Permanent isolated micrographia from traumatic basal ganglia injury.

Micrographia is a rare neurological finding in isolation. Most cases of isolated micrographia have been found in association with focal ischemia of the left basal ganglia. Here, we present a case of post-traumatic micrographia stemming from contusion to the left basal ganglia.

The nature of facilitation and interference in the multilingual language system: insights from treatment in a case of trilingual aphasia.

The rehabilitation study described here sets out to test the premise of Abutalebi and Green's neurocognitive model--specifically, that language selection and control are components of overall cognitive control. We follow a trilingual woman (first language, L1: Amharic; second language, L2: English; third language, L3: French) with damage to the left frontal lobe and left basal ganglia who presented with cognitive control and naming deficits, through two periods of semantic treatment (French, followed by English) to alleviate naming deficits. The results showed that while the participant improved on trained items, she did not show within- or cross-language generalization. In addition, error patterns revealed a substantial increase of interference of the currently trained language into the nontrained language during each of the two treatment phases. These results are consistent with Abutalebi and Green's neurocognitive model and support the claim that language selection and control are components of overall cognitive control.

Single fetal demise in monochorionic pregnancies: incidence and patterns of cerebral injury.

OBJECTIVE: To evaluate the incidence, type and severity of cerebral injury in the surviving monochorionic (MC) cotwin after single fetal demise in twin pregnancies. METHODS: All MC pregnancies with single fetal demise that were evaluated at the Leiden University Medical Center between 2002 and 2013 were included. Perinatal characteristics, neonatal outcome and the presence of cerebral injury, observed on neuroimaging, were recorded for all cotwin survivors. RESULTS: A total of 49 MC pregnancies with single fetal demise, including one MC triplet, were included in the study (n = 50 cotwins). Median gestational age at occurrence of single fetal demise was 25 weeks and median interval between single fetal demise and live birth was 61 days, with a median gestational age at birth of 36 weeks. Severe cerebral injury was diagnosed in 13 (26%) of the 50 cotwins and was detected antenatally in 4/50 (8%) and postnatally in 9/50 (18%) cases. Cerebral injury was mostly due to hypoxic-ischemic injury resulting in cystic periventricular leukomalacia, middle cerebral artery infarction or injury to basal ganglia, thalamus and/or cortex. Risk factors associated with severe cerebral injury were advanced gestational age at the occurrence of single fetal demise (odds ratio (OR), 1.14 (95% CI, 1.01-1.29) for each week of gestation; P = 0.03), twin-twin transfusion syndrome developing prior to single fetal demise (OR, 5.0 (95% CI, 1.30-19.13); P = 0.02) and a lower gestational age at birth (OR, 0.83 (95% CI, 0.69-0.99) for each week of gestation; P = 0.04). CONCLUSIONS: Single fetal demise in MC pregnancies is associated with severe cerebral injury occurring in 1 in 4 surviving cotwins. Routine antenatal and postnatal neuroimaging, followed by standardized long-term follow-up, is mandatory.

The effect of claustrum lesions on human consciousness and recovery of function.

Crick and Koch proposed that the claustrum plays a crucial role in consciousness. Their proposal was based on the structure and connectivity of the claustrum that suggested it had a role in coordinating a set of diverse brain functions. Given the few human studies investigating this claim, we decided to study the effects of claustrum lesions on consciousness in 171 combat veterans with penetrating traumatic brain injuries. Additionally, we studied the effects of claustrum lesions and loss of consciousness on long-term cognitive abilities. Claustrum damage was associated with the duration, but not frequency, of loss of consciousness, indicating that the claustrum may have an important role in regaining, but not maintaining, consciousness. Total brain volume loss, but not claustrum lesions, was associated with long-term recovery of neurobehavioral functions. Our findings constrain the current understanding of the neurobehavioral functions of the claustrum and its role in maintaining and regaining consciousness.

Differential expression of synaptic proteins in unilateral 6-OHDA lesioned rat model-A comparative proteomics approach.

Parkinson's disease (PD) is characterized as a movement disorder due to lesions in the basal ganglia. As the major input region of the basal ganglia, striatum plays a vital role in coordinating movements. It receives afferents from the cerebral cortex and projects afferents to the internal segment of the globus pallidus and substantia nigra pars reticulate. Additionally, accumulating evidences support a role for synaptic dysfunction in PD. Therefore, the present study explores the changes in protein abundance involved in synaptic disorders in unilateral lesioned 6-OHDA rat model. Based on (18) O/(16) O-labeling technique, striatal proteins were separated using online 2D-LC, and identified by nano-ESI-quadrupole-TOF. A total of 370 proteins were identified, including 76 significantly differentially expressed proteins. Twenty-two downregulated proteins were found in composition of vesicle, ten of which were involved in neuronal transmission and recycling across synapses. These include N-ethylmaleimide-sensitive fusion protein attachment receptor proteins (SNAP-25, syntaxin-1A, syntaxin-1B, VAMP2), synapsin-1, septin-5, clathrin heavy chain 1, AP-2 complex subunit beta, dynamin-1, and endophilin-A1. Moreover, MS result for syntaxin-1A was confirmed by Western blot analysis. Overall, these synaptic changes induced by neurotoxin may serve as a reference for understanding the functional mechanism of striatum in PD.

Oculomotor disturbances in HIV-positive individuals treated with methadone.

INTRODUCTION: Methadone substitution is claimed to be the most effective way of pharmacological management of human immunodeficiency virus (HIV) positive patients addicted to opioids. Possible and clinically the most relevant drug interactions are those between methadone and antiretroviral agents [13,18,25,32]. HIV causes cognitive impairment by infiltrating the central nervous system (CNS) in the initial phase of infection. The consequence of this is damage to the hippocampus, caudate nucleus, and basal ganglia [2,26]. METHODS: Eighty-six patients from the substitution program group were examined. The trial was conducted twice: before and about 1.5 hours after the administration of a therapeutic dose of methadone. The antisaccades task (AT) and latency task (LT) were performed using a saccadometer diagnostic system. RESULTS: The statistical analysis showed that the mean duration of latency measured by AT in HIV(-) and HIV(+) subjects after the administration of a therapeutic dose of methadone was significantly increased (p=0.03 HIV(-); p=0.04 HIV(+)). There was a statistically significant increase in the mean latency after the administration of methadone in HIV(+) subjects when compared to the control group measured by LT (p=0.03). CONCLUSION: The statistical analysis confirms the change in the saccadic refixation parameters in patients addicted to opioids. Methadone influences saccadic dynamic parameters less in HIV(+) than in HIV(-) drug users. Oculomotor disturbances are probably related to the neurotropic effects of HIV leading to damage of the striatum, which plays an important role in psychomotor functions.

Levodopa treatment of late onset extrapyramidal movements in a child after high voltage electrocution.

We present the case of a 12-year-old girl with abnormal extrapyramidal movements associated with basal ganglia lesions after electrical injury. After her injury, our patient initially did well and recovered from acute cardiovascular and hemodynamic instability, and the results of her neurological examination, head computed tomography scan, and electroencephalogram were normal on discharge from hospital. Two weeks after discharge, she developed extrapyramidal movements, and head magnetic resonance imaging showed areas of bilateral, symmetrical enhanced associated with signal intensity in the basal ganglia, hypoxic encephalopathy, and cerebral edema that may have occurred secondary to the cardiopulmonary arrest that she suffered immediately after her accident. The symptoms disappeared after low dose levodopa was instituted and have not recurred during the 15 months of treatment. Injury and death from electric current, although rare, are not uncommon and occur mostly as a result of accidental contact with a live wire. This is the first case report documenting the use of levodopa for extrapyramidal movements secondary to high-tension electrocution.

[Forensic medical assessment of the role of the injury and pathology in the development of basal subarachnoidal hemorrhage].

The comparative analysis of clinical and pathomorphological forensic medical literature and the original investigations of basal subarachnoidal hemorrhage carried out by the author during 25 years provided a basis for morphological diagnostics of traumatic and non-traumatic subarachnoidal hemorrhage with special reference to variants of forensic medical assessment of the role of injuries and pathologies in the development of basal subarachnoidal hemorrhage.

Dual pre-motor contribution to songbird syllable variation.

Many forms of learning, including songbird vocal learning, rely on the brain's ability to use pre-motor variation and sensory feedback to guide behavior toward a specific target or goal. In the vocal control system of zebra finches (Taeniopygia guttata) the pre-motor mechanisms of vocal variation are thought to be vested primarily in a neural pathway that includes the basal ganglia. A second circuit that includes avian analogues of mammalian pre-motor and motor cortex (the vocal motor pathway) generates the patterned structure of learned adult song. Here, we tested the ability of the basal ganglia pathway to generate pre-motor vocal variation within the spectral and temporal dimensions of zebra finch song structure. In adult birds, ablation of the basal ganglia pathway significantly reduced the spectral and temporal dispersion of individual song syllables, with the exception of syllable pitch, where the reduction was not statistically significant when compared against surgical controls. We found a similar pattern of results using longitudinal comparisons (juvenile vs adult) to isolate the contribution of the basal ganglia pathway to spectral dispersion in populations of developing song syllables--variation in syllable pitch was significantly smaller than in all other measured spectral features. The results indicate that pre-motor variation generated by the basal ganglia pathway may be sufficient to adjust vocal output toward highly acoustically dispersed targets of imitation, but suggest that complete acquisition of the pronounced variation in syllable pitch that characterizes adult song will necessitate a gradual developmental interaction between the basal ganglia and vocal motor pathways.

Ventral striatum and orbitofrontal cortex are both required for model-based, but not model-free, reinforcement learning.

In many cases, learning is thought to be driven by differences between the value of rewards we expect and rewards we actually receive. Yet learning can also occur when the identity of the reward we receive is not as expected, even if its value remains unchanged. Learning from changes in reward identity implies access to an internal model of the environment, from which information about the identity of the expected reward can be derived. As a result, such learning is not easily accounted for by model-free reinforcement learning theories such as temporal difference reinforcement learning (TDRL), which predicate learning on changes in reward value, but not identity. Here, we used unblocking procedures to assess learning driven by value- versus identity-based prediction errors. Rats were trained to associate distinct visual cues with different food quantities and identities. These cues were subsequently presented in compound with novel auditory cues and the reward quantity or identity was selectively changed. Unblocking was assessed by presenting the auditory cues alone in a probe test. Consistent with neural implementations of TDRL models, we found that the ventral striatum was necessary for learning in response to changes in reward value. However, this area, along with orbitofrontal cortex, was also required for learning driven by changes in reward identity. This observation requires that existing models of TDRL in the ventral striatum be modified to include information about the specific features of expected outcomes derived from model-based representations, and that the role of orbitofrontal cortex in these models be clearly delineated.

Adversive seizures associated with periodic lateralised epileptiform discharges (PLEDs) after left orbital contusion.

We report a patient who presented with adversive seizures associated with periodic lateralised epileptiform discharges (PLEDs), a month after head trauma. The PLEDs predominantly involving the left frontal contacts became more frequent at the onset of adversive seizures during EEG. Brain MRI demonstrated a contusion scar in the left orbital cortex with reduced diffusion, not only around this orbital lesion but also in the ipsilateral anteromedial thalamus. Single photon emission computed tomography revealed focal cerebral hyperperfusion in the left medial orbitofrontal region, basal ganglia, and thalamus. The abnormal metabolism involving the thalamus and striatum could be associated with the ipsilateral orbital contusion and might have been caused by cortical-subcortical, trans-synaptic hyperactivity. Further studies are warranted to determine the role of subcortical structures in the generation of PLEDs and adversive seizures. [Published with video sequences].

General movements in full-term infants with perinatal asphyxia are related to Basal Ganglia and thalamic lesions.

OBJECTIVE: To correlate the site and severity of brain lesions seen on magnetic resonance imaging (MRI) with the quality of general movements in term infants with hypoxic-ischemic encephalopathy (HIE) and compare the prognostic value of general movements and MRI for motor outcome. STUDY DESIGN: Early brain MRI scans in 34 term infants with HIE not treated with hypothermia were reviewed and scored for site of injury and lesion pattern by an experienced neuroradiologist. General movement quality and trajectories at 1 and 3 postnatal months were evaluated. Motor outcome was assessed at 24 months. RESULTS: MRI scores for the basal ganglia and thalami, posterior limb of the internal capsule, white matter, and cortex and lesion patterns were correlated with 1-month and 3-month general movements and general movement trajectories; central gray matter scores were correlated most strongly with cramped-synchronized general movements and abnormal motor outcome. MRI scores were 100% sensitive and 72.2% specific for motor outcome, and cramped-synchronized general movements were 100% specific and 68.7% sensitive for motor outcome. CONCLUSIONS: In term infants with HIE, the site and severity of brain lesions seen on early MRI are highly correlated with general movements. Central gray matter damage leads to cramped-synchronized general movements and poor motor outcome. Early MRI scans and general movements are complementary tools for predicting motor outcome.

Altered AMPA receptor expression with treadmill exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury.

Dopamine depletion leads to impaired motor performance and increased glutamatergic-mediated hyperexcitability of medium spiny neurons in the basal ganglia. Intensive treadmill exercise improves motor performance in both saline treatment and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. In the present study, we investigated the effect of high-intensity treadmill exercise on changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit expression, because these receptor channels confer the majority of fast excitatory neurotransmission in the brain, and their subunit composition provides a key mechanism for regulating synaptic strength and synaptic neuroplasticity and is important in modulating glutamatergic neurotransmission. Within the dorsolateral striatum of MPTP mice, treadmill exercise increased GluR2 subunit expression, with no significant effect on GluR1. Furthermore, neurophysiological studies demonstrated a reduction in the size of excitatory postsynaptic currents (EPSCs) in striatal medium spiny neurons (as determined by the input-output relationship), reduced amplitude of spontaneous EPSCs, and a loss of polyamine-sensitive inward rectification, all supportive of an increase in heteromeric AMPAR channels containing the GluR2 subunit. Phosphorylation of GluR2 at serine 880 in both saline-treated and MPTP mice suggests that exercise may also influence AMPAR trafficking and thus synaptic strength within the striatum. Finally, treadmill exercise also altered flip isoforms of GluR2 and GluR1 mRNA transcripts. These findings suggest a role for AMPARs in mediating the beneficial effects of exercise and support the idea that adaptive changes in GluR2 subunit expression may be important in modulating experience-dependent neuroplasticity of the injured basal ganglia.

Involvement of the limbic basal ganglia in ethanol withdrawal convulsivity in mice is influenced by a chromosome 4 locus.

Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains ethanol (alcohol) use/abuse and may contribute to relapse in alcoholics. Although no animal model duplicates alcoholism, models for specific factors, like the withdrawal syndrome, are useful for identifying potential genetic and neural determinants of liability in humans. We generated congenic mice that confirm a quantitative trait locus (QTL) on chromosome 4 with a large effect on predisposition to alcohol withdrawal. Using c-Fos expression as a high-resolution marker of neuronal activation, congenic mice demonstrated significantly less neuronal activity associated with ethanol withdrawal than background strain mice in the substantia nigra pars reticulata (SNr), subthalamic nucleus (STN), rostromedial lateral globus pallidus, and ventral pallidum. Notably, neuronal activation in subregions of the basal ganglia associated with limbic function was more intense than in subregions associated with sensorimotor function. Bilateral lesions of caudolateral SNr attenuated withdrawal severity after acute and repeated ethanol exposures, whereas rostrolateral SNr and STN lesions did not reduce ethanol withdrawal severity. Caudolateral SNr lesions did not affect pentylenetetrazol-enhanced convulsions. Our results suggest that this QTL impacts ethanol withdrawal via basal ganglia circuitry associated with limbic function and that the caudolateral SNr plays a critical role. These are the first analyses to elucidate circuitry by which a confirmed addiction-relevant QTL influences behavior. This mouse QTL is syntenic with human chromosome 9p. Given the growing body of evidence that a gene(s) on chromosome 9p influences alcoholism, our results can facilitate human research on alcohol dependence and withdrawal.

Motor sequence chunking is impaired by basal ganglia stroke.

Our main aim was to determine whether individuals with stroke that affected the basal ganglia, organized movement sequences into chunks in the same fashion as neurologically intact individuals. To address this question, we compared motor response times during the performance of repeated sequences that were learned, and thus may be planned in advance, with random sequences where there is minimal if any advance preparation or organization of responses. The pattern of responses illustrated that, after basal ganglia stroke, individuals do not chunk elements of the repeated sequence into functional sub-sequences of movement to the same extent as neurologically intact age-matched people. Limited chunking of learned movements after stroke may explain past findings that show overall slower responses even when sequences of action are learned by this population. Further, our data in combination with other work, suggest that chunking may be a function of the basal ganglia.

Effects of treadmill exercise on dopaminergic transmission in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury.

Studies have suggested that there are beneficial effects of exercise in patients with Parkinson's disease, but the underlying molecular mechanisms responsible for these effects are poorly understood. Studies in rodent models provide a means to examine the effects of exercise on dopaminergic neurotransmission. Using intensive treadmill exercise, we determined changes in striatal dopamine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse. C57BL/6J mice were divided into four groups: (1) saline, (2) saline plus exercise, (3) MPTP, and (4) MPTP plus exercise. Exercise was started 5 d after MPTP lesioning and continued for 28 d. Treadmill running improved motor velocity in both exercise groups. All exercised animals also showed increased latency to fall (improved balance) using the accelerating rotarod compared with nonexercised mice. Using HPLC, we found no difference in striatal dopamine tissue levels between MPTP plus exercise compared with MPTP mice. There was an increase detected in saline plus exercise mice. Analyses using fast-scan cyclic voltammetry showed increased stimulus-evoked release and a decrease in decay of dopamine in the dorsal striatum of MPTP plus exercise mice only. Immunohistochemical staining analysis of striatal tyrosine hydroxylase and dopamine transporter proteins showed decreased expression in MPTP plus exercise mice compared with MPTP mice. There were no differences in mRNA transcript expression in midbrain dopaminergic neurons between these two groups. However, there was diminished transcript expression in saline plus exercise compared with saline mice. Our findings suggest that the benefits of treadmill exercise on motor performance may be accompanied by changes in dopaminergic neurotransmission that are different in the injured (MPTP-lesioned) compared with the noninjured (saline) nigrostriatal system.

Memory, mood, dopamine, and serotonin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury.

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse serves as a model of basal ganglia injury and Parkinson's disease. The present study investigated the effects of MPTP-induced lesioning on associative memory, conditioned fear, and affective behavior. Male C57BL/6 mice were administered saline or MPTP and separate groups were evaluated at either 7 or 30 days post-lesioning. In the social transmission of food preference test, mice showed a significant decrease in preference for familiar food 30 days post-MPTP compared to controls. Mice at both 7 and 30 days post-MPTP lesioning had increased fear extinction compared to controls. High Performance Liquid Chromatography analysis of tissues homogenates showed dopamine and serotonin were depleted in the striatum, frontal cortex, and amygdala. No changes in anxiety or depression were detected by the tail suspension, sucrose preference, light-dark preference, or hole-board tests. In conclusion, acute MPTP lesioning regimen in mice causes impairments in associative memory and conditioned fear, no mood changes, and depletion of dopamine and serotonin throughout the brain.

Management of Penetrating Brain Injury Caused by a Nail Gun: Three Case Reports and Literature Review.

BACKGROUND: Penetrating brain injury (PBI) caused by a nail gun is an extremely rare neurosurgical emergency that poses a challenge for neurosurgeons because of its rarity and complexity. CASE DESCRIPTION: Here we present 3 cases of PBI caused by a nail gun. In the first case, the nail entered through the right parietal bone and lodged in the right parietal lobe and basal ganglia. In the second case, the nail entered through the right occipital bone and lodged in the right occipital lobe. In the third case, the nail entered through the right parietal bone and lodged in the right frontal and parietal lobes. All patients underwent surgical removal of the nail. The first patient presented with reduced left-side strength, whereas the second and third patients were neurologically intact on presentation. CONCLUSIONS: PBI caused by a nail gun can present with differing clinical manifestations, and most cases require immediate surgery. A rational management strategy should provide a good postoperative prognosis with minimal neurologic deficits in these patients.

Abulia following penetrating brain injury during endoscopic sinus surgery with disruption of the anterior cingulate circuit: case report.

BACKGROUND: It is common knowledge that the frontal lobes mediate complex human behavior and that damage to these regions can cause executive dysfunction, apathy, disinhibition and personality changes. However, it is less well known that subcortical structures such as the caudate and thalamus are part of functionally segregated fronto-subcortical circuits, that can also alter behavior after injury. CASE PRESENTATION We present a 57 year old woman who suffered penetrating brain injury during endoscopic sinus surgery causing right basal ganglia injury which resulted in an abulic syndrome. CONCLUSION: Abulia does not result solely from cortical injury but can occur after disruption anywhere in the anterior cingulate circuit--in the case of our patient, most prominently at the right caudate.