Open AccessArticle
Long-Term Task- and Dopamine-Dependent Dynamics of Subthalamic Local Field Potentials in Parkinson’s Disease
Brain Sci. 2016, 6(4), 57; doi:10.3390/brainsci6040057 (registering DOI) -
Abstract
Subthalamic nucleus (STN) local field potentials (LFP) are neural signals that have been shown to reveal motor and language behavior, as well as pathological parkinsonian states. We use a research-grade implantable neurostimulator (INS) with data collection capabilities to record STN-LFP outside the operating
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Subthalamic nucleus (STN) local field potentials (LFP) are neural signals that have been shown to reveal motor and language behavior, as well as pathological parkinsonian states. We use a research-grade implantable neurostimulator (INS) with data collection capabilities to record STN-LFP outside the operating room to determine the reliability of the signals over time and assess their dynamics with respect to behavior and dopaminergic medication. Seven subjects were implanted with the recording augmented deep brain stimulation (DBS) system, and bilateral STN-LFP recordings were collected in the clinic over twelve months. Subjects were cued to perform voluntary motor and language behaviors in on and off medication states. The STN-LFP recorded with the INS demonstrated behavior-modulated desynchronization of beta frequency (13–30 Hz) and synchronization of low gamma frequency (35–70 Hz) oscillations. Dopaminergic medication did not diminish the relative beta frequency oscillatory desynchronization with movement. However, movement-related gamma frequency oscillatory synchronization was only observed in the medication on state. We observed significant inter-subject variability, but observed consistent STN-LFP activity across recording systems and over a one-year period for each subject. These findings demonstrate that an INS system can provide robust STN-LFP recordings in ambulatory patients, allowing for these signals to be recorded in settings that better represent natural environments in which patients are in a variety of medication states. Full article
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Open AccessArticle
Cerebellar Intermittent Theta-Burst Stimulation and Motor Control Training in Individuals with Cervical Dystonia
Brain Sci. 2016, 6(4), 56; doi:10.3390/brainsci6040056 -
Abstract
Background: There is emerging evidence that cervical dystonia is a neural network disorder with the cerebellum as a key node. The cerebellum may provide a target for neuromodulation as a therapeutic intervention in cervical dystonia. Objective: This study aimed to assess effects of
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Background: There is emerging evidence that cervical dystonia is a neural network disorder with the cerebellum as a key node. The cerebellum may provide a target for neuromodulation as a therapeutic intervention in cervical dystonia. Objective: This study aimed to assess effects of intermittent theta-burst stimulation of the cerebellum on dystonia symptoms, quality of life, hand motor dexterity and cortical neurophysiology using transcranial magnetic stimulation. Methods: Sixteen participants with cervical dystonia were randomised into real or sham stimulation groups. Cerebellar neuromodulation was combined with motor training for the neck and an implicit learning task. The intervention was delivered over 10 working days. Outcome measures included dystonia severity and pain, quality of life, hand dexterity, and motor-evoked potentials and cortical silent periods recorded from upper trapezius muscles. Assessments were taken at baseline and after 5 and 10 days, with quality of life also measured 4 and 12 weeks later. Results: Intermittent theta-burst stimulation improved dystonia severity (Day 5, −5.44 points; p = 0.012; Day 10, −4.6 points; p = 0.025), however, effect sizes were small. Quality of life also improved (Day 5, −10.6 points, p = 0.012; Day 10, −8.6 points, p = 0.036; Week 4, −12.5 points, p = 0.036; Week 12, −12.4 points, p = 0.025), with medium or large effect sizes. There was a reduction in time to complete the pegboard task pre to post intervention (both p < 0.008). Cortical neurophysiology was unchanged by cerebellar neuromodulation. Conclusion: Intermittent theta-burst stimulation of the cerebellum may improve cervical dystonia symptoms, upper limb motor control and quality of life. The mechanism likely involves promoting neuroplasticity in the cerebellum although the neurophysiology remains to be elucidated. Cerebellar neuromodulation may have potential as a novel treatment intervention for cervical dystonia, although larger confirmatory studies are required. Full article
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Open AccessArticle
No Effect of Cathodal Transcranial Direct Current Stimulation on Fear Memory in Healthy Human Subjects
Brain Sci. 2016, 6(4), 55; doi:10.3390/brainsci6040055 -
Abstract
Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS
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Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS of the right dorsolateral prefrontal cortex during fear reconsolidation in humans. Methods: Seventeen young, healthy subjects were randomly assigned to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal—cathodal, left supraorbital—anodal) for 20 min at 1 mA, or sham stimulation. A day later, fear responses of both groups were compared. Results: On Day 3, during fear response assessment, there were no significant differences between the tDCS and sham group (p > 0.05). Conclusion: We conclude that cathodal tDCS of the right dorsolateral prefrontal cortex (right prefrontal—cathodal, left supraorbital—anodal) did not influence fear memories. Full article
Open AccessArticle
Long-Term Plasticity in Reflex Excitability Induced by Five Weeks of Arm and Leg Cycling Training after Stroke
Brain Sci. 2016, 6(4), 54; doi:10.3390/brainsci6040054 -
Abstract
Neural connections remain partially viable after stroke, and access to these residual connections provides a substrate for training-induced plasticity. The objective of this project was to test if reflex excitability could be modified with arm and leg (A & L) cycling training. Nineteen
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Neural connections remain partially viable after stroke, and access to these residual connections provides a substrate for training-induced plasticity. The objective of this project was to test if reflex excitability could be modified with arm and leg (A & L) cycling training. Nineteen individuals with chronic stroke (more than six months postlesion) performed 30 min of A & L cycling training three times a week for five weeks. Changes in reflex excitability were inferred from modulation of cutaneous and stretch reflexes. A multiple baseline (three pretests) within-subject control design was used. Plasticity in reflex excitability was determined as an increase in the conditioning effect of arm cycling on soleus stretch reflex amplitude on the more affected side, by the index of modulation, and by the modulation ratio between sides for cutaneous reflexes. In general, A & L cycling training induces plasticity and modifies reflex excitability after stroke. Full article
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Open AccessReview
Prediction of Walking and Arm Recovery after Stroke: A Critical Review
Brain Sci. 2016, 6(4), 53; doi:10.3390/brainsci6040053 -
Abstract
Clinicians often base their predictions of walking and arm recovery on multiple predictors. Multivariate prediction models may assist clinicians to make accurate predictions. Several reviews have been published on the prediction of motor recovery after stroke, but none have critically appraised development and
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Clinicians often base their predictions of walking and arm recovery on multiple predictors. Multivariate prediction models may assist clinicians to make accurate predictions. Several reviews have been published on the prediction of motor recovery after stroke, but none have critically appraised development and validation studies of models for predicting walking and arm recovery. In this review, we highlight some common methodological limitations of models that have been developed and validated. Notable models include the proportional recovery model and the PREP algorithm. We also identify five other models based on clinical predictors that might be ready for further validation. It has been suggested that neurophysiological and neuroimaging data may be used to predict arm recovery. Current evidence suggests, but does not show conclusively, that the addition of neurophysiological and neuroimaging data to models containing clinical predictors yields clinically important increases in predictive accuracy. Full article
Open AccessArticle
Prenatal Alcohol Exposure Affects Progenitor Cell Numbers in Olfactory Bulbs and Dentate Gyrus of Vervet Monkeys
Brain Sci. 2016, 6(4), 52; doi:10.3390/brainsci6040052 -
Abstract
Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover
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Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts vervet monkey (Chlorocebus sabeus) to (1) investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2) determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years). Using design-based stereology, we found an age-related decrease of actively proliferating cells in the olfactory bulb and dentate gyrus for both control and FAE groups. Furthermore, at the neonatal time point, the FAE group had fewer actively proliferating cells as compared to the control group. These data are unique with respect to fetal ethanol effects on progenitor proliferation in the primate brain and suggest that the olfactory bulb may be a useful structure for studies of cellular proliferation. Full article
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Open AccessArticle
The Relationship between Estrogen and Nitric Oxide in the Prevention of Cardiac and Vascular Anomalies in the Developing Zebrafish (Danio Rerio)
Brain Sci. 2016, 6(4), 51; doi:10.3390/brainsci6040051 -
Abstract
It has been known that both estrogen (E2) and nitric oxide (NO) are critical for proper cardiovascular system (CVS) function. It has also been demonstrated that E2 acts as an upstream effector in the nitric oxide (NO) pathway. Results from this study indicate
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It has been known that both estrogen (E2) and nitric oxide (NO) are critical for proper cardiovascular system (CVS) function. It has also been demonstrated that E2 acts as an upstream effector in the nitric oxide (NO) pathway. Results from this study indicate that the use of a nitric oxide synthase (NOS) inhibitor (NOSI) which targets specifically neuronal NOS (nNOS or NOS1), proadifen hydrochloride, caused a significant depression of fish heart rates (HR) accompanied by increased arrhythmic behavior. However, none of these phenotypes were evident with either the inhibition of endothelial NOS (eNOS) or inducible NOS (iNOS) isoforms. These cardiac arrhythmias could also be mimicked by inhibition of E2 synthesis with the aromatase inhibitor (AI), 4-OH-A, in a manner similar to that of nNOSI. In both scenarios, by using an NO donor (DETA-NO) in either NO + nNOSI or E2 + AI co-treatments, fish could be significantly rescued from decreased HR and increased arrhythmias. However, the addition of an NOS inhibitor (L-NAME) to the E2 + AI co-treatment fish prevented the rescue of low heart rates and arrhythmias, which strongly implicates the NO pathway as a downstream E2 targeted molecule for the maintenance of healthy cardiomyocyte contractile conditions in the developing zebrafish. Cardiac arrhythmias could be mimicked by the S-nitrosylation pathway inhibitor DTT (1,4-dithiothreitol) but not by ODQ (1H-[1–3]oxadiazolo[4,3-a]quinoxalin-1-one), the inhibitor of the NO receptor molecule sGC in the cGMP-dependent pathway. In both the nNOSI and AI-induced arrhythmic conditions, 100% of the fish expressed the phenotype, but could be rapidly rescued with maximum survival by a washout with dantrolene, a ryanodine Ca2+ channel receptor blocker, compared to the time it took for rescue using a control salt solution. In addition, of the three NOS isoforms, eNOS was the one most implicated in the maintenance of an intact developing fish vascular system. In conclusion, results from this study have shown that nNOS is the prominent isoform that is responsible, in part, for maintaining normal heart rates and prevention of arrhythmias in the developing zebrafish heart failure model. These phenomena are related to the upstream stimulatory regulation by E2. On the other hand, eNOS has a minimal effect and iNOS has little to no influence on this phenomenon. Data also suggests that nNOS acts on the zebrafish cardiomyocytes through the S-nitrosylation pathway to influence the SR ryanidine Ca2+ channels in the excitation-coupling phenomena. In contrast, eNOS is the prominent isoform that influences blood vessel development in this model. Full article
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Open AccessArticle
Language Problems and ADHD Symptoms: How Specific Are the Links?
Brain Sci. 2016, 6(4), 50; doi:10.3390/brainsci6040050 -
Abstract
Symptoms of inattention and hyperactivity frequently co-occur with language difficulties in both clinical and community samples. We explore the specificity and strength of these associations in a heterogeneous sample of 254 children aged 5 to 15 years identified by education and health professionals
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Symptoms of inattention and hyperactivity frequently co-occur with language difficulties in both clinical and community samples. We explore the specificity and strength of these associations in a heterogeneous sample of 254 children aged 5 to 15 years identified by education and health professionals as having problems with attention, learning and/or memory. Parents/carers rated pragmatic and structural communication skills and behaviour, and children completed standardised assessments of reading, spelling, vocabulary, and phonological awareness. A single dimension of behavioural difficulties including both hyperactivity and inattention captured behaviour problems. This was strongly and negatively associated with pragmatic communication skills. There was less evidence for a relationship between behaviour and language structure: behaviour ratings were more weakly associated with the use of structural language in communication, and there were no links with direct measures of literacy. These behaviour problems and pragmatic communication difficulties co-occur in this sample, but impairments in the more formal use of language that impact on literacy and structural communication skills are tied less strongly to behavioural difficulties. One interpretation is that impairments in executive function give rise to both behavioural and social communication problems, and additional or alternative deficits in other cognitive abilities impact on the development of structural language skills. Full article
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Open AccessCommunication
Corticospinal Excitability in Children with Congenital Hemiparesis
Brain Sci. 2016, 6(4), 49; doi:10.3390/brainsci6040049 -
Abstract
Transcranial magnetic stimulation (TMS) can be used as an assessment or intervention to evaluate or influence brain activity in children with hemiparetic cerebral palsy (CP) commonly caused by perinatal stroke. This communication report analyzed data from two clinical trials using TMS to assess
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Transcranial magnetic stimulation (TMS) can be used as an assessment or intervention to evaluate or influence brain activity in children with hemiparetic cerebral palsy (CP) commonly caused by perinatal stroke. This communication report analyzed data from two clinical trials using TMS to assess corticospinal excitability in children and young adults with hemiparetic CP. The results of this communication revealed a higher probability of finding a motor evoked potential (MEP) on the non-lesioned hemisphere compared to the lesioned hemisphere (p = 0.005). The resting motor threshold (RMT) was lower on the non-lesioned hemisphere than the lesioned hemisphere (p = 0.013). There was a significantly negative correlation between age and RMT (rs = −0.65, p = 0.003). This communication provides information regarding MEP responses, motor thresholds (MTs) and the association with age during TMS assessment in children with hemiparetic CP. Such findings contribute to the development of future pediatric studies in neuroplasticity and neuromodulation to influence motor function and recovery after perinatal stroke. Full article
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Open AccessArticle
Vocal Tremor: Novel Therapeutic Target for Deep Brain Stimulation
Brain Sci. 2016, 6(4), 48; doi:10.3390/brainsci6040048 -
Abstract
Tremulous voice is characteristically associated with essential tremor, and is referred to as essential vocal tremor (EVT). Current estimates suggest that up to 40% of individuals diagnosed with essential tremor also present with EVT, which is associated with an impaired quality of life.
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Tremulous voice is characteristically associated with essential tremor, and is referred to as essential vocal tremor (EVT). Current estimates suggest that up to 40% of individuals diagnosed with essential tremor also present with EVT, which is associated with an impaired quality of life. Traditional EVT treatments have demonstrated limited success in long-term management of symptoms. However, voice tremor has been noted to decrease in patients receiving deep brain stimulation (DBS) with the targeting of thalamic nuclei. In this study, we describe our multidisciplinary procedure for awake, frameless DBS with optimal stimulation targets as well as acoustic analysis and laryngoscopic assessment to quantify tremor reduction. Finally, we investigate the most recent clinical evidence regarding the procedure. Full article
Open AccessReview
Rescue Procedures after Suboptimal Deep Brain Stimulation Outcomes in Common Movement Disorders
Brain Sci. 2016, 6(4), 46; doi:10.3390/brainsci6040046 -
Abstract
Deep brain stimulation (DBS) is a unique, functional neurosurgical therapy indicated for medication refractory movement disorders as well as some psychiatric diseases. Multicontact electrodes are placed in “deep” structures within the brain with targets varying depending on the surgical indication. An implanted programmable
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Deep brain stimulation (DBS) is a unique, functional neurosurgical therapy indicated for medication refractory movement disorders as well as some psychiatric diseases. Multicontact electrodes are placed in “deep” structures within the brain with targets varying depending on the surgical indication. An implanted programmable pulse generator supplies the electrodes with a chronic, high frequency electrical current that clinically mimics the effects of ablative lesioning techniques. DBS’s efficacy has been well established for its movement disorder indications (Parkinson’s disease, essential tremor, and dystonia). However, clinical outcomes are sometimes suboptimal, even in the absence of common, potentially reversible complications such as hardware complications, infection, poor electrode placement, and poor programming parameters. This review highlights some of the rescue procedures that have been explored in suboptimal DBS cases for Parkinson’s disease, essential tremor, and dystonia. To date, the data is limited and difficult to generalize, but a large majority of published reports demonstrate positive results. The decision to proceed with such treatments should be made on a case by case basis. Larger studies are needed to clearly establish the benefit of rescue procedures and to establish for which patient populations they may be most appropriate. Full article
Open AccessReview
Disorders of Consciousness: Painless or Painful Conditions?—Evidence from Neuroimaging Studies
Brain Sci. 2016, 6(4), 47; doi:10.3390/brainsci6040047 -
Abstract
The experience of pain in disorders of consciousness is still debated. Neuroimaging studies, using functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET), multichannel electroencephalography (EEG) and laser-evoked potentials, suggest that the perception of pain increases with the level of consciousness. Brain activation
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The experience of pain in disorders of consciousness is still debated. Neuroimaging studies, using functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET), multichannel electroencephalography (EEG) and laser-evoked potentials, suggest that the perception of pain increases with the level of consciousness. Brain activation in response to noxious stimuli has been observed in patients with unresponsive wakefulness syndrome (UWS), which is also referred to as a vegetative state (VS), as well as those in a minimally conscious state (MCS). However, all of these techniques suggest that pain-related brain activation patterns of patients in MCS more closely resemble those of healthy subjects. This is further supported by fMRI findings showing a much greater functional connectivity within the structures of the so-called pain matrix in MCS as compared to UWS/VS patients. Nonetheless, when interpreting the results, a distinction is necessary between autonomic responses to potentially harmful stimuli and conscious experience of the unpleasantness of pain. Even more so if we consider that the degree of residual functioning and cortical connectivity necessary for the somatosensory, affective and cognitive-evaluative components of pain processing are not yet clear. Although procedurally challenging, the particular value of the aforementioned techniques in the assessment of pain in disorders of consciousness has been clearly demonstrated. The study of pain-related brain activation and functioning can contribute to a better understanding of the networks underlying pain perception while addressing clinical and ethical questions concerning patient care. Further development of technology and methods should aim to increase the availability of neuroimaging, objective assessment of functional connectivity and analysis at the level of individual cases as well as group comparisons. This will enable neuroimaging to truly become a clinical tool to reliably investigate pain in severely brain-injured patients as well as an asset for research. Full article
Open AccessArticle
The Cluster Variation Method: A Primer for Neuroscientists
Brain Sci. 2016, 6(4), 44; doi:10.3390/brainsci6040044 -
Abstract
Effective Brain–Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial
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Effective Brain–Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial that will help them to understand how the CVM statistical thermodynamics formulation can model 2-D pattern distributions expressing structural and functional dynamics in the brain. The premise is that local-in-time free energy minimization works alongside neural connectivity adaptation, supporting the development and stabilization of consistent stimulus-specific responsive activation patterns. The equilibrium distribution of local patterns, or configuration variables, is defined in terms of a single interaction enthalpy parameter (h) for the case of an equiprobable distribution of bistate (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for the case of non-equiprobable distribution) yields equilibrium configuration variable values. Modeling 2-D neural activation distribution patterns with the representational layer of a computational engine, we can thus correlate variational free energy minimization with specific configuration variable distributions. The CVM triplet configuration variables also map well to the notion of a M = 3 functional motif. This paper addresses the special case of an equiprobable unit distribution, for which an analytic solution can be found. Full article
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Open AccessArticle
Effect of Experimental Cutaneous Hand Pain on Corticospinal Excitability and Short Afferent Inhibition
Brain Sci. 2016, 6(4), 45; doi:10.3390/brainsci6040045 -
Abstract
Sensorimotor integration is altered in people with chronic pain. While there is substantial evidence that pain interferes with neural activity in primary sensory and motor cortices, much less is known about its impact on integrative sensorimotor processes. Here, the short latency afferent inhibition
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Sensorimotor integration is altered in people with chronic pain. While there is substantial evidence that pain interferes with neural activity in primary sensory and motor cortices, much less is known about its impact on integrative sensorimotor processes. Here, the short latency afferent inhibition (SAI) paradigm was used to assess sensorimotor integration in the presence and absence of experimental cutaneous heat pain applied to the hand. Ulnar nerve stimulation was combined with transcranial magnetic stimulation to condition motor evoked potentials (MEPs) in the first dorsal interosseous muscle. Four interstimulus intervals (ISI) were tested, based on the latency of the N20 component of the afferent sensory volley (N20−5 ms, N20+2 ms, N20+4 ms, N20+10 ms). In the PAIN condition, MEPs were smaller compared to the NEUTRAL condition (p = 0.005), and were modulated as a function of the ISI (p = 0.012). Post-hoc planned comparisons revealed that MEPs at N20+2 and N20+4 were inhibited compared to unconditioned MEPs. However, the level of inhibition (SAI) was similar in the PAIN and NEUTRAL conditions. This suggests that the interplay between pain and sensorimotor integration is not mediated through direct and rapid pathways as assessed by SAI, but rather might involve higher-order integrative areas. Full article
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Open AccessArticle
Prenatal Ethanol Exposure and Whisker Clipping Disrupt Ultrasonic Vocalizations and Play Behavior in Adolescent Rats
Brain Sci. 2016, 6(4), 43; doi:10.3390/brainsci6040043 -
Abstract
Prenatal ethanol exposure can result in social deficits in humans and animals, including altered social interaction and poor communication. Rats exposed to ethanol prenatally show reduced play fighting, and a combination of prenatal ethanol exposure and neonatal whisker clipping further reduces play fighting
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Prenatal ethanol exposure can result in social deficits in humans and animals, including altered social interaction and poor communication. Rats exposed to ethanol prenatally show reduced play fighting, and a combination of prenatal ethanol exposure and neonatal whisker clipping further reduces play fighting compared with ethanol exposure alone. In this study, we explored whether expression of hedonic ultrasonic vocalizations (USVs) correlated with the number of playful attacks by ethanol-exposed rats, rats subjected to postnatal sensory deprivation by whisker clipping or both compared to control animals. In normally developing rats, hedonic USVs precede such interactions and correlate with the number of play interactions exhibited in dyads. Pregnant Long-Evans rats were fed an ethanol-containing liquid diet or a control diet. After birth, male and female pups from each litter were randomly assigned to the whisker-clipped or non-whisker-clipped condition. Animals underwent a social interaction test with a normally developing play partner during early or late-adolescence. USVs were recorded during play. Prenatal ethanol exposure reduced both play and hedonic USVs in early adolescence compared to control rats and persistently reduced social play. Interestingly, ethanol exposure, whisker clipping and the combination abolished the significant correlation between hedonic USVs and social play detected in control rats in early adolescence. This relationship remained disrupted in late adolescence only in rats subjected to both prenatal ethanol and whisker clipping. Thus, both insults more persistently disrupted the relationship between social communication and social play. Full article
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Open AccessArticle
Morphology of Donor and Recipient Nerves Utilised in Nerve Transfers to Restore Upper Limb Function in Cervical Spinal Cord Injury
Brain Sci. 2016, 6(4), 42; doi:10.3390/brainsci6040042 -
Abstract
Loss of hand function after cervical spinal cord injury (SCI) impacts heavily on independence. Multiple nerve transfer surgery has been applied successfully after cervical SCI to restore critical arm and hand functions, and the outcome depends on nerve integrity. Nerve integrity is assessed
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Loss of hand function after cervical spinal cord injury (SCI) impacts heavily on independence. Multiple nerve transfer surgery has been applied successfully after cervical SCI to restore critical arm and hand functions, and the outcome depends on nerve integrity. Nerve integrity is assessed indirectly using muscle strength testing and intramuscular electromyography, but these measures cannot show the manifestation that SCI has on the peripheral nerves. We directly assessed the morphology of nerves biopsied at the time of surgery, from three patients within 18 months post injury. Our objective was to document their morphologic features. Donor nerves included teres minor, posterior axillary, brachialis, extensor carpi radialis brevis and supinator. Recipient nerves included triceps, posterior interosseus (PIN) and anterior interosseus nerves (AIN). They were fixed in glutaraldehyde, processed and embedded in Araldite Epon for light microscopy. Eighty percent of nerves showed abnormalities. Most common were myelin thickening and folding, demyelination, inflammation and a reduction of large myelinated axon density. Others were a thickened perineurium, oedematous endoneurium and Renaut bodies. Significantly, very thinly myelinated axons and groups of unmyelinated axons were observed indicating regenerative efforts. Abnormalities exist in both donor and recipient nerves and they differ in appearance and aetiology. The abnormalities observed may be preventable or reversible. Full article
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Open AccessReview
Immunomodulators as Therapeutic Agents in Mitigating the Progression of Parkinson’s Disease
Brain Sci. 2016, 6(4), 41; doi:10.3390/brainsci6040041 -
Abstract
Parkinson’s disease (PD) is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of
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Parkinson’s disease (PD) is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of PD, and are implicated in the cell death in this region. Neuroinflammation is evidently involved in PD pathology and mitigating the inflammatory cascade has been a therapeutic strategy. Age is the number one risk factor for PD and thus needs to be considered in the context of disease pathology. Here, we discuss the role of neuroinflammation within the context of aging as it applies to the development of PD, and the potential for two representative compounds, fractalkine and astaxanthin, to attenuate the pathophysiology that modulates neurodegeneration that occurs in Parkinson’s disease. Full article
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Open AccessOpinion
Deep Brain Stimulation: In Search of Reliable Instruments for Assessing Complex Personality-Related Changes
Brain Sci. 2016, 6(3), 40; doi:10.3390/brainsci6030040 -
Abstract
During the last 25 years, more than 100,000 patients have been treated with Deep Brain Stimulation (DBS). While human clinical and animal preclinical research has shed light on the complex brain-signaling disturbances that underpin e.g., Parkinson’s disease (PD), less information is available when
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During the last 25 years, more than 100,000 patients have been treated with Deep Brain Stimulation (DBS). While human clinical and animal preclinical research has shed light on the complex brain-signaling disturbances that underpin e.g., Parkinson’s disease (PD), less information is available when it comes to complex psychosocial changes following DBS interventions. In this contribution, we propose to more thoroughly investigate complex personality-related changes following deep brain stimulation through refined and reliable instruments in order to help patients and their relatives in the post-surgery phase. By pursuing this goal, we first outline the clinical importance DBS has attained followed by discussing problematic and undesired non-motor problems that accompany some DBS interventions. After providing a brief definition of complex changes, we move on by outlining the measurement problem complex changes relating to non-motor symptoms currently are associated with. The latter circumstance substantiates the need for refined instruments that are able to validly assess personality-related changes. After providing a brief paragraph with regard to conceptions of personality, we argue that the latter is significantly influenced by certain competencies which themselves currently play only a tangential role in the clinical DBS-discourse. Increasing awareness of the latter circumstance is crucial in the context of DBS because it could illuminate a link between competencies and the emergence of personality-related changes, such as new-onset impulse control disorders that have relevance for patients and their relatives. Finally, we elaborate on the field of application of instruments that are able to measure personality-related changes. Full article
Open AccessArticle
Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study
Brain Sci. 2016, 6(3), 39; doi:10.3390/brainsci6030039 -
Abstract
New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and
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New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode. Full article
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Open AccessReview
Deep Brain Stimulation in Huntington’s Disease—Preliminary Evidence on Pathophysiology, Efficacy and Safety
Brain Sci. 2016, 6(3), 38; doi:10.3390/brainsci6030038 -
Abstract
Huntington’s disease (HD) is one of the most disabling degenerative movement disorders, as it not only affects the motor system but also leads to cognitive disabilities and psychiatric symptoms. Deep brain stimulation (DBS) of the pallidum is a promising symptomatic treatment targeting the
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Huntington’s disease (HD) is one of the most disabling degenerative movement disorders, as it not only affects the motor system but also leads to cognitive disabilities and psychiatric symptoms. Deep brain stimulation (DBS) of the pallidum is a promising symptomatic treatment targeting the core motor symptom: chorea. This article gives an overview of preliminary evidence on pathophysiology, safety and efficacy of DBS in HD. Full article
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