Eye movement desensitization and reprocessing for post-stroke post-traumatic stress disorder: Case report using the three-phase approach.

Medically-induced post-traumatic stress disorder (PTSD) is substantially more prevalent than PTSD in the general population. In people with stroke, it can impact as many as 23% of patients, with negative effects on mental health as well as stroke-related disability. Medically-induced PTSD may have unique features compared to other forms of PTSD, and therefore there is a pressing need to evaluate existing treatments for PTSD in this context. The current study reports on the feasibility, safety, and efficacy of Eye Movement Desensitization and Reprocessing (EMDR) for PTSD subsequent to a pontine stroke. Using a quasi-experimental case design, a 44-year-old Caucasian woman received EMDR delivered via telehealth. Self-report measures were obtained at baseline, pre-EMDR, and post-EMDR, with brief neuropsychological testing pre/post-EMDR. After 3 sessions of EMDR, the patient no longer met criteria for PTSD, and showed clinically significant reductions in depressive and generalized anxiety symptoms. With proper safety provisions, it is feasible to deliver EMDR via telehealth to alleviate post-stroke PTSD. Reduced linguistic demands of EMDR may be particularly appealing for persons with neurological disorders as compared to other trauma therapies. Further work is also needed to understand the parameters of baseline neuropsychological function that could impact response to intervention.

Convergence of forepaw somatosensory and motor cortical projections in the striatum, claustrum, thalamus, and pontine nuclei of cats.

The basal ganglia and pontocerebellar systems regulate somesthetic-guided motor behaviors and receive prominent inputs from sensorimotor cortex. In addition, the claustrum and thalamus are forebrain subcortical structures that have connections with somatosensory and motor cortices. Our previous studies in rats have shown that primary and secondary somatosensory cortex (S1 and S2) send overlapping projections to the neostriatum and pontine nuclei, whereas, overlap of primary motor cortex (M1) and S1 was much weaker. In addition, we have shown that M1, but not S1, projects to the claustrum in rats. The goal of the current study was to compare these rodent projection patterns with connections in cats, a mammalian species that evolved in a separate phylogenetic superorder. Three different anterograde tracers were injected into the physiologically identified forepaw representations of M1, S1, and S2 in cats. Labeled fibers terminated throughout the ipsilateral striatum (caudate and putamen), claustrum, thalamus, and pontine nuclei. Digital reconstructions of tracer labeling allowed us to quantify both the normalized distribution of labeling in each subcortical area from each tracer injection, as well as the amount of tracer overlap. Surprisingly, in contrast to our previous findings in rodents, we observed M1 and S1 projections converging prominently in striatum and pons, whereas, S1 and S2 overlap was much weaker. Furthermore, whereas, rat S1 does not project to claustrum, we confirmed dense claustral inputs from S1 in cats. These findings suggest that the basal ganglia, claustrum, and pontocerebellar systems in rat and cat have evolved distinct patterns of sensorimotor cortical convergence.

Glutamate, Glutamine, GABA and Oxidative Products in the Pons Following Cortical Injury and Their Role in Motor Functional Recovery.

Brain injury leads to an excitatory phase followed by an inhibitory phase in the brain. The clinical sequelae caused by cerebral injury seem to be a response to remote functional inhibition of cerebral nuclei located far from the motor cortex but anatomically related to the injury site. It appears that such functional inhibition is mediated by an increase in lipid peroxidation (LP). To test this hypothesis, we report data from 80 rats that were allocated to the following groups: the sham group (n = 40), in which rats received an intracortical infusion of artificial cerebrospinal fluid (CSF); the injury group (n = 20), in which rats received CSF containing ferrous chloride (FeCl2, 50 mM); and the recovery group (n = 20), in which rats were injured and allowed to recover. Beam-walking, sensorimotor and spontaneous motor activity tests were performed to evaluate motor performance after injury. Lipid fluorescent products (LFPs) were measured in the pons. The total pontine contents of glutamate (GLU), glutamine (GLN) and gamma-aminobutyric acid (GABA) were also measured. In injured rats, the motor deficits, LFPs and total GABA and GLN contents in the pons were increased, while the GLU level was decreased. In contrast, in recovering rats, none of the studied variables were significantly different from those in sham rats. Thus, motor impairment after cortical injury seems to be mediated by an inhibitory pontine response, and functional recovery may result from a pontine restoration of the GLN-GLU-GABA cycle, while LP may be a primary mechanism leading to remote pontine inhibition after cortical injury.

Novel Diffusion-Weighted Imaging Score Showed Good Prognostic Value for Acute Basilar Artery Occlusion Following Endovascular Treatment: The Pons-Midbrain and Thalamus Score.

BACKGROUND AND PURPOSE: Prognostic factors for outcome of endovascular treatment remains to be investigated in patients with acute basilar artery occlusion. We aimed to assess the prognostic value of a novel pretreatment diffusion-weighted imaging score: The Pons-Midbrain and Thalamus (PMT) score. METHODS: Eligible patients who underwent endovascular treatment due to acute basilar artery occlusion were reviewed. The PMT score was a diffusion-weighted imaging-based semiquantitative scale in which the infarctions of pons, midbrain, and thalamus were fully considered. The PMT score was assessed as well as the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score and Brain Stem Score. Good outcomes were defined as a modified Rankin Scale score of ≤3 at 90-day and successful reperfusion as Thrombolysis in Cerebral Infarction grades 2b/3. The associations between baseline clinical parameters and good outcomes were evaluated with logistic regression. RESULTS: A total of 107 patients with pretreatment magnetic resonance imaging were included in this cohort. The baseline PMT score (median [interquartile range], 3 [1-5] versus 7 [5-9]; P<0.001) and Brain Stem Score (median [interquartile range], 2 [1-4] versus 3 [2-5]; P=0.001) were significantly lower in good outcome group; the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score was higher in good outcome group without statistical significance. As a result of receiver operating characteristic curve analyses, the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score showed poor prognostic accuracy for good outcome (area under the curve, 0.60 [95% CI, 0.49-0.71]; P=0.081); The baseline PMT score showed significantly better prognostic accuracy for 90-day good outcome than the Brain Stem Score and National Institutes of Health Stroke Scale (area under the curve, 0.80 versus 0.68 versus 0.78, P=0.003). In addition, favorable PMT score <7 (odds ratio, 22.0 [95% CI, 6.0-80.8], P<0.001), Brain Stem Score <3 (odds ratio, 4.65 [95% CI, 2.05-10.55], P<0.001) and baseline National Institutes of Health Stroke Scale <23 (odds ratio, 8.0 [95% CI, 2.5-25.6], P<0.001) were associated with improved good outcome. CONCLUSIONS: In patients with acute basilar artery occlusion following endovascular treatment, the pretreatment diffusion-weighted imaging based PMT score showed good prognostic value for clinical outcome.

Impact of ovariectomy and CO2 inhalation on microglia morphology in select brainstem and hypothalamic areas regulating breathing in female rats.

The neural network that regulates breathing shows a significant sexual dimorphism. Ovarian hormones contribute to this distinction as, in rats, ovariectomy reduces the ventilatory response to CO2. Microglia are neuroimmune cells that are sensitive to neuroendocrine changes in their environment. When reacting to challenging conditions, these cells show changes in their morphology that reflect an augmented capacity for producing pro- and anti-inflammatory cytokines. Based on evidence suggesting that microglia contribute to sex-based differences in reflexive responses to hypercapnia, we hypothesized that ovariectomy and hypercapnia promote microglial reactivity in selected brain areas that regulate breathing. We used ionized calcium-binding-adapter molecule-1 (Iba1) immunolabeling to compare the density and morphology of microglia in the locus coeruleus (LC), the caudal medullary raphe, the caudal part of the nucleus of the tractus solitarius (cNTS), and the paraventricular nucleus of the hypothalamus (PVN). Tissue was obtained from SHAM (metaestrus) female rats or following ovariectomy. Rats were exposed to normocapnia or hypercapnia (5% CO2, 20 min). Ovariectomy and hypercapnia did not affect microglial density in any of the structures studied. Ovariectomy promoted a reactive phenotype in the cNTS and LC, as indicated by a larger morphological index. In these structures, hypercapnia had a relatively modest opposing effect; the medullary raphe or the PVN were not affected. We conclude that ovarian hormones attenuate microglial reactivity in CO2/H+ sensing structures. These data suggest that microglia may contribute to neurological diseases in which anomalies of respiratory control are associated with cyclic fluctuations of ovarian hormones or menopause.

Social isolation uncovers a circuit underlying context-dependent territory-covering micturition.

The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploited a behavioral paradigm in which mice, depending on strain, social experience, and sensory context, either vigorously cover an arena with small urine spots or deposit urine in a few isolated large spots. We refer to these micturition modes as, respectively, high and low territory-covering micturition (TCM) and find that the presence of a urine stimulus robustly induces high TCM in socially isolated mice. Comparison of the brain networks activated by social isolation and by urine stimuli to those upstream of the PMC identified the lateral hypothalamic area as a potential modulator of micturition modes. Indeed, chemogenetic manipulations of the lateral hypothalamus can switch micturition behavior between high and low TCM, overriding the influence of social experience and sensory context. Our results suggest that both inhibitory and excitatory signals arising from a network upstream of the PMC are integrated to determine context- and social-experience-dependent micturition patterns.

Hyperhomocysteinemia induced locked-in syndrome in a young adult due to folic acid deficiency.

'Locked-in syndrome (LIS)' is a neurological disorder, often missed initially and can have grave consequences. A rare case of LIS caused due to folic acid deficiency-induced hyperhomocysteinemia is being described here. A 16-year-old boy presented with complaints of sudden onset weakness of all the four limbs with loss of voice for one day. All the tendon reflexes were increased, bilateral planters were extensor and sensory system was intact. Patient was conscious and responded to verbal commands by ocular movements in vertical direction. Hence, a diagnosis of LIS was made. Magnetic resonance imaging of the head revealed an acute infarct in ventral pons. Serum homocysteine level was elevated (20.65 µmol/l) and folic acid level was severely low (1.7 nmol/ml). Cause of LIS was found to be hyperhomocysteinemia induced stroke in the pons, related to folic acid deficiency. The patient was managed with antiplatelet agents and folic acid supplementation and was discharged subsequently. Recognition of LIS is important as casual remarks at bedside can severely traumatize an already paralyzed but conscious and awake patient. Folic acid deficiency can lead to hyperhomocysteinemia, which can cause strokes and even LIS. Prevention of hyperhomocysteinemia may possibly prevent such neurological disasters.

Portable neuromodulation induces neuroplasticity to re-activate motor function recovery from brain injury: a high-density MEG case study.

BACKGROUND: In a recent high-profile case study, we used functional magnetic resonance imaging (fMRI) to monitor improvements in motor function related to neuroplasticity following rehabilitation for severe traumatic brain injury (TBI). The findings demonstrated that motor function improvements can occur years beyond current established limits. The current study extends the functional imaging investigation to characterize neuromodulation effects on neuroplasticity to further push the limits. METHODS: Canadian Soldier Captain (retired) Trevor Greene (TG) survived a severe open-TBI when attacked with an axe during a 2006 combat tour in Afghanistan. TG has since continued intensive daily rehabilitation to recover motor function, experiencing an extended plateau using conventional physical therapy. To overcome this plateau, we paired translingual neurostimulation (TLNS) with the continuing rehabilitation program. RESULTS: Combining TLNS with rehabilitation resulted in demonstrable clinical improvements along with corresponding changes in movement evoked electro-encephalography (EEG) activity. High-density magneto-encephalography (MEG) characterized cortical activation changes in corresponding beta frequency range (27 Hz). MEG activation changes corresponded with reduced interhemispheric inhibition in the post-central gyri regions together with increased right superior/middle frontal activation suggesting large scale network level changes. CONCLUSIONS: The findings provide valuable insight into the potential importance of non-invasive neuromodulation to enhance neuroplasticity mechanisms for recovery beyond the perceived limits of rehabilitation.

A novel diagnostic tool for the evaluation of hypothalamic-pituitary region and diagnosis of growth hormone deficiency: pons ratio.

Backgrounds Limitations in the evaluation of the pituitary size and changes according to pubertal status make its validity questionable. Recently, in a small-scale study, pons ratio (PR) has been suggested as a more sensitive tool for diagnosis and etiological evaluation of growth hormone deficiency (GHD). The aim of the study is to evaluate the diagnostic value of PR in the diagnosis of GHD. Methods We retrospectively evaluated the pituitary magnetic resonance imaging (MRI) of 133 patients with a diagnosis of GHD. Primary axis (PA) was assigned as a line crossing the mid-sagittal dorsum sella and fourth ventricle. PR was defined as the pons height above the PA divided by total pons height. The PR of patients with GHD was compared to subjects without GHD. Results Study included 133 patients with GHD and 47 controls. In total, 121 (91%) patients had isolated GHD and 12 (9%) patients had multiple pituitary hormone deficiency. The PR of the patient group (mean: 0.32 ± 0.89; range: 0.14-0.63) was significantly higher than controls (mean: 0.26 ± 0.067; range 0.19-0.44) (p: 0.000). The optimal cut-off value of PR for GHD diagnosis was 0.27 (sensitivity 71% specificity 56%). There was a negative correlation between anterior pituitary height (APH)-SDS and PR (p: 0.002; r: -0.27). APH was increased, but PR remained unchanged in pubertal patients (p: 0.089). Conclusions PR measurement is a noninvasive, practical method with a cost-benefit clinical value. As it is not affected by pubertal status, PR is potentially a more sensitive tool for evaluation of pituitary gland in GHD patients compared to APH.

Seesaw nystagmus with internuclear ophthalmoplegia from bilateral dorsomedial pons and left thalamus infarction: a case report.

BACKGROUND: We describe for the first time the clinical features and mechanisms of a bilateral dorsomedial pons and left thalamus infarction with seesaw nystagmus and internuclear ophthalmoplegia. CASE PRESENTATION: A 62-year-old Chinese man was hospitalized for sudden-onset dizziness, diplopia, and gait disturbance. A neurological examination revealed seesaw nystagmus and internuclear ophthalmoplegia. Magnetic resonance imaging disclosed an acute infarction confined to the bilateral dorsomedial pons and left thalamus. Subsequently, 2 weeks of antithrombotic therapy led to an improvement in his symptoms. CONCLUSIONS: This case illustrates that the acute onset of seesaw nystagmus and internuclear ophthalmoplegia accompanied by risk factors for cerebrovascular diseases are highly suggestive of brainstem infarction.

Startle suppression after mild traumatic brain injury is associated with an increase in pro-inflammatory cytokines, reactive gliosis and neuronal loss in the caudal pontine reticular nucleus.

Mild traumatic brain injury (mTBI) can produce somatic symptoms such as headache, dizziness, fatigue, sleep disturbances and sensorimotor dysfunction. Sensorimotor function can be measured by tests such as the acoustic startle reflex (ASR), an evolutionarily conserved defensive response to a brief yet sharp acoustic stimulus. mTBI produces a long-lasting suppression of ASR in rodents and humans; however, the mechanism of this suppression is unknown. The present study examined whether inflammatory processes in the brainstem (particularly the caudal pontine reticular nucleus, PnC) could account for the suppression of ASR after mTBI, because the PnC is an essential nucleus of the ASR circuit. Furthermore, while inflammation after mTBI is commonly observed in brain regions proximal to the site of impact (cortex and hippocampus), the effects of mTBI in brainstem structures remains largely understudied. The present study demonstrated a suppression of ASR one day after injury and lasting at least three weeks after an mTBI, replicating previous findings. Within the PnC, transient elevations of IL-1ß and TNF-α mRNA were observed at one day after injury, while IL-1α mRNA exhibited a delayed increase at three weeks after injury. Reactive gliosis (via IBA-1-ir for microglia and GFAP-ir for astrocytes) were also observed in the PnC, at one day and seven days after injury, respectively. Finally, the number of giant neurons (the major functional cell population in the PnC) was decreased three weeks after injury. The results indicate that glial activation precedes neuronal loss in the PnC, and correlates with the behavioral suppression of the ASR. The results also raise implications for brainstem involvement in the development of post-traumatic symptoms.

Pons to Posterior Cingulate Functional Projections Predict Affective Processing Changes in the Elderly Following Eight Weeks of Meditation Training.

Evidence indicates meditation facilitates affective regulation and reduces negative affect. It also influences resting-state functional connectivity between affective networks and the posterior cingulate (PCC)/precuneus, regions critically implicated in self-referential processing. However, no longitudinal study employing active control group has examined the effect of meditation training on affective processing, PCC/precuneus connectivity, and their association. Here, we report that eight-week meditation, but not relaxation, training 'neutralized' affective processing of positive and negative stimuli in healthy elderly participants. Additionally, meditation versus relaxation training increased the positive connectivity between the PCC/precuneus and the pons, the direction of which was largely directed from the pons to the PCC/precuneus, as revealed by dynamic causal modeling. Further, changes in connectivity between the PCC/precuneus and pons predicted changes in affective processing after meditation training. These findings indicate meditation promotes self-referential affective regulation based on increased regulatory influence of the pons on PCC/precuneus, which new affective-processing strategy is employed across both resting state and when evaluating affective stimuli. Such insights have clinical implications on interventions on elderly individuals with affective disorders.

Deafferentation in thalamic and pontine areas in severe traumatic brain injury.

PURPOSE: Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. METHODS: Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. RESULTS: Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. CONCLUSION: Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI.

Bedside evaluation of smooth pursuit eye movements in acute sensory stroke patients.

BACKGROUND AND PURPOSE: Unilateral saccadic pursuit is reported to be suggestive of a pontine lesion in sensory stroke patients. We attempted to verify this eye sign in just-hospitalized pontine sensory stroke patients. METHODS: Horizontal smooth pursuit eye movements were evaluated upon hospital arrival in 4 pontine sensory stroke patients and were compared with those in 6 thalamic sensory stroke patients. Eye movements were evaluated with the patient lying down on the emergency room or stroke care unit bed by means of a newly developed video-oculography-based eye movement recording system equipped to project a moving laser pointer onto the ceiling. RESULTS: Laterality of horizontal smooth pursuit gain in pontine sensory stroke patients was evident upon arrival; in thalamic sensory stroke patients, horizontal smooth pursuit gain was equal in both directions. These characteristics were easily detected at bedside. CONCLUSION: Unilateral saccadic pursuit in pontine sensory stroke patients may be a practical diagnostic sign that can be detected even in the emergency room. The video-oculography-based recording system equipped to project a moving laser pointer onto the ceiling may be useful for detecting this eye sign.

The Preliminary Study of Quantitative Morphology of the Corpus Callosum, Thalamus, Cerebellum and Pons in Autistic Disorder and Developmental Language Disorder / 신경정신의학

OBJECTIVES: This study aimed to planimetrically measure the corpus callosum, cerebellum, pons and thalamus in the boys with autistic disorder and developmental language disorder. METHODS: The midsagittal brain MR images of 8 autistic and 8 developmental language disorder subjects who met the DSM-III-R diagnostic criteria and 10 comparison subjects were collected. MR images were redigitalized with flatbed scanner and the data were analyzed with NIH IMAGE 1.61 software. Pixel counting and area measurements were done. The corpus callosum was divided into seven regions and the cerebellar vermis was divided into three regions. RESULTS: In autistic subjects, the rostrum of corpus callosum was found to have significantly smaller area than comparison and developmental language disorder subjects. In developmental language disorder subjects, the thalamus was significantly larger than comparison subjects. The cerebellar vermis and pons did not differ among three groups. CONCLUSION: The rostrum of the corpus callosum in autistic disorder was significantly smaller. This finding supports the theory of abnormal prefrontal lobe development in autistic disorder.