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Brain Sci., Volume 8, Issue 4 (April 2018) – 26 articles

Cover Story (view full-size image): The cover image shows a representation of the molecular model of the dopamine transporter (DAT) and important residues in the primary binding pocket. We discuss in vitro and in silico approaches distinguishing the pharmacological, functional and structural changes of the novel psychoactive substances (NPS), diphenidine (DPH) and 2-methoxydiphenidine (2-MXP), when bound to DAT. Our data suggest that DPH can have addictive liability, unlike 2-MXP, despite their chemical similarities. The computational findings corroborate the above and explain the conformational responses and atomistic processes within DAT during its interactions with the dissociative NPS. View this paper
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17 pages, 3115 KiB  
Article
Prediction of Human Performance Using Electroencephalography under Different Indoor Room Temperatures
by Tapsya Nayak, Tinghe Zhang, Zijing Mao, Xiaojing Xu, Lin Zhang, Daniel J. Pack, Bing Dong and Yufei Huang
Brain Sci. 2018, 8(4), 74; https://doi.org/10.3390/brainsci8040074 - 23 Apr 2018
Cited by 16 | Viewed by 5505
Abstract
Varying indoor environmental conditions is known to affect office worker’s performance; wherein past research studies have reported the effects of unfavorable indoor temperature and air quality causing sick building syndrome (SBS) among office workers. Thus, investigating factors that can predict performance in changing [...] Read more.
Varying indoor environmental conditions is known to affect office worker’s performance; wherein past research studies have reported the effects of unfavorable indoor temperature and air quality causing sick building syndrome (SBS) among office workers. Thus, investigating factors that can predict performance in changing indoor environments have become a highly important research topic bearing significant impact in our society. While past research studies have attempted to determine predictors for performance, they do not provide satisfactory prediction ability. Therefore, in this preliminary study, we attempt to predict performance during office-work tasks triggered by different indoor room temperatures (22.2 °C and 30 °C) from human brain signals recorded using electroencephalography (EEG). Seven participants were recruited, from whom EEG, skin temperature, heart rate and thermal survey questionnaires were collected. Regression analyses were carried out to investigate the effectiveness of using EEG power spectral densities (PSD) as predictors of performance. Our results indicate EEG PSDs as predictors provide the highest R2 (> 0.70), that is 17 times higher than using other physiological signals as predictors and is more robust. Finally, the paper provides insight on the selected predictors based on brain activity patterns for low- and high-performance levels under different indoor-temperatures. Full article
(This article belongs to the Special Issue Brain-Computer Interfaces for Human Augmentation)
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17 pages, 812 KiB  
Review
Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review
by Fabrizio Schifano, Stefania Chiappini, John M. Corkery and Amira Guirguis
Brain Sci. 2018, 8(4), 73; https://doi.org/10.3390/brainsci8040073 - 22 Apr 2018
Cited by 56 | Viewed by 12478
Abstract
Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a [...] Read more.
Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a range of medications which have emerged as being used recreationally, either on their own or in combination with NPS. Among gabapentinoids, pregabalin may present with higher addictive liability levels than gabapentin, with pregabalin being mostly identified in the context of opioid, polydrug intake. For antidepressants, their dopaminergic, stimulant-like, bupropion activities may explain their recreational value and diversion from the therapeutic intended use. In some vulnerable clients, a high dosage of venlafaxine (‘baby ecstasy’) is ingested for recreational purposes, whilst the occurrence of a clinically-relevant withdrawal syndrome may be a significant issue for all venlafaxine-treated patients. Considering second generation antipsychotics, olanzapine appears to be ingested at very large dosages as an ‘ideal trip terminator’, whilst the immediate-release quetiapine formulation may possess proper abuse liability levels. Within the image- and performance- enhancing drugs (IPEDs) group, the beta-2 agonist clenbuterol (‘size zero pill’) is reported to be self-administered for aggressive slimming purposes. Finally, high/very high dosage ingestion of the antidiarrhoeal loperamide has shown recent increasing levels of popularity due to its central recreational, anti-withdrawal, opiatergic effects. The emerging abuse of prescription drugs within the context of a rapidly modifying drug scenario represents a challenge for psychiatry, public health and drug-control policies. Full article
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23 pages, 3117 KiB  
Article
The GABAA Receptor α2 Subunit Activates a Neuronal TLR4 Signal in the Ventral Tegmental Area that Regulates Alcohol and Nicotine Abuse
by Irina Balan, Kaitlin T. Warnock, Adam Puche, Marjorie C. Gondre-Lewis, Harry June and Laure Aurelian
Brain Sci. 2018, 8(4), 72; https://doi.org/10.3390/brainsci8040072 - 21 Apr 2018
Cited by 14 | Viewed by 6389
Abstract
Alcoholism initiates with episodes of excessive alcohol drinking, known as binge drinking, which is one form of excessive drinking (NIAAA Newsletter, 2004) that is related to impulsivity and anxiety (Ducci et al., 2007; Edenberg et al., 2004) and is also predictive of smoking [...] Read more.
Alcoholism initiates with episodes of excessive alcohol drinking, known as binge drinking, which is one form of excessive drinking (NIAAA Newsletter, 2004) that is related to impulsivity and anxiety (Ducci et al., 2007; Edenberg et al., 2004) and is also predictive of smoking status. The predisposition of non-alcohol exposed subjects to initiate binge drinking is controlled by neuroimmune signaling that includes an innately activated neuronal Toll-like receptor 4 (TLR4) signal. This signal also regulates cognitive impulsivity, a heritable trait that defines drug abuse initiation. However, the mechanism of signal activation, its function in dopaminergic (TH+) neurons within the reward circuitry implicated in drug-seeking behavior [viz. the ventral tegmental area (VTA)], and its contribution to nicotine co-abuse are still poorly understood. We report that the γ-aminobutyric acidA receptor (GABAAR) α2 subunit activates the TLR4 signal in neurons, culminating in the activation (phosphorylation/nuclear translocation) of cyclic AMP response element binding (CREB) but not NF-kB transcription factors and the upregulation of corticotropin-releasing factor (CRF) and tyrosine hydroxylase (TH). The signal is activated through α2/TLR4 interaction, as evidenced by co-immunoprecipitation, and it is present in the VTA from drug-untreated alcohol-preferring P rats. VTA infusion of neurotropic herpes simplex virus (HSV) vectors for α2 (pHSVsiLA2) or TLR4 (pHSVsiTLR4) but not scrambled (pHSVsiNC) siRNA inhibits signal activation and both binge alcohol drinking and nicotine sensitization, suggesting that the α2-activated TLR4 signal contributes to the regulation of both alcohol and nicotine abuse. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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14 pages, 632 KiB  
Article
Subjective Socioeconomic Status Moderates the Association between Discrimination and Depression in African American Youth
by Shervin Assari, Brianna Preiser, Maryam Moghani Lankarani and Cleopatra H. Caldwell
Brain Sci. 2018, 8(4), 71; https://doi.org/10.3390/brainsci8040071 - 20 Apr 2018
Cited by 74 | Viewed by 15244
Abstract
Background: Most of the literature on the association between socioeconomic status (SES) and health is focused on the protective effects of SES. However, a growing literature suggests that high SES may also operate as a vulnerability factor. Aims: Using a national sample of [...] Read more.
Background: Most of the literature on the association between socioeconomic status (SES) and health is focused on the protective effects of SES. However, a growing literature suggests that high SES may also operate as a vulnerability factor. Aims: Using a national sample of African American youth, this study compared the effects of perceived discrimination on major depressive disorder (MDD) based on SES. Methods: The current cross-sectional study included 810 African American youth who participated in the National Survey of American Life-Adolescent supplement. The independent variable was perceived discrimination. Lifetime, 12-month, and 30-day MDD were the dependent variables. Age and gender were covariates. Three SES indicators (subjective SES, income, and poverty index) were moderators. We used logistic regressions for data analysis. Results: Perceived discrimination was associated with higher risk of lifetime, 12-month, and 30-day MDD. Interactions were found between subjective SES and perceived discrimination on lifetime, 12-month, and 30-day MDD, suggesting a stronger effect of perceived discrimination in youth with high subjective SES. Objective measures of SES (income and poverty index) did not interact with perceived discrimination on MDD. Conclusion: While perceived discrimination is a universally harmful risk factor for MDD, its effect may depend on the SES of the individual. Findings suggest that high subjective SES may operate as a vulnerability factor for African American youth. Full article
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15 pages, 1625 KiB  
Article
Sex Specific Alterations in α4*Nicotinic Receptor Expression in the Nucleus Accumbens
by Joan Y. Holgate, Josephine R. Tarren and Selena E. Bartlett
Brain Sci. 2018, 8(4), 70; https://doi.org/10.3390/brainsci8040070 - 19 Apr 2018
Cited by 3 | Viewed by 5069
Abstract
Background: The mechanisms leading from traumatic stress to social, emotional and cognitive impairment and the development of mental illnesses are still undetermined and consequently there remains a critical need to develop therapies for preventing the adverse consequences of traumatic stress. Research indicates [...] Read more.
Background: The mechanisms leading from traumatic stress to social, emotional and cognitive impairment and the development of mental illnesses are still undetermined and consequently there remains a critical need to develop therapies for preventing the adverse consequences of traumatic stress. Research indicates nicotinic acetylcholine receptors containing α4 subunits (α4*nAChRs) are both impacted by stress and capable of modulating the stress response. In this study, we investigated whether varenicline, a partial α4β2*nAChR agonist which reduces nicotine, alcohol and sucrose consumption, can reduce stress, a driving factor in substance use disorders. We also examined the effect of stress on nucleus accumbens (NAc) α4*nAChR expression. Methods: Transgenic mice with fluorescent tags attached to α4*nAChRs were administered varenicline and/or yohimbine (a pharmacological stressor) and plasma corticosterone and NAc α4*nAChR expression were measured. A separated group of mice were exposed to maternal separation (MS) during post-natal day (P) 2–14, then restraint stressed (30 min) at six weeks of age. Body weight, anxiety-like behaviours (elevated plus maze), plasma corticosterone and NAc α4*nAChR levels were measured. Results: Varenicline attenuated yohimbine-induced plasma corticosterone increases with no effect on NAc α4*nAChR expression. MS reduced unrestrained plasma corticosterone levels in both sexes. In females, MS increased body weight and NAc α4*nAChR expression, whereas, in males, MS and restraint caused a greater change in anxiety-like behaviours and plasma corticosterone levels. Restraint altered NAc α4*nAChR expression in both male and female MS mice. Conclusions: The effects of stress on NAc α4*nAChR are sex-dependent. While varenicline attenuated acute stress-induced rises in corticosterone levels, future studies are required to determine whether varenicline is effective for relieving the effects of stress. Full article
(This article belongs to the Special Issue Sex Differences in the Healthy and Diseased Brain)
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22 pages, 344 KiB  
Article
Epilepsy and Neuromodulation—Randomized Controlled Trials
by Churl-Su Kwon, Valeria Ripa, Omar Al-Awar, Fedor Panov, Saadi Ghatan and Nathalie Jetté
Brain Sci. 2018, 8(4), 69; https://doi.org/10.3390/brainsci8040069 - 18 Apr 2018
Cited by 32 | Viewed by 6838
Abstract
Neuromodulation is a treatment strategy that is increasingly being utilized in those suffering from drug-resistant epilepsy who are not appropriate for resective surgery. The number of double-blinded RCTs demonstrating the efficacy of neurostimulation in persons with epilepsy is increasing. Although reductions in seizure [...] Read more.
Neuromodulation is a treatment strategy that is increasingly being utilized in those suffering from drug-resistant epilepsy who are not appropriate for resective surgery. The number of double-blinded RCTs demonstrating the efficacy of neurostimulation in persons with epilepsy is increasing. Although reductions in seizure frequency is common in these trials, obtaining seizure freedom is rare. Invasive neuromodulation procedures (DBS, VNS, and RNS) have been approved as therapeutic measures. However, further investigations are necessary to delineate effective targeting, minimize side effects that are related to chronic implantation and to improve the cost effectiveness of these devices. The RCTs of non-invasive modes of neuromodulation whilst showing much promise (tDCS, eTNS, rTMS), require larger powered studies as well as studies that focus at better targeting techniques. We provide a review of double-blinded randomized clinical trials that have been conducted for neuromodulation in epilepsy. Full article
(This article belongs to the Special Issue Diagnosis and Surgical Treatment of Epilepsy)
17 pages, 2334 KiB  
Article
What Is Going On? The Process of Generating Questions about Emotion and Social Cognition in Bipolar Disorder and Schizophrenia with Cartoon Situations and Faces
by Bryan D. Fantie, Mary H. Kosmidis, Maria Giannakou, Sotiria Moza, Athanasios Karavatos and Vassilis P. Bozikas
Brain Sci. 2018, 8(4), 68; https://doi.org/10.3390/brainsci8040068 - 17 Apr 2018
Viewed by 4453
Abstract
Regarding the notion of putative “best” practices in social neuroscience and science in general, we contend that following established procedures has advantages, but prescriptive uniformity in methodology can obscure flaws, bias thinking, stifle creativity, and restrict exploration. Generating hypotheses is at least as [...] Read more.
Regarding the notion of putative “best” practices in social neuroscience and science in general, we contend that following established procedures has advantages, but prescriptive uniformity in methodology can obscure flaws, bias thinking, stifle creativity, and restrict exploration. Generating hypotheses is at least as important as testing hypotheses. To illustrate this process, we describe the following exploratory study. Psychiatric patients have difficulties with social functioning that affect their quality of life adversely. To investigate these impediments, we compared the performances of patients with schizophrenia and those with bipolar disorder to healthy controls on a task that involved matching photographs of facial expressions to a faceless protagonist in each of a series of drawn cartoon emotion-related situations. These scenarios involved either a single character (Nonsocial) or multiple characters (Social). The Social scenarios were also Congruent, with everyone in the cartoon displaying the same emotion, or Noncongruent (with everyone displaying a different emotion than the protagonist should). In this preliminary study, both patient groups produced lower scores than controls (p < 0.001), but did not perform differently from each other. All groups performed best on the social-congruent items and worst on the social-noncongruent items (p < 0.001). Performance varied inversely with illness duration, but not symptom severity. Complete emotional, social, cognitive, or perceptual inability is unlikely because these patient groups could still do this task. Nevertheless, the differences we saw could be meaningful functionally and clinically significant and deserve further exploration. Therefore, we stress the need to continue developing novel, alternative ways to explore social cognition in patients with psychiatric disorders and to clarify which elements of the multidimensional process contribute to difficulties in daily functioning. Full article
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17 pages, 3108 KiB  
Article
Revisiting Strephosymbolie: The Connection between Interhemispheric Transfer and Developmental Dyslexia
by Roberta Daini, Paola De Fabritiis, Chiara Ginocchio, Carlo Lenti, Cristina Michela Lentini, Donatella Marzorati and Maria Luisa Lorusso
Brain Sci. 2018, 8(4), 67; https://doi.org/10.3390/brainsci8040067 - 17 Apr 2018
Cited by 6 | Viewed by 4836
Abstract
The hypothesis that an atypical hemispheric specialization is associated to developmental dyslexia (DD) is receiving renewed interest, lending some support to Orton’s theory. In this article, we investigated whether interhemispheric transfer processes (IHT) are likely to be involved in developmental dyslexia. In this [...] Read more.
The hypothesis that an atypical hemispheric specialization is associated to developmental dyslexia (DD) is receiving renewed interest, lending some support to Orton’s theory. In this article, we investigated whether interhemispheric transfer processes (IHT) are likely to be involved in developmental dyslexia. In this study, we tested 13 children with developmental dyslexia and 13 matched controls (aged 8 to 13 years) in four different tasks. In a tactile transfer task, the dyslexic children’s performance was less accurate. In a standard Poffenberger paradigm, dyslexic children performed slower than the controls in all conditions and did not show any difference between crossed and uncrossed conditions. Furthermore, they showed an increased asymmetry of performance according to the responding hand, while controls gave more coherent responses. In a visual task of object orientation discrimination, dyslexic children had slower Response Times (RTs) than controls, especially for mirror-reversed objects in the right visual field. Finally, a higher number of dyslexic children showed mirror-drawing or mirror-writing with respect to controls. Our results as a whole show that children with DD are impaired in interhemispheric transfer, although the differences in performance among dyslexic individuals suggest the impairment of different psychophysiological mechanisms. As such, a common origin in terms of connectivity problems is proposed. Full article
(This article belongs to the Special Issue Dyslexia, Dysgraphia and Related Developmental Disorders)
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8 pages, 228 KiB  
Article
Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Parkinson Disease with Prior Pallidotomy or Thalamotomy
by Elena A. Khabarova, Natalia P. Denisova, Aleksandr B. Dmitriev, Konstantin V. Slavin and Leo Verhagen Metman
Brain Sci. 2018, 8(4), 66; https://doi.org/10.3390/brainsci8040066 - 16 Apr 2018
Cited by 14 | Viewed by 4572
Abstract
Objective. To evaluate the efficacy of deep brain stimulation of the subthalamic nucleus (STN DBS) in patients with Parkinson disease (PD) who previously underwent lesioning of the basal ganglia. Material and methods. The study included 22 patients who underwent STN DBS. Eleven patients [...] Read more.
Objective. To evaluate the efficacy of deep brain stimulation of the subthalamic nucleus (STN DBS) in patients with Parkinson disease (PD) who previously underwent lesioning of the basal ganglia. Material and methods. The study included 22 patients who underwent STN DBS. Eleven patients had undergone prior unilateral pallidotomy (n = 6) or VL/VIM thalamotomy (n = 5) while the other 11 patients had not. The primary outcome was the change from baseline in the motor subscore of the Unified Parkinson Disease Rating Scale (UPDRS-III) 12 months after STN DBS. Secondary outcomes included change in motor response complications (UPDRS-IV) and change in levodopa equivalent daily dose (LEDD). Results. In the group with prior lesioning UPDRS-III improved by 45%, from 51.5 ± 9.0% (range, 35–65) to 26.5 ± 8.4 (range, 21–50) (p < 0.01) and UPDRS-IV by 75%, from 8.0 ± 2.01 (range, 5–11) to 2.1 ± 0.74 (range, 1–3) (p < 0.01). In the group without prior lesioning UPDRS-III improved by 61%, from 74.2% ± 7.32 (range, 63–82) to 29.3 ± 5.99 (range, 20–42) (p < 0.01) and UPDRS-IV by 77%, from 9.1 ± 2.46 (range, 5–12) to 2.0 ± 1.1 (range, 1–4) (p < 0.01). Comparing the two groups (with and without lesioning) no significant differences were found either in UPDRS-III (p > 0.05) or UPDRS-IV scores (p > 0.05) at 12 months post-DBS. The LEDD was reduced by 51.4%, from 1008.2 ± 346.4 to 490.0 ± 194.3 in those with prior surgery (p < 0.01) and by 55.0%, from 963.4 ± 96.2 to 433.3 ± 160.2 in those without (p < 0.01).UPDRS-III improved by 51.8%, from 53.7 ± 4.6 (range, 50–62) to 25.0 ± 3.8 (range, 21–31) in those with prior pallidotomy (p < 0.01), and by 37.5%, from 48.8 ± 12.6 (range, 35–65) to 29.8 ± 13.6 (range, 22–50) in those with prior thalamotomy (p < 0.01). This numerical difference in improvement was not statistically significant (p > 0.05). Conclusion. Our comparative study indicates that bilateral STN DBS is effective and can be used in patients with Parkinson disease with prior unilateral stereotactic destructive operations on subcortical structures. The results in our patient cohort are generally consistent with previously published reports of smaller series from multiple centers worldwide. Full article
22 pages, 64992 KiB  
Article
The Effect of Axon Resealing on Retrograde Neuronal Death after Spinal Cord Injury in Lamprey
by Guixin Zhang, William Rodemer, Taemin Lee, Jianli Hu and Michael E. Selzer
Brain Sci. 2018, 8(4), 65; https://doi.org/10.3390/brainsci8040065 - 14 Apr 2018
Cited by 11 | Viewed by 5614
Abstract
Failure of axon regeneration in the central nervous system (CNS) of mammals is due to both extrinsic inhibitory factors and to neuron-intrinsic factors. The importance of intrinsic factors is illustrated in the sea lamprey by the 18 pairs of large, individually identified reticulospinal [...] Read more.
Failure of axon regeneration in the central nervous system (CNS) of mammals is due to both extrinsic inhibitory factors and to neuron-intrinsic factors. The importance of intrinsic factors is illustrated in the sea lamprey by the 18 pairs of large, individually identified reticulospinal (RS) neurons, whose axons are located in the same spinal cord tracts but vary greatly in their ability to regenerate after spinal cord transection (TX). The neurons that are bad regenerators also undergo very delayed apoptosis, signaled early by activation of caspases. We noticed that the neurons with a low probability of axon regeneration tend to be larger than the good regenerators. We postulate that the poorly regenerating larger neurons have larger caliber axons, which reseal more slowly, allowing more prolonged entry of toxic signals (e.g., Ca++) into the axon at the injury site. To test this hypothesis, we used a dye-exclusion assay, applying membrane-impermeable dyes to the cut ends of spinal cords at progressively longer post-TX intervals. Axons belonging to the very small neurons (not individually identified) of the medial inferior RS nucleus resealed within 15 min post-TX. Almost 75% of axons belonging to the medium-sized identified RS neurons resealed within 3 h. At this time, only 36% of the largest axons had resealed, often taking more than 24 h to exclude the dye. There was an inverse relationship between an RS neuron’s size and the probability that its axon would regenerate (r = −0.92) and that the neuron would undergo delayed apoptosis, as indicated by staining with a fluorescently labeled inhibitor of caspases (FLICA; r = 0.73). The artificial acceleration of resealing with polyethylene glycol (PEG) reduced retrograde neuronal apoptosis by 69.5% at 2 weeks after spinal cord injury (SCI), suggesting that axon resealing is a critical determinant of cell survival. Ca++-free Ringer’s solution with EGTA prolonged the sealing time and increased apoptotic signaling, suggesting that factors other than Ca++ diffusion into the injured tip contribute to retrograde death signaling. A longer distance of the lesion from the cell body reduced apoptotic signaling independent of the axon sealing time. Full article
(This article belongs to the Special Issue Novel Mechanisms and Strategies for Neural Repair)
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8 pages, 240 KiB  
Article
Exploring Behavioral Correlates of Afferent Inhibition
by Claudia V. Turco, Mitchell B. Locke, Jenin El-Sayes, Mark Tommerdahl and Aimee J. Nelson
Brain Sci. 2018, 8(4), 64; https://doi.org/10.3390/brainsci8040064 - 11 Apr 2018
Cited by 15 | Viewed by 4931
Abstract
(1) Background: Afferent inhibition is the attenuation of the muscle response evoked from transcranial magnetic stimulation (TMS) by a prior conditioning electrical stimulus to a peripheral nerve. It is unclear whether the magnitude of afferent inhibition relates to sensation and movement; (2) Methods: [...] Read more.
(1) Background: Afferent inhibition is the attenuation of the muscle response evoked from transcranial magnetic stimulation (TMS) by a prior conditioning electrical stimulus to a peripheral nerve. It is unclear whether the magnitude of afferent inhibition relates to sensation and movement; (2) Methods: 24 healthy, young adults were tested. Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) were obtained following median and digital nerve stimulation. Temporal tactile acuity was assessed with a temporal order judgement (TOJ) task, spatial tactile acuity was assessed using a grating orientation task (GOT), and fine manual dexterity was assessed with the Pegboard task; (3) Results: Correlation analyses revealed no association between the magnitude of SAI or LAI with performance on the TOJ, GOT, or Pegboard tasks; (4) Conclusion: The magnitude of SAI and LAI does not relate to performance on the sensory and motor tasks tested. Future studies are needed to better understand whether the afferent inhibition phenomenon relates to human behavior. Full article
19 pages, 37555 KiB  
Article
Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter—In Silico and In Vitro Exploration of Dissociative Diarylethylamines
by Michelle A. Sahai, Colin Davidson, Neelakshi Dutta and Jolanta Opacka-Juffry
Brain Sci. 2018, 8(4), 63; https://doi.org/10.3390/brainsci8040063 - 07 Apr 2018
Cited by 15 | Viewed by 8661
Abstract
Novel psychoactive substances (NPS) may have unsuspected addiction potential through possessing stimulant properties. Stimulants normally act at the dopamine transporter (DAT) and thus increase dopamine (DA) availability in the brain, including nucleus accumbens, within the reward and addiction pathway. This paper aims to [...] Read more.
Novel psychoactive substances (NPS) may have unsuspected addiction potential through possessing stimulant properties. Stimulants normally act at the dopamine transporter (DAT) and thus increase dopamine (DA) availability in the brain, including nucleus accumbens, within the reward and addiction pathway. This paper aims to assess DAT responses to dissociative diarylethylamine NPS by means of in vitro and in silico approaches. We compared diphenidine (DPH) and 2-methoxydiphenidine (methoxphenidine, 2-MXP/MXP) for their binding to rat DAT, using autoradiography assessment of [125I]RTI-121 displacement in rat striatal sections. The drugs’ effects on electrically-evoked DA efflux were measured by means of fast cyclic voltammetry in rat accumbens slices. Computational modeling, molecular dynamics and alchemical free energy simulations were used to analyse the atomistic changes within DAT in response to each of the five dissociatives: DPH, 2-MXP, 3-MXP, 4-MXP and 2-Cl-DPH, and to calculate their relative binding free energy. DPH increased DA efflux as a result of its binding to DAT, whereas MXP had no significant effect on either DAT binding or evoked DA efflux. Our computational findings corroborate the above and explain the conformational responses and atomistic processes within DAT during its interactions with the dissociative NPS. We suggest DPH can have addictive liability, unlike MXP, despite the chemical similarities of these two NPS. Full article
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18 pages, 4404 KiB  
Article
The Validity of Functional Near-Infrared Spectroscopy Recordings of Visuospatial Working Memory Processes in Humans
by Joëlle S. Witmer, Eva A. Aeschlimann, Andreas J. Metz, Stefan J. Troche and Thomas H. Rammsayer
Brain Sci. 2018, 8(4), 62; https://doi.org/10.3390/brainsci8040062 - 05 Apr 2018
Cited by 4 | Viewed by 4875
Abstract
Functional near infrared spectroscopy (fNIRS) is increasingly used for investigating cognitive processes. To provide converging evidence for the validity of fNIRS recordings in cognitive neuroscience, we investigated functional activation in the frontal cortex in 43 participants during the processing of a visuospatial working [...] Read more.
Functional near infrared spectroscopy (fNIRS) is increasingly used for investigating cognitive processes. To provide converging evidence for the validity of fNIRS recordings in cognitive neuroscience, we investigated functional activation in the frontal cortex in 43 participants during the processing of a visuospatial working memory (WM) task and a sensory duration discrimination (DD) task functionally unrelated to WM. To distinguish WM-related processes from a general effect of increased task demand, we applied an adaptive approach, which ensured that subjective task demand was virtually identical for all individuals and across both tasks. Our specified region of interest covered Brodmann Area 8 of the left hemisphere, known for its important role in the execution of WM processes. Functional activation, as indicated by an increase of oxygenated and a decrease of deoxygenated hemoglobin, was shown for the WM task, but not in the DD task. The overall pattern of results indicated that hemodynamic responses recorded by fNIRS are sensitive to specific visuospatial WM capacity-related processes and do not reflect a general effect of increased task demand. In addition, the finding that no such functional activation could be shown for participants with far above-average mental ability suggested different cognitive processes adopted by this latter group. Full article
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18 pages, 4272 KiB  
Concept Paper
Is Dyslexia a Brain Disorder?
by Athanassios Protopapas and Rauno Parrila
Brain Sci. 2018, 8(4), 61; https://doi.org/10.3390/brainsci8040061 - 05 Apr 2018
Cited by 45 | Viewed by 24995
Abstract
Specific word reading difficulty, commonly termed ‘developmental dyslexia’, refers to the low end of the word reading skill distribution but is frequently considered to be a neurodevelopmental disorder. This term implies that brain development is thought to be disrupted, resulting in an abnormal [...] Read more.
Specific word reading difficulty, commonly termed ‘developmental dyslexia’, refers to the low end of the word reading skill distribution but is frequently considered to be a neurodevelopmental disorder. This term implies that brain development is thought to be disrupted, resulting in an abnormal and dysfunctional brain. We take issue with this view, pointing out that there is no evidence of any obvious neurological abnormality in the vast majority of cases of word reading difficulty cases. The available relevant evidence from neuroimaging studies consists almost entirely of correlational and group-differences studies. However, differences in brains are certain to exist whenever differences in behavior exist, including differences in ability and performance. Therefore, findings of brain differences do not constitute evidence for abnormality; rather, they simply document the neural substrate of the behavioral differences. We suggest that dyslexia is best viewed as one of many expressions of ordinary ubiquitous individual differences in normal developmental outcomes. Thus, terms such as “dysfunctional” or “abnormal” are not justified when referring to the brains of persons with dyslexia. Full article
(This article belongs to the Special Issue Dyslexia, Dysgraphia and Related Developmental Disorders)
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8 pages, 622 KiB  
Article
Long-Term Satisfaction and Patient-Centered Outcomes of Deep Brain Stimulation in Parkinson’s Disease
by Jessica A. Karl, Bichun Ouyang, Kalea Colletta and Leo Verhagen Metman
Brain Sci. 2018, 8(4), 60; https://doi.org/10.3390/brainsci8040060 - 01 Apr 2018
Cited by 21 | Viewed by 5669
Abstract
Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective and proven treatment option for patients with advanced Parkinson’s disease (PD). Long-term outcomes (>5 years) have demonstrated sustained improvement in objective motor symptoms; however, few studies have evaluated patient-centered outcomes other than [...] Read more.
Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective and proven treatment option for patients with advanced Parkinson’s disease (PD). Long-term outcomes (>5 years) have demonstrated sustained improvement in objective motor symptoms; however, few studies have evaluated patient-centered outcomes other than quality of life (QOL). A locally developed DBS-patient-centered outcomes questionnaire was administered to PD patients >5 years post-DBS. All questions were scored on a ten-point scale, whereby 0 represented the most ‘positive’ answer and 10 the most ‘negative’ answer. Pre-operative scales were repeated at the time of survey. Fifty-two patients (mean 8.2 ± 2.6 years post-DBS) were included. Satisfaction was high with median score (range) of 1/10 (0–8) at the time of survey. Patients endorsed having made the correct decision by undergoing DBS, with a score of 0 (0–10), would choose to have DBS again, with a score of 0 (0–10), and would recommend DBS to others, with a score of 0 (0–10). Pre-operative expectation target was set at a high level with a score of 2 (0–10). Parkinson’s Disease QOL (PDQ-39) Questionnaire Summary Index (SI) scores were, mean (SD), 2.1 (18.2) above baseline (p = 0.44). Those with worsening in PDQ-39-SI scores had less satisfaction with DBS (rs = 0.57, p ≤ 0.0001). This is the first study to assess long-term patient satisfaction with STN DBS. We are currently collecting data prospectively to confirm the results of these preliminary findings. Full article
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11 pages, 260 KiB  
Review
Quality of Life and Stigma in Epilepsy, Perspectives from Selected Regions of Asia and Sub-Saharan Africa
by Warren Boling, Margaret Means and Anita Fletcher
Brain Sci. 2018, 8(4), 59; https://doi.org/10.3390/brainsci8040059 - 01 Apr 2018
Cited by 37 | Viewed by 6830
Abstract
Epilepsy is an important and common worldwide public health problem that affects people of all ages. A significant number of individuals with epilepsy will be intractable to medication. These individuals experience an elevated mortality rate and negative psychosocial consequences of recurrent seizures. Surgery [...] Read more.
Epilepsy is an important and common worldwide public health problem that affects people of all ages. A significant number of individuals with epilepsy will be intractable to medication. These individuals experience an elevated mortality rate and negative psychosocial consequences of recurrent seizures. Surgery of epilepsy is highly effective to stop seizures in well-selected individuals, and seizure freedom is the most desirable result of epilepsy treatment due to the positive improvements in psychosocial function and the elimination of excess mortality associated with intractable epilepsy. Globally, there is inadequate data to fully assess epilepsy-related quality of life and stigma, although the preponderance of information we have points to a significant negative impact on people with epilepsy (PWE) and families of PWE. This review of the psychosocial impact of epilepsy focuses on regions of Asia and Sub-Saharan Africa that have been analyzed with population study approaches to determine the prevalence of epilepsy, treatment gaps, as well as factors impacting psychosocial function of PWE and their families. This review additionally identifies models of care for medically intractable epilepsy that have potential to significantly improve psychosocial function. Full article
(This article belongs to the Special Issue Diagnosis and Surgical Treatment of Epilepsy)
20 pages, 342 KiB  
Article
Exploration of the Use of New Psychoactive Substances by Individuals in Treatment for Substance Misuse in the UK
by Rosalind Gittins, Amira Guirguis, Fabrizio Schifano and Ian Maidment
Brain Sci. 2018, 8(4), 58; https://doi.org/10.3390/brainsci8040058 - 30 Mar 2018
Cited by 19 | Viewed by 8072
Abstract
Substance misuse services need to meet the growing demand and needs of individuals using new psychoactive substances (NPS). A review of the literature identified a paucity of research regarding NPS use by these individuals and UK guidelines outline the need for locally tailored [...] Read more.
Substance misuse services need to meet the growing demand and needs of individuals using new psychoactive substances (NPS). A review of the literature identified a paucity of research regarding NPS use by these individuals and UK guidelines outline the need for locally tailored strategies. The purpose of this qualitative study was to identify and explore key themes in relation to the use of NPS by individuals receiving community treatment for their substance use. Electronic records identified demographics and semi-structured interviews were undertaken. A thematic analysis of transcripts identified a variety of substance use histories; 50% were prescribed opiate substitutes and 25% used NPS as a primary substance. All were males, age range 26–59 years (SD = 9), who predominantly smoked cannabinoids and snorted/injected stimulant NPS. The type of NPS used was determined by affordability, availability, side-effect profile and desired effects (physical and psychological: 25% reported weight loss as motivation for their use). Poly-pharmacy, supplementation and displacement of other drugs were prevalent. In conclusion, NPS use and associated experiences vary widely among people receiving substance use treatment. Development of effective recovery pathways should be tailored to individuals, and include harm reduction strategies, psychosocial interventions, and effective signposting. Services should be vigilant for NPS use, “on top” use and diversion of prescriptions. Full article
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38 pages, 5085 KiB  
Review
Brain–Computer Interface Spellers: A Review
by Aya Rezeika, Mihaly Benda, Piotr Stawicki, Felix Gembler, Abdul Saboor and Ivan Volosyak
Brain Sci. 2018, 8(4), 57; https://doi.org/10.3390/brainsci8040057 - 30 Mar 2018
Cited by 248 | Viewed by 20111
Abstract
A Brain–Computer Interface (BCI) provides a novel non-muscular communication method via brain signals. A BCI-speller can be considered as one of the first published BCI applications and has opened the gate for many advances in the field. Although many BCI-spellers have been developed [...] Read more.
A Brain–Computer Interface (BCI) provides a novel non-muscular communication method via brain signals. A BCI-speller can be considered as one of the first published BCI applications and has opened the gate for many advances in the field. Although many BCI-spellers have been developed during the last few decades, to our knowledge, no reviews have described the different spellers proposed and studied in this vital field. The presented speller systems are categorized according to major BCI paradigms: P300, steady-state visual evoked potential (SSVEP), and motor imagery (MI). Different BCI paradigms require specific electroencephalogram (EEG) signal features and lead to the development of appropriate Graphical User Interfaces (GUIs). The purpose of this review is to consolidate the most successful BCI-spellers published since 2010, while mentioning some other older systems which were built explicitly for spelling purposes. We aim to assist researchers and concerned individuals in the field by illustrating the highlights of different spellers and presenting them in one review. It is almost impossible to carry out an objective comparison between different spellers, as each has its variables, parameters, and conditions. However, the gathered information and the provided taxonomy about different BCI-spellers can be helpful, as it could identify suitable systems for first-hand users, as well as opportunities of development and learning from previous studies for BCI researchers. Full article
(This article belongs to the Special Issue Brain-Computer Interfaces for Human Augmentation)
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12 pages, 6565 KiB  
Article
Oxamate, but Not Selective Targeting of LDH-A, Inhibits Medulloblastoma Cell Glycolysis, Growth and Motility
by Cara J. Valvona and Helen L. Fillmore
Brain Sci. 2018, 8(4), 56; https://doi.org/10.3390/brainsci8040056 - 30 Mar 2018
Cited by 41 | Viewed by 6301
Abstract
Medulloblastoma is the most common malignant paediatric brain tumour and current therapies often leave patients with severe neurological disabilities. Four major molecular groups of medulloblastoma have been identified (Wnt, Shh, Group 3 and Group 4), which include additional, recently defined subgroups with different [...] Read more.
Medulloblastoma is the most common malignant paediatric brain tumour and current therapies often leave patients with severe neurological disabilities. Four major molecular groups of medulloblastoma have been identified (Wnt, Shh, Group 3 and Group 4), which include additional, recently defined subgroups with different prognosis and genetic characteristics. Lactate dehydrogenase A (LDHA) is a key enzyme in the aerobic glycolysis pathway, an abnormal metabolic pathway commonly observed in cancers, associated with tumour progression and metastasis. Studies indicate MBs have a glycolytic phenotype; however, LDHA has not yet been explored as a therapeutic target for medulloblastoma. LDHA expression was examined in medulloblastoma subgroups and cell lines. The effects of LDHA inhibition by oxamate or LDHA siRNA on medulloblastoma cell line metabolism, migration and proliferation were examined. LDHA was significantly overexpressed in Group 3 and Wnt MBs compared to non-neoplastic cerebellum. Furthermore, we found that oxamate significantly attenuated glycolysis, proliferation and motility in medulloblastoma cell lines, but LDHA siRNA did not. We established that aerobic glycolysis is a potential therapeutic target for medulloblastoma, but broader LDH inhibition (LDHA, B, and C) may be more appropriate than LDHA inhibition alone. Full article
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2 pages, 159 KiB  
Comment
Comments on: “Transcranial Direct Current Stimulation for Obsessive-Compulsive Disorder: A Systematic Review”
by Mohammad Alwardat and Mohammad Etoom
Brain Sci. 2018, 8(4), 55; https://doi.org/10.3390/brainsci8040055 - 27 Mar 2018
Viewed by 3672
Abstract
Dear Editor, Brunelin et al. [1] recently conducted a systematic review that evaluated the effect of applied transcranial direct current stimulation (tDCS) on patients with obsessive compulsive disorder (OCD).[...] Full article
11 pages, 1628 KiB  
Article
Enhanced Sensitivity to Subphonemic Segments in Dyslexia: A New Instance of Allophonic Perception
by Willy Serniclaes and M’ballo Seck
Brain Sci. 2018, 8(4), 54; https://doi.org/10.3390/brainsci8040054 - 26 Mar 2018
Cited by 7 | Viewed by 4731
Abstract
Although dyslexia can be individuated in many different ways, it has only three discernable sources: a visual deficit that affects the perception of letters, a phonological deficit that affects the perception of speech sounds, and an audio-visual deficit that disturbs the association of [...] Read more.
Although dyslexia can be individuated in many different ways, it has only three discernable sources: a visual deficit that affects the perception of letters, a phonological deficit that affects the perception of speech sounds, and an audio-visual deficit that disturbs the association of letters with speech sounds. However, the very nature of each of these core deficits remains debatable. The phonological deficit in dyslexia, which is generally attributed to a deficit of phonological awareness, might result from a specific mode of speech perception characterized by the use of allophonic (i.e., subphonemic) units. Here we will summarize the available evidence and present new data in support of the “allophonic theory” of dyslexia. Previous studies have shown that the dyslexia deficit in the categorical perception of phonemic features (e.g., the voicing contrast between /t/ and /d/) is due to the enhanced sensitivity to allophonic features (e.g., the difference between two variants of /d/). Another consequence of allophonic perception is that it should also give rise to an enhanced sensitivity to allophonic segments, such as those that take place within a consonant cluster. This latter prediction is validated by the data presented in this paper. Full article
(This article belongs to the Special Issue Dyslexia, Dysgraphia and Related Developmental Disorders)
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14 pages, 309 KiB  
Review
Down Syndrome, Obesity, Alzheimer’s Disease, and Cancer: A Brief Review and Hypothesis
by Daniel W. Nixon
Brain Sci. 2018, 8(4), 53; https://doi.org/10.3390/brainsci8040053 - 24 Mar 2018
Cited by 12 | Viewed by 8007
Abstract
Down syndrome (trisomy 21), a complex mix of physical, mental, and biochemical issues, includes an increased risk of Alzheimer’s disease and childhood leukemia, a decreased risk of other tumors, and a high frequency of overweight/obesity. Certain features related to the third copy of [...] Read more.
Down syndrome (trisomy 21), a complex mix of physical, mental, and biochemical issues, includes an increased risk of Alzheimer’s disease and childhood leukemia, a decreased risk of other tumors, and a high frequency of overweight/obesity. Certain features related to the third copy of chromosome 21 (which carries the APP gene and several anti-angiogenesis genes) create an environment favorable for Alzheimer’s disease and unfavorable for cancer. This environment may be enhanced by two bioactive compounds from fat cells, leptin, and adiponectin. This paper outlines these fat-related disease mechanisms and suggests new avenues of research to reduce disease risk in Down syndrome. Full article
6 pages, 1052 KiB  
Concept Paper
Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson’s Disease
by Manuel Menéndez-González, Huber S. Padilla-Zambrano, Cristina Tomás-Zapico and Benjamin Fernández García
Brain Sci. 2018, 8(4), 52; https://doi.org/10.3390/brainsci8040052 - 23 Mar 2018
Cited by 12 | Viewed by 6270
Abstract
This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson’s disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought [...] Read more.
This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson’s disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought to be crucial in the pathogenesis of PD. Recent research has shown that small amounts of monomeric and oligomeric α-synuclein are released from neuronal cells by exocytosis and that this extracellular alpha-synuclein contributes to neurodegeneration, progressive spreading of alpha-synuclein pathology, and neuroinflammation. In PD, extracellular oligomeric-α-synuclein moves in constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we expect that continuous depletion of oligomeric-α-synuclein in the CSF will produce a steady clearance of the protein in the ISF, preventing transmission and deposition in the brain. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Neurodegenerative Diseases)
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7 pages, 1394 KiB  
Case Report
Sensory Trick in a Patient with Cervical Dystonia: Insights from Magnetoencephalography
by Abhimanyu Mahajan, Andrew Zillgitt, Susan M. Bowyer and Christos Sidiropoulos
Brain Sci. 2018, 8(4), 51; https://doi.org/10.3390/brainsci8040051 - 22 Mar 2018
Cited by 11 | Viewed by 5552
Abstract
Background: The proposed mechanisms for the sensory trick include peripheral sensory feedback to aid in correcting abnormal posture or movement. Case report: A 53-year-old woman with cervical dystonia underwent magnetoencephalography pre- and post-botulinum toxin injection and sensory trick, which was described as yawning. [...] Read more.
Background: The proposed mechanisms for the sensory trick include peripheral sensory feedback to aid in correcting abnormal posture or movement. Case report: A 53-year-old woman with cervical dystonia underwent magnetoencephalography pre- and post-botulinum toxin injection and sensory trick, which was described as yawning. Study revealed connectivity between the left frontal and inferior frontal gyrus before yawning, which changed to the visual cortex and right middle frontal gyrus with yawning. Beta frequencies reduced and gamma frequencies increased after yawning. Discussion: The increase in gamma frequency bands may indicate increased GABAergic activity. Increase in connectivity in the right cerebellar region underscores the importance of cerebellum in pathogenesis of dystonia. Full article
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14 pages, 10674 KiB  
Article
Connexin 43 Controls the Astrocyte Immunoregulatory Phenotype
by Anne-Cécile Boulay, Alice Gilbert, Vanessa Oliveira Moreira, Corinne Blugeon, Sandrine Perrin, Juliette Pouch, Stéphane Le Crom, Bertrand Ducos and Martine Cohen-Salmon
Brain Sci. 2018, 8(4), 50; https://doi.org/10.3390/brainsci8040050 - 22 Mar 2018
Cited by 15 | Viewed by 6043
Abstract
Astrocytes are the most abundant glial cells of the central nervous system and have recently been recognized as crucial in the regulation of brain immunity. In most neuropathological conditions, astrocytes are prone to a radical phenotypical change called reactivity, which plays a key [...] Read more.
Astrocytes are the most abundant glial cells of the central nervous system and have recently been recognized as crucial in the regulation of brain immunity. In most neuropathological conditions, astrocytes are prone to a radical phenotypical change called reactivity, which plays a key role in astrocyte contribution to neuroinflammation. However, how astrocytes regulate brain immunity in healthy conditions is an understudied question. One of the astroglial molecule involved in these regulations might be Connexin 43 (Cx43), a gap junction protein highly enriched in astrocyte perivascular endfeet-terminated processes forming the glia limitans. Indeed, Cx43 deletion in astrocytes (Cx43KO) promotes a continuous immune recruitment and an autoimmune response against an astrocyte protein, without inducing any brain lesion. To investigate the molecular basis of this unique immune response, we characterized the polysomal transcriptome of hippocampal astrocytes deleted for Cx43. Our results demonstrate that, in the absence of Cx43, astrocytes adopt an atypical reactive status with no change in most canonical astrogliosis markers, but with an upregulation of molecules promoting immune recruitment, complement activation as well as anti-inflammatory processes. Intriguingly, while several of these upregulated transcriptional events suggested an activation of the γ-interferon pathway, no increase in this cytokine or activation of related signaling pathways were found in Cx43KO. Finally, deletion of astroglial Cx43 was associated with the upregulation of several angiogenic factors, consistent with an increase in microvascular density in Cx43KO brains. Collectively, these results strongly suggest that Cx43 controls immunoregulatory and angiogenic properties of astrocytes. Full article
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20 pages, 3176 KiB  
Review
Diagnosis and Surgical Treatment of Drug-Resistant Epilepsy
by Chinekwu Anyanwu and Gholam K. Motamedi
Brain Sci. 2018, 8(4), 49; https://doi.org/10.3390/brainsci8040049 - 21 Mar 2018
Cited by 38 | Viewed by 9494
Abstract
Despite appropriate trials of at least two antiepileptic drugs, about a third of patients with epilepsy remain drug resistant (intractable; refractory). Epilepsy surgery offers a potential cure or significant improvement to those with focal onset drug-resistant seizures. Unfortunately, epilepsy surgery is still underutilized [...] Read more.
Despite appropriate trials of at least two antiepileptic drugs, about a third of patients with epilepsy remain drug resistant (intractable; refractory). Epilepsy surgery offers a potential cure or significant improvement to those with focal onset drug-resistant seizures. Unfortunately, epilepsy surgery is still underutilized which might be in part because of the complexity of presurgical evaluation. This process includes classifying the seizure type, lateralizing and localizing the seizure onset focus (epileptogenic zone), confirming the safety of the prospective brain surgery in terms of potential neurocognitive deficits (language and memory functions), before devising a surgical plan. Each one of the above steps requires special tests. In this paper, we have reviewed the process of presurgical evaluation in patients with drug-resistant focal onset epilepsy. Full article
(This article belongs to the Special Issue Diagnosis and Surgical Treatment of Epilepsy)
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