Intensity‐based masking: A tool to improve functional connectivity results of resting‐state fMRI

Seed‐based functional connectivity (FC) of resting‐state functional MRI data is a widely used methodology, enabling the identification of functional brain networks in health and disease. Based on signal correlations across the brain, FC measures are highly sensitive to noise. A somewhat neglected source of noise is the fMRI signal attenuation found in cortical regions in close vicinity to sinuses and air cavities, mainly in the orbitofrontal, anterior frontal and inferior temporal cortices. BOLD signal recorded at these regions suffers from dropout due to susceptibility artifacts, resulting in an attenuated signal with reduced signal‐to‐noise ratio in as many as 10% of cortical voxels. Nevertheless, signal attenuation is largely overlooked during FC analysis. Here we first demonstrate that signal attenuation can significantly influence FC measures by introducing false functional correlations and diminishing existing correlations between brain regions. We then propose a method for the detection and removal of the attenuated signal (“intensity‐based masking”) by fitting a Gaussian‐based model to the signal intensity distribution and calculating an intensity threshold tailored per subject. Finally, we apply our method on real‐world data, showing that it diminishes false correlations caused by signal dropout, and significantly improves the ability to detect functional networks in single subjects. Furthermore, we show that our method increases inter‐subject similarity in FC, enabling reliable distinction of different functional networks. We propose to include the intensity‐based masking method as a common practice in the pre‐processing of seed‐based functional connectivity analysis, and provide software tools for the computation of intensity‐based masks on fMRI data. Hum Brain Mapp 37:2407–2418, 2016. © 2016 Wiley Periodicals, Inc .     

Task-dependent organization of brain regions active during rest

The human brain demonstrates complex yet systematic patterns of neural activity at rest. We examined whether functional connectivity among those brain regions typically active during rest depends on ongoing and recent task demands and individual differences. We probed the temporal coordination among these regions during periods of language comprehension and during the rest periods that followed comprehension. Our findings show that the topography of this “rest network” varies with exogenous processing demands. The network encompassed more highly interconnected regions during rest than during listening, but also when listening to unsurprising vs. surprising information. Furthermore, connectivity patterns during rest varied as a function of recent listening experience. Individual variability in connectivity strength was associated with cognitive function: more attentive comprehenders demonstrated weaker connectivity during language comprehension, and a greater differentiation between connectivity during comprehension and rest. The regions we examined have generally been thought to form an invariant physiological and functional network whose activity reflects spontaneous cognitive processes. Our findings suggest that their function extends beyond the mediation of unconstrained thought, and that they play an important role in higher-level cognitive function.     

Latent inhibition and overswitching in schizophrenia

Attention disorders in schizophrenia are manifested in two different ways. On the one hand, the schizophrenia patient tends to keep a learned response even after it ceases to be relevant (perseveration). On the other hand, the schizophrenia patient tends to replace an adaptive response without being given a reason to do so (overswitching). In the present study, overswitching was investigated in relation to latent inhibition (LI), which is the normal ability to ignore nonrelevant stimuli. A new tool--the Combined Attention Test--was used for this purpose in a group of 41 unmedicated schizophrenia patients, divided into subgroups of patients with predominantly positive and negative symptoms, and 24 normal controls. The results show that positive schizophrenia patients, who exhibited high levels of overswitching, also revealed impaired LI, while the negative schizophrenia group, as well as normal controls, exhibited intact LI. These findings suggest that overswitching is a specific attention deficit in positive schizophrenia. We discuss the possibility that impaired LI is a consequence of overswitching and comment on the putative neurophysiology.     

Bone strength in multiple sclerosis: cortical midtibial speed-of-sound assessment

It has been previously suggested that multiple sclerosis (MS) patients are at increased risk for osteoporosis due to reduced mobility, decreased exposure to sunlight and recurrent steroid treatment. In order to systematically evaluate bone strength we assessed 256 MS patients (171 females, 75 males) through quantitative ultrasound measurement of cortical bone. Tibial speed of sound (SOS, m/sec) was measured at midpoint of the tibial shaft using a Soundscan 2000 (Myriad Ultrasound Systems, Rehovot, Israel) and results were compared to age- and gender-matched population norms. T-score distribution in male MS patients was similar to normal population. In contrast, for female MS patients T-score distribution was significantly different from population norms, reflected by increased SOS in 30.4% (T-score intervals 1-2 and >2 above normal values; P=0.001), compared with 7.4% in controls. These findings held true for both female patients younger and older than 45 years of age. Increased neurological disability and specifically motor involvement were more frequent in female patients with increased SOS (P<0.05). Bone strength was preserved in MS patients. In a subgroup of female patients increased SOS was conceivably related to spasticity.     

Early prediction of encephalopathic transformation in children with benign epilepsy with centro-temporal spikes

BackgroundMost children with Benign epilepsy with centro-temporal spikes (BECTS) undergo remission during late adolescence and do not require treatment. In a small group of patients, the condition may evolve to encephalopathic syndromes including epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), or Landau-Kleffner Syndrome (LKS). Development of prediction models for early identification of at-risk children is of utmost importance.AimTo develop a predictive model of encephalopathic transformation using data-driven approaches, reveal complex interactions to identify potential risk factors.MethodsData were collected from a cohort of 91 patients diagnosed with BECTS treated between the years 2005–2017 at a pediatric neurology institute. Data on the initial presentation was collected based on a novel BECTS ontology and used to discover potential risk factors and to build a predictive model. Statistical and machine learning methods were compared.ResultsA subgroup of 18 children had encephalopathic transformation. The least absolute shrinkage and selection operator (LASSO) regression Model with Elastic Net was able to successfully detect children with ECSWS or LKS. Sensitivity and specificity were 0.83 and 0.44. The most notable risk factors were fronto-temporal and temporo-parietal localization of epileptic foci, semiology of seizure involving dysarthria or somatosensory auras.ConclusionNovel prediction model for early identification of patients with BECTS at risk for ECSWS or LKS. This model can be used as a screening tool and assist physicians to consider special management for children predicted at high-risk. Clinical application of machine learning methods opens new frontiers of personalized patient care and treatment.     

Mental health reforms in Europe: Israel's rehabilitation in the community of persons with mental disabilities law: challenges and opportunities

This column describes an innovative, government-sponsored, countrywide mental health reform focusing on rehabilitation and community integration of persons with serious mental illness, which was enacted into law in Israel in 2000. The reform was part of the country's efforts to shift the locus of treatment and care from psychiatric institutions to the community. The authors review preliminary evidence of the impact of reform and offer cautionary notes regarding the future direction of its implementation. The decade after the law's enactment saw an impressive increase in rehabilitation services, a significant reduction in the number of psychiatric beds, and major changes in government budget allocations. The authors examine factors that may endanger the viability of reform and discuss lessons to be learned from the Israeli experience.     

Cerebellar astrocytoma presenting as deterioration of handwriting in a child

Deterioration of handwriting in an 11-year-old boy over a 2 month period was found to be caused by a cerebellar astrocytoma. The clinical picture was characterised by a lack of the classic symptoms of increased intracranial pressure. The only positive neurological findings pointed to an isolated right cerebellar symptomatology expressed by mild intention tremor and decreased tone of the right hand.Progressive deterioration of handwriting can be an ominous sign and it should be known to all professionals, as a lack of awareness can cause delay in expert referral and diagnosis.     

Topical treatment with povidone iodine reduces nitrogen mustard-induced skin collagenolytic activity

Recently we have shown that post-exposure treatment with povidone iodine (PI) protects against nitrogen and sulfur mustard-induced skin lesions. Since proteolytic activity is involved in skin damage caused by chemical irritants, we have studied the effect of iodine on mechlorethamine (HN2)-induced skin collagenolytic activities in the haired guinea pig model. The matrix metalloproteinase-9 (MMP-9) activity increased by 30, 46, 12 and 23% after 3, 24, 48 and 72 h of HN2 exposure, respectively, whereas the MMP-2 was elevated by 8, 65, 8 and 30%, respectively. Topical treatment with PI at 15 and 120 min after HN2 exposure decreased the MMP-9 activity by 67% and 60%, respectively, when skin was analyzed 3 h after exposure. The same trend was observed in the MMP-2 and MMP-1 activities after PI treatment. A stronger effect of PI treatment 15 min following exposure was observed in skin analyzed 24 h after exposure, i.e. a decrease of 83% and 88% in MMP-9 and MMP-2 activities, respectively. Similar findings were observed with an interval of 120 min between HN2 exposure and PI treatment. A much weaker effect was observed on MMP-1 activity. A similar trend of PI-induced reduction in the three types of collagenase activity was found in skin analyzed 48 and 72 h after exposure. Reduced collagenolytic activity may serve as one of the mechanisms by which iodine protects the skin against chemical insult.