Bilateral effect of acupuncture on cerebrum and cerebellum in ischaemic stroke patients with hemiparesis: a randomised clinical and neuroimaging trial.

BACKGROUND: Acupuncture involving the limb region may be effective for stroke rehabilitation clinically, but the visualised and explanatory evidence is limited. Our objectives were to assess the specific effects of acupuncture for ischaemic stroke (IS) patients with hemiparesis and investigate its therapy-driven modification in functional connectivity. METHODS: IS patients were randomly assigned (2:1) to receive 10 sessions of hand-foot 12 needles acupuncture (HA, n=30) or non-acupoint (NA) acupuncture (n=16), enrolling gender-matched and age-matched healthy controls (HCs, n=34). The clinical outcomes were the improved Fugl-Meyer Assessment scores including upper and lower extremity (ΔFM, ΔFM-UE, ΔFM-LE). The neuroimaging outcome was voxel-mirrored homotopic connectivity (VMHC). Static and dynamic functional connectivity (sFC, DFC) analyses were used to study the neuroplasticity reorganisation. RESULTS: 46 ISs (mean(SD) age, 59.37 (11.36) years) and 34 HCs (mean(SD) age, 52.88 (9.69) years) were included in the per-protocol analysis of clinical and neuroimaging. In clinical, ΔFM scores were 5.00 in HA group and 2.50 in NA group, with a dual correlation between ΔFM and ΔVMHC (angular: r=0.696, p=0.000; cerebellum: r=-0.716, p=0.000) fitting the linear regression model (R2=0.828). In neuroimaging, ISs demonstrated decreased VMHC in bilateral postcentral gyrus and cerebellum (Gaussian random field, GRF corrected, voxel p<0.001, cluster p<0.05), which fitted the logistic regression model (AUC=0.8413, accuracy=0.7500). Following acupuncture, VMHC in bilateral superior frontal gyrus orbital part was increased with cerebro-cerebellar changes, involving higher sFC between ipsilesional superior frontal gyrus orbital part and the contralesional orbitofrontal cortex as well as cerebellum (GRF corrected, voxel p<0.001, cluster p<0.05). The coefficient of variation of VMHC was decreased in bilateral posterior cingulate gyrus (PPC) locally (GRF corrected, voxel p<0.001, cluster p<0.05), with integration states transforming into segregation states overall (p<0.05). There was no acupuncture-related adverse event. CONCLUSIONS: The randomised clinical and neuroimaging trial demonstrated acupuncture could promote the motor recovery and modified cerebro-cerebellar VMHC via bilateral static and dynamic reorganisations for IS patients with hemiparesis.

Hemispheric Utilization of Alpha Oscillatory Dynamics as a Unique Biomarker of Neural Compensation in Females with Fragile X Syndrome.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a trinucleotide expansion on the FMR1 gene and characterized by intellectual disability, sensory hypersensitivity, executive function difficulties, and social anxiety. Recently, efforts to define neural biomarkers for FXS have highlighted disruptions to power in the alpha frequency band; however the dynamic mechanisms supporting these findings are poorly understood. The current study aimed to explore the temporal and hemispheric dynamics supporting alpha phenotypes in FXS and their relationship with neural phenotypes related to auditory processing using electroencephalography during an auditory evoked task. Adolescents and adults (N = 36) with FXS and age/sex matched typically developing controls (N = 40) completed an auditory chirp task. Frontal alpha power in the prestimulus period was decomposed into "bursts" using percentile thresholding, then assessed for number of bursts per second (burst count) and burst length. Data were compared across left and right hemispheres to assess lateralization of neural activity. Individuals with FXS showed more differences in alpha power compared to TDC primarily in the right hemisphere. Notably, alpha hemisphere outcomes in males with FXS were driven by the number of times they entered a dynamically relevant period of alpha (burst count) rather than length of time spent in alpha. Females with FXS showed reduced burst counts but remained in sustained high alpha states for longer periods of time. Length of time spent in alpha may reflect a modulatory or compensatory mechanism capable of recovering sensory processing abilities in females with FXS resulting in a less severe clinical presentation. Right hemisphere abnormalities may impact sensory processing differences between males and females with FXS. The relationship between alpha burst length, count, sex, and hemisphere may shed light on underlying mechanisms for previously observed alpha power abnormalities in FXS and their variation by sex.

Early and Bi-hemispheric seizure onset in a rat glioblastoma Multiforme model.

GBM is the most life-threatening neurological disease with annual incidence of âˆ¼ 5 cases per 100,000 people and a median survival of less than 15 months. Seizures are the first clinical symptoms in 40%-45% of patients with GBM and its epileptogenic mechanisms are poorly understood, largely due to the challenge to develop a clinically-relevant animal model and the unknown latent period. In this study, we used continuous video-EEG monitoring to detect the earliest interictal and ictal events in a CRISPR- IUE GBM rat model that shares pathological and clinical features with those observed in human patients. To our best knowledge, we showed for the first time that interictal epileptiform discharges emerged during early postnatal weeks and the first ictal event occurred during the fourth postnatal week. We also showed GBM animals showed independent bi-hemispheric epileptogenic events, suggesting a widespread circuitry dysregulation. Together, our work identified the temporal- and spatial frame of epileptogenic network in a highly clinically-relevant GBM animal model, paving ways for mechanistic studies at molecular, cellular and circuitry levels.

Obesity risk is associated with altered cerebral glucose metabolism and decreased µ-opioid and CB1 receptor availability.

BACKGROUND: Obesity is a pressing public health concern worldwide. Novel pharmacological means are urgently needed to combat the increase of obesity and accompanying type 2 diabetes (T2D). Although fully established obesity is associated with neuromolecular alterations and insulin resistance in the brain, potential obesity-promoting mechanisms in the central nervous system have remained elusive. In this triple-tracer positron emission tomography study, we investigated whether brain insulin signaling, µ-opioid receptors (MORs) and cannabinoid CB1 receptors (CB1Rs) are associated with risk for developing obesity. METHODS: Subjects were 41 young non-obese males with variable obesity risk profiles. Obesity risk was assessed by subjects' physical exercise habits, body mass index and familial risk factors, including parental obesity and T2D. Brain glucose uptake was quantified with [18F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [11C]carfentanil and CB1Rs with [18F]FMPEP-d2. RESULTS: Subjects with higher obesity risk had globally increased insulin-stimulated brain glucose uptake (19 high-risk subjects versus 19 low-risk subjects), and familial obesity risk factors were associated with increased brain glucose uptake (38 subjects) but decreased availability of MORs (41 subjects) and CB1Rs (36 subjects). CONCLUSIONS: These results suggest that the hereditary mechanisms promoting obesity may be partly mediated via insulin, opioid and endocannabinoid messaging systems in the brain.

Monitoring and modifying brain oxygenation in patients at risk of hypoxic ischaemic brain injury after cardiac arrest.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Coronary artery disease and its impact on the pulsatile brain: A functional NIRS study.

Recent studies have reported that optical indices of cerebral pulsatility are associated with cerebrovascular health in older adults. Such indices, including cerebral pulse amplitude and the pulse relaxation function (PRF), have been previously applied to quantify global and regional cerebral pulsatility. The aim of the present study was to determine whether these indices are modulated by cardiovascular status and whether they differ between individuals with low or high cardiovascular risk factors (LCVRF and HCVRF) and coronary artery disease (CAD). A total of 60 older adults aged 57-79 were enrolled in the study. Participants were grouped as LCVRF, HCVRF, and CAD. Participants were asked to walk freely on a gym track while a near-infrared spectroscopy (NIRS) device recorded hemodynamics data. Low-intensity, short-duration walking was used to test whether a brief cardiovascular challenge could increase the difference of pulsatility indices with respect to cardiovascular status. Results indicated that CAD individuals have higher global cerebral pulse amplitude compared with the other groups. Walking reduced global cerebral pulse amplitude and PRF in all groups but did not increase the difference across the groups. Instead, walking extended the spatial distribution of cerebral pulse amplitude to the anterior prefrontal cortex when CAD was compared to the CVRF groups. Further research is needed to determine whether cerebral pulse amplitude extracted from data acquired with NIRS, which is a noninvasive, inexpensive method, can provide an index to characterize the cerebrovascular status associated with CAD.

Unilateral Spatial Neglect without Hemiplegia: The Output-Mode Effect Revisited.

BACKGROUND: The occurrence of unilateral spatial neglect (USN) in non-hemiplegic right-hemisphere damaged patients is rare. Earlier studies of such patients revealed a significant advantage when typical neglect tests were performed by the patient's left hand as compared to the dominant right hand. The mechanism underlying this "output-mode effect" remains elusive. METHODS: We analyzed the temporal dynamics of this effect using line-bisection task in 9 non-hemiplegic stroke patients with left-USN. RESULTS: In 4 patients tested shortly after stroke onset (≤ 6 weeks), the impact of hand laterality was variable (left-hand advantage in one patient; right-hand advantage in 2 patients; similar performance in both hands in one patient). Only later (> 6 weeks) a clear advantage of the left hand emerged in the majority of patients, similar to the earlier reports which were all based on late testing. CONCLUSIONS: We found variable dynamics in the expression of the output-mode effect in the first weeks following stroke onset, which may reflect changes of inter-hemispheric balance, related to recovery processes. We propose that therapeutic interventions aiming to manipulate the inter-hemispheric balance (e.g., by non-invasive brain stimulation) take into account the existence of such dynamics and their highly variate nature.

Alterations in cerebral and cardiac mitochondrial function in a porcine model of acute carbon monoxide poisoning.

OBJECTIVES: The purpose of this study is the development of a porcine model of carbon monoxide (CO) poisoning to investigate alterations in brain and heart mitochondrial function. DESIGN: Two group large animal model of CO poisoning. SETTING: Laboratory. SUBJECTS: Ten swine were divided into two groups: Control (n = 4) and CO (n = 6). INTERVENTIONS: Administration of a low dose of CO at 200 ppm to the CO group over 90 min followed by 30 min of re-oxygenation at room air. The Control group received room air for 120 min. MEASUREMENTS: Non-invasive optical monitoring was used to measure cerebral blood flow and oxygenation. Cerebral microdialysis was performed to obtain semi real time measurements of cerebral metabolic status. At the end of the exposure, both fresh brain (cortical and hippocampal tissue) and heart (apical tissue) were immediately harvested to measure mitochondrial respiration and reactive oxygen species (ROS) generation and blood was collected to assess plasma cytokine concentrations. MAIN RESULTS: Animals in the CO group showed significantly decreased Complex IV-linked mitochondrial respiration in hippocampal and apical heart tissue but not cortical tissue. There also was a significant increase in mitochondrial ROS generation across all measured tissue types. The CO group showed a significantly higher cerebral lactate-to-pyruvate ratio. Both IL-8 and TNFα were significantly increased in the CO group compared with the Control group obtained from plasma. While not significant there was a trend to an increase in optically measured cerebral blood flow and hemoglobin concentration in the CO group. CONCLUSIONS: Low-dose CO poisoning is associated with early mitochondrial disruption prior to an observable phenotype highlighting the important role of mitochondrial function in the pathology of CO poisoning. This may represent an important intervenable pathway for therapy and intervention.

Differentiating syndrome of inappropriate ADH, reset osmostat, cerebral/renal salt wasting using fractional urate excretion.

OBJECTIVES: Clinical and laboratory data of reset osmostat (RO) and cerebral/renal salt wasting (C/RSW) mimic syndrome of inappropriate antidiuretic hormone (SIADH) and can pose diagnostic challenges because of significant overlapping between clinical and laboratory findings. Failure to correctly diagnose hyponatremia may result in increased mortality risk, longer hospital stay, and is cost-effective. We aim to illustrate clinical and laboratory similarities and difference among patients with hyponatremic disorders and discuss the diagnostic value of factional uprate excretion (FEurate) to differentiate SIADH from RO and C/RSW. CASE PRESENTATIONS: We report the use of FEurate in the evaluation of three patients with hyponatremia and elevated urine osmolality in the absence of edema or clinical evidence of dehydration to differentiate SIADH from RO and C/RSW. CONCLUSIONS: Measurement of FEurate may offset in part the diagnostic confusion imparted by the diagnoses of SIADH, RO, and C/RSW.

Correlation Between Speech Repetition Function and the Arcuate Fasciculus in the Dominant Hemisphere Detected by Diffusion Tensor Imaging Tractography in Stroke Patients with Aphasia.

BACKGROUND Repetition disorder can be used as an important criterion for aphasia classification, and damaged arcuate fasciculus in the dominate hemisphere has been reported to be closely related to repetition disorder, but the underlying neurological mechanism remains unclear. MATERIAL AND METHODS Fifteen stroke patients with poststroke aphasia and 9 healthy controls were included in the study. The value of fractional anisotropy (FA) in the dominate arcuate fasciculus in stroke patients and healthy controls were measured using DTI. We also assessed their repetition dysfunction with the Aphasia Battery of Chinese (ABC) assessment and calculated the correlation between the FA values in the dominate arcuate fasciculus and ABC scores of word repetition and sentence repetition. RESULTS There was a moderate correlation between the total score of repetition evaluation and the FA value of injured arcuate fasciculus in the dominant hemisphere (r=0.551, P=0.033). We found no correlation between the score of word repetition and the FA value of injured arcuate fasciculus in the dominant hemisphere (r=0.330, P=0.230), but there was a strong correlation between the score of sentence repetition and the FA value of injured arcuate fasciculus in the dominant hemisphere (r=0.795, P≤0.001). CONCLUSIONS We found that unintegrated left arcuate fasciculus might be related to the repetition dysfunction after stroke, especially sentence repetition deficit, which suggests that sentence repetition evaluation could be used to indicate the integrity of the arcuate fasciculus in the dominant hemisphere after stroke.

An Integrative Review of Cerebral Salt Wasting Syndrome.

BACKGROUND: Although cerebral salt wasting syndrome (CSWS) is widely recognized, its clinical characteristics, diagnostic criteria, and management have not been clearly defined. This study was undertaken to comprehensively review current literature and provide a more complete picture of CSWS. This review also aimed to provide information for nurses on how to differentiate cerebral salt wasting syndrome from syndrome of inappropriate antidiuretic hormone secretion. METHODS: An integrative review was performed. Searches were conducted between May and July 2018. The primary information sources were CINAHL, Google Scholar, MEDLINE, PubMed, Scopus, and Web of Science. Included articles were published from 1954 to July 2018. RESULTS: The essential features of CSWS are hyponatremia, hypovolemia, and increased urine output. Treatment regimens may be determined based on the acuity and severity of hyponatremia and hypovolemia as well as evident symptoms and signs. CONCLUSION: This review may help neuroscience nurses become knowledgeable about CSWS for the drafting of appropriate nursing care plans and also be able to differentiate CSWS from syndrome of inappropriate antidiuretic hormone secretion as early as possible for timely and proper management.

Advantages of methohexital over amobarbital in determining hemispheric language and memory lateralization in the Wada test - A retrospective study.

OBJECTIVE: Due to supply shortage, amobarbital, the traditional anesthetic agent in Wada testing, was replaced by methohexital in many epilepsy centers. This study aimed to compare the two barbiturates to identify possible advantages or disadvantages of methohexital as compared to amobarbital with regard to the adequacy of language and memory testing during the Wada test. METHODS: Data from 75 patients with temporal lobe epilepsy who underwent bilateral Wada tests using either amobarbital (n = 53) or methohexital (n = 22) as part of presurgical work-up were analyzed retrospectively. The two subgroups were compared regarding hemispheric language and memory lateralization results and Wada testing characteristics, and the adequacy of language and memory testing was assessed. RESULTS: We observed shorter durations of motor-, speech-, and EEG recovery after each injection in patients receiving methohexital compared to amobarbital. In addition, significantly more items could be presented during effective hemispheric inactivation in the methohexital group. Moreover, significant correlations of Wada memory scores with standard neuropsychological memory test scores could be found in the methohexital group. SIGNIFICANCE: Our findings confirm that methohexital is not only equally suitable for Wada testing but has several advantages over amobarbital. Wada testing can be performed more efficiently and under more constant hemispheric inactivation using methohexital. Furthermore, the adequacy of language and memory testing during the Wada test might be affected by the anesthetic agent used.

Effect of age on the gap-prepulse inhibition of the cortical N1-P2 complex in humans as a step towards an objective measure of tinnitus.

The gap-prepulse inhibition of the acoustic startle reflex has been widely used as a behavioral method for tinnitus screening in animal studies. The cortical-evoked potential gap-induced inhibition has also been investigated in animals as well as in human subjects. The present study aimed to investigate the effect of age on the cortical N1-P2 complex in the gap-prepulse inhibition paradigm. Fifty-seven subjects, aged 20 to 68 years, without continuous tinnitus, were tested with two effective gap conditions (embedded gap of 50- or 20-ms duration). Retest sessions were performed within one month. A significant gap-induced inhibition of the N1-P2 complex was found in both gap durations. Age differently affected the inhibition, depending on gap duration. With a 50-ms gap, the inhibition decreased significantly with the increase in age. This age-inhibition relationship was not found when using a 20-ms gap. The results were reproducible in the retest session. Our findings suggest that the interaction between age and gap duration should be considered when applying the gap-induced inhibition of the cortical-evoked potential as an objective measure of tinnitus in human subjects. Further studies with tinnitus patients are warranted to identify gap duration that would minimize the effects of age and maximize the difference in the inhibition between those with and without tinnitus.

Common and separable neural alterations in substance use disorders: A coordinate-based meta-analyses of functional neuroimaging studies in humans.

Delineating common and separable neural alterations in substance use disorders (SUD) is imperative to understand the neurobiological basis of the addictive process and to inform substance-specific treatment strategies. Given numerous functional MRI (fMRI) studies in different SUDs, a meta-analysis could provide an opportunity to determine robust shared and substance-specific alterations. The present study employed a coordinate-based meta-analysis covering fMRI studies in individuals with addictive cocaine, cannabis, alcohol, and nicotine use. The primary meta-analysis demonstrated common alterations in primary dorsal striatal, and frontal circuits engaged in reward/salience processing, habit formation, and executive control across different substances and task-paradigms. Subsequent sub-analyses revealed substance-specific alterations in frontal and limbic regions, with marked frontal and insula-thalamic alterations in alcohol and nicotine use disorders respectively. Examining task-specific alterations across substances revealed pronounced frontal alterations during cognitive processes yet stronger striatal alterations during reward-related processes. Finally, an exploratory meta-analysis revealed that neurofunctional alterations in striatal and frontal reward processing regions can already be determined with a high probability in studies with subjects with comparably short durations of use. Together the findings emphasize the role of dysregulations in frontostriatal circuits and dissociable contributions of these systems in the domains of reward-related and cognitive processes which may contribute to substance-specific behavioral alterations.

Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS: Structural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Posterior reversible encephalopathy syndrome as an underlying cause for encephalopathy in a sepsis patient in the intensive care unit: A case report.

Posterior reversible encephalopathy (PRES) is a clinical and radiological syndrome characterized by neurological findings and vasogenic edema in the posterior regions of the cerebral hemispheres. Sepsis and septic shock have recently been recognized as an etiological factor in PRES. In this case report, we are presenting a patient with intraabdominal sepsis and PRES followed in the intensive care unit with an unfavorable neurological outcome. Wider recognition of PRES as a cause of encephalopathy in sepsis patients is necessary.

Transcriptomic Landscape and Functional Characterization of Induced Pluripotent Stem Cell-Derived Cerebral Organoids in Schizophrenia.

Importance: Three-dimensional cerebral organoids generated from patient-derived induced pluripotent stem cells (iPSCs) may be used to interrogate cellular-molecular underpinnings of schizophrenia. Objective: To determine transcriptomic profiles and functional characteristics of cerebral organoids from patients with schizophrenia using gene expression studies, complemented with investigations of mitochondrial function through measurement of real-time oxygen consumption rate, and functional studies of neuronal firing with microelectrode arrays. Design, Setting, and Participants: This case-control study was conducted at Massachusetts General Hospital between 2017 and 2019. Transcriptomic profiling of iPSC-derived cerebral organoids from 8 patients with schizophrenia and 8 healthy control individuals was undertaken to identify cellular pathways that are aberrant in schizophrenia. Induced pluripotent stem cells and cerebral organoids were generated from patients who had been diagnosed as having schizophrenia and from heathy control individuals. Main Outcomes and Measures: Transcriptomic analysis of iPSC-derived cerebral organoids from patients with schizophrenia show differences in expression of genes involved in synaptic biology and neurodevelopment and are enriched for genes implicated in schizophrenia genome-wide association studies (GWAS). Results: The study included iPSC lines generated from 11 male and 5 female white participants, with a mean age of 38.8 years. RNA sequencing data from iPSC-derived cerebral organoids in schizophrenia showed differential expression of genes involved in synapses, in nervous system development, and in antigen processing. The differentially expressed genes were enriched for genes implicated in schizophrenia, with 23% of GWAS genes showing differential expression in schizophrenia and control organoids: 10 GWAS genes were upregulated in schizophrenia organoids while 15 GWAS genes were downregulated. Analysis of the gene expression profiles suggested dysregulation of genes involved in mitochondrial function and those involved in modulation of excitatory and inhibitory pathways. Studies of mitochondrial respiration showed lower basal consumption rate, adenosine triphosphate production, proton leak, and nonmitochondrial oxygen consumption in schizophrenia cerebral organoids, without any differences in the extracellular acidification rate. Microelectrode array studies of cerebral organoids showed no differences in baseline electrical activity in schizophrenia but revealed a diminished response to stimulation and depolarization. Conclusions and Relevance: Investigations of patient-derived cerebral organoids in schizophrenia revealed gene expression patterns suggesting dysregulation of a number of pathways in schizophrenia, delineated differences in mitochondrial function, and showed deficits in response to stimulation and depolarization in schizophrenia.

Dysregulation of inflammation, neurobiology, and cognitive function in PTSD: an integrative review.

Compelling evidence from animal and human research suggest a strong link between inflammation and posttraumatic stress disorder (PTSD). Furthermore, recent findings support compromised neurocognitive function as a key feature of PTSD, particularly with deficits in attention and processing speed, executive function, and memory. These cognitive domains are supported by brain structures and neural pathways that are disrupted in PTSD and which are implicated in fear learning and extinction processes. The disruption of these supporting structures potentially results from their interaction with inflammation. Thus, the converging evidence supports a model of inflammatory dysregulation and cognitive dysfunction as combined mechanisms underpinning PTSD symptomatology. In this review, we summarize evidence of dysregulated inflammation in PTSD and further explore how the neurobiological underpinnings of PTSD, in the context of fear learning and extinction acquisition and recall, may interact with inflammation. We then present evidence for cognitive dysfunction in PTSD, highlighting findings from human work. Potential therapeutic approaches utilizing novel pharmacological and behavioral interventions that target inflammation and cognition also are discussed.

Ipsilateral Corticospinal Tract Excitability Contributes to the Severity of Mirror Movements in Unilateral Cerebral Palsy: A Case Series.

Mirror movements (MM) can be a clinical manifestation of unilateral cerebral palsy (UCP) causing involuntary movements when attempting to use either hand for functional activities. Atypical development of the corticospinal tract (CST) contributes to impairments in observed motor movements and functional activities. However, little is known about the underlying neurophysiology and contribution of the CST to MM. The current case study characterizes MM in 13 children and young adults with UCP ranging in age from 7 to 19 years and includes clinical and neurophysiologic variables. Clinical profiles included MM of each hand (ie, Woods and Teuber), bimanual coordination and hand use (Assisting Hand Assessment [AHA]), and perception of performance (Canadian Occupational Performance Measure [COPM]). We measured the strength of motor-evoked potentials (MEP) elicited from single-pulse transcranial magnetic stimulation (TMS) of each hemisphere to create a ratio of hemispheric responses. Our sample included three types of CST circuitry: ipsilateral (n = 5), bilateral (n = 3), and contralateral (n = 4). The MEP ratio ranged from 0 to 1.45 (median 0.11) with greater MM observed in participants with ratios greater than 0.5. We observed a positive relationship between the MEP ratio and the more-affected MM score, meaning participants with larger ipsilateral responses from contralesional stimulation (eg, the contralesional hemisphere was stimulated with TMS resulting in an ipsilateral MEP response), as compared with contralateral responses, displayed greater MM than those that did not. There was no relationship between MM and function as measured by the AHA or COPM. These findings suggest a role of the contralesional hemisphere to MM, which could serve as a therapeutic target for interventions.