Electrical Stimulation of the Mesencephalic Locomotor Region Has No Impact on Blood-Brain Barrier Alterations after Cerebral Photothrombosis in Rats.

Blood-brain barrier (BBB) disruption is a critical event after ischemic stroke, which results in edema formation and hemorrhagic transformation of infarcted tissue. BBB dysfunction following stroke is partly mediated by proinflammatory agents. We recently have shown that high frequency stimulation of the mesencephalic locomotor region (MLR-HFS) exerts an antiapoptotic and anti-inflammatory effect in the border zone of cerebral photothrombotic stroke in rats. Whether MLR-HFS also has an impact on BBB dysfunction in the early stage of stroke is unknown. In this study, rats were subjected to photothrombotic stroke of the sensorimotor cortex and implantation of a stimulating microelectrode into the ipsilesional MLR. Thereafter, either HFS or sham stimulation of the MLR was applied for 24 h. After scarifying the rats, BBB disruption was assessed by determining albumin extravasation and tight junction integrity (claudin 3, claudin 5, and occludin) using Western blot analyses and immunohistochemistry. In addition, by applying zymography, expression of pro-metalloproteinase-9 (pro-MMP-9) was analyzed. No differences were found regarding infarct size and BBB dysfunction between stimulated and unstimulated animals 24 h after induction of stroke. Our results indicate that MLR-HFS neither improves nor worsens the damaged BBB after stroke. Attenuating cytokines/chemokines in the perilesional area, as mediated by MLR-HFS, tend to play a less significant role in preventing the BBB integrity.

Current understanding of photophobia, visual networks and headaches.

OBJECTIVE: To review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders. BACKGROUND: Photophobia is a poorly understood light-induced phenomenon that emerges in a variety of neurological and ophthalmological conditions. Over the years, multiple mechanisms have been proposed to explain its causes; however, scarce research and lack of systematic assessment of photophobia in patients has made the search for answers quite challenging. In the field of headaches, significant progress has been made recently on how specific visual networks contribute to photophobia features such as light-induced intensification of headache, increased perception of brightness and visual discomfort, which are frequently experienced by migraineurs. Such progress improved our understanding of the phenomenon and points to abnormal processing of light by both cone/rod-mediated image-forming and melanopsin-mediated non-image-forming visual pathways, and the consequential transfer of photic signals to multiple brain regions involved in sensory, autonomic and emotional regulation. CONCLUSION: Photophobia phenotype is diverse, and the relative contribution of visual, trigeminal and autonomic systems may depend on the disease it emerges from. In migraine, photophobia could result from photic activation of retina-driven pathways involved in the regulation of homeostasis, making its association with headache more complex than previously thought.

Yin-and-yang bifurcation of opioidergic circuits for descending analgesia at the midbrain of the mouse.

In the descending analgesia pathway, opioids are known to disinhibit the projections from the periaqueductal gray (PAG) to the rostral ventromedial medulla (RVM), leading to suppression of pain signals at the spinal cord level. The locus coeruleus (LC) has been proposed to engage in the descending pathway through noradrenergic inputs to the spinal cord. Nevertheless, how the LC is integrated in the descending analgesia circuit has remained unknown. Here, we show that the opioidergic analgesia pathway is bifurcated in structure and function at the PAG. A knockout as well as a PAG-specific knockdown of phospholipase C ß4 (PLCß4), a signaling molecule for G protein-coupled receptors, enhanced swim stress-induced and morphine-induced analgesia in mice. Immunostaining after simultaneous retrograde labeling from the RVM and the LC revealed two mutually exclusive neuronal populations at the PAG, each projecting either to the LC or the RVM, with PLCß4 expression only in the PAG-LC projecting cells that provide a direct synaptic input to LC-spinal cord (SC) projection neurons. The PAG-LC projection neurons in wild-type mice turned quiescent in response to opiates, but remained active in the PLCß4 mutant, suggesting a possibility that an increased adrenergic function induced by the persistent PAG-LC activity underlies the enhanced opioid analgesia in the mutant. Indeed, the enhanced analgesia in the mutant was reversed by blocking α2-noradrenergic receptors. These findings indicate that opioids suppress descending analgesia through the PAG-LC pathway, while enhancing it through the PAG-RVM pathway, i.e., two distinct pathways with opposing effects on opioid analgesia. These results point to a therapeutic target in pain control.

Olfactory vector hypothesis for encephalitis lethargica.

Viruses have long been implicated in the pathogenesis of classical encephalitis lethargica, which was first described by Constantin von Economo in 1917. In this article, I propose the hypothesis that an airborne virus travels along the olfactory conduit to infect the olfactory bulb; this local infection or induced neuroinflammation, in turn, retrogradely targets certain neuronal populations with sleep-wake regulatory functions in the hypothalamus and midbrain, leading to the development of wakeful inactivity, a hallmark clinical feature of the disease. Furthermore, the olfactory vector hypothesis may also explain the pathomechanism of the debilitating complication of the disease, i.e., postencephalitic parkinsonism, in terms of a recently discovered nigro-olfactory projection.

Intrinsic functional connectivity alterations in progressive supranuclear palsy: Differential effects in frontal cortex, motor, and midbrain networks.

BACKGROUND: The topography of functional network changes in progressive supranuclear palsy can be mapped by intrinsic functional connectivity MRI. The objective of this study was to study functional connectivity and its clinical and behavioral correlates in dedicated networks comprising the cognition-related default mode and the motor and midbrain functional networks in patients with PSP. METHODS: Whole-brain-based "resting-state" functional MRI and high-resolution T1-weighted magnetic resonance imaging data together with neuropsychological and video-oculographic data from 34 PSP patients (22 with Richardson subtype and 12 with parkinsonian subtype) and 35 matched healthy controls were subjected to network-based functional connectivity and voxel-based morphometry analysis. RESULTS: After correction for global patterns of brain atrophy, the group comparison between PSP patients and controls revealed significantly decreased functional connectivity (P < 0.05, corrected) in the prefrontal cortex, which was significantly correlated with cognitive performance (P = 0.006). Of note, midbrain network connectivity in PSP patients showed increased connectivity with the thalamus, on the one hand, whereas, on the other hand, lower functional connectivity within the midbrain was significantly correlated with vertical gaze impairment, as quantified by video-oculography (P = 0.004). PSP Richardson subtype showed significantly increased functional motor network connectivity with the medial prefrontal gyrus. CONCLUSIONS: PSP-associated neurodegeneration was attributed to both decreased and increased functional connectivity. Decreasing functional connectivity was associated with worse behavioral performance (ie, dementia severity and gaze palsy), whereas the pattern of increased functional connectivity may be a potential adaptive mechanism. © 2017 International Parkinson and Movement Disorder Society.

Circadian Rhythms and Substance Abuse: Chronobiological Considerations for the Treatment of Addiction.

Reward-related learning, including that associated with drugs of abuse, is largely mediated by the dopaminergic mesolimbic pathway. Mesolimbic neurophysiology and motivated behavior, in turn, are modulated by the circadian timing system which generates ∼24-h rhythms in cellular activity. Both drug taking and seeking and mesolimbic dopaminergic neurotransmission can vary widely over the day. Moreover, circadian clock genes are expressed in ventral tegmental area dopaminergic cells and in mesolimbic target regions where they can directly modulate reward-related neurophysiology and behavior. There also exists a reciprocal influence between drug taking and circadian timing as the administration of drugs of abuse can alter behavioral rhythms and circadian clock gene expression in mesocorticolimbic structures. These interactions suggest that manipulations of the circadian timing system may have some utility in the treatment of substance abuse disorders. Here, the literature on bidirectional interactions between the circadian timing system and drug taking is briefly reviewed, and potential chronotherapeutic considerations for the treatment of addiction are discussed.

Thalamic hypoperfusion and disrupted cerebral blood flow networks in idiopathic generalized epilepsy: Arterial spin labeling and graph theoretical analysis.

PURPOSE: The aim of this study was to investigate interictal cerebral blood flow (CBF) distributions and graph theoretical networks in idiopathic generalized epilepsy (IGE) using arterial spin labeling (ASL) imaging and anatomical covariance methods of graph theoretical analysis. MATERIAL AND METHODS: We recruited 19 patients with IGE and 19 age-/gender-matched healthy controls. Their CBF images were obtained by pseudo-continuous ASL imaging and compared using statistical parametric mapping 8 software (SPM8) and Graph Analysis Toolbox (GAT). RESULTS: The ASL imaging could detect interictal hypoperfusion in the thalamus, upper midbrain, and left cerebellum in IGE. Additionally, the graph theoretical analyses revealed characteristic findings of the CBF network of IGE, including significantly reduced resilience to attacks and changes of regional clustering especially in the bilateral temporo-occipital areas and lateral frontal lobes. There was no significance in the comparisons of network metrics. CONCLUSION: These findings could contribute to a better understanding of the pathophysiology of IGE.

A magnetic resonance imaging finding in children with cerebral palsy: Symmetrical central tegmental tract hyperintensity.

BACKGROUND: Central tegmental tract is an extrapyramidal tract between red nucleus and inferior olivary nucleus which is located in the tegmentum pontis bilaterally and symmetrically. The etiology of the presence of central tegmental tract hyperintensity on MRI is unclear. PURPOSE: In this study our aim is to evaluate the frequency of central tegmental tract lesions in patients with cerebral palsy and control group, as well as to determine whether there is an association between central tegmental tract lesions and cerebral palsy types. MATERIALS AND METHODS: Clinical and MRI data of 200 patients with cerebral palsy in study group (87 female, 113 male; mean age, 5.81years; range, 0-16years) and 258 patients in control group (114 female, 144 male; mean age, 6.28years; range, 0-16years) were independently evaluated by two reader for presence of central tegmental tract hyperintensity and other associated abnormalities. RESULTS: Central tegmental tract hyperintensities on T2WI were detected in 19% of the study group (38/200) and 3.5% of the control group (9/258) (p<0.0001). Among the total of 38 central tegmental tract lesions in study group, the frequency of central tegmental tract hyperintensity was 16% (24/150) in spastic cerebral palsy and 35% (14/40) in dyskinetic cerebral palsy (p=0.0131). CONCLUSION: The prevalence of central tegmental tract hyperintensity is higher in patients with cerebral palsy particularly in dyskinetic type. We suggest that there is an increased association of the tegmental lesions with dyskinetic CP. Patients with cerebral palsy and ischemic changes were more likely to have central tegmental tract lesions. According to our results we advocate that an ischemic process may have a role in the etiopathogenesis.

Intracranial application of near-infrared light in a hemi-parkinsonian rat model: the impact on behavior and cell survival.

OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson's disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective. METHODS Two NIr powers (333 nW and 0.16 mW), modes of delivery (pulse and continuous), and total doses (634 mJ and 304 J) were tested, together with the feasibility of a midbrain implant site, one considered for later use in primates. Following a striatal 6-OHDA injection, the NIr optical fiber device was implanted surgically into the midline midbrain area of Wistar rats. Animals were tested for apomorphine-induced rotations, and then, 23 days later, their brains were aldehyde fixed for routine immunohistochemical analysis. RESULTS The results showed that there was no evidence of tissue toxicity by NIr in the midbrain. After 6-OHDA lesion, regardless of mode of delivery or total dose, NIr reduced apomorphine-induced rotations at the stronger, but not at the weaker, power. The authors found that neuroprotection, as assessed by tyrosine hydroxylase expression in midbrain dopaminergic cells, could account for some, but not all, of the observed behavioral improvements; the groups that were associated with fewer rotations did not all necessarily have a greater number of surviving cells. There may have been other "symptomatic" elements contributing to behavioral improvements in these rats. CONCLUSIONS In summary, when delivered at the appropriate power, delivery mode, and dosage, NIr treatment provided both improved behavior and neuroprotection in 6-OHDA-lesioned rats.

Dynamic changes in sleep-related breathing abnormalities in bilateral paramedian mesencephalon and thalamus stroke: a follow-up case study.

BACKGROUND: Bilateral paramedian thalamic stroke is characterized by hypersomnia, vertical gaze palsy, amnestic alteration, and apathic state. Combined lesion of the paramedian thalamus and mesencephalon bilaterally is extremely rare. Little is known about the breathing disturbances of the particular region due to the lesion. The following describes the specific case of a woman, age 62, with bilateral paramedian thalamic and mesencephalic stroke. Initially, the patient's complaints exhibited altered vigilance and vertical gaze palsy. Notably, following the acute phase, fluctuating hypersomnia was detected. The MRI (brain) revealed an ischemic lesion in the medial part of the mesencephalon and paramedian thalamus, bilaterally. AIMS: The aim of the present study is to elucidate the involvement and characteristics of sleep-related breathing abnormalities in the clinical manifestation of the combined paramedian thalamic and mesencephalic stroke. METHODS: Polysomnographic recordings were accomplished seven times with 1-week interval between the consecutive recordings, toward investigating the early changes of sleep and sleep-related breathing abnormalities. RESULTS: Sleep structure examination featured a decrease in N3 and REM ratio and an increase in N1 and N2 ratio with minimal improvement during the recovery period. In contrast, significant changes were found in the breathing pattern: the initial central apnea dominance was followed by obstructive apneas with a gradual decrease of the total pathological respiratory events. CONCLUSION: In addition to the structural abnormality of the sleep regulating network, sleep-disordered breathing is another possible cause of hypersomnia in patients afflicted with the present localization of the lesion.

Chronic exposure to broadband noise at moderate sound pressure levels spatially shifts tone-evoked responses in the rat auditory midbrain.

Noise-induced hearing disorders are a significant public health concern. One cause of such disorders is exposure to high sound pressure levels (SPLs) above 85 dBA for eight hours/day. High SPL exposures occur in occupational and recreational settings and affect a substantial proportion of the population. However, an even larger proportion is exposed to more moderate SPLs for longer durations. Therefore, there is significant need to better understand the impact of chronic, moderate SPL exposures on auditory processing, especially in the absence of hearing loss. In this study, we applied functional magnetic resonance imaging (fMRI) with tonal acoustic stimulation on an established broadband rat exposure model (65 dB SPL, 30 kHz low-pass, 60 days). The auditory midbrain response of exposed subjects to 7 kHz stimulation (within exposure bandwidth) shifts dorsolaterally to regions that typically respond to lower stimulation frequencies. This shift is quantified by a region of interest analysis that shows that fMRI signals are higher in the dorsolateral midbrain of exposed subjects and in the ventromedial midbrain of control subjects (p<0.05). Also, the center of the responsive region in exposed subjects shifts dorsally relative to that of controls (p<0.05). A similar statistically significant shift (p<0.01) is observed using 40 kHz stimulation (above exposure bandwidth). The results suggest that high frequency midbrain regions above the exposure bandwidth spatially expand due to exposure. This expansion shifts lower frequency regions dorsolaterally. Similar observations have previously been made in the rat auditory cortex. Therefore, moderate SPL exposures affect auditory processing at multiple levels, from the auditory cortex to the midbrain.

N-Propargyl Caffeate Amide (PACA) Potentiates Nerve Growth Factor (NGF)-Induced Neurite Outgrowth and Attenuates 6-Hydroxydopamine (6-OHDA)-Induced Toxicity by Activating the Nrf2/HO-1 Pathway.

Insufficient production of neurotrophic factors is implicated in the pathogenesis of various neurodegenerative disorders. The aim of the present study was to evaluate the potential of N-propargyl caffeate amide (PACA) to enhance nerve growth factor (NGF)-induced neurite outgrowth and the underlying mechanisms. We discovered that PACA not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine (6-OHDA) neurotoxicity in dopaminergic PC12 cells and primary rat midbrain neurons. To identify the PACA-binding proteins, we introduced a biotin tag to the covalent PACA-protein adducts via "click chemistry" alkyne-azido cycloaddition. As a result, kelch-like ECH-associated protein 1 (Keap1) was isolated as the predominant protein from PACA treated PC12 cells. We demonstrated that the formation of PACA-Keap1 conjugates induced the nuclear translocation of transcription factor Nrf2 and the expression of antioxidant heme oxygenase-1 (HO-1). Importantly, specific HO-1 inhibitor SnPP diminished the neuroprotective and neuritogenic activities of PACA. Moreover, PACA attenuated 6-OHDA-induced production of neurotoxic reactive oxygen species and reactive nitrogen species. PACA also preserved mitochondrial membrane integrity and enhanced the cellular resistance against 6-OHDA neurotoxicity. These results suggest that PACA may exhibit neuroprotective and neuritogenic activities via activating the Nrf2/HO-1 antioxidant pathway.

Maneb-induced dopaminergic neuronal death is not affected by loss of mitochondrial complex I activity: results from primary mesencephalic dopaminergic neurons cultured from individual Ndufs4+/+ and Ndufs4-/- mouse embryos.

Primary cultures from embryonic mouse ventral mesencephalon are widely used for investigating the mechanisms of dopaminergic neuronal death in Parkinson's disease models. Specifically, single mouse or embryo cultures from littermates can be very useful for comparative studies involving transgenic mice when the neuron cultures are to be prepared before genotyping. However, preparing single mouse embryo culture is technically challenging because of the small number of cells present in the mesencephalon of each embryo (150 000-300 000), of which only 0.5-5% are tyrosine hydroxylase-positive, dopaminergic neurons. In this study, we optimized the procedure for preparing primary mesencephalic neuron cultures from individual mouse embryos. Mesencephalic neurons were dissociated delicately, plated on Aclar film coverslips, and incubated in DMEM supplemented with fetal bovine serum for 5 days and then N2 supplement was added for 1 day, which resulted in the best survival of dopaminergic neurons from each embryo. Using this optimized method, we prepared mesencephalic neuron cultures from single Ndufs4 or Ndufs4 embryos and investigated the role of mitochondrial complex I in maneb-induced dopamine neuron death. Our results suggest that maneb toxicity to dopamine neurons is not affected by the loss of mitochondrial complex I activity in Ndufs4 cultures.

Unilateral medial frontal cortex lesions cause a cognitive decision-making deficit in rats.

The medial frontal cortex (MFC) is critical for cost-benefit decision-making. Generally, cognitive and reward-based behaviour in rodents is not thought to be lateralised within the brain. In this study, however, we demonstrate that rats with unilateral MFC lesions show a profound change in decision-making on an effort-based decision-making task. Furthermore, unilateral MFC lesions have a greater effect when the rat has to choose to put in more effort for a higher reward when it is on the contralateral side of space to the lesion. Importantly, this could not be explained by motor impairments as these animals did not show a turning bias in separate experiments. In contrast, rats with unilateral dopaminergic midbrain lesions did exhibit a motoric turning bias, but were unimpaired on the effort-based decision-making task. This rare example of a cognitive deficit caused by a unilateral cortical lesion in the rat brain indicates that the MFC may have a specialised and lateralised role in evaluating the costs and benefits of actions directed to specific spatial locations.

Hypnotherapeutic treatment for anxiety-related relational discord: a short-term hypnotherapeutic protocol.

Hypnotherapeutic interventions are currently used to treat both anxiety disorders and relational discord between couples, yet few hypnotherapeutic interventions specifically address anxiety disorders within the context of a romantic partnership. This article explores a short-term hypnotherapeutic treatment protocol designed for couples' therapy in which the relational dynamic has been impacted by one partner's anxiety disorder. Anxiety not only causes suffering for the anxious patient, but can negatively impact intimate relationships as well. The hypnotherapeutic treatment protocol advanced in this article is specifically designed to address relational discord which is fueled by the presence of one partner's anxiety, and complements more standard individual treatment for anxiety disorders. Strategies to assess for the presence of relational discord with individual patients presenting with an anxiety disorder are included, as well as implications for longer-term couples' treatment.

Clinical spectrum of artery of Percheron infarct: clinical-radiological correlations.

BACKGROUND: The occlusion of the artery of Percheron results in bilateral thalamic and mesencephalic infarctions. In this series, we attempted to classify the subtypes of clinical presentations and long-term prognosis with regards to radiological patterns. METHODS: We sought the clinical and radiological findings of 15 (8 men and 7 women; mean age 48 years) consecutive patients with Percheron artery infarct over 10 years. We classified the clinical symptoms according to the presence of a mental status disturbance (MSD), behavioral amnesic impairment (BAI), aphasia/dysarthria, ocular movement disorders (OMDs), motor deficit, cerebellar signs, and others. The Percheron artery infarct images were classified as bilateral paramedian thalamic with rostral midbrain infarction (BPTRMI), bilateral paramedian thalamic without midbrain infarction (BPTWMI), bilateral paramedian and anterior thalamic with midbrain infarction (BPATMI), and bilateral paramedian and anterior thalamic without midbrain infarction. The outcome was evaluated using a modified Rankin Scale (mRS). RESULTS: OMD and MSD were the most common clinical manifestations in patients with BPTRMI (n = 8). BAI and MSD were the main clinical findings in patients with BPTWMI (n = 6). A patient with BPATMI had a combination of clinical manifestations. After a mean follow-up of 55 months, a good outcome (mRS score ≤ 2) was present in 25% of the patients with BPTRMI, 67% of the patients with BPTWMI, and in 1 patient with BPATMI. CONCLUSIONS: Our findings suggest that it is possible to identify clinical and radiological subgroups of Percheron artery infarct. The long-term follow-up outcome is generally good, except in cases with midbrain involvement.

A variant on the kappa opioid receptor gene (OPRK1) is associated with stress response and related drug craving, limbic brain activation and cocaine relapse risk.

Stress increases drug craving and relapse risk. The kappa opioid receptor gene (OPRK1) mediates stress responses. Here, we examined whether the OPRK1 rs6989250 C>G affects stress-induced cocaine craving and cortisol responses, subsequent cocaine relapse risk and the neural response to stress using functional magnetic resonance imaging (fMRI) in cocaine dependence. Sixty-seven treatment-engaged, abstinent cocaine-dependent African-Americans were genotyped (CG: N=10; CC: N=57) and participated in a 3-day experiment in which they were exposed to personalized script-driven imagery of stress, drug cues and neutral scenarios, one condition per day, randomly assigned and counterbalanced across subjects. Repeated measures of craving and cortisol were obtained. The subjects were followed prospectively for 90 days to assess relapse risk. A follow-up preliminary fMRI experiment assessed neural responses to stress, drug cue and neutral conditions in matched CG (N=5) and CC (N=8) subgroups. We found greater stress-induced craving (P=0.019), higher cortisol during stress and cue relative to the neutral condition (P's<0.003), and increased cocaine relapse risk (P=0.0075) in the CG compared with the CC group. The CG relative to the CC group also showed greater activation of limbic and midbrain regions during stress and cues relative to the neutral condition with additional stress-induced activation in the right amygdala/hippocampus (P<0.05, whole-brain corrected). These results suggest that OPRK1 is associated with stress-induced craving and cortisol, hyperactive hypothalamus/thalamus-midbrain-cerebellum responses, and also associated with greater subsequent cocaine relapse risk. Future studies to replicate these findings in a larger sample size are warranted.

The effect of short moderate stress on the midbrain corticotropin-releasing factor system in a macaque model of functional hypothalamic amenorrhea.

OBJECTIVE: To study the effect of moderate stress on corticotropin-releasing factor (CRF) components in the serotonergic midbrain region in a monkey model of functional hypothalamic amenorrhea. DESIGN: After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days before euthanasia. SETTING: Primate research center. ANIMAL(S): Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n = 5), medium stress resilient (n = 4), or stress sensitive (SS, n = 4). INTERVENTION(S): Five days of diet in a novel room with unfamiliar conspecifics. MAIN OUTCOME MEASURE(S): Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of urocortin 1 (UCN1) cells; the density of UCN1 axons; the expression of CRF receptor 1 (CRF-R1) and CRF-R2 in the dorsal raphe nucleus. RESULT(S): The CRF innervation was higher in HSR than in SS animals; UCN1 cell number was higher in HSR than in SS animals and UCN1 axon bouton density was not different; all opposite of nonstressed animals. The CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than in SS animals. The relative expression of CRF-R1 and CRF-R2 was similar to nonstressed animals. CONCLUSION(S): The HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. The CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals.

Spontaneous hyperactivity in the auditory midbrain: relationship to afferent input.

Hyperactivity in the form of increased spontaneous firing rates of single neurons develops in the guinea pig inferior colliculus (IC) after unilateral loud sound exposures that result in behavioural signs of tinnitus. The hyperactivity is found in those parts of the topographic frequency map in the IC where neurons possess characteristic frequencies (CFs) closely related to the region in the cochlea where lasting sensitivity changes occur as a result of the loud sound exposure. The observed hyperactivity could be endogenous to the IC, or it could be driven by hyperactivity at lower stages of the auditory pathway. In addition to the dorsal cochlear nucleus (DCN) hyperactivity reported by others, specific cell types in the ventral cochlear nucleus (VCN) also show hyperactivity in this animal model suggesting that increased drive from several regions of the lower brainstem could contribute to the observed hyperactivity in the midbrain. In addition, spontaneous afferent drive from the cochlea itself is necessary for the maintenance of hyperactivity up to about 8 weeks post cochlear trauma. After 8 weeks however, IC hyperactivity becomes less dependent on cochlear input, suggesting that central neurons transition from a state of hyperexcitability to a state in which they generate their own endogenous firing. The results suggest that there might be a "therapeutic window" for early-onset tinnitus, using treatments that reduce cochlear afferent firing.

Neurocysticercosis presenting as a vertical one-and-a-half syndrome with associated contralesional horizontal gaze paresis.

We describe a patient presenting with vertical one-and-a-half syndrome and concomitant contralesional horizontal gaze paresis as the result of a solitary neurocysticercosis (NCC) lesion in the right midbrain extending into the thalamomesencephalic junction. The patient received an albendazole-dexamethasone course which resulted in resolution of his symptoms. The neuro-ophthalmological complications of NCC are reviewed and the clinical topography of the neuro-ophthalmological findings of this unusual observation are discussed.