

Background: Changes in brain structural connections appear to be important in the pathophysiology of substance use disorders, but their role in behavioral addictions, such as gambling disorder (GD), is unclear. GD also offers a model to study addiction mechanisms without pharmacological confounding factors. Here, we used multimodal MRI data to examine the integrity of white matter connections in individuals with GD. We hypothesized that the affected areas would be in the fronto-striatal-thalamic circuit. Methods: Twenty individuals with GD (mean age: 64 years, GD duration: 15.7 years) and 40 age- and sex-matched healthy controls (HCs) underwent detailed clinical examinations together with brain 3T MRI scans (T1, T2, FLAIR and DWI). White matter (WM) analysis involved fractional anisotropy and lesion load, while gray matter (GM) analysis included voxel- and surface-based morphometry. These measures were compared between groups, and correlations with GD-related behavioral characteristics were examined. Results: Individuals with GD showed reduced WM integrity in the left and right frontal parts of the corona radiata and corpus callosum (pFWE < 0.05). WM gambling symptom severity (SOGS score) was negatively associated to WM integrity in these areas within the left hemisphere (p < 0.05). Individuals with GD also exhibited higher WM lesion load in the left anterior corona radiata (pFWE < 0.05). GM volume in the left thalamus and GM thickness in the left orbitofrontal cortex were reduced in the GD group (pFWE < 0.05). Conclusions: Similar to substance addictions, the fronto-striatal-thalamic circuit is also affected in GD, suggesting that this circuitry may have a crucial role in addictions, independent of pharmacological substances.

Altered temporal connectivity and reduced meta-state dynamism in adolescents born very preterm.

Adolescents born very preterm have an increased risk for anxiety, social difficulties and inattentiveness, i.e. the 'preterm behavioural phenotype'. The extreme end of these traits comprises the core diagnostic features of attention and hyperactivity disorders and autism spectrum disorder, which have been reported to show aberrant dynamic resting-state functional network connectivity. This study aimed to compare this dynamism between adolescents born very preterm and controls. A resting-state functional magnetic resonance imaging was performed on 24 adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) and 32 controls born full term (≥37 weeks of gestation) at 13 years of age. Group-wise comparisons of dynamic connectivity between the resting-state networks were performed using both hard clustering and meta-state analysis of functional network connectivity. The very preterm group yielded a higher fraction of time spent in the least active connectivity state in hard clustering state functional network connectivity, even though no group differences in pairwise connectivity patterns were discovered. The meta-state analysis showed a decreased fluidity and dynamic range in the very preterm group compared with controls. Our results suggest that the 13-year-old adolescents born very preterm differ from controls in the temporal characteristics of functional connectivity. The findings may reflect the long-lasting effects of prematurity and the clinically acknowledged 'preterm behavioural phenotype'.

The neural bases of expressive suppression: A systematic review of functional neuroimaging studies.

Expressive suppression refers to the inhibition of emotion-expressive behavior (e.g., facial expressions of emotion). Although it is a commonly used emotion regulation strategy with well-documented consequences for well-being, little is known about its underlying mechanisms. In this systematic review, we for the first time synthesize functional neuroimaging studies on the neural bases of expressive suppression in non-clinical populations. The 12 studies included in this review contrasted the use of expressive suppression to simply watching emotional stimuli. Results showed that expressive suppression consistently increased activation of frontoparietal regions, especially the dorsolateral and ventrolateral prefrontal cortices and inferior parietal cortex, but decreased activation in temporo-occipital areas. Results regarding the involvement of the insula and amygdala were inconsistent with studies showing increased, decreased, or no changes in activation. These mixed findings underscore the importance of distinguishing expressive suppression from other forms of suppression and highlight the need to pay more attention to experimental design and neuroimaging data analysis procedures. We discuss these conceptual and methodological issues and provide suggestions for future research.

Performance in Hand Coordination Tasks and Concurrent Functional MRI Findings in 13-Year-Olds Born Very Preterm.

BACKGROUND: Fine motor and coordination problems are frequently reported among adolescents born preterm. We aimed to assess performance in hand coordination tasks and to compare concurrent brain activation between adolescents born very preterm and at term at 13 years. METHODS: A total of 34 right-handed adolescents born very preterm (gestational age less than 32 weeks/birth weight ≤1500 grams) and 37 controls born at term during 2003 to 2006 in Turku University Hospital, Finland, were recruited. At 13 years, finger opposition and diadochokinesis were assessed, and brain functional magnetic resonance imaging data were acquired while the adolescents performed unimanual hand coordination tasks in response to visual cue. RESULTS: Adolescents born very preterm performed similar to controls in hand coordination tasks. The very preterm group evoked greater brain activation than the controls in the right precentral gyrus and in the right postcentral gyrus during left-hand finger opposition and in the right postcentral gyrus during left-hand diadochokinesis. Within the very preterm group, lower gestational age was associated with reduced activation in the left superior parietal lobule during right-hand diadochokinesis. Regarding left-hand tasks, lower gestational age was associated with stronger activation in the right cerebellar lobule V and left cerebellar lobule VI during finger opposition and stronger activation in the right superior parietal lobule during diadochokinesis. CONCLUSIONS: Very preterm birth affected hand coordination-related brain activation. Most of the effects were found for nondominant hand. Clinical performance during the hand coordination tasks was similar in adolescents born very preterm and controls.

Functional Magnetic Resonance Imaging during Visual Perception Tasks in Adolescents Born Prematurely.

OBJECTIVES: Impairments in visual perception are among the most common developmental difficulties related to being born prematurely, and they are often accompanied by problems in other developmental domains. Neural activation in participants born prematurely and full-term during tasks that assess several areas of visual perception has not been studied. To better understand the neural substrates of the visual perceptual impairments, we compared behavioral performance and brain activations during visual perception tasks in adolescents born very preterm (birth weight ≤1500 g or gestational age <32 weeks) and full-term. METHODS: Tasks assessing visual closure, discrimination of a deviating figure, and discrimination of figure and ground from the Motor-Free Visual Perception Test, Third Edition were performed by participants born very preterm (n = 37) and full-term (n = 34) at 12 years of age during functional magnetic resonance imaging. RESULTS: Behavioral performance in the visual perception tasks did not differ between the groups. However, during the visual closure task, brain activation was significantly stronger in the group born very preterm in a number of areas including the frontal, anterior cingulate, temporal, and posterior medial parietal/cingulate cortices, as well as in parts of the cerebellum, thalamus, and caudate nucleus. CONCLUSIONS: Differing activations during the visual closure task potentially reflect a compensatory neural process related to premature birth or lesser neural efficiency or may be a result of the use of compensatory behavioral strategies in the study group born very preterm.

Visual Perceptual Skills in Very Preterm Children: Developmental Course and Associations With Neural Activation.

BACKGROUND: The objective of this study was to examine how nonverbal skills at age five years relate to visual perception and brain activation during visual perception tasks at age 12 years in very preterm subjects without visual or other neurodevelopmental impairments or major brain pathologies. METHODS: At age five years, 36 prematurely born (birth weight ≤1500 g or gestational age less than 32 weeks) and 31 term-born control children were assessed with the nonverbal subtests of the Wechsler Preschool and Primary Scale of Intelligence-Revised and the NEPSY-Second Edition. At age 12 years the same children were re-assessed with tasks from the Motor-Free Visual Perception Test, Third Edition, during functional magnetic resonance imaging. RESULTS: Test performance at age five years was significantly poorer in the very preterm group than the control subjects, but at age 12 years performance was similar in both groups. In the very preterm group, better nonverbal skills at age five years were significantly associated with stronger neural activation during the visual perception task at age 12 years. No associations between nonverbal skills at age five years and brain activation at age 12 years appeared in the control group. CONCLUSIONS: The associations between better nonverbal skills and stronger neural activation during visual perception task only observed in the very preterm group may reflect delayed development of the visual perception network and/or prematurity-related neural plasticity. The developmental follow-up of very preterm children should include psychological assessment of nonverbal skills at least until age five years.

Does TMS on V3 block conscious visual perception?

Primary visual cortex (V1) and extrastriate V2 are necessary for the emergence of visual consciousness, but the effects of involvement of extrastriate V3 on visual consciousness is unclear. The objective of this study was to examine the causal role of V3 in visual consciousness in humans. We combined neuronavigated transcranial magnetic stimulation (TMS) with a computational model of the TMS-induced electric field to test whether or not the intact processing of visual input in V3, like in V1 and V2, is necessary for conscious visual perception. We targeted the stimulation both to V2 and to V3. If TMS of V3 blocks conscious visual perception of stimuli, then activation in V3 is a causally necessary prerequisite for conscious perception of stimuli. According to the alternative hypothesis, TMS of V3 will not block the conscious visual perception of stimuli, because the pathways from V1 to the higher cortical areas that go around V3 provide sufficient visual input for the emergence of conscious visual perception. The results showed that TMS interfered with conscious perception of features, detection of stimulus presence and the ability to discriminate the letter stimuli both when TMS was targeted either to V3 or to V2. For the conscious detection of stimulus presence, the effect was significantly stronger when V2 was stimulated than when V3 was stimulated. The results of the present study suggest that in addition to the primary visual cortex and V2, also V3 causally contributes to the generation of the most basic form of visual consciousness. Importantly, the results also indicate that V3 is necessary for visual perception in general, not only for visual consciousness.

TMS-EEG reveals hemispheric asymmetries in top-down influences of posterior intraparietal cortex on behavior and visual event-related potentials.

Clinical data and behavioral studies using transcranial magnetic stimulation (TMS) suggest right-hemisphere dominance for top-down modulation of visual processing in humans. We used concurrent TMS-EEG to directly test for hemispheric differences in causal influences of the right and left intraparietal cortex on visual event-related potentials (ERPs). We stimulated the left and right posterior part of intraparietal sulcus (IPS1) while the participants were viewing and rating the visibility of bilaterally presented Gabor patches. Subjective visibility ratings showed that TMS of right IPS shifted the visibility toward the right hemifield, while TMS of left IPS did not have any behavioral effect. TMS of right IPS, but not left one, reduced the amplitude of posterior N1 potential, 180-220ms after stimulus-onset. The attenuation of N1 occurred bilaterally over the posterior areas of both hemispheres. Consistent with previous TMS-fMRI studies, this finding suggests that the right IPS has top-down control on the neural processing in visual cortex. As N1 most probably reflects reactivation of early visual areas, the current findings support the view that the posterior parietal cortex in the right hemisphere amplifies recurrent interactions in ventral visual areas during the time-window that is critical for conscious perception.

Risk-Taking Behavior in a Computerized Driving Task: Brain Activation Correlates of Decision-Making, Outcome, and Peer Influence in Male Adolescents.

Increased propensity for risky behavior in adolescents, particularly in peer groups, is thought to reflect maturational imbalance between reward processing and cognitive control systems that affect decision-making. We used functional magnetic resonance imaging (fMRI) to investigate brain functional correlates of risk-taking behavior and effects of peer influence in 18-19-year-old male adolescents. The subjects were divided into low and high risk-taking groups using either personality tests or risk-taking rates in a simulated driving task. The fMRI data were analyzed for decision-making (whether to take a risk at intersections) and outcome (pass or crash) phases, and for the influence of peer competition. Personality test-based groups showed no difference in the amount of risk-taking (similarly increased during peer competition) and brain activation. When groups were defined by actual task performance, risk-taking activated two areas in the left medial prefrontal cortex (PFC) significantly more in low than in high risk-takers. In the entire sample, risky decision-specific activation was found in the anterior and dorsal cingulate, superior parietal cortex, basal ganglia (including the nucleus accumbens), midbrain, thalamus, and hypothalamus. Peer competition increased outcome-related activation in the right caudate head and cerebellar vermis in the entire sample. Our results suggest that the activation of the medial (rather than lateral) PFC and striatum is most specific to risk-taking behavior of male adolescents in a simulated driving situation, and reflect a stronger conflict and thus increased cognitive effort to take risks in low risk-takers, and reward anticipation for risky decisions, respectively. The activation of the caudate nucleus, particularly for the positive outcome (pass) during peer competition, further suggests enhanced reward processing of risk-taking under peer influence.

Brain structural correlates of risk-taking behavior and effects of peer influence in adolescents.

Adolescents are characterized by impulsive risky behavior, particularly in the presence of peers. We discriminated high and low risk-taking male adolescents aged 18-19 years by assessing their propensity for risky behavior and vulnerability to peer influence with personality tests, and compared structural differences in gray and white matter of the brain with voxel-based morphometry (VBM) and diffusion tensor imaging (DTI), respectively. We also compared the brain structures according to the participants' actual risk-taking behavior in a simulated driving task with two different social conditions making up a peer competition situation. There was a discrepancy between the self-reported personality test results and risky driving behavior (running through an intersection with traffic lights turning yellow, chancing a collision with another vehicle). Comparison between high and low risk-taking adolescents according to personality test results revealed no significant difference in gray matter volume and white matter integrity. However, comparison according to actual risk-taking behavior during task performance revealed significantly higher white matter integrity in the high risk-taking group, suggesting that increased risky behavior during adolescence is not necessarily attributed to the immature brain as conventional wisdom says.

No effects of short-term GSM mobile phone radiation on cerebral blood flow measured using positron emission tomography.

The present study investigated the effects of 902.4 MHz global system for mobile communications (GSM) mobile phone radiation on cerebral blood flow using positron emission tomography (PET) with the (15) O-water tracer. Fifteen young, healthy, right-handed male subjects were exposed to phone radiation from three different locations (left ear, right ear, forehead) and to sham exposure to test for possible exposure effects on brain regions close to the exposure source. Whole-brain [¹5O]H2O-PET images were acquired 12 times, 3 for each condition, in a counterbalanced order. Subjects were exposed for 5 min in each scan while performing a simple visual vigilance task. Temperature was also measured in the head region (forehead, eyes, cheeks, ear canals) during exposure. The exposure induced a slight temperature rise in the ear canals but did not affect brain hemodynamics and task performance. The results provided no evidence for acute effects of short-term mobile phone radiation on cerebral blood flow.

GSM mobile phone radiation suppresses brain glucose metabolism.

We investigated the effects of mobile phone radiation on cerebral glucose metabolism using high-resolution positron emission tomography (PET) with the (18)F-deoxyglucose (FDG) tracer. A long half-life (109 minutes) of the (18)F isotope allowed a long, natural exposure condition outside the PET scanner. Thirteen young right-handed male subjects were exposed to a pulse-modulated 902.4 MHz Global System for Mobile Communications signal for 33 minutes, while performing a simple visual vigilance task. Temperature was also measured in the head region (forehead, eyes, cheeks, ear canals) during exposure. (18)F-deoxyglucose PET images acquired after the exposure showed that relative cerebral metabolic rate of glucose was significantly reduced in the temporoparietal junction and anterior temporal lobe of the right hemisphere ipsilateral to the exposure. Temperature rise was also observed on the exposed side of the head, but the magnitude was very small. The exposure did not affect task performance (reaction time, error rate). Our results show that short-term mobile phone exposure can locally suppress brain energy metabolism in humans.

Central executive function in mild cognitive impairment: a PET activation study.

Using positron emission tomography (PET), we explored the neural correlates of an executive function, dual tasking, in patients with amnestic mild cognitive impairment (aMCI) and in elderly controls. The experiment employed simple auditory and visual tasks that were presented both in isolation and simultaneously to create a task condition requiring enhanced attentional control. Behaviorally, both groups performed well, albeit the patients made more errors on the visual task. The PET analysis focused at prefrontal regions where group differences in task-related activation patterns were expected. During dual task performance, the patients showed attenuated activity in the left inferior frontal region when compared to the controls. This suggests abnormalities in the neural processes underlying attentional control in aMCI.

Brain activity during selective listening to natural speech.

Human brain functions involved in selective attention to particular sounds have been studied extensively with non-invasive measurements of electro-magnetic and hemodynamic brain activity. Here we review studies indicating that selection of the attended sounds for further processing occurs in the auditory cortex. The exact locus of this selection process in the auditory cortex appears to depend on the auditory attribute, i.e., location or pitch, separating the attended sounds from the irrelevant ones. Recent neuroimaging studies extend this finding from processing of non-speech sounds to attentional selection of relevant speech differing by its location or speaker identity from concurrent irrelevant speech. These studies suggest also that selective listening to speech depends less on prefrontal control functions than other kinds of listening tasks demanding selective attention.

Neural correlates of naming newly learned objects in MCI.

Our objective was to study the neural correlates of naming of newly learned unfamiliar objects in subjects with mild cognitive impairment (MCI) and in age-matched controls, by using positron emission tomography (PET). Prior to the PET scanning, each subject underwent a 4-day long training period in which 40 names of rare unfamiliar objects were taught. The stimuli consisted of five categories: unfamiliar objects for which both the name and the definition (=semantic support) were given during training, unfamiliar objects with only the name given, unfamiliar objects with no information given, familiar objects and visual noise patterns. The unfamiliar objects mainly represented ancient domestic tools unknown to modern-day people. When naming newly learned objects trained without semantic support, the MCI group showed increased activation in the anterior cingulate when compared with the controls. Our results suggest that the naming of newly learned objects posed additional executive and attentional demands on the patients.

Functional brain imaging, clinical and neurophysiological outcome of visual rehabilitation in a chronic stroke patient.

PURPOSE: To study rehabilitation outcome in a chronic visual field defect patient using positron emission tomography (PET) imaging, clinical, and neurophysiological measures. METHODS: A patient with chronic visual field defect was rehabilitated using a computer program over a three-month period. Evaluations of rehabilitation effects were done before and after training, and after a three-month follow-up with perimetry, visual evoked potentials (VEP), subjective questionnaire, and PET activation studies of regional cerebral blood flow (rCBF). RESULTS: In perimetry, the visual field increased during the training, and the patient also experienced subjective improvement. In VEP, a previously absent P100 component was identified after the training. In PET, increases in rCBF were diffuse immediately after the training, and more occipital after the late follow-up. A significant positive correlation between the increase in rCBF and improvement in clinical measures was found in the lingual gyrus in the contralesional hemisphere. CONCLUSIONS: All clinical measures showed improvement after rehabilitation, and this was maintained during the follow-up. In PET, a more generalized effect, found at the beginning, later concentrated in the occipital cortex. The results suggest that visual training may cause plastic changes in the brain, and that these changes can be detected both with clinical measures and with functional imaging.

Neural correlates of morphological decomposition in a morphologically rich language: an fMRI study.

By employing visual lexical decision and functional MRI, we studied the neural correlates of morphological decomposition in a highly inflected language (Finnish) where most inflected noun forms elicit a consistent processing cost during word recognition. This behavioral effect could reflect suffix stripping at the visual word form level and/or subsequent meaning integration at the semantic-syntactic level. The first alternative predicts increased activation for inflected vs. monomorphemic words in the left occipitotemporal cortex while the second alternative predicts left inferior frontal gyrus and/or left posterior temporal activation increases. The results show significant activation effects in the latter areas. This provides support for the second alternative, i.e., that the morphological processing cost stems from the semantic-syntactic level.

Selective attention to human voice enhances brain activity bilaterally in the superior temporal sulcus.

Regional cerebral blood flow was measured with positron emission tomography (PET) in 10 healthy male volunteers. They heard two binaurally delivered concurrent stories, one spoken by a male voice and the other by a female voice. A third story was presented at the same time as a text running on a screen. The subjects were instructed to attend silently to one of the stories at a time. In an additional resting condition, no stories were delivered. PET data showed that in comparison with the reading condition, the brain activity in the speech-listening conditions was enhanced bilaterally in the anterior superior temporal sulcus including cortical areas that have been reported to be specifically sensitive to human voice. Previous studies on attention to non-linguistic sounds and visual objects, in turn, showed prefrontal activations that are presumably related to attentional control functions. However, comparisons of the present speech-listening and reading conditions with each other or with the resting condition indicated no prefrontal activity, except for an activation in the inferior frontal cortex that was presumably associated with semantic and syntactic processing of the attended story. Thus, speech listening, as well as reading, even in a distracting environment appears to depend less on the prefrontal control functions than do other types of attention-demanding tasks, probably because selective attention to speech and written text are over-learned actions rehearsed daily.

Naming of newly learned objects: a PET activation study.

The present study tracked the naming-related brain activity by positron emission tomography (PET) when successfully learned unfamiliar objects were named. Ten Finnish-speaking subjects participated in the study. Prior to the PET scan, each subject underwent a 4-day long training period in which 40 names of rare unfamiliar objects were taught. The stimulus categories were as follows: unfamiliar but real objects for which both the name and the definition were given during training, only the name was given, no information was given. In addition, familiar objects and visual noise patterns were used. The unfamiliar items mainly represented ancient domestic tools unknown to modern-day people. As semantic support did not affect the PET results, all trained items were pooled together. The trained objects vs. familiar objects contrast revealed rCBF increases in the left inferior frontal cortex (Broca's area), the left anterior temporal area, and the cerebellum. Likewise, the trained objects vs. unfamiliar objects (for which no information was given) contrast revealed more extensive left frontal (roughly Broca's area) and cerebellar rCBF increases, while anterior temporal activation was bilateral. Familiar objects, contrasted with both visual noise patterns and a rest condition, elicited activation increases in expected areas, i.e., bilateral occipital regions and the fusiform gyrus. Our results indicate that the naming of newly learned objects recruits more extensive brain areas than the naming of familiar items, namely a network that includes left-dominant frontotemporal areas and cerebellum. Its activity is tentatively related to enhanced lexical-semantic and lexical-phonological retrieval, as well as associative memory processes.