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Biomedical subjects

Paul R Carney

Publications and source records attributed to Paul R Carney.

13 recordsLinked to original sources
PubMed2025

Precision Genomics: A Reality Having Universal Impact in a New Era of Psychiatry - Lessons Learned, Past and Present.

Addiction neuroscience explores the complex interplay between genetic, neurobiological, environmental, and socio-spiritual factors underlying substance and behavioral addictions. Over the past three decades, research in this domain has identified critical molecular and epigenetic mechanisms-particularly those affecting dopaminergic signaling and reward pathways-that contribute to both vulnerability and resilience to addictive behaviors. Central to this understanding is the concept of reward deficiency syndrome (RDS), first introduced by Kenneth Blum, which posits that hypodopaminergic functioning predisposes individuals to seek maladaptive rewards. Advances in neurogenetics, including the identification of key polymorphisms such as the DRD2 A1 allele, have paved the way for precision tools like the genetic addiction risk severity (GARS®) test. This test, alongside pro-dopaminergic nutraceutical interventions like KB220, demonstrates the potential for early detection and individualized treatment of "pre-addiction" risk states. Despite ongoing reliance on opioids for opioid use disorder (OUD), emerging paradigms advocate for dopamine homeostasis through non-addictive, integrative approaches. Furthermore, the integration of whole genome sequencing data can be used for Genome-Wide Association Studies (GWAS), multi-omics, and machine learning into clinical practice holds promise for advancing personalized medicine in addiction treatment. As the field progresses, addressing health equity and improving genomic representation across populations remain critical goals. This evolving framework underscores the importance of leveraging genomic insights to prevent, predict, and personalize interventions for addiction and mental illness at scale.

Disorder↗
PubMed2006

Evolving into epilepsy: Multiscale electrophysiological analysis and imaging in an animal model.

Epilepsy research for the design of seizure detection/prediction neuroprosthetics has been faced with the search for electrophysiologic control parameters that can be used to infer the epileptic state of the animal and be leveraged at a later time to deliver neurotherapeutic feedback. The analysis presented here uses multi-microelectrode array technology to provide an electrophysiologic quantification of a hippocampal neural ensemble during the latent period of epileptogenesis. Through the use of signal processing system identification methodologies, we were able to assess the spatial and temporal interrelations of ensembles of hippocampal neurons and relate them to the evolution of the epileptic condition. High-field magnetic resonance (MR) imaging was used to determine the location of electrode placement and to evaluate hippocampal pyramidal cell structural damage. Long-term single unit activity analysis suggests that hippocampal neurons in both CA1-2 and dentate regions increase the number of occurrences and duration of their bursting activity after injury to the contra-lateral hippocampus. The trends inferred from both single neuron and ensemble analysis suggests that the evolution into epilepsy is not abrupt but modulates gradually from the time of injury.

Action Potentials↗
PubMed2006

Peripheral neuropathy in genetic mitochondrial diseases.

Peripheral neuropathy is an underrecognized but common occurrence in genetic mitochondrial disorders. To gain insight into the frequency and clinical presentation of this complication, nerve conduction studies were performed on 43 subjects with congenital lactic acidosis enrolled in a controlled clinical trial of oral dichloroacetate. Median and peroneal motor conduction studies and median and sural sensory conduction studies were performed on each patient. The mean amplitude of the peroneal motor nerve (P < 0.001) and the conduction velocities of the median (P < 0.001) and peroneal (P < 0.001) motor nerves were uniformly lower in our subjects than in healthy literature control subjects. There were no significant differences in sensory nerve conduction studies. A generalized reduction in motor nerve conduction velocity was the dominant electrophysiological abnormality in the patients in this study and was independent of age, sex, or congenital mitochondrial disorder. We postulate that cellular energy failure is the most likely common cause of peripheral neuropathy in patients with genetic mitochondrial diseases, owing to the high demand for adenosine triphosphate via aerobic carbohydrate metabolism by nerve tissue.

Acidosis, Lactic↗
PubMed2006

Focal epileptiform spikes in conjuction with K-complexes.

Dyshormia or epileptiform spikes occurring within K-complexes have been described in patients with generalized epilepsy, with one study reporting that generalized spikes occurred frequently in association with K-complexes. We report the rate of focal epileptiform spikes occurring within K-complexes in localization-related epilepsy. Presurgical or diagnostic long-term video-EEG results of 40 consecutive patients with epilepsy (13 patients with right temporal lobe epilepsy, 20 patients with left temporal lobe epilepsy, and 7 patients with frontal lobe epilepsy) were reviewed. Sleep samples were reviewed and the numbers of K-complexes, spikes, and spikes within K-complexes were recorded. The comparison group consisted of 40 consecutive patients with nonepileptic events who were monitored with long-term video EEG. Focal epileptiform spikes occurring within K-complexes occurred in 2 of 13 (15%) patients with right temporal lobe patients, 6 of 20 (30%) patients with left temporal lobe, and 3 of 7 (42%) patients with extratemporal lobe epilepsy. In most patients, spikes occurring during K-complexes were rare. We identified spikes occurring during K-complexes in patients with localization-related epilepsy. The sharply contoured components of K-complexes or associated sleep spindles may obscure focal spikes within K-complexes. Nevertheless, K-complexes may be associated with focal epileptiform discharges.

Adolescent↗
PubMed2006

Structural modifications in chronic microwire electrodes for cortical neuroprosthetics: a case study.

Long-term viability of chronic invasive neural probes is a necessary condition for extracting robust control signals directly from neural tissue. Although immune/tissue response is a leading factor in the degradation of single neuron recording, we investigate a second component of signal degradation connected to the structural changes associated with microwire electrodes chronically exposed to extracelluar environments in vivo. Scanning electron microscopy is used to assess the surface modifications to the electrodes after an implantation duration of four weeks in rats. The electrode developed a smooth fracture surface, a reduction of the metal diameter, and pitting in the insulation of the electrode structure. Over the duration of implantation, recording properties of the electrode were marked by a reduction in the peak-to-peak amplitude in neuronal firing.

Action Potentials↗
PubMed2006

Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children.

OBJECTIVE: Open-label studies indicate that oral dichloroacetate (DCA) may be effective in treating patients with congenital lactic acidosis. We tested this hypothesis by conducting the first double-blind, randomized, control trial of DCA in this disease. METHODS: Forty-three patients who ranged in age from 0.9 to 19 years were enrolled. All patients had persistent or intermittent hyperlactatemia, and most had severe psychomotor delay. Eleven patients had pyruvate dehydrogenase deficiency, 25 patients had 1 or more defects in enzymes of the respiratory chain, and 7 patients had a mutation in mitochondrial DNA. Patients were preconditioned on placebo for 6 months and then were randomly assigned to receive an additional 6 months of placebo or DCA, at a dose of 12.5 mg/kg every 12 hours. The primary outcome results were (1) a Global Assessment of Treatment Efficacy, which incorporated tests of neuromuscular and behavioral function and quality of life; (2) linear growth; (3) blood lactate concentration in the fasted state and after a carbohydrate meal; (4) frequency and severity of intercurrent illnesses and hospitalizations; and (5) safety, including tests of liver and peripheral nerve function. OUTCOME: There were no significant differences in Global Assessment of Treatment Efficacy scores, linear growth, or the frequency or severity of intercurrent illnesses. DCA significantly decreased the rise in blood lactate caused by carbohydrate feeding. Chronic DCA administration was associated with a fall in plasma clearance of the drug and with a rise in the urinary excretion of the tyrosine catabolite maleylacetone and the heme precursor delta-aminolevulinate. CONCLUSIONS: In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

Acidosis, Lactic↗
PubMed2005

Isolated idiopathic hypomagnesemia presenting as aphasia and seizures.

Isolated hypomagnesemia of the idiopathic form is a rare condition that is known to present as generalized motor seizures in children. This report describes a 4-year-old African-American male who presented with a predominant symptom of sudden onset aphasia and no clear initial motor seizure activity. An evaluation revealed an isolated and severe hypomagnesemia (initial serum magnesium levels <1.0 mg/dL) and inappropriate renal handling of magnesium (fractional excretion of magnesium >40% under conditions of hypomagnesemia). The child had subsequent generalized tonic-clonic seizures that were brought under control with valproic acid therapy and magnesium supplementation. Six months after the diagnosis, he had regained 50-60% of his speech and had no further staring spells or motor seizure activity after the initial episode. Isolated and idiopathic hypomagnesemia caused by defective renal reabsorption of magnesium is a rare familial condition with variable inheritance. Aphasia as the solitary presenting symptom has not been described before. The exact pathophysiology of hypomagnesemic aphasia and seizures is not known but may relate to disinhibition of specific types of glutamate receptors. In the present case, neuronal depolarization may have been localized to language areas in the temporal lobes.

Aphasia↗
PubMed2004

Daytime behavior and sleep disturbance in childhood epilepsy.

The purpose of this research is to further explore the relationship between sleep disturbance and daytime behavior in children with epilepsy. Parent-rating questionnaires and child symptom self-report measures were employed to evaluate daytime behavior in 30 children with epilepsy and sleep-disordered symptoms. Overnight polysomnography was used to assess for nocturnal sleep problems such as obstructive sleep apnea, nocturnal seizures, periodic leg movements, and sleep fragmentation. We hypothesized that children with epilepsy would exhibit both clinically significant behavioral and sleep problems. Results indicate that 80% of children with epilepsy exhibited sleep disruption because of either clinically significant obstructive apnea syndrome, disturbance of sleep architecture, or sleep fragmentation. These findings further suggest that daytime behavior problems encountered in children with epilepsy may be attributed to specific disruptions in sleep regulation.

Adolescent↗
PubMed2003

Sleep disturbance in children with epilepsy.

This study employed a validated pediatric sleep questionnaire to evaluate for sleep-disordered symptoms in children with epilepsy (n=14). Results were compared with those for age-matched children (n=14) with known obstructive sleep apnea. Subjects were enrolled from an outpatient epilepsy clinic and a pediatric sleep disorders clinic. We hypothesized that children with epilepsy would (1) report symptoms of sleep disturbance similar to those of children with documented obstructive sleep apnea, and (2) display behavioral disturbances on parent and child behavioral symptom measures. Results indicate that more than 50% of children with epilepsy had behavioral problems (n=14). No differences in snoring, excessive daytime sleepiness, and restless sleep were seen between the two subject groups. Results suggest that neurobehavioral problems in children with epilepsy may in part be attributed to an underlying sleep disturbance.

Adolescent↗
PubMed2003

Adaptive epileptic seizure prediction system.

Current epileptic seizure "prediction" algorithms are generally based on the knowledge of seizure occurring time and analyze the electroencephalogram (EEG) recordings retrospectively. It is then obvious that, although these analyses provide evidence of brain activity changes prior to epileptic seizures, they cannot be applied to develop implantable devices for diagnostic and therapeutic purposes. In this paper, we describe an adaptive procedure to prospectively analyze continuous, long-term EEG recordings when only the occurring time of the first seizure is known. The algorithm is based on the convergence and divergence of short-term maximum Lyapunov exponents (STLmax) among critical electrode sites selected adaptively. A warning of an impending seizure is then issued. Global optimization techniques are applied for selecting the critical groups of electrode sites. The adaptive seizure prediction algorithm (ASPA) was tested in continuous 0.76 to 5.84 days intracranial EEG recordings from a group of five patients with refractory temporal lobe epilepsy. A fixed parameter setting applied to all cases predicted 82% of seizures with a false prediction rate of 0.16/h. Seizure warnings occurred an average of 71.7 min before ictal onset. Similar results were produced by dividing the available EEG recordings into half training and testing portions. Optimizing the parameters for individual patients improved sensitivity (84% overall) and reduced false prediction rate (0.12/h overall). These results indicate that ASPA can be applied to implantable devices for diagnostic and therapeutic purposes.

Algorithms↗
PubMed2003

Juvenile-onset Leigh syndrome with an acute polyneuropathy at presentation.

Subacute necrotizing encephalomyelopathy or Leigh syndrome can be associated with a polyneuropathy. By far, the most commonly encountered neuropathy is a chronic neuropathy with features of demyelination, which can be the presenting manifestation of Leigh syndrome. On rare occasions, the neuropathy encountered can represent a more acute process. We describe a rare case of juvenile-onset Leigh syndrome presenting with an acute polyneuropathy.

Age of Onset↗
PubMed2002

Primary antiphospholipid syndrome presenting with a branch retinal artery occlusion in a 15-year-old boy.

Acute vascular events are rare in the pediatric population, but there is an association with the presence of antiphospholipid antibodies. When there is no other underlying medical disorder, this is referred to as primary antiphospholipid syndrome. We present a case of a 15-year-old boy who developed an acute superior branch retinal artery occlusion. Complete evaluation revealed significant elevations in antiphospholipid antibodies. To our knowledge, there are no cases in children of primary antiphospholipid syndrome presenting with this clinical manifestation.

Adolescent↗