Modulation of the N13 component of the somatosensory evoked potentials in an experimental model of central sensitization in humans.

The N13 component of somatosensory evoked potential (N13 SEP) represents the segmental response of dorsal horn neurons. In this neurophysiological study, we aimed to verify whether N13 SEP might reflect excitability changes of dorsal horn neurons during central sensitization. In 22 healthy participants, we investigated how central sensitization induced by application of topical capsaicin to the ulnar nerve territory of the hand dorsum modulated N13 SEP elicited by ulnar nerve stimulation. Using a double-blind placebo-controlled crossover design, we also tested whether pregabalin, an analgesic drug with proven efficacy on the dorsal horn, influenced capsaicin-induced N13 SEP modulation. Topical application of capsaicin produced an area of secondary mechanical hyperalgesia, a sign of central sensitization, and increased the N13 SEP amplitude but not the peripheral N9 nor the cortical N20-P25 amplitude. This increase in N13 SEP amplitude paralleled the mechanical hyperalgesia and persisted for 120 min. Pregabalin prevented the N13 SEP modulation associated with capsaicin-induced central sensitization, whereas capsaicin application still increased N13 SEP amplitude in the placebo treatment session. Our neurophysiological study showed that capsaicin application specifically modulates N13 SEP and that this modulation is prevented by pregabalin, thus suggesting that N13 SEP may reflect changes in dorsal horn excitability and represent a useful biomarker of central sensitization in human studies.

How different experimental models of secondary hyperalgesia change the nociceptive flexion reflex.

OBJECTIVE: In this neurophysiological study in healthy humans, we assessed how central sensitization induced by either high-frequency stimulation (HFS) or topical capsaicin application modulates features of the RIII reflex response. The ability of these stimuli to engage the endogenous pain modulatory system was also tested. METHODS: In 26 healthy participants we elicited an RIII reflex using suprathreshold stimulation of the sural nerve. Subsequently HFS or capsaicin were applied to the foot and the RIII reflex repeated after 15 minutes. Contact heating of the volar forearm served as the heterotopic test stimulus to probe activation of the endogenous pain modulatory system. RESULTS: HFS significantly reduced the pain threshold by 29% and the RIII reflex threshold by 20%. Capsaicin significantly reduced the pain threshold by 17% and the RIII reflex threshold by 18%. Both HFS and capsaicin left RIII reflex size unaffected. Numerical Rating Scale (NRS) pain scores elicited by the heterotopic noxious heat stimulus were unaffected by capsaicin and slightly increased by HFS. CONCLUSIONS: HFS and capsaicin similarly modulated the pain threshold and RIII reflex threshold, without a concomitant inhibitory effect of the endogenous pain modulatory system. SIGNIFICANCE: Our neurophysiological study supports the use of the RIII reflex in investigating central sensitization in humans.

Electrophysiological assessment methodology of sensory processing dysfunction in schizophrenia and dementia of the Alzheimer type.

Schizophrenia and Alzheimer's disease impacts on various sensory processings are extensively reviewed in the present publication. This article describes aspects of a research project whose aim is to delineate the neurobiology that may underlie Social Withdrawal in Alzheimer's disease, Schizophrenia and Major Depression. This is a European-funded IMI 2 project, identified as PRISM (Psychiatric Ratings using Intermediate Stratified Markers). This paper focuses specifically on the selected electrophysiological paradigms chosen based on a comprehensive review of all relevant literature and practical constraints. The choice of the electrophysiological biomarkers were fundamentality based their metrics and capacity to discriminate between populations. The selected electrophysiological paradigms are resting state EEG, auditory mismatch negativity, auditory and visual based oddball paradigms, facial emotion processing ERP's and auditory steady-state response. The primary objective is to study the effect of social withdrawal on various biomarkers and endophenotypes found altered in the target populations. This has never been studied in relationship to social withdrawal, an important component of CNS diseases.

Using all-payer claims data for health surveillance of people with intellectual and developmental disabilities.

BACKGROUND: To address limitations and challenges associated with current health surveillance of people with intellectual and developmental disabilities (IDD), this study investigates the use of all-payer claims data to identify and characterise this population. METHOD: All-payer claims data from 2010 to 2014 were used to study people with IDD in New Hampshire. Starting with the Centers for Medicare and Medicaid Services' algorithm, IDD was defined using ICD-9 diagnosis codes. Additional ICD-9 codes for developmental disabilities were included to build the knowledge base begun by recent research conducted on Medicaid claimants in five other states. RESULTS: Findings showed the enhanced algorithm offers a replicable and feasible way to conduct health surveillance of people with IDD at the state level. CONCLUSION: Substantive and significant differences between Medicaid and commercial claimants suggest that using all-payer claims provides a richer and more complete method for health surveillance of people with IDD.

Differential effects of NMDA antagonists on high frequency and gamma EEG oscillations in a neurodevelopmental model of schizophrenia.

Neuroanatomical, electrophysiological and behavioural abnormalities following timed prenatal methylazoxymethanol acetate (MAM) treatment in rats model changes observed in schizophrenia. In particular, MAM treatment on gestational day 17 (E17) preferentially disrupts limbic-cortical circuits, and is a promising animal model of schizophrenia. The hypersensitivity of this model to the NMDA receptor antagonist-induced hyperactivity has been proposed to mimic the increase in sensitivity observed in schizophrenia patients following PCP and Ketamine administration. However, how this increase in sensitivity in both patients and animals translates to differences in EEG oscillatory activity is unknown. In this study we have shown that MAM-E17 treated animals have an increased response to the hyperlocomotor and wake promoting effects of Ketamine, PCP, and MK801 but not to the competitive antagonist SDZ 220,581. These behavioural changes were accompanied by altered EEG responses to the NMDAR antagonists, most evident in the gamma and high frequency (HFO) ranges; altered sensitivity of these neuronal network oscillations in MAM-exposed rats is regionally selective, and reflects altered interneuronal function in this neurodevelopmental model.

Lymphangioleiomyomatosis: a case-control study of perinatal and early life events.

BACKGROUND: Lymphangioleiomyomatosis (LAM), a rare disease affecting women, is caused by somatic mutations in the tuberous sclerosis complex genes. METHODS: A case-control questionnaire study was carried out examining parental and family history, prenatal events, and early life events to try to shed light on the aetiology of the condition. Forty five patients identified from a national LAM register completed a questionnaire and 31 were compared with 117 age and sex matched control subjects using conditional logistic regression. RESULTS: No differences were found in perinatal events, childhood infections, and parental or family history, except that patients were more likely to be an only child (odds ratio (OR) 4.3 (95% confidence interval (CI), 1.5 to 11.8)) and have a relative with uterine fibroids (OR 4.2 (1.4 to 13)). Patients with LAM had had fewer pregnancies and fewer children but no differences in miscarriage rates. A non-matched analysis using all 45 cases and 117 controls gave similar results. CONCLUSIONS: No features in the family history, perinatal events, or early life events were detected that were associated with having LAM. Being more likely to be an only child and having an increased family history of uterine fibroids may, if confirmed, indicate some differences in reproductive function within the families of affected individuals.

Incidence of hypoglycemia in the low-birth-weight neonate.

Of 179 consecutively born single infants whose birth weights were below the twenty-fifth percentile for gestational age, four were hypoglycemic in the first 18 hours of age with true blood glucose levels of 17 mg. per 100 ml. or less. All four had symptoms referable to the respiratory system and the two deaths were from pulmonary causes.