Recognition of Human Emotions from Cerebral Blood Flow Changes in the Frontal Region: A Study with Event‐Related Near‐Infrared Spectroscopy

ABSTRACT

BACKGROUNDS AND PURPOSE

The aim of this study is to develop a near‐infrared spectroscopy (NIRS)‐based system that recognizes pleasant and unpleasant human emotions based on cerebral blood flow (CBF) in order to understand the minds of patients whose brain function is severely impaired. The forehead region is easily accessible to NIRS measurements, whereas the role of the anterior prefrontal cortex (PFC) in the processing of emotion remains to be elucidated.

METHODS

Initially, using event‐related NIRS we examined changes in oxygenated hemoglobin (oxy‐Hb) as an indicator of regional CBF changes, which reflect brain activity directly related to emotions, but not to cognitive operations in the anterior frontal regions, during viewing affective pictures. The event‐related potentials (ERPs), systemic blood pressure, and pulse rate were also measured simultaneously.

RESULTS

The event‐related analysis of changes in oxy‐Hb for a 6 s‐picture presentation period showed that very unpleasant emotion was accompanied by an increase in oxy‐Hb in the bilateral ventrolateral PFCs, while very pleasant emotion was accompanied by a decrease in oxy‐Hb in the left dorsolateral PFC. There were no significant differences in either ERPs or autonomic nervous system activities between the two emotional states.

CONCLUSION

These findings suggest the possibility of recognizing patients’ emotions from CBF changes.

     

Randomized,double‐blind comparison of aripiprazole/sertraline combination and placebo/sertraline combination in patients with major depressive disorder

Aim

This study compared the efficacy and safety of aripiprazole/sertraline combination (ASC) and placebo/sertraline combination (PSC) in patients with major depressive disorder (MDD) who showed an inadequate response to sertraline 100 mg/day.

Methods

The study comprised a screening period, an 8‐week prospective treatment (single‐blind sertraline 25–100 mg/day) period, and a 6‐week double‐blind treatment period. Patients with DSM‐5‐defined MDD were enrolled. Following the prospective treatment, non‐responders were randomly assigned to the ASC group (aripiprazole 3–12 mg/day/sertraline 100 mg/day) or the PSC group (sertraline 100 mg/day). The primary efficacy end‐point was the mean change in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score from baseline to 6 weeks.

Results

A total of 412 patients were randomly assigned to either the ASC group (n = 209) or the PSC group (n = 203). Mean change in MADRS total score was significantly greater in patients with ASC than PSC (?9.2 vs ?7.2; P = 0.0070). Treatment‐emergent adverse events (TEAE) that occurred in ≥10% of patients with ASC versus PSC were nasopharyngitis (13.4% vs 11.3%) and akathisia (12.9% vs 3.4%). All TEAE reported in the ASC group were mild or moderate in severity. Rates of discontinuations due to TEAE were low in both the ASC (1.9%) and PSC (1.5%) groups. There were no notable issues in safety assessments in the ASC group compared with the PSC group.

Conclusion

In patients with MDD who showed an inadequate response to treatment with sertraline 100 mg/day, ASC was efficacious and well tolerated.

     

Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia in Japan: A 6‐week,randomized, double‐blind,placebo‐controlled study

Aim

This study aimed to evaluate the efficacy, safety, and tolerability of brexpiprazole compared to placebo in Japanese patients with acute schizophrenia (SCZ).

Methods

We conducted a 6‐week, multicenter, double‐blind, placebo‐controlled, phase 2/3 study in Japan. Patients with acute SCZ were randomized (1:1:1:1) to receive brexpiprazole 1 mg, 2 mg, 4 mg, or placebo once a day. The primary endpoint was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total scores.

Results

In the 459 patients that were randomized, brexpiprazole 2 mg showed a significant improvement versus placebo (treatment difference: ?7.32, P = 0.0124), although brexpiprazole 4 mg showed numerical improvements (treatment difference: ?3.86, P = 0.1959), and brexpiprazole 1 mg showed only minimal change (treatment difference: ?0.63, P = 0.8330). Treatment‐emergent adverse events with an incidence of ≥5% and ≥2 times the rate of placebo in the brexpiprazole groups were vomiting, elevated blood prolactin, diarrhea, nausea, and dental caries. Most treatment‐emergent adverse events were mild or moderate in severity. There were no clinically significant changes in electrocardiogram parameters, bodyweight, laboratory values, or vital signs in the brexpiprazole groups.

Conclusion

Brexpiprazole was efficacious and well tolerated in Japanese adult patients with acute SCZ.

     

Spreading depolarizations trigger caveolin‐1–dependent endothelial transcytosis

Objective

Cortical spreading depolarizations (CSDs) are intense and ubiquitous depolarization waves relevant for the pathophysiology of migraine and brain injury. CSDs disrupt the blood–brain barrier (BBB), but the mechanisms are unknown.

Methods

A total of six CSDs were evoked over 1 hour by topical application of 300 mM of KCl or optogenetically with 470 nm (blue) LED over the right hemisphere in anesthetized mice (C57BL/6 J wild type, Thy1‐ChR2‐YFP line 18, and cav‐1^–/–). BBB disruption was assessed by Evans blue (2% EB, 3 ml/kg, intra‐arterial) or dextran (200 mg/kg, fluorescein, 70,000 MW, intra‐arterial) extravasation in parietotemporal cortex at 3 to 24 hours after CSD. Endothelial cell ultrastructure was examined using transmission electron microscopy 0 to 24 hours after the same CSD protocol in order to assess vesicular trafficking, endothelial tight junctions, and pericyte integrity. Mice were treated with vehicle, isoform nonselective rho‐associated kinase (ROCK) inhibitor fasudil (10 mg/kg, intraperitoneally 30 minutes before CSD), or ROCK‐2 selective inhibitor KD025 (200 mg/kg, per oral twice‐daily for 5 doses before CSD).

Results

We show that CSD‐induced BBB opening to water and large molecules is mediated by increased endothelial transcytosis starting between 3 and 6 hours and lasting approximately 24 hours. Endothelial tight junctions, pericytes, and basement membrane remain preserved after CSDs. Moreover, we show that CSD‐induced BBB disruption is exclusively caveolin‐1–dependent and requires rho‐kinase 2 activity. Importantly, hyperoxia failed to prevent CSD‐induced BBB breakdown, suggesting that the latter is independent of tissue hypoxia.

Interpretation

Our data elucidate the mechanisms by which CSDs lead to transient BBB disruption, with diagnostic and therapeutic implications for migraine and brain injury.

     

Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial (6002-US-005)

Objective

Based on new understanding of nondopaminergic pathways involved in Parkinson's disease (PD) pathophysiology, a selective adenosine A_2A receptor antagonist, istradefylline, shows promise for the treatment of PD.

Methods

Istradefylline (40mg/day) was studied in levodopa‐treated PD subjects experiencing prominent wearing‐off motor fluctuations. At 23 North American sites, 196 subjects were randomized in a double‐blind, 12‐week outpatient clinical trial of istradefylline (114 completing the trial) or placebo (58 completing the trial). The primary efficacy measure was change from baseline to end point in the percentage of daily awake “off” time, recorded by subjects using a patient PD diary. Secondary end points evaluated “on” time (including “on time with dyskinesia”), the Unified Parkinson's Disease Rating Scale, and a Clinical Global Impression–Improvement of Illness score. Clinical laboratory, electrocardiograms, vital signs, and adverse event monitoring comprised the safety monitoring.

Results

After randomization, approximately 88% of subjects completed the double‐blind period. Compared with baseline, the decrease of daily awake “off” time for istradefylline was a mean (± standard deviation) of ?10.8 ± 16.6% (95% confidence interval, ?13.46 to ?7.52) and for placebo, ?4.0 ± 15.7% (95% confidence interval, ?7.73–0.31; p = 0.007 using two‐way analysis of variance). This effect corresponded to changes from baseline in total daily awake “off” time of ?1.8 ± 2.8 hours for istradefylline and ?0.6 ± 2.7 hours for placebo (p = 0.005). Treatment‐emergent adverse effects with istradefylline were generally mild.

Interpretation

Istradefylline was safe, well tolerated, and offered a clinically meaningful reduction in “off” time without increased troublesome dyskinesia. Ann Neurol 2008

     

Disorder‐specific dysfunction in right inferior prefrontal cortex during two inhibition tasks in boys with attention‐deficit hyperactivity disorder compared to boys with obsessive–compulsive disorder

Background:

Inhibitory dysfunction is a key behavioral and cognitive phenotype of attention‐deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD). Both disorders show neuropsychological deficits and fronto‐striatal dysfunction during tasks of motor response inhibition and cognitive flexibility. This study investigates differences and commonalities in functional neural networks mediating inhibitory control between adolescents with ADHD and those with OCD to identify disorder‐specific neurofunctional markers that distinguish these two inhibitory disorders.

Methods:

Event‐related fMRI was used to compare brain activation between 20 healthy boys, 18 (Stop task) or 12 boys (Switch task) with ADHD, and 10 boys with OCD during a tracking Stop task that measures inhibition and stopping failure and during a visual–spatial switching task measuring cognitive flexibility.

Results:

Both patient groups shared brain dysfunction compared to healthy controls in right orbitofrontal (successful inhibition) and left dorsolateral prefrontal cortices (failed inhibition). Right inferior prefrontal dysfunction, however, was disorder‐specific to ADHD during both tasks. Left inferior prefrontal dysfunction during the Switch task was significant in children with ADHD relative to controls, but only reached a trend in patients with OCD. Patients with ADHD furthermore showed disorder‐specific dysfunction in left basal ganglia and cingulate gyrus during the Switch task.

Conclusions:

Patients with ADHD compared to those with OCD have both common and distinct dysfunctions during inhibitory control. The most consistently reported functional abnormality in children with ADHD in right inferior prefrontal cortex during inhibitory control appears to be disorder‐specific when compared to patients with OCD and may be a specific neurofunctional biomarker of ADHD. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.

     

Using spaced retrieval and Montessori‐based activities in improving eating ability for residents with dementia

Objectives

To construct a training protocol for spaced retrieval (SR) and to investigate the effectiveness of SR and Montessori‐based activities in decreasing eating difficulty in older residents with dementia.

Methods

A single evaluator, blind, and randomized control trial was used. Eighty‐five residents with dementia were chosen from three special care units for residents with dementia in long‐term care facilities in Taiwan. To avoid any confounding of subjects, the three institutions were randomized into three groups: spaced retrieval, Montessori‐based activities, and a control group. The invention consisted of three 30–40 min sessions per week, for 8 weeks.

Results

After receiving the intervention, the Edinburgh Feeding Evaluation in Dementia (EdFED) scores and assisted feeding scores for the SR and Montessori‐based activity groups were significantly lower than that of the control group. However, the frequencies of physical assistance and verbal assistance for the Montessori‐based activity group after intervention were significantly higher than that of the control group, which suggests that residents who received Montessori‐based activity need more physical and verbal assistance during mealtimes. In terms of the effects of nutritional status after intervention, Mini‐Nutritional Assessment (MNA) in the SR group was significantly higher than that of the control group.

Conclusion

This study confirms the efficacy of SR and Montessori‐based activities for eating difficulty and eating ability. A longitudinal study to follow the long‐term effects of SR and Montessori‐based activities on eating ability and nutritional status is recommended. Copyright © 2010 John Wiley & Sons, Ltd.

     

Sparse multiple factor analysis to integrate genetic data,neuroimaging features,and attention‐deficit/hyperactivity disorder domains

Objectives

We proposed the application of a multivariate cross‐sectional framework based on a combination of a variable selection method and a multiple factor analysis (MFA) in order to identify complex meaningful biological signals related to attention‐deficit/hyperactivity disorder (ADHD) symptoms and hyperactivity/inattention domains.

Methods

The study included 135 children from the general population with genomic and neuroimaging data. ADHD symptoms were assessed using a questionnaire based on ADHD‐DSM‐IV criteria. In all analyses, the raw sum scores of the hyperactivity and inattention domains and total ADHD were used. The analytical framework comprised two steps. First, zero‐inflated negative binomial linear model via penalized maximum likelihood (LASSO‐ZINB) was performed. Second, the most predictive features obtained with LASSO‐ZINB were used as input for the MFA.

Results

We observed significant relationships between ADHD symptoms and hyperactivity and inattention domains with white matter, gray matter regions, and cerebellum, as well as with loci within chromosome 1.

Conclusions

Multivariate methods can be used to advance the neurobiological characterization of complex diseases, improving the statistical power with respect to univariate methods, allowing the identification of meaningful biological signals in Imaging Genetic studies.

     

Advanced time‐series analysis of MEG data as a method to explore olfactory function in healthy controls and Parkinson's disease patients

Objectives:

To determine whether time‐series analysis of magnetoencephalography (MEG) data is a suitable method to study brain activity related to olfactory information processing, and to detect differences in odor‐induced brain activity between patients with Parkinson's disease (PD) and controls.

Methods:

Whole head 151‐channel MEG recordings were obtained in 21 controls and 20 patients with PD during a 10‐min olfactory stimulus paradigm, consisting of 10 alternating rest‐stimulus cycles (30 s each), using phenylethyl alcohol administered by means of a Burghart olfactometer. Relative spectral power and synchronization likelihood (SL; an unbiased measure of functional connectivity) were calculated for delta, theta, alpha1, alpha2, beta, and gamma frequency bands.

Results:

In controls, olfactory stimulation produced an increase in theta power and a decrease in beta power. In patients with PD, there was a decrease in alpha1 power. No significant interaction between group and condition was found for spectral power. SL analysis revealed a significantly different response to olfactory stimulation in patients with PD compared to controls. In controls, the odor stimulus induced a decrease in local beta band SL. The response in patients with PD involved a decrease in intrahemispheric alpha2 band SL.

Conclusion:

This is the first study to show that time‐series analysis of MEG data, including spectral power and SL, can be used to detect odor‐induced changes in brain activity. In addition, differences in odor‐induced brain activity were found between patients with PD and controls using analysis of SL, but not of spectral power. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.

     

Disagreeing about development: An analysis of parent‐teacher agreement in ADHD symptom trajectories across the elementary school years

Objectives

It is well‐known that in cross‐sectional analyses, agreement between informants is modest as best when rating attention‐deficit/hyperactivity disorder and other disruptive behaviour disorder symptoms. We here aimed to develop recommendations for the use of multi‐informant data in the context of longitudinal developmental analyses that examine symptom trajectories over time.

Method

Using parallel process modelling, we estimated parent–teacher agreement in inattention and hyperactivity/impulsivity symptom initial levels and slopes across the elementary school years (ages 7, 9, and 11) for a community sample of n = 1,388 youth. We also used these models to examine whether initial levels and slopes differed significantly across informants.

Results

Informant agreement was low to moderate and higher for inattention slopes (r = .47) than for hyperactivity/impulsivity slopes (r = .23). Parents and teachers reported opposite developmental trends for inattention with teachers reporting declines and parents reporting increases over time. Parents reported overall higher levels of hyperactivity/impulsivity, but there were no average informant differences in slopes.

Conclusion

Of the options available, we recommend specifying separate but correlated factors for different informants in developmental analyses of attention‐deficit/hyperactivity disorder. This can be achieved within latent growth curve and growth mixture models.

     

Changes in resting-state brain networks in writer's cramp

Objectives:

Writer's cramp (WC) is characterized by excessive cocontractions of agonist and antagonist hand and forearm muscles during writing. Changes in functional magnetic resonance imaging activation patterns in such conditions can be ambiguous as they might either reflect some aspect of the primary pathophysiological mechanism or, alternatively, may be the result of adaptive actions during task execution. To circumvent this problem, we examined WC patients during rest, i.e., without a task, using independent component analysis (ICA) applied to the blood oxygen level‐dependent time series.

Methods:

Functionally connected brain networks during rest were defined by ICA to assess differences between WC patients (n = 16) and healthy controls (n = 16). Analysis was carried out using FMRIB's Software Library.

Results:

Two functional networks showed between‐group differences, the sensorimotor network and the default‐mode network. In WC patients, the connectivity was reduced in the left postcentral area and increased in basal ganglia in contrast to healthy controls. These changes were not reversed after treatment with botulinum toxin.

Conclusions:

In line with other studies, the results show a dysfunction in cortico‐subcortical circuits in WC involving somatosensory cortex, areas interfacing the sensory and motor systems, and putamen contralateral to symptomatic hand. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

     

Safety and efficacy from a 6‐week double‐blind study and a 52‐week open‐label extension of aripiprazole in adolescents with schizophrenia in Japan

Aim

The purpose of this study was to evaluate the safety and efficacy of aripiprazole in adolescents with schizophrenia (SCZ) in Japan.

Methods

In a 6‐week, randomized, double‐blind, dose‐comparison study, adolescents (aged 13–17 years) with SCZ were randomized to receive aripiprazole 2, 6–12, or 24–30 mg/day. Patients who completed the 6‐week study participated in a 52‐week, flexible‐dose, open‐label extension (OLE) study of aripiprazole (initial dose: 2 mg/day, maintenance dose: 6–24 mg/day, maximum dose: 30 mg/day).

Results

In the 6‐week study, the percentage of patients completing treatment was: 77.1% (27/35) for 2 mg/day; 80.0% (24/30) for 6–12 mg/day; and 85.4% (35/41) for 24–30 mg/day. The least squares mean change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to endpoint (primary efficacy endpoint, last observation carried forward) was ?19.6 for 2 mg/day, ?16.5 for 6–12 mg/day, and ? 21.6 for 24–30 mg/day. The most common (≥20% patients in any group) treatment‐emergent adverse events (TEAE) were nausea, akathisia, insomnia, and somnolence. Most TEAE were mild or moderate in severity. There were no deaths. In the OLE, 60.3% (41/68) of patients completed treatment, and the PANSS total score decreased by ?7.9 from OLE baseline to week 52. The most common (≥20% patients) TEAE were nasopharyngitis and somnolence. Most TEAE were mild or moderate in severity. There were no deaths.

Conclusion

These study results suggest that aripiprazole would be safe and well tolerated in both short‐ and long‐term treatment for adolescents with SCZ in Japan.

     

Characteristic Neuroimaging in Patients with Tumefactive Demyelinating Lesions Exceeding 30 mm

ABSTRACT

BACKGROUND AND PURPOSE

Features of tumefactive demyelinating lesion (TDL) on magnetic resonance imaging (MRI) can facilitate the differential diagnosis of TDL and neoplastic lesions, but vary considerably among patients. The larger TDL grows, the more difficult it becomes to differentiate TDL from neoplastic lesions. The purpose of this study was to elucidate typical MRI features in 12 patients with large TDL (>30 mm in diameter).

METHODS

We identified 12 patients with large TDL (six men, six women; age range 17‐64 years, median age 27 years) and studied the clinical histories and the results of laboratory and various radiological studies in these patients. All cases of clinically definite multiple sclerosis were diagnosed in accordance with McDonald's revised criteria.

RESULTS

Common MRI features of large TDLs included variable degrees of mass effect (71%) and edema (100%), a T2 hypointense rim (79%), venular enhancement (57%), and peripheral restriction on diffusion‐weighted images (50%). Ring enhancement (38%), open‐ring enhancement (31%), or decreased N‐acetylaspartate ratios on magnetic resonance spectroscopy (22%) were less frequently observed. Brain angiography demonstrated venous dilatations on and around the TDL.

CONCLUSIONS

The diagnosis of large TDL is challenging. Our findings suggest that multiple venous dilatations on and around TDLs on angiography can facilitate diagnosis.

     

Evaluation of the neutrophil/lymphocyte ratio,platelet/lymphocyte ratio,and mean platelet volume as inflammatory markers in children with attention‐deficit hyperactivity disorder

Aim

The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and mean platelet volume (MPV) have recently been used as indicators of a systemic inflammatory response. The aim of this study was to investigate the relations of the NLR, PLR, MLR, and MPV with attention‐deficit hyperactivity disorder (ADHD).

Methods

The study group consisting of 82 children diagnosed with ADHD was compared with a healthy control (HC) group of 70 age‐, sex‐, and body‐mass‐index‐matched subjects. The NLR, PLR, MLR, and MPV were measured according to the complete blood count.

Results

The NLR, PLR, MLR, MPV, and neutrophil count of the ADHD group were significantly higher than those of the HC group. The lymphocyte counts of the patients were significantly lower than those of the HC group.

Conclusion

Inflammation might play a role in the etiopathogenesis of ADHD. The NLR, PLR, MLR, and MPV may be potential inflammation markers for ADHD in children.

     

An open‐label extension long‐term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan

Aim

The purpose of this study was to evaluate the long‐term safety and efficacy of aripiprazole in treating irritability in pediatric patients (6–17 years) with autistic disorder (AD) in Japan.

Methods

In this open‐label extension study, patients who had completed a previous randomized, double‐blind, placebo‐controlled 8‐week study were enrolled and were flexibly dosed with aripiprazole (1–15 mg/day) until the new indication of irritability in pediatric autism spectrum disorder was approved in Japan.

Results

Seventy (81%) out of 86 enrolled patients completed week‐48 assessments. The mean duration of treatment was 694.9 days. The mean daily dose of aripiprazole over the treatment period was 7.2 mg and the mean of the final dose was 8.5 mg. The most common treatment‐emergent adverse events (TEAE; ≥20%) included nasopharyngitis, somnolence, influenza, and increased weight. The majority of these TEAE were mild or moderate in severity, and there were no deaths, and no clinically relevant findings in laboratory values except prolactin decrease, vital signs, height, or ECG parameters. At week 48 (observed case), the mean change from baseline in the Irritability subscale score for the Aberrant Behavior Checklist Japanese Version was ?6.3 in prior placebo patients and ?2.6 in prior aripiprazole patients.

Conclusion

Aripiprazole was generally safe, well tolerated, and effective in the long‐term treatment of irritability associated with AD in Japanese pediatric patients.

     

Correlation study of optimized voxel-based morphometry and (1)H MRS in patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Purpose:

To assess whether structural and metabolic brain abnormalities are correlated in MTLE/HS syndrome.

Methods:

Optimized voxel‐based morphometry (VBM) of gray matter concentration (GMC) and gray matter volume (GMV) and proton magnetic resonance spectroscopy measurements from both‐sided hippocampal and thalamic regions were performed in 20 MTLE/HS patients and 20 sex‐ and age‐matched healthy controls. The local GMC and GMV values were calculated in both the affected and unaffected hippocampi and ipsilateral and contralateral thalami in patients and healthy subjects, and these were compared. VBM variables and NAA, NAA/Cr and NAA/(Cr+Cho) values from the investigated brain regions were correlated.

Results:

(1) Analysis revealed significantly more extensive GMV reduction than GMC reduction in patients' affected hippocampus. In addition, significant GMV reduction was observed in the ipsilateral thalamus in MTLE/HS patients. (2) Significant decreases in all VBM and MRS variables were revealed in the affected hippocampus. Whilst practically normal GMC values were revealed in patients' both‐sided thalamic regions, a significant decrease in local GMV and metabolic measurements were found in the patients' ipsilateral thalamus. (3) Pearson's correlations between structural and metabolic abnormalities were significant for the ipsilateral thalamus only.

Conclusion:

Structural and metabolic abnormalities as detected by optimized voxel‐based morphometry and ¹H MRS in hippocampal and thalamic regions are only partially correlated in MTLE/HS patients. It seems therefore reasonable that both methods reflect different aspects of brain pathology, which, at least to some degree, might be independently ongoing. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.

     

Brain MRI Lesion Load at 1.5T and 3T versus Clinical Status in Multiple Sclerosis

ABSTRACT

BACKGROUND/PURPOSE

To assess correlation between brain lesions and clinical status with 1.5T and 3T magnetic resonance imaging (MRI).

METHODS

Brain MRI fluid‐attenuated inversion‐recovery (FLAIR) sequences were performed in 32 multiple sclerosis (MS) patients. Expanded Disability Status Scale (EDSS) score (mean ± standard deviation) was 2 ± 2.0 (range 0‐8), disease duration 9.3 ± 8.0 (range .8‐29) years.

RESULTS

FLAIR lesion volume (FLLV) at 3T was higher than at 1.5T (P= .01). Correlation between 1.5T FLLV and EDSS score was poor, while 3T FLLV correlated moderately and significantly (r_s= .39, P= .03). When controlling for age and depression, correlations between FLLV and cognitive measures were significant at 1.5T for the Judgment of Line Orientation test (JLO) (r_s=−.44, P= .05), the Symbol Digit Modalities Test (SDMT) (r_s=−.49, P= .02), and the California Verbal Learning Test Delayed Free Recall (CVLT DR) (r_s=−.44, P= .04). Correlations at 3T were also significant for these tests, but of greater magnitude: JLO (r_s=−.70, P= .0005), SDMT (r_s=−.73, P= .0001), CVLT DR (r_s=−.061, P= .003). Additional significant correlations obtained only at 3T included the 2 second‐paced auditory serial addition test (r_s=−.55, P= .01), the Brief Visuospatial Memory Test‐Delayed Free Recall (r_s=−.56, P= .007), and the California Verbal Learning Test Total Recall (r_s=−.42, P= .05).

CONCLUSION

MRI at 3T may boost sensitivity and improve validity in MS brain lesion assessment.

     

Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease

Background:

Histopathological studies and animal models suggest that hippocampal subfields may be differently affected by aging, Alzheimer's disease (AD), and other diseases. High‐resolution images at 4 Tesla depict details of the internal structure of the hippocampus allowing for in vivo volumetry of different subfields. The aims of this study were as follows: (1) to determine patterns of volume loss in hippocampal subfields in normal aging, AD, and amnestic mild cognitive impairment (MCI). (2) To determine if measurements of hippocampal subfields provide advantages over total hippocampal volume for differentiation between groups.

Methods:

Ninety‐one subjects (53 controls (mean age: 69.3 ± 7.3), 20 MCI (mean age: 73.6 ± 7.1), and 18 AD (mean age: 69.1 ± 9.5) were studied with a high‐resolution T2 weighted imaging sequence aimed at the hippocampus. Entorhinal cortex (ERC), subiculum, CA1, CA1‐CA2 transition zone (CA1‐2), CA3 & dentate gyrus (CA3&DG) were manually marked in the anterior third of the hippocampal body. Hippocampal volume was obtained from the Freesurfer and manually edited.

Results:

Compared to controls, AD had smaller volumes of ERC, subiculum, CA1, CA1‐2, and total hippocampal volumes. MCI had smaller CA1‐2 volumes. Discriminant analysis and power analysis showed that CA1‐2 was superior to total hippocampal volume for distinction between controls and MCI.

Conclusion:

The patterns of subfield atrophy in AD and MCI were consistent with patterns of neuronal cell loss/reduced synaptic density described by histopathology. These preliminary findings suggest that hippocampal subfield volumetry might be a better measure for diagnosis of early AD and for detection of other disease effects than measurement of total hippocampus. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.

     

The Clinical and Radiological Spectrum of Posterior Reversible Encephalopathy Syndrome: A Retrospective Series of 24 Patients

ABSTRACT

BACKGROUND AND PURPOSE

Some patients with posterior reversible encephalopathy syndrome (PRES) present with atypical clinical and neuroimaging findings. The purpose of this study is to review the clinical and neuroimaging findings in patients diagnosed with PRES.

METHODS

We retrospectively included all patients diagnosed with PRES between January 2005 and March 2009. We reviewed demographic, clinical and laboratory data, neuroimaging findings, and prognosis.

RESULTS

Twenty‐four patients were included with a median age of 19 years. The clinical presentations included seizures (91.7%), headache (83.3%), visual disturbance (62.5%), encephalophathy (29.2%), and paralysis (8.3%). Co‐morbidities included systemic lupus erythematous (29.2%), kidney disease (20.8%), eclampsia (20.8%), renal artery stenosis (12.5%), Takayasu arteritis (4.2%), Sheehan's syndrome (4.2%), allergic purpura (4.2%), and acute intermittent porphyria (4.2%). Acute elevation of blood pressure was found in 22 patients (91.7%). Ten patients (41.7%) used steroids or immunosuppressants, three (12.5%) had acute renal failure before the symptoms. Atypical neuroimaging features included involvement of the frontal lobe (54.2%), basal ganglia (4.2%) or cortex (8.3%), and irreversible lesions (3/18, 16.7%).

CONCLUSIONS

A large proportion of patients with PRES may present with atypical neuroimaging findings. Apart from the known risk factors, such as hypertension, immunosuppressants, and renal failure of various etiologies may be the precipitants of PRES.

     

Reduced prefrontal hemodynamic response in adult attention‐deficit hyperactivity disorder as measured by near‐infrared spectroscopy

Aim

Recent developments in near‐infrared spectroscopy (NIRS) have enabled non‐invasive clarification of brain functions in psychiatric disorders. In pediatric attention‐deficit hyperactivity disorder (ADHD), reduced prefrontal hemodynamic responses have been observed with NIRS repeatedly. However, there are few studies of adult ADHD by multi‐channel NIRS. Therefore, in this study, we used multi‐channel NIRS to examine the characteristics of prefrontal hemodynamic responses during the Stroop Color–Word Task (SCWT) in adult ADHD patients and in age‐ and sex‐matched control subjects.

Methods

Twelve treatment‐naïve adults with ADHD and 12 age‐ and sex‐matched healthy control subjects participated in the present study after giving consent. We used 24‐channel NIRS to measure the oxygenated hemoglobin (oxy‐Hb) changes at the frontal lobes of participants during the SCWT. We compared the oxy‐Hb changes between adults with ADHD and control subjects by t ‐tests with Bonferroni correction.

Results

During the SCWT, the oxy‐Hb changes observed in the ADHD group were significantly smaller than those in the control group in channels 11, 16, 18, 21, 22, 23, and 24, corresponding to the prefrontal cortex. At channels 16, 21, 23, and 24 of the ADHD group, there were negative correlations between the symptomatic severity and the oxy‐Hb changes.

Conclusion

The present study suggests that adults with ADHD have reduced prefrontal hemodynamic response as measured by NIRS.