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1.  Issue Information 
Brain and Behavior  2015;5(7):i-iii.
PMCID: PMC4511282  PMID: 26221575
2.  Frozen moments: flashback memories of critical incidents in emergency personnel 
Brain and Behavior  2015;5(7):e00325.
Emergency Department personnel regularly face highly stressful situations or critical incidents (CIs) that may subsequently be recalled as unbidden intrusive memories. In their most extreme form, such memories are reexperienced as if they were happening again in the present, as flashbacks. This study examined (1) which CIs are associated with flashback memories; (2) candidate person and work-related features that predict flashback memories; and (3) the association between flashback memories and anxiety, depression, and emotional exhaustion.
Emergency nurses (N = 91; 80.2% female) were recruited from two urban teaching hospitals and filled in self-report questionnaires.
A majority (n = 59, 65%) experienced intrusive memories; almost half of the sample reported that their memories had flashback character. Those involved in resuscitations in the past week were at a fourfold risk for experiencing flashbacks. Having worked more consecutive days without taking time off was associated with a somewhat lower incidence of flashbacks. Moreover, older individuals who reported more work-related conflicts were at greater risk for experiencing flashback memories than their younger colleagues with heightened work conflict and flashback memory scores, respectively. Flashback memories were associated with heightened symptoms of anxiety, depression, and emotional exhaustion.
The present findings have implications for evidence-based health promotion in emergency personnel and other individuals regularly exposed to CIs.
PMCID: PMC4511283  PMID: 26221567
Anxiety; burnout; depression; emergency department; emotional memory; flashback; intrusion
3.  Left hippocampus–amygdala complex macro- and microstructural variation is associated with BDNF plasma levels in healthy elderly individuals 
Brain and Behavior  2015;5(7):e00334.
Deep brain gray matter (GM) structures are involved in several neurodegenerative disorders and are affected by aging. In this study, we investigated the potential relationship between levels of brain-derived neurotrophic factor (BDNF), a putative biomarker of age- and clinically relevant brain dysfunctions, and the presence of structural modifications that were evaluated by magnetic resonance imaging in six deep GM structures.
Volume changes and diffusion tensor imaging (DTI) scalars were studied in the thalamus, putamen, hippocampus, caudate nucleus, amygdala and pallidum of a cohort of 120 healthy subjects. The cohort included young (18–39 years old), adult (40–59 years old) and elderly (60–76 years old) subjects.
No correlations were seen in the young and adult cohorts. In the elderly group, we observed reduced BDNF levels that correlated with increased DTI-based mean diffusivity occurring in the left hippocampus along with decreased normalized volume in the left amygdala.
These findings suggest that, in elderly subjects, BDNF may exert regional and lateralized effects that allow the integrity of two strategic deep GM areas such as the hippocampus and the amygdala.
PMCID: PMC4511284  PMID: 26221568
BDNF; brain volume; DTI
4.  Relative brain signature: a population-based feature extraction procedure to identify functional biomarkers in the brain of alcoholics 
Brain and Behavior  2015;5(7):e00335.
A novel feature extraction technique, Relative-Brain-Signature (RBS), which characterizes subjects' relationship to populations with distinctive neuronal activity, is presented. The proposed method transforms a set of Electroencephalography's (EEG) time series in high dimensional space to a space of fewer dimensions by projecting time series onto orthogonal subspaces.
We apply our technique to an EEG data set of 77 abstinent alcoholics and 43 control subjects. To characterize subjects' relationship to the alcoholic and control populations, one RBS vector with respect to the alcoholic and one with respect to the control population is constructed. We used the extracted RBS vectors to identify functional biomarkers over the brain of alcoholics. To achieve this goal, the classification algorithm was used to categorize subjects into alcoholics and controls, which resulted in 78% accuracy.
Results and Conclusions
Using the results of the classification, regions with distinctive functionality in alcoholic subjects are detected. These affected regions, with respect to their spatial extent, are frontal, anterior frontal, centro-parietal, parieto-occiptal, and occipital lobes. The distribution of these regions over the scalp indicates that the impact of the alcohol in the cerebral cortex of the alcoholics is spatially diffuse. Our finding suggests that these regions engage more of the right hemisphere relative to the left hemisphere of the alcoholics' brain.
PMCID: PMC4511285  PMID: 26221569
Alcoholism; classification; electroencephalography's; functional biomarker
5.  Application of ICA to realistically simulated 1H-MRS data 
Brain and Behavior  2015;5(7):e00345.
1H-MRS signals from brain tissues capture information on in vivo brain metabolism and neuronal biomarkers. This study aims to advance the use of independent component analysis (ICA) for spectroscopy data by objectively comparing the performance of ICA and LCModel in analyzing realistic data that mimics many of the known properties of in vivo data.
This work identifies key features of in vivo 1H-MRS signals and presents methods to simulate realistic data, using a basis set of 12 metabolites typically found in the human brain. The realistic simulations provide a much needed ground truth to evaluate performances of various MRS analysis methods. ICA is applied to collectively analyze multiple realistic spectra and independent components identified with our generative model to obtain ICA estimates. These same data are also analyzed using LCModel and the comparisons between the ground-truth and the analysis estimates are presented. The study also investigates the potential impact of modeling inaccuracies by incorporating two sets of model resonances in simulations.
The simulated fid signals incorporating line broadening, noise, and residual water signal closely resemble the in vivo signals. Simulation analyses show that the resolution performances of both LCModel and ICA are not consistent across metabolites and that while ICA resolution can be improved for certain resonances, ICA is as effective as, or better than, LCModel in resolving most model resonances.
The results show that ICA can be an effective tool in comparing multiple spectra and complements existing approaches for providing quantified estimates.
PMCID: PMC4511286  PMID: 26221570
LCModel analysis; MRS ICA; proton spectroscopy; realistic simulations; spectral ICA
6.  Repetitive speech elicits widespread deactivation in the human cortex: the “Mantra” effect? 
Brain and Behavior  2015;5(7):e00346.
Mantra (prolonged repetitive verbal utterance) is one of the most universal mental practices in human culture. However, the underlying neuronal mechanisms that may explain its powerful emotional and cognitive impact are unknown. In order to try to isolate the effect of silent repetitive speech, which is used in most commonly practiced Mantra meditative practices, on brain activity, we studied the neuronal correlates of simple repetitive speech in nonmeditators – that is, silent repetitive speech devoid of the wider context and spiritual orientations of commonly practiced meditation practices.
We compared, using blood oxygenated level-dependent (BOLD) functional magnetic resonance imaging (fMRI), a simple task of covertly repeating a single word to resting state activity, in 23 subjects, none of which practiced meditation before.
We demonstrate that the repetitive speech was sufficient to induce a widespread reduction in BOLD signal compared to resting baseline. The reduction was centered mainly on the default mode network, associated with intrinsic, self-related processes. Importantly, contrary to most cognitive tasks, where cortical-reduced activation in one set of networks is typically complemented by positive BOLD activity of similar magnitude in other cortical networks, the repetitive speech practice resulted in unidirectional negative activity without significant concomitant positive BOLD. A subsequent behavioral study showed a significant reduction in intrinsic thought processes during the repetitive speech condition compared to rest.
Our results are compatible with a global gating model that can exert a widespread induction of negative BOLD in the absence of a corresponding positive activation. The triggering of a global inhibition by the minimally demanding repetitive speech may account for the long-established psychological calming effect associated with commonly practiced Mantra-related meditative practices.
PMCID: PMC4511287  PMID: 26221571
Default mode network; fMRI; global inhibition; mantra; meditation
7.  Acute anoxic changes in peripheral nerve: anatomic and physiologic correlations 
Brain and Behavior  2015;5(7):e00347.
The response of the peripheral nerve to anoxia is modulated by many factors including glucose and temperature. The purposes of this article are to demonstrate the effects of these factors on the pathological changes induced by anoxia and to compare the electrophysiologic changes and pathological changes in the same nerves.
Sciatic nerves were harvested from rats and placed in a perfusion apparatus where neurophysiologic responses could be recorded continuously during a 16 h experiment. After the experiment, light microscopy and electron microscopy were performed.
Light microscopic images showed mild changes from anoxia at normoglycemia. Hypoglycemic anoxia produced massive axonal swelling while hyperglycemic anoxia produced apparent changes in the myelin. Anoxic changes were not uniform in all axons. Electron microscopy showed only minor disruptions of the cytoskeleton with anoxia during normoglycemia. At the extremes of glucose concentration especially with hyperglycemia, there was a more severe disruption of intermediate filaments and loss of axonal structure with anoxia. Hypothermia protected axons from the effect of anoxia and produced peak axonal swelling in the 17–30°C range.
The combination of hyperglycemia or hypoglycemia and anoxia produces extremely severe axonal disruption. Changes in axonal diameter are complex and are influenced by many factors.
PMCID: PMC4511288  PMID: 26221572
Anoxia; glucose; peripheral nerve
8.  Striatal activity and reduced white matter increase frontal activity in youths with family histories of alcohol and other substance-use disorders performing a go/no-go task 
Brain and Behavior  2015;5(7):e00352.
Youths with a family history of alcohol and other drug use disorders (FH+) are at greater risk of developing substance-use disorders relative to those with no such family histories (FH−). We previously reported that FH+ youths have elevated activity in the supplementary motor area (SMA) and dorsal striatum while performing go/no-go tasks and have reduced frontal white matter integrity. A better understanding of relationships between these variables would provide insight into how frontostriatal circuitry is altered in FH+ youths, which may be an important contributor to their elevated risk.
In this study, we used structural equation modeling (SEM) to test interactions between activity in the SMA and dorsal striatum in 72 FH+ and 32 FH− youths during go/no-go task performance and to determine whether increased activity in these regions in FH+ youths can be at least partially explained by reduced frontal white matter integrity, as indexed by anterior corona radiata fractional anisotropy and N-acetylaspartate.
Increased dorsal striatum activity explained most (∽75%) of the elevated SMA activity in FH+ youths, and the combined contributions of increased dorsal striatal activity, and decreased white matter integrity fully explained the elevated SMA activity.
These results suggest the elevated frontal cortical activity in FH+ youths is driven both by their increased striatal activity via downstream projections and reduced white matter integrity in frontal cortical projections, the latter likely increasing frontal cortical activity due to increased energy demands required for action potential propagation. As part of our ongoing longitudinal studies we will examine how these frontostriatal alterations relate to risk for developing substance-use disorders.
PMCID: PMC4511289  PMID: 26221573
Family history; functional magnetic resonance imaging; go/no-go task; risk; substance use; white matter integrity
9.  Assessment of chemotherapy-induced peripheral neuropathy using the LDIFLARE technique: a novel technique to detect neural small fiber dysfunction 
Brain and Behavior  2015;5(7):e00354.
The diagnosis and quantification of chemotherapy-induced peripheral neuropathy (CIPN) remains a challenge. Conventional methods including quantitative sensory testing (QST), nerve conduction tests, and biopsy are unable to detect subclinical changes, and do not consistently correlate with severity of patients' symptoms and functional impairment. This study aims to determine the utility of the LDI (laser Doppler imager) FLARE technique in the diagnosis of CIPN and whether it correlates with symptom severity.
Materials and Methods
We assessed 24 patients with established CIPN [12 due to platinum analogs (PA) and 12 to Taxanes (TX)] and 24 matched healthy controls (HC). All underwent neurophysiological examination including vibration perception threshold (VPT), sural nerve amplitude (SNAP) and conduction velocity (SNCV), LDIFLARE, and fasting biochemistry. The QLQ-CIPN20 questionnaire was used to assess symptom severity.
HC, combined chemotherapy (CG), PA, and TX groups were matched for age, sex, BMI, and blood pressure. The LDIFLARE was significantly reduced in CG compared to HC (P =< 0.0001), whereas SNAP (P = 0.058) and SNCV (P = 0.054) were not. The LDIFLARE correlated with the QLQ-CIPN20 symptom scores in all three categories namely, CG (P =< 0.0001), PA (P = 0.001) and TX (P = 0.027) whilst, VPT, SNAP, and SNCV did not.
Our findings suggest that the LDIFLARE technique is more helpful in confirming the diagnosis of CIPN in patients with distal sensory symptoms than current commonly used methods. Moreover, this novel test fulfils the unmet need for a diagnostic test that relates to the severity of symptoms. This may be useful in quantifying early changes in small fibre function indicating early CIPN.
PMCID: PMC4511290  PMID: 26221574
CIPN; EORTC; LDIFLARE; nerve conduction velocity and amplitude; QLQ-CIPN20
10.  Issue Information 
Brain and Behavior  2015;5(6):i-iii.
PMCID: PMC4467769  PMID: 26085969
11.  Patterns of gray matter atrophy in atypical parkinsonism syndromes: a VBM meta-analysis 
Brain and Behavior  2015;5(6):e00329.
Background and Purpose
Accurate diagnosis of Atypical Parkinsonian Syndromes (APS) is important due to differences in prognosis and management, but remains a challenge in the clinical setting. The purpose of our meta-analysis was to identify characteristic patterns of gray matter atrophy in Corticobasal Degeneration (CBD), Progressive Supranuclear Palsy (PSP), Multisystem-Atrophy Parkinsonian type (MSA-P), and Idiopathic Parkinson's Disease (IPD).
Materials and Methods
Whole-brain meta-analysis was performed on 39 published voxel-based morphometry (VBM) articles (consisting of 404 IPD, 87 MSA-P, 165 CBD, and 176 PSP subjects) using the modified Anatomic Likelihood Estimation method. Based on these results, contrast analyses were then utilized to determine areas of atrophy shared by as well as unique to each disorder.
CBD was characterized by asymmetric gray matter atrophy in multiple cortical regions, while the thalamus-midbrain and insula were predominantly involved in PSP. The striatum and superior cerebellum were affected in MSA-P, while IPD demonstrated an anterior cerebral pattern. Although there was a mild overlap among PSP, CBD, and MSA-P, significant regions of atrophy unique to each disorder were identified, including (1) the superior parietal lobule in CBD (2) putamen in MSA-P (3) insula and medial dorsal nucleus in PSP.
Our results suggest that there are characteristic patterns of atrophy in APS. Guided by these findings, future studies on the individual subject level may lead to the development of robust imaging biomarkers.
PMCID: PMC4467770  PMID: 26085961
Neurodegenerative diseases; neuroimaging; Parkinson's disease
12.  A P300-based cognitive assessment battery 
Brain and Behavior  2015;5(6):e00336.
It is well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are capable of higher cognitive processes.
Here, we develop a series of EEG paradigms that probe several core aspects of cognition at the bedside without the need for motor responses and explore the sensitivity of this approach in a group of healthy controls.
Using analysis of ERPs alone, this method can determine with high reliability whether individual participants are able to attend a stimulus stream, maintain items in working memory, or solve complex grammatical reasoning problems.
We suggest that this approach could form the basis of a brain-based battery for assessing higher cognition in patients with severe motor impairments or disorders of consciousness.
PMCID: PMC4467771  PMID: 26085962
Attention; cognitive assessment; EEG; P300; reasoning; working memory
13.  Effectiveness of glatiramer acetate compared to other multiple sclerosis therapies 
Brain and Behavior  2015;5(6):e00337.
To assess the effectiveness of glatiramer acetate (GA) compared to other multiple sclerosis (MS) therapies in routine clinical practice.
Materials and methods
Observational cohort study carried out in MS patients treated with GA (GA cohort) or other MS therapies –switched from GA– (non-GA cohort). Study data were obtained through review of our MS patient database. The primary endpoint was the Expanded Disability Status Scale (EDSS) scores reached at the end of treatment/last check-up.
A total of 180 patients were included: GA cohort n = 120, non-GA cohort n = 60. Patients in the GA cohort showed better EDSS scores at the end of treatment/last check-up (mean ± SD, 2.8 ± 1.8 vs. 3.9 ± 2.2; P = 0.001) and were 1.65 times more likely to show better EDSS scores compared to the non-GA cohort (odds ratio, 0.606; 95%CI, 0.436–0.843; P = 0.003). Patients in the GA cohort showed longer mean time to reach EDSS scores of 6 (209.1 [95%CI, 187.6–230.6] vs. 164.3 [95%CI, 137.0–191.6] months; P = 0.004) and slower disability progression (hazard ratio, 0.415 [95%CI, 0.286–0.603]; P < 0.001). The annualized relapse rate was lower in the GA cohort (mean ± SD, 0.5 ± 0.5 vs. 0.8 ± 0.5; P = 0.001) and patients’ quality of life was improved in this study cohort compared to the non-GA cohort (mean ± SD, 0.7 ± 0.1 vs. 0.6 ± 0.2; P = 0.01).
GA may slow down the progression of EDSS scores to a greater extent than other MS therapies, as well as achieving a greater reduction in relapses and a greater improvement in patients’ quality of life. Switching from GA to other MS therapies has not proved to entail a better response to treatment.
PMCID: PMC4467772  PMID: 26085963
Clinical practice; effectiveness; glatiramer acetate; multiple sclerosis; therapy; treatment
14.  Using arterial spin labeling to examine mood states in youth 
Brain and Behavior  2015;5(6):e00339.
Little is known about the neural correlates of mood states and the specific physiological changes associated with their valence and duration, especially in young people. Arterial spin labeling (ASL) imaging is particularly well-suited to study sustained cerebral states in young people, due to its robustness to low-frequency drift, excellent interscan reliability, and noninvasiveness. Yet, it has so far been underutilized for understanding the neural mechanisms underlying mood states in youth.
In this exploratory study, 21 healthy adolescents aged 16 to 18 took part in a mood induction experiment. Neutral, sad, and happy mood states were induced using film clips and explicit instructions. An ASL scan was obtained following presentation of each film clip.
Mood induction led to robust changes in self-reported mood ratings. Compared to neutral, sad mood was associated with increased regional cerebral blood flow (rCBF) in the left middle frontal gyrus and anterior prefrontal cortex, and decreased rCBF in the right middle frontal gyrus and the inferior parietal lobule. A decrease in self-reported mood from neutral to sad condition was associated with increased rCBF in the precuneus. Happy mood was associated with increased rCBF in medial frontal and cingulate gyri, the subgenual anterior cingulate cortex, and ventral striatum, and decreased rCBF in the inferior parietal lobule. The level of current self-reported depressive symptoms was negatively associated with rCBF change in the cerebellum and lingual gyrus following both sad and happy mood inductions.
Arterial spin labeling is sensitive to experimentally induced mood changes in healthy young people. The effects of happy mood on rCBF patterns were generally stronger than the effects of sad mood.
PMCID: PMC4467773  PMID: 26085964
Adolescents; happiness; mood; perfusion magnetic resonance imaging
15.  Intraventricular cerebrospinal fluid temperature analysis using MR diffusion-weighted imaging thermometry in Parkinson's disease patients, multiple system atrophy patients, and healthy subjects 
Brain and Behavior  2015;5(6):e00340.
We examined the temperature of the intraventricular cerebrospinal fluid (Tv) in patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA) in comparison with healthy subjects, and we examined normal changes in this temperature with aging.
Tv was estimated by magnetic resonance (MR) diffusion-weighted imaging (DWI) thermometry in 36 PD patients (19 males, 17 females), 34 MSA patients (17 males, 17 females), 64 age-matched controls (27 men, 37 women), and 114 all-age adult controls (47 men, 67 women; 28–89 years old). The volume of lateral ventricles was also estimated using FreeSurfer in all subjects. Tv and ventricular volume data were compared among the PD and MSA patients and age-matched controls. We also evaluated the relationship between Tv and age in the 114 all-age controls, controlling for ventricular volume. Men and women were analyzed separately.
The male PD and MSA patients had significantly higher Tv values compared to the male controls, with no significant difference in ventricular volume among them. There was no significant difference in Tv between the female patients and controls. In the all-age male controls, there was a significant negative correlation between Tv and age controlling for ventricular volume, and this was not observed in the women.
DWI thermometry is a useful and easy method for demonstrating an altered intracranial environment in male patients and healthy controls, but not in females. DWI thermometry can thus be used to help to explore the pathophysiology of Parkinsonian syndromes and to differentiate individuals affected by neurodegenerative disease with autonomic dysfunction from those without it.
PMCID: PMC4467774  PMID: 26085965
Cerebrospinal fluid; diffusion-weighted imaging thermometry; multiple system atrophy; Parkinson's disease; temperature
16.  Differentiating atypical parkinsonian syndromes—a way forward? 
Brain and Behavior  2015;5(6):e00341.
PMCID: PMC4467775  PMID: 26085966
17.  Eye movement desensitization and reprocessing (EMDR) therapy in the treatment of depression: a matched pairs study in an inpatient setting 
Brain and Behavior  2015;5(6):e00342.
Depression is a severe mental disorder that challenges mental health systems worldwide as the success rates of all established treatments are limited. Eye Movement Desensitization and Reprocessing (EMDR) therapy is a scientifically acknowledged psychotherapeutic treatment for PTSD. Given the recent research indicating that trauma and other adverse life experiences can be the basis of depression, the aim of this study was to determine the effectiveness of EMDR therapy with this disorder.
In this study, we recruited a group of 16 patients with depressive episodes in an inpatient setting. These 16 patients were treated with EMDR therapy by reprocessing of memories related to stressful life events in addition to treatment as usual (TAU). They were compared to a group of 16 controls matched regarding diagnosis, degree of depression, sex, age and time of admission to hospital, which were receiving TAU only.
Sixty-eight percent of the patients in the EMDR group showed full remission at end of treatment. The EMDR group showed a greater reduction in depressive symptoms as measured by the SCL-90-R depression subscale. This difference was significant even when adjusted for duration of treatment. In a follow-up period of more than 1 year the EMDR group reported less problems related to depression and less relapses than the control group.
EMDR therapy shows promise as an effective treatment for depressive disorders. Larger controlled studies are necessary to replicate our findings.
PMCID: PMC4467776  PMID: 26085967
AIP model; depression; EMDR; pathogenic memory; stressful life experiences
18.  Rightward dominance in temporal high-frequency electrical asymmetry corresponds to higher resting heart rate and lower baroreflex sensitivity in a heterogeneous population 
Brain and Behavior  2015;5(6):e00343.
Explore potential use of a temporal lobe electrical asymmetry score to discriminate between sympathetic and parasympathetic tendencies in autonomic cardiovascular regulation.
131 individuals (82 women, mean age 43.1, range 13–83) with diverse clinical conditions completed inventories for depressive (CES-D or BDI-II) and insomnia-related (ISI) symptomatology, and underwent five-minute recordings of heart rate and blood pressure, allowing calculation of heart rate variability and baroreflex sensitivity (BRS), followed by one-minute, two-channel, eyes-closed scalp recordings of brain electrical activity. A temporal lobe high-frequency (23–36 Hz) electrical asymmetry score was calculated for each subject by subtracting the average amplitude in the left temporal region from amplitude in the right temporal region, and dividing by the lesser of the two.
Depressive and insomnia-related symptomatology exceeding clinical threshold levels were reported by 48% and 50% of subjects, respectively. Using a cutoff value of 5% or greater to define temporal high-frequency asymmetry, subjects with leftward compared to rightward asymmetry were more likely to report use of a sedative-hypnotic medication (42% vs. 22%, P = 0.02). Among subjects with asymmetry of 5% or greater to 30% or greater, those with rightward compared to leftward temporal high-frequency asymmetry had higher resting heart rate (≥5% asymmetry, 72.3 vs. 63.8, P = 0.004; ≥10%, 71.5 vs. 63.0, P = 0.01; ≥20%, 72.2 vs. 64.2, P = 0.05; ≥30%, 71.4 vs. 64.6, P = 0.05). Subjects with larger degrees of rightward compared to leftward temporal high-frequency asymmetry had lower baroreflex sensitivity (≥40% asymmetry, 10.6 vs. 16.4, P = 0.03; ≥50% asymmetry, 10.4 vs. 16.7, P = 0.05).
In a heterogeneous population, individuals with rightward compared to leftward temporal high-frequency electrical asymmetry had higher resting heart rate and lower BRS. Two-channel recording of brain electrical activity from bilateral temporal regions appears to hold promise for further investigation as a means to assess cortical activity associated with autonomic cardiovascular regulation.
PMCID: PMC4467777  PMID: 26085968
Autonomic nervous system; heart rate variability; hemispheric asymmetry; neurotechnology; RDoC; temporal lobe
19.  Pain in multiple system atrophy and progressive supranuclear palsy compared to Parkinson's disease 
Brain and Behavior  2015;5(5):e00320.
Pain is a common nonmotor symptom in Parkinson's disease (PD). The pathophysiology of pain in PD is not well understood. Pain characteristics have rarely been studied in atypical parkinsonian disorders such as Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP).
Aim of the study
We aimed to evaluate pain intensity, location, and associated symptoms in atypical parkinsonian disorders compared to PD.
Twenty-one patients with MSA, 16 patients with PSP, and 65 patients with PD were screened for pain using question 1.9 of the MDS-UPDRS. Pain intensity was quantified using the short form McGill Pain Questionnaire (SFMPQ). Pain locations were documented. Motor disability was measured using UPDRS-III. Affective symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS).
Pain was significantly more common and more severe in PD and MSA compared to PSP (P < 0.01). Pain locations were similar with limb pain being the most common followed by neck and back pain. Pain intensity correlated with HADS scores but not motor severity.
Pain is more common and more intense in PD and MSA than PSP. Differences in distribution of neurodegenerative pathologies may underlie these differential pain profiles.
PMCID: PMC4389053  PMID: 25874161
Multiple system atrophy; neuropathic; pain; Parkinson's disease; progressive supranuclear palsy
20.  The neural correlates of subjectively perceived and passively matched loudness perception in auditory phantom perception 
Brain and Behavior  2015;5(5):e00331.
A fundamental question in phantom perception is determining whether the brain creates a network that represents the sound intensity of the auditory phantom as measured by tinnitus matching (in dB), or whether the phantom perception is actually only a representation of the subjectively perceived loudness.
In tinnitus patients, tinnitus loudness was tested in two ways, by a numeric rating scale for subjectively perceived loudness and a more objective tinnitus-matching test, albeit it is still a subjective measure.
Passively matched tinnitus does not correlate with subjective numeric rating scale, and has no electrophysiological correlates. Subjective loudness, in a whole-brain analysis, is correlated with activity in the left anterior insula (alpha), the rostral/dorsal anterior cingulate cortex (beta), and the left parahippocampus (gamma). A ROI analysis finds correlations with the auditory cortex (high beta and gamma) as well. The theta band links gamma band activity in the auditory cortex and parahippocampus via theta–gamma nesting.
Apparently the brain generates a network that represents subjectively perceived tinnitus loudness only, which is context dependent. The subjective loudness network consists of the anterior cingulate/insula, the parahippocampus, and the auditory cortex. The gamma band activity in the parahippocampus and the auditory cortex is functionally linked via theta–gamma nested lagged phase synchronization.
PMCID: PMC4389054  PMID: 25874164
Context; gamma; intensity; loudness; nesting; parahippocampus; theta; tinnitus
21.  The impact of transcranial direct current stimulation on inhibitory control in young adults 
Brain and Behavior  2015;5(5):e00332.
There is increasing evidence that the dorso-lateral prefrontal cortex (DLPFC), a brain region related to reward and motivational processes, is involved in effective response inhibition and that decreased activity in this region coincides with reduced inhibitory capacity. Using transcranial direct current stimulation (tDCS) to manipulate cortical activation, this study examined whether cross-hemispheric tDCS over the DLPFC affected performance on an inhibitory control task.
Neurologically intact participants performed a modified Stroop color-word matching task before and after completing one of two tDCS conditions; (1) anodal stimulation over the left DLPFC or (2) sham tDCS.
There was a statistically significant effect of tDCS condition on Stroop reaction time (RT) pre-post tDCS change scores. Participants who received anodal stimulation over the left DLPFC demonstrated statistically significant faster RT change scores on the Stroop items compared to participants in the sham condition. Although errors on Stroop incongruent items decreased before and after receiving the tDCS treatment, there were no significant differences in errors on Stroop items between the anodal stimulation over left DLPFC and sham tDCS conditions. Anodal tDCS, which is known to elevate neural excitation, may have enhanced activation levels in the left DLPFC and minimized impairment of inhibitory control, resulting in better task performance.
Current findings provide preliminary evidence that increased excitation of the left DLPFC improves inhibitory control and are a step toward understanding the potential of tDCS for moderating deficits in inhibitory control.
PMCID: PMC4389055  PMID: 25874165
Dorsolateral prefrontal cortex; executive functioning; self-control; stroop; transcranial direct current stimulation
22.  Functional network mediates age-related differences in reaction time: a replication and extension study 
Brain and Behavior  2015;5(5):e00324.
A functional activation (i.e., ordinal trend) pattern was previously identified in both young and older adults during task-switching performance, the expression of which correlated with reaction time. The current study aimed to (1) replicate this functional activation pattern in a new group of fMRI activation data, and (2) extend the previous study by specifically examining whether the effect of aging on reaction time can be explained by differences in the activation of the functional activation pattern.
A total of 47 young and 50 older participants were included in the extension analysis. Participants performed task-switching as the activation task and were cued by the color of the stimulus for the task to be performed in each block. To test for replication, two approaches were implemented. The first approach tested the replicability of the predictive power of the previously identified functional activation pattern by forward applying the pattern to the Study II data and the second approach was rederivation of the activation pattern in the Study II data.
Both approaches showed successful replication in the new data set. Using mediation analysis, expression of the pattern from the first approach was found to partially mediate age-related effects on reaction time such that older age was associated with greater activation of the brain pattern and longer reaction time, suggesting that brain activation efficiency (defined as “the rate of activation increase with increasing task difficulty” in Neuropsychologia 47, 2009, 2015) of the regions in the Ordinal trend pattern directly accounts for age-related differences in task performance.
The successful replication of the functional activation pattern demonstrates the versatility of the Ordinal Trend Canonical Variates Analysis, and the ability to summarize each participant's brain activation map into one number provides a useful metric in multimodal analysis as well as cross-study comparisons.
PMCID: PMC4389056  PMID: 25874162
Aging; functional magnetic resonance imaging; mediation; ordinal trend covariance analysis; study replication; task-switching
23.  Modulation of the ∽20-Hz motor-cortex rhythm to passive movement and tactile stimulation 
Brain and Behavior  2015;5(5):e00328.
Integration of afferent somatosensory input with motor-cortex output is essential for accurate movements. Prior studies have shown that tactile input modulates motor-cortex excitability, which is reflected in the reactivity of the ∽20-Hz motor-cortex rhythm. ∽20-Hz rebound is connected to inhibition or deactivation of motor cortex whereas suppression has been associated with increased motor cortex activity. Although tactile sense carries important information for controlling voluntary actions, proprioception likely provides the most essential feedback for motor control.
To clarify how passive movement modulates motor-cortex excitability, we studied with magnetoencephalography (MEG) the amplitudes and peak latencies of suppression and rebound of the ∽20-Hz rhythm elicited by tactile stimulation and passive movement of right and left index fingers in 22 healthy volunteers.
Passive movement elicited a stronger and more robust ∽20-Hz rebound than tactile stimulation. In contrast, the suppression amplitudes did not differ between the two stimulus types.
Our findings suggest that suppression and rebound represent activity of two functionally distinct neuronal populations. The ∽20-Hz rebound to passive movement could be a suitable tool to study the functional state of the motor cortex both in healthy subjects and in patients with motor disorders.
PMCID: PMC4396160  PMID: 25874163
Beta rebound; beta rhythm; magnetoencephalography; motor-cortex excitability; proprioception; sensorimotor integration
24.  Functional connectivity of the striatum in experts of stenography 
Brain and Behavior  2015;5(5):e00333.
Stenography, or shorthand, is a unique set of skills that involves intensive training which is nearly life-long and orchestrating various brain functional modules, including auditory, linguistic, cognitive, mnemonic, and motor. Stenography provides cognitive neuroscientists with a unique opportunity to investigate the neural mechanisms underlying the neural plasticity that enables such a high degree of expertise. However, shorthand is quickly being replaced with voice recognition technology. We took this nearly final opportunity to scan the brains of the last alive shorthand experts of the Japanese language.
Thirteen right-handed stenographers and fourteen right-handed controls participated in the functional magnetic resonance imaging (fMRI) study.
The fMRI data revealed plastic reorganization of the neural circuits around the putamen. The acquisition of expert skills was accompanied by structural and functional changes in the area. The posterior putamen is known as the execution center of acquired sensorimotor skills. Compared to nonexperts, the posterior putamen in stenographers had high covariation with the cerebellum and midbrain.The stenographers' brain developed different neural circuits from those of the nonexpert brain.
The current data illustrate the vigorous plasticity in the putamen and in its connectivity to other relevant areas in the expert brain. This is a case of vigorous neural plastic reorganization in response to massive overtraining, which is rare especially considering that it occurred in adulthood.
PMCID: PMC4396401  PMID: 25874166
Long-term neural plasticity; putamen; stenography
25.  Issue Information 
Brain and Behavior  2015;5(5):i-iii.
PMCID: PMC4430243

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