Brain aging and psychometric intelligence: a longitudinal study.

In this study, we examined a large sample of 231 generally healthy older adults across 4 years with regard to several brain anatomical measures (volumes of total grey matter volume: GM, normal appearing white matter: NAWM, lateral ventricle: LV, and white matter hypointensities: WMH) and psychometric intelligence (verbal and non-verbal). The dataset comprised four measurement occasions (baseline, 1-, 2-, and 4-year follow-ups). With this longitudinal data set, we evaluated level-level, level-change, and change-change relationships between the anatomical and psychometric measures using latent growth curve models. Our analyses indicate that GM and NAWM decreased significantly over the course of 4 years with annual percent changes of - 0.73% and - 0.79%, respectively. WMH and LV volumes increase with annual percent changes of 7.3% and 4%, respectively. Verbal and nonverbal IQ measures remained stable in our sample. In addition, we uncovered evidence for level-level and -change associations between several of the brain anatomical measures. With regard to brain-IQ associations, we observed a positive level-level association for GM and NAWM, indicating that participants with larger brain volumes demonstrate higher IQ measures. No substantial evidence was identified for level- or change-change associations between any of the brain metrics and the IQ measures. Taken together, these results suggest that while healthy older adults demonstrated age-related neuroanatomical decline over a time span of 4 years, these degenerative changes are not necessarily linked to simultaneous cognitive deterioration.

Training emotion regulation through real-time fMRI neurofeedback of amygdala activity.

Being in control of one's emotions is not only desirable in many everyday situations but is also a great challenge in a variety of mental disorders. Successful intentional emotion regulation is related to down-regulation of amygdala activity. Training mental interventions supported by neurofeedback of one's own amygdala activity using real-time (rt-)fMRI might be beneficial for mental health and well-being. Rt-fMRI guided amygdala-downregulation using cognitive interventions such as a "reality check", however, have not been well-investigated. Fifteen healthy subjects underwent four rt-fMRI sessions with neurofeedback of their own amygdala activity while applying a reality check as an emotion regulation strategy in order to down-regulate their amygdala signal during a stimulation with emotional pictures. The Control group comprised of eleven subjects also trained emotion regulation but without obtaining feedback. We hypothesized more prominent down-regulation of amygdala activity at the end of the training in the Feedback group. We investigated effects over time and between groups and further task specific connectivity of the amygdala by using psychophysiological interaction analyses. Four weekly amygdala-based feedback sessions resulted in significantly decreased amygdala activity (p = 0.003, d = 0.93), also compared to the Control group (p = 0.014, d = 1.12). Task specific connectivity of the amygdala with the anterior cingulate cortex, hippocampus and distinct prefrontal areas was increased in the Feedback group. Training of emotion regulation supported by rt-fMRI neurofeedback resulted in a prominent amygdala down-regulation compared to training without feedback. The finding implicates successful emotion regulation, compliant with emotion control models, through an easily applicable reality check strategy. Rt-fMRI neurofeedback may support emotion regulation learning and bears clinical potential for psychotherapy.

Neurodevelopmental origins of abnormal cortical morphology in dissociative identity disorder.

OBJECTIVE: To examine the two constitutes of cortical volume (CV), that is, cortical thickness (CT) and surface area (SA), in individuals with dissociative identity disorder (DID) with the view of gaining important novel insights into the underlying neurobiological mechanisms mediating DID. METHODS: This study included 32 female patients with DID and 43 matched healthy controls. Between-group differences in CV, thickness, and SA, the degree of spatial overlap between differences in CT and SA, and their relative contribution to differences in regional CV were assessed using a novel spatially unbiased vertex-wise approach. Whole-brain correlation analyses were performed between measures of cortical anatomy and dissociative symptoms and traumatization. RESULTS: Individuals with DID differed from controls in CV, CT, and SA, with significantly decreased CT in the insula, anterior cingulate, and parietal regions and reduced cortical SA in temporal and orbitofrontal cortices. Abnormalities in CT and SA shared only about 3% of all significantly different cerebral surface locations and involved distinct contributions to the abnormality of CV in DID. Significant negative associations between abnormal brain morphology (SA and CV) and dissociative symptoms and early childhood traumatization (0 and 3 years of age) were found. CONCLUSIONS: In DID, neuroanatomical areas with decreased CT and SA are in different locations in the brain. As CT and SA have distinct genetic and developmental origins, our findings may indicate that different neurobiological mechanisms and environmental factors impact on cortical morphology in DID, such as early childhood traumatization.

Pattern of structural brain changes in social anxiety disorder after cognitive behavioral group therapy: a longitudinal multimodal MRI study.

Social anxiety disorder (SAD) is characterized by fears of social and performance situations. Cognitive behavioral group therapy (CBGT) has in general positive effects on symptoms, distress and avoidance in SAD. Prior studies found increased cortical volumes and decreased fractional anisotropy (FA) in SAD compared with healthy controls (HCs). Thirty-three participants diagnosed with SAD attended in a 10-week CBGT and were scanned before and after therapy. We applied three neuroimaging methods-surface-based morphometry, diffusion tensor imaging and network-based statistics-each with specific longitudinal processing protocols, to investigate CBGT-induced structural brain alterations of the gray and white matter (WM). Surface-based morphometry revealed a significant cortical volume reduction (pre- to post-treatment) in the left inferior parietal cortex, as well as a positive partial correlation between treatment success (indexed by reductions in Liebowitz Social Anxiety Scale) and reductions in cortical volume in bilateral dorsomedial prefrontal cortex. Diffusion tensor imaging analysis revealed a significant increase in FA in bilateral uncinate fasciculus and right inferior longitudinal fasciculus. Network-based statistics revealed a significant increase of structural connectivity in a frontolimbic network. No partial correlations with treatment success have been found in WM analyses. For, we believe, the first time, we present a distinctive pattern of longitudinal structural brain changes after CBGT measured with three established magnetic resonance imaging analyzing techniques. Our findings are in line with previous cross-sectional, unimodal SAD studies and extent them by highlighting anatomical brain alterations that point toward the level of HCs in parallel with a reduction in SAD symptomatology.

Age prediction on the basis of brain anatomical measures.

In this study, we examined whether age can be predicted on the basis of different anatomical features obtained from a large sample of healthy subjects (n = 3,144). From this sample we obtained different anatomical feature sets: (1) 11 larger brain regions (including cortical volume, thickness, area, subcortical volume, cerebellar volume, etc.), (2) 148 cortical compartmental thickness measures, (3) 148 cortical compartmental area measures, (4) 148 cortical compartmental volume measures, and (5) a combination of the above-mentioned measures. With these anatomical feature sets, we predicted age using 6 statistical techniques (multiple linear regression, ridge regression, neural network, k-nearest neighbourhood, support vector machine, and random forest). We obtained very good age prediction accuracies, with the highest accuracy being R2 = 0.84 (prediction on the basis of a neural network and support vector machine approaches for the entire data set) and the lowest being R2 = 0.40 (prediction on the basis of a k-nearest neighborhood for cortical surface measures). Interestingly, the easy-to-calculate multiple linear regression approach with the 11 large brain compartments resulted in a very good prediction accuracy (R2 = 0.73), whereas the application of the neural network approach for this data set revealed very good age prediction accuracy (R2 = 0.83). Taken together, these results demonstrate that age can be predicted well on the basis of anatomical measures. The neural network approach turned out to be the approach with the best results. In addition, it was evident that good prediction accuracies can be achieved using a small but nevertheless age-representative dataset of brain features. Hum Brain Mapp 38:997-1008, 2017. © 2016 Wiley Periodicals, Inc.

Neural correlates of mindful self-awareness in mindfulness meditators and meditation-naïve subjects revisited.

Mindful self-awareness is central to mindfulness meditation and plays a key role in its salutary effects. It has been related to decreased activation in cortical midline structures (CMS) and amygdala, and increased activation in somatosensory regions. However, findings in untrained individuals are contradictory, and scarce in experienced meditators. Using fMRI, we investigated experienced mindfulness meditators (LTM, n=21, average 4652 practice-hours) and matched meditation-naïve participants (MNP, n=19) during short periods of mindful self-awareness (FEEL) and self-referential thinking (THINK). We report somatosensory activations and decreases in CMS during FEEL for both groups, but significantly stronger decreases in prefrontal CMS in LTM. LTM further showed decreases in language-related and amygdala regions, but the latter was not significantly different between groups. Overall, higher activations in amygdala and mid-line regions during FEEL were related to levels of depressiveness. Neural patterns of mindful self-awareness emerge already in MNP but more pronounced in LTM. Specifically, meditation training might reduce self-reference and verbalization during mindful awareness. We further corroborate the suggested link between mindfulness and healthy self-related functions on the neural level. Longitudinal studies need to corroborate these findings.

Altered processing of self-related emotional stimuli in mindfulness meditators.

Mental health benefits of mindfulness techniques are thought to involve changes in self-processing, such as decreased attachment to the self, higher self-compassion and lower emotional reactivity to inner experience. However, self-related emotion processing in regular mindfulness practitioners is not extensively studied. In the current work we investigate differential neural and behavioral correlates of self-criticism and self-praise in 22 mid-to-long-term mindfulness meditators (LTM) compared to 22 matched meditation-naïve participants (MNP). In an fMRI experiment, participants were presented with blocks of individually selected positive (self-praise, SP), negative (self-critical, SC), negative but not-self-critical (NNSC), and general, neutral (NT) adjectives, and reported their affective state after the blocks. On the neural level, both SP and SC yielded more activation in the dorso-medial prefrontal cortex (DMPFC) in LTM compared to MNP. Activation in this region correlated positively with non-react scores of the Five Facets Mindfulness Questionnaire (FFMQ) and showed decreased functional connectivity to posterior midline and parietal regions in LTM compared to MNP during both self-related appraisals. Further, we found evidence for emotional reactivity in LTM on the neural level, particularly during SP. On the behavioral level, a mixed effects analysis revealed significantly higher differences in affective ratings after blocks of SC compared to SP in MNP compared to LTM. Differences in DMPFC activation and affective ratings point towards increased awareness, potentially mindful regulation of SC and SP in LTM, while decreased connectivity to other regions of the default mode network could reflect a decreased self-focus in this group. As such, our results illustrate differences in self-related emotional processes in meditators and offer clinically relevant insights into mechanisms of mindful emotion regulation when facing self-criticism and self-praise.

Differential EMG biofeedback for children with ADHD: a control method for neurofeedback training with a case illustration.

The objective of the present paper was to develop a differential electromyographic biofeedback (EMG-BF) training for children with attention-deficit/hyperactivity disorder (ADHD) matching multiple neurofeedback training protocols in order to serve as a valid control training. This differential EMG-BF training method feeds back activity from arm muscles involved in fine motor skills such as writing and grip force control. Tonic EMG-BF training (activation and deactivation blocks, involving bimanual motor tasks) matches the training of EEG frequency bands, while phasic EMG-BF training (short activation and deactivation trials) was developed as an equivalent to the training of slow cortical potentials. A case description of a child who learned to improve motor regulation in most task conditions and showed a clinically relevant reduction of behavioral ADHD symptoms illustrates the training course and outcome. Differential EMG-BF training is feasible and provides well-matched control conditions for neurofeedback training in ADHD research. Future studies should investigate its value as a specific intervention for children diagnosed with ADHD and comorbid sensorimotor problems.

Effects of limb immobilization on brain plasticity.

OBJECTIVE: Little is known about the effects of reduced sensory input and motor output in the human brain. Therefore, we conducted a longitudinal study to investigate whether limb immobilization after unilateral arm injury is reflected in structural plastic changes in gray matter (cortical thickness) and white matter (fractional anisotropy [FA]). METHODS: We examined 10 right-handed subjects with injury of the right upper extremity that required at least 14 days of limb immobilization. Subjects underwent 2 MRI examinations, the first within 48 hours postinjury and the second after an average time interval of 16 days of immobilization. Based on the MRI scans, we measured cortical thickness of sensorimotor regions and FA of the corticospinal tracts. RESULTS: After immobilization, we revealed a decrease in cortical thickness in the left primary motor and somatosensory area as well as a decrease in FA in the left corticospinal tract. In addition, the motor skill of the left (noninjured) hand improved and is related to increased cortical thickness and FA in the right motor cortex. CONCLUSIONS: The present study illustrates that cortical thickness of the sensorimotor cortex and FA of the corticospinal tract changed during right arm immobilization and that these changes are associated with skill transfer from the right to the left hand. Thus, immobilization induces rapid reorganization of the sensorimotor system. Given that limb immobilization is a standard intervention technique in constraint-induced therapy, therapists should be aware of both the positive and negative effects of this intervention.

Tracing toothache intensity in the brain.

Identification of brain regions that differentially respond to pain intensity may improve our understanding of trigeminally mediated nociception. This report analyzed cortical responses to painless and painful electrical stimulation of a right human maxillary canine tooth. Functional magnetic resonance images were obtained during the application of five graded stimulus strengths, from below, at, and above the individually determined pain thresholds. Study participants reported each stimulus on a visual rating scale with respect to evoked sensation. Based on hemodynamic responses of all pooled stimuli, a cerebral network was identified that largely corresponds to the known lateral and medial nociceptive system. Further analysis of the five graded stimulus strengths revealed positive linear correlations for the anterior insula bilaterally, the contralateral (left) anterior mid-cingulate, as well as contralateral (left) pregenual cingulate cortices. Cerebral toothache intensity coding on a group level can thus be attributed to specific subregions within the cortical pain network.

Temporal and spatial patterns of cortical activation during assisted lower limb movement.

Human gait is a complex process in the central nervous system that results from the integrity of various mechanisms, including different cortical and subcortical structures. In the present study, we investigated cortical activity during lower limb movement using EEG. Assisted by a dynamic tilt table, all subjects performed standardized stepping movements in an upright position. Source localization of the movement-related potential in relation to spontaneous EEG showed activity in brain regions classically associated with human gait such as the primary motor cortex, the premotor cortex, the supplementary motor cortex, the cingulate cortex, the primary somatosensory cortex and the somatosensory association cortex. Further, we observed a task-related power decrease in the alpha and beta frequency band at electrodes overlying the leg motor area. A temporal activation and deactivation of the involved brain regions as well as the chronological sequence of the movement-related potential could be mapped to specific phases of the gait-like leg movement. We showed that most cortical capacity is needed for changing the direction between the flexion and extension phase. An enhanced understanding of the human gait will provide a basis to improve applications in the field of neurorehabilitation and brain-computer interfaces.

Neural correlates of 'pessimistic' attitude in depression.

BACKGROUND: Preparing for potentially threatening events in the future is essential for survival. Anticipating the future to be unpleasant is also a cognitive key feature of depression. We hypothesized that 'pessimism'-related emotion processing would characterize brain activity in major depression.MethodDuring functional magnetic resonance imaging, depressed patients and a healthy control group were cued to expect and then perceive pictures of known emotional valences--pleasant, unpleasant and neutral--and stimuli of unknown valence that could have been either pleasant or unpleasant. Brain activation associated with the 'unknown' expectation was compared with the 'known' expectation conditions. RESULTS: While anticipating pictures of unknown valence, activation patterns in depressed patients within the medial and dorsolateral prefrontal areas, inferior frontal gyrus, insula and medial thalamus were similar to activations associated with expecting unpleasant pictures, but not with expecting positive pictures. The activity within a majority of these areas correlated with the depression scores. Differences between healthy and depressed persons were found particularly for medial and dorsolateral prefrontal and insular activations. CONCLUSIONS: Brain activation in depression during expecting events of unknown emotional valence was comparable with activation while expecting certainly negative, but not positive events. This neurobiological finding is consistent with cognitive models supposing that depressed patients develop a 'pessimistic' attitude towards events with an unknown emotional meaning. Thereby, particularly the role of brain areas associated with the processing of cognitive and executive control and of the internal state is emphasized in contributing to major depression.

Interindividual differences in the perception of dental stimulation and related brain activity.

For identical diagnoses in the trigeminal innervation territory, individual differences have been clinically observed among the symptoms reported, such as dysesthesia and pain. Different subjective perceptions of unpleasantness and pain intensity may have different cortical substrates. The aim of this study was to identify brain areas in which activation depends on the subjective perception (intensity and unpleasantness) of electric dental stimulation. Electrical stimuli of increasing intensity were applied to maxillary canines in 14 healthy volunteers. Ratings for stimulus intensity and unpleasantness perceived across the stimulation session were reported postscan on 11-point numerical scales. The rating values were then included as covariates in the functional magnetic resonance imaging (fMRI) group analysis. Interindividual differences of intensity ratings were reflected in differential activity of the following brain areas: superior parietal lobule, superior temporal gyrus/anterior insula, inferior and middle temporal gyrus, lingual gyrus, anterior cingulate, and caudate nucleus. Differences related to unpleasantness ratings were reflected in the lingual gyrus. In conclusion, differences of perceived intensity between individuals are reflected in the differential activity of a set of brain areas distinct from those regions, reflecting rating differences of unpleasantness.

Randomized controlled trial investigating the effect of music on the virtual reality laparoscopic learning performance of novice surgeons.

BACKGROUND: Findings have shown that music affects cognitive performance, but little is known about its influence on surgical performance. The hypothesis of this randomized controlled trial was that arousing (activating) music has a beneficial effect on the surgical performance of novice surgeons in the setting of a laparoscopic virtual reality task. METHODS: For this study, 45 junior surgeons with no previous laparoscopic experience were randomly assigned to three equal groups. Group 1 listened to activating music; group 2 listened to deactivating music; and group 3 had no music (control) while each participant solved a surgical task five times on a virtual laparoscopic simulator. The assessed global task score, the total task time, the instrument travel distances, and the surgeons' heart rate were assessed. RESULTS: All surgical performance parameters improved significantly with experience (task repetition). The global score showed a trend for a between-groups difference, suggesting that the group listening to activating music had the worst performance. This observation was supported by a significant between-groups difference for the first trial but not subsequent trials (activating music, 35 points; deactivating music, 66 points; no music, 91 points; p = 0.002). The global score (p = 0.056) and total task time (p = 0.065) showed a trend toward improvement when participants considered the music pleasant rather than unpleasant. CONCLUSIONS: Music in the operating theater may have a distracting effect on novice surgeons performing new tasks. Surgical trainers should consider categorically switching off music during teaching procedures.

The involvement of primary motor cortex in mental rotation revealed by transcranial magnetic stimulation.

We used single-pulse transcranial magnetic stimulation of the left primary hand motor cortex and motor evoked potentials of the contralateral right abductor pollicis brevis to probe motor cortex excitability during a standard mental rotation task. Based on previous findings we tested the following hypotheses. (i) Is the hand motor cortex activated more strongly during mental rotation than during reading aloud or reading silently? The latter tasks have been shown to increase motor cortex excitability substantially in recent studies. (ii) Is the recruitment of the motor cortex for mental rotation specific for the judgement of rotated but not for nonrotated Shepard & Metzler figures? Surprisingly, motor cortex activation was higher during mental rotation than during verbal tasks. Moreover, we found strong motor cortex excitability during the mental rotation task but significantly weaker excitability during judgements of nonrotated figures. Hence, this study shows that the primary hand motor area is generally involved in mental rotation processes. These findings are discussed in the context of current theories of mental rotation, and a likely mechanism for the global excitability increase in the primary motor cortex during mental rotation is proposed.

Decreased white-matter density in a left-sided fronto-temporal network in children with developmental language disorder: evidence for anatomical anomalies in a motor-language network.

The neurophysiological and neuroanatomical foundations of developmental language disorder (DLD) are still a matter of dispute. A main argument is that children with DLD show atypical anatomical asymmetries of speech-relevant brain areas, which possibly affect efficient language processing. In contrast to previous anatomical studies in DLD children, this study employed voxel based morphometry (VBM) in order to search for brain anomalies outside the classical language areas. Children with DLD (n=21) and healthy children (n=21) matched for age, sex, hand preference, and education were studied using high-resolution MRI scans. Using a new variant of the voxel-based morphometry technique (augmented VBM), the brains of children with DLD and control children were compared with respect to white matter (WM) and grey matter (GM) differences. In addition, simple hand motor tests were used to uncover possible motor impairments in DLD children. We found decreased WM volumes in a left-hemispheric network comprising the motor cortex, the dorsal premotor cortex, the ventral premotor cortex, and the planum polare on the superior temporal gyrus. In addition, DLD children exhibited motor impairments in most of the applied motor tests. These results provide strong evidence that children with DLD have anomalous anatomy in a left-sided network comprising motor and language areas. Thus, this study supports the suggestion that motor and language functions are equally impaired because the underlying anatomical underpinnings are regionally identical.

Extensive training of elementary finger tapping movements changes the pattern of motor cortex excitability.

There is evidence of a strong capacity for functional and structural reorganization in the human motor system. However, past research has focused mainly on complex movement sequences over rather short training durations. In this study we investigated changes in corticospinal excitability associated with longer training of elementary, maximum-speed tapping movements. All participating subjects were consistent right-handers and were trained using either the right (experiment 1) or the left thumb (experiment 2). Transcranial magnetic stimulation was applied to obtain motor evoked potentials (MEPs) from the abductor pollicis brevis (APB) muscle of the right and the left hand before and after training. As a result of training, a significant increase was observed in tapping speed accompanied by increased MEPs, recorded from the trained APB muscle, following contralateral M1 stimulation. In the case of subdominant-hand training we additionally demonstrate increased MEP amplitudes evoked at the right APB (untrained hand) in the first training week. Enhanced corticospinal excitability associated with practice of elementary movements may constitute a necessary precursor for inducing plastic changes within the motor system. The involvement of the ipsilateral left M1 likely reflects the predominant role of the left M1 in the general control (modification) of simple motor parameters in right-handed subjects.

Parasagittal asymmetries of the corpus callosum.

Significant relationships have been reported between midsagittal areas of the corpus callosum and the degree of interhemispheric transfer, functional lateralization and structural brain asymmetries. No study, however, has examined whether parasagittal callosal asymmetries (i.e. those close to the midline of the brain), which may be of specific functional consequence, are present in the human brain. Thus, we applied magnetic resonance imaging and novel computational surface-based methods to encode hemispheric differences in callosal thickness at a very high resolution. Discrete callosal areas were also compared between the hemispheres. Furthermore, acknowledging the frequently reported sex differences in callosal morphology, parasagittal callosal asymmetries were examined within each gender. Results showed significant rightward asymmetries of callosal thickness predominantly in the anterior body and anterior third of the callosum, suggesting a more diffuse functional organization of callosal projections in the right hemisphere. Asymmetries were increased in men, supporting the assumption of a sexually dimorphic organization of male and female brains that involves hemispheric relations and is reflected in the organization and distribution of callosal fibers.

Gender effects on cortical thickness and the influence of scaling.

Using magnetic resonance imaging and well-validated computational cortical pattern matching methods in a large and well-matched sample of healthy subjects (n = 60), we analyzed the regional specificity of gender-related cortical thickness differences across the lateral and medial cortices at submillimeter resolution. To establish the influences of brain size correction on gender effects, comparisons were performed with and without applying affine transformations to scale each image volume to a template. We revealed significantly greater cortical thickness in women compared to men, after correcting for individual differences in brain size, while no significant regional thickness increases were observed in males. The pattern and direction of the results were similar without brain size correction, although effects were less pronounced and a small cortical region in the lateral temporal lobes showed greater thickness in males. Our gender-specific findings support a dimorphic organization in male and female brains that appears to involve the architecture of the cortical mantle and that manifests as increased thickness in female brains. This sexual dimorphism favoring women, even without correcting for brain size, may have functional significance and possibly account for gender-specific abilities and/or behavioral differences between sexes.

A curvature-based approach to estimate local gyrification on the cortical surface.

Using magnetic resonance imaging and a new method to analyze local surface shape, we examined the effects of gender on gyrification in a large and well-matched sample of healthy subjects. Unlike traditional 2D methods that produce whole-brain measurements of cortical complexity or more sophisticated 3D parametric mesh-based techniques that allow only different sections (lobes) of the cortex to be investigated, we employed a novel approach with increased spatial resolution. Although our method is sensitive to similar cortical features like the classic whole-brain gyrification index (depths of sulci and heights of gyri), we are now able to provide detailed and regionally specific estimates of cortical convolution at thousands of points across the cortical surface without introducing any bias through the rater or the selected orientation of the slices. We revealed pronounced gender differences, showing increased gyrification in frontal and parietal regions in females compared to males that agree with recent regions-of-interest findings. In addition, we detected higher female gyrification in temporal and occipital cortices that was not previously identified in studies using more global measures. No cortical area was significantly more convoluted in males compared to females. Our results demonstrate the sensitivity of this automated approach for identifying very local changes in gyrification. This technique may serve to isolate regionally specific changes in fissuration/gyrification in neurodevelopmental or neuropsychiatric disorders.