39 results on '"Joel Frohlich"'
Search Results
2. Editorial: Dissociations between neural activity and conscious state: a key to understanding consciousness
- Author
-
Joel Frohlich, Julia S. Crone, Pedro A. M. Mediano, Daniel Toker, and Daniel Bor
- Subjects
EEG ,consciousness ,sleep ,general anesthesia ,disorders of consciousness ,biomarkers ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2023
- Full Text
- View/download PDF
3. Neural complexity is a common denominator of human consciousness across diverse regimes of cortical dynamics
- Author
-
Joel Frohlich, Jeffrey N. Chiang, Pedro A. M. Mediano, Mark Nespeca, Vidya Saravanapandian, Daniel Toker, John Dell’Italia, Joerg F. Hipp, Shafali S. Jeste, Catherine J. Chu, Lynne M. Bird, and Martin M. Monti
- Subjects
Biology (General) ,QH301-705.5 - Abstract
EEG measurements in children with Angelman or duplication 15q11.2-13.1 syndrome reveal a dissociation between consciousness and sleep-like spectral content, with complexity-based measures superseding other markers of consciousness.
- Published
- 2022
- Full Text
- View/download PDF
4. Not with a 'zap' but with a 'beep': Measuring the origins of perinatal experience
- Author
-
Joel Frohlich, Tim Bayne, Julia S. Crone, Alessandra DallaVecchia, Asger Kirkeby-Hinrup, Pedro A.M. Mediano, Julia Moser, Karolina Talar, Alireza Gharabaghi, and Hubert Preissl
- Subjects
Infant ,Fetus ,Perinatal ,Consciousness ,Perturbational complexity ,MEG ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
When does the mind begin? Infant psychology is mysterious in part because we cannot remember our first months of life, nor can we directly communicate with infants. Even more speculative is the possibility of mental life prior to birth. The question of when consciousness, or subjective experience, begins in human development thus remains incompletely answered, though boundaries can be set using current knowledge from developmental neurobiology and recent investigations of the perinatal brain. Here, we offer our perspective on how the development of a sensory perturbational complexity index (sPCI) based on auditory (“beep-and-zip”), visual (“flash-and-zip”), or even olfactory (“sniff-and-zip”) cortical perturbations in place of electromagnetic perturbations (“zap-and-zip”) might be used to address this question. First, we discuss recent studies of perinatal cognition and consciousness using techniques such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and, in particular, magnetoencephalography (MEG). While newborn infants are the archetypal subjects for studying early human development, researchers may also benefit from fetal studies, as the womb is, in many respects, a more controlled environment than the cradle. The earliest possible timepoint when subjective experience might begin is likely the establishment of thalamocortical connectivity at 26 weeks gestation, as the thalamocortical system is necessary for consciousness according to most theoretical frameworks. To infer at what age and in which behavioral states consciousness might emerge following the initiation of thalamocortical pathways, we advocate for the development of the sPCI and similar techniques, based on EEG, MEG, and fMRI, to estimate the perinatal brain's state of consciousness.
- Published
- 2023
- Full Text
- View/download PDF
5. Electrophysiological Abnormalities in Angelman Syndrome Correlate With Symptom Severity
- Author
-
Joerg F. Hipp, Joel Frohlich, Marius Keute, Wen-Hann Tan, and Lynne M. Bird
- Subjects
Angelman syndrome ,Biomarkers ,Clinical scales ,EEG ,UBE3A ,Psychiatry ,RC435-571 - Abstract
Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by the absence of functional UBE3A in neurons. Excess low-frequency oscillations as measured with electroencephalography (EEG) have been identified as a characteristic finding, but the relationship of this EEG finding to the symptomatology of AS and its significance in the pathophysiology of AS remain unknown. Methods: We used correlations and machine learning to investigate the cross-sectional and longitudinal relationship between EEG spectral power and motor, cognitive, and language skills (Bayley Scales of Infant and Toddler Development, Third Edition); adaptive behavior (Vineland Adaptive Behavior Scales, Second Edition); AS-specific symptoms (AS Clinical Severity Scale); and the age of epilepsy onset in a large sample of children (age: 1–18 years) with AS due to a chromosomal deletion of 15q11-q13 (45 individuals with 72 visits). Results: We found that after accounting for age differences, participants with stronger EEG delta-band abnormality had earlier onset of epilepsy and lower performance scores across symptom domains including cognitive, motor, and communication. Combing spatial and spectral information beyond the delta frequency band increased the cross-sectional association with clinical severity on average by approximately 45%. Furthermore, we found evidence for longitudinal correlations of EEG delta-band power within several performance domains, including the mean across Bayley Scales of Infant and Toddler Development, Third Edition, scores. Conclusions: Our results show an association between EEG abnormalities and symptom severity in AS, underlining the significance of the former in the pathophysiology of AS. Furthermore, our work strengthens the rationale for using EEG as a biomarker in the development of treatments for AS, a concept that may apply more generally to neurodevelopmental disorders.
- Published
- 2021
- Full Text
- View/download PDF
6. Author Correction: Neural complexity is a common denominator of human consciousness across diverse regimes of cortical dynamics
- Author
-
Joel Frohlich, Jeffrey N. Chiang, Pedro A. M. Mediano, Mark Nespeca, Vidya Saravanapandian, Daniel Toker, John Dell’Italia, Joerg F. Hipp, Shafali S. Jeste, Catherine J. Chu, Lynne M. Bird, and Martin M. Monti
- Subjects
Biology (General) ,QH301-705.5 - Published
- 2023
- Full Text
- View/download PDF
7. Properties of beta oscillations in Dup15q syndrome
- Author
-
Vidya Saravanapandian, Joel Frohlich, Joerg F. Hipp, Carly Hyde, Aaron W. Scheffler, Peyman Golshani, Edwin H. Cook, Lawrence T. Reiter, Damla Senturk, and Shafali S. Jeste
- Subjects
Dup15q syndrome ,Autism ,Biomarkers ,EEG ,GABA ,UBE3A ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract Background Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism, intellectual disability, hypotonia, and epilepsy. The 15q region harbors genes critical for brain development, particularly UBE3A and a cluster of gamma-aminobutyric acid type A receptor (GABAAR) genes. We recently described an electrophysiological biomarker of the syndrome, characterized by excessive beta oscillations (12–30 Hz), resembling electroencephalogram (EEG) changes induced by allosteric modulation of GABAARs. In this follow-up study, we tested a larger cohort of children with Dup15q syndrome to comprehensively examine properties of this EEG biomarker that would inform its use in future clinical trials, specifically, its (1) relation to basic clinical features, such as age, duplication type, and epilepsy; (2) relation to behavioral characteristics, such as cognition and adaptive function; (3) stability over time; and (4) reproducibility of the signal in clinical EEG recordings. Methods We computed EEG power and beta peak frequency (BPF) in a cohort of children with Dup15q syndrome (N = 41, age range 9–189 months). To relate EEG parameters to clinical (study 1) and behavioral features (study 2), we examined age, duplication type, epilepsy, cognition, and daily living skills (DLS) as predictors of beta power and BPF. To evaluate stability over time (study 3), we derived the intraclass correlation coefficients (ICC) from beta power and BPF computed from children with multiple EEG recordings (N = 10, age range 18–161 months). To evaluate reproducibility in a clinical setting (study 4), we derived ICCs from beta power computed from children (N = 8, age range 19–96 months), who had undergone both research EEG and clinical EEG. Results The most promising relationships between EEG and clinical traits were found using BPF. BPF was predicted both by epilepsy status (R 2 = 0.11, p = 0.038) and the DLS component of the Vineland Adaptive Behavior Scale (R 2 = 0.17, p = 0.01). Beta power and peak frequency showed high stability across repeated visits (beta power ICC = 0.93, BPF ICC = 0.92). A reproducibility analysis revealed that beta power estimates are comparable between research and clinical EEG (ICC = 0.94). Conclusions In this era of precision health, with pharmacological and neuromodulatory therapies being developed and tested for specific genetic etiologies of neurodevelopmental disorders, quantification and examination of mechanistic biomarkers can greatly improve clinical trials. To this end, the robust beta oscillations evident in Dup15q syndrome are clinically reproducible and stable over time. With future preclinical and computational studies that will help disentangle the underlying mechanism, it is possible that this biomarker could serve as a robust measure of drug target engagement or a proximal outcome measure in future disease modifying intervention trials.
- Published
- 2020
- Full Text
- View/download PDF
8. Sedation-Induced Burst Suppression Predicts Positive Outcome Following Traumatic Brain Injury
- Author
-
Joel Frohlich, Micah A. Johnson, David L. McArthur, Evan S. Lutkenhoff, John Dell'Italia, Courtney Real, Vikesh Shrestha, Norman M. Spivak, Jesús E. Ruiz Tejeda, Paul M. Vespa, and Martin M. Monti
- Subjects
traumatic brain injury (TBI) ,burst suppression ,barbiturates ,coma ,disorders of consciousness ,EEG biomarker ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
While electroencephalogram (EEG) burst-suppression is often induced therapeutically using sedatives in the intensive care unit (ICU), there is hitherto no evidence with respect to its association to outcome in moderate-to-severe neurological patients. We examined the relationship between sedation-induced burst-suppression (SIBS) and outcome at hospital discharge and at 6-month follow up in patients surviving moderate-to-severe traumatic brain injury (TBI). For each of 32 patients recovering from coma after moderate-to-severe TBI, we measured the EEG burst suppression ratio (BSR) during periods of low responsiveness as assessed with the Glasgow Coma Scale (GCS). The maximum BSR was then used to predict the Glasgow Outcome Scale extended (GOSe) at discharge and at 6 months post-injury. A multi-model inference approach was used to assess the combination of predictors that best fit the outcome data. We found that BSR was positively associated with outcomes at 6 months (P = 0.022) but did not predict outcomes at discharge. A mediation analysis found no evidence that BSR mediates the effects of barbiturates or propofol on outcomes. Our results provide initial observational evidence that burst suppression may be neuroprotective in acute patients with TBI etiologies. SIBS may thus be useful in the ICU as a prognostic biomarker.
- Published
- 2021
- Full Text
- View/download PDF
9. Mechanisms underlying the EEG biomarker in Dup15q syndrome
- Author
-
Joel Frohlich, Lawrence T. Reiter, Vidya Saravanapandian, Charlotte DiStefano, Scott Huberty, Carly Hyde, Stormy Chamberlain, Carrie E. Bearden, Peyman Golshani, Andrei Irimia, Richard W. Olsen, Joerg F. Hipp, and Shafali S. Jeste
- Subjects
Dup15q syndrome ,GABA ,UBE3A ,Biomarkers ,Autism ,EEG ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz). Both paternal Dup15q syndrome cases displayed beta power comparable to the reference cohort. Conclusions Our results suggest a critical role for GABAergic transmission in the Dup15q syndrome beta EEG phenotype, which cannot be explained by UBE3A dysfunction alone. If this mechanism is confirmed, the phenotype may be used as a marker of GABAergic pathology in clinical trials for Dup15q syndrome.
- Published
- 2019
- Full Text
- View/download PDF
10. Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome
- Author
-
Joel Frohlich, Lawrence T. Reiter, Vidya Saravanapandian, Charlotte DiStefano, Scott Huberty, Carly Hyde, Stormy Chamberlain, Carrie E. Bearden, Peyman Golshani, Andrei Irimia, Richard W. Olsen, Joerg F. Hipp, and Shafali S. Jeste
- Subjects
Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Following publication of the original article [1], we have been notified that the Ethics statement of the articles should be changed. The Ethics statement now reads:
- Published
- 2019
- Full Text
- View/download PDF
11. A Quantitative Electrophysiological Biomarker of Duplication 15q11.2-q13.1 Syndrome.
- Author
-
Joel Frohlich, Damla Senturk, Vidya Saravanapandian, Peyman Golshani, Lawrence T Reiter, Raman Sankar, Ronald L Thibert, Charlotte DiStefano, Scott Huberty, Edwin H Cook, and Shafali S Jeste
- Subjects
Medicine ,Science - Abstract
Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism spectrum disorder (ASD). A distinct electrophysiological (EEG) pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome.In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11), age-and-IQ-matched children with ASD (n = 10) and age-matched typically developing (TD) children (n = 9) and computed relative power in 6 frequency bands for 9 regions of interest (ROIs). Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27) across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions.In the first study, spontaneous beta1 (12-20 Hz) and beta2 (20-30 Hz) power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1-4 Hz) was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1). In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome.Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome.
- Published
- 2016
- Full Text
- View/download PDF
12. Not with a 'zap' but with a 'beep':Measuring the origins of perinatal experience
- Author
-
Joel Frohlich, Tim Bayne, Julia Crone, Alessandra Dallavecchia, Asger Kirkeby-Hinrup, Pedro Mediano, Julia Moser, Karolina Talar, Alireza Gharabaghi, and Hubert Preissl
- Subjects
Fetus ,MEG ,Neurology ,Consciousness ,Cognitive Neuroscience ,Infant ,Perturbational complexity ,Perinatal - Abstract
When does the mind begin? Infant psychology is mysterious in part because we cannot remember our first months of life, nor can we directly communicate with infants. Even more speculative is the possibility of mental life prior to birth. The question of when consciousness, or subjective experience, begins in human development thus remains incompletely answered, though boundaries can be set using current knowledge from developmental neurobiology and recent investigations of the perinatal brain. Here, we offer our perspective on how the development of a sensory perturbational complexity index (sPCI) based on auditory (“beep-and-zip”), visual (“flash-and-zip”), or even olfactory (“sniff-and-zip”) cortical perturbations in place of electromagnetic perturbations (“zap-and-zip”) might be used to address this question. First, we discuss recent studies of perinatal cognition and consciousness using techniques such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and, in particular, magnetoencephalography (MEG). While newborn infants are the archetypal subjects for studying early human development, researchers may also benefit from fetal studies, as the womb is, in many respects, a more controlled environment than the cradle. The earliest possible timepoint when subjective experience might begin is likely the establishment of thalamocortical connectivity at 26 weeks gestation, as the thalamocortical system is necessary for consciousness according to most theoretical frameworks. To infer at what age and in which behavioral states consciousness might emerge following the initiation of thalamocortical pathways, we advocate for the development of the sPCI and similar techniques, based on EEG, MEG, and fMRI, to estimate the perinatal brain's state of consciousness.
- Published
- 2023
13. Impact of neuromodulation on post-stroke aphasia: a multimodal randomized controlled study
- Author
-
Zhong Sheng Zheng, Kevin Xing-Long Wang, Henry Millan, Sharon Lee, Melissa Howard, Aaron Rothbart, Joel Frohlich, Emily Rosario, and Caroline Schnakers
- Abstract
BackgroundTranscranial direct current stimulation (tDCS) combined with speech and language therapy (SLT) may increase the effectiveness of recovery in post-stroke aphasia. However, inconsistent responses have been observed, in part due to small sample sizes, limited comprehensive assessments, and poor mechanistic understanding of intervention related recovery.MethodsUsing a double-blind, randomized, sham-controlled design, we investigated the efficacy of anodal Broca’s tDCS combined with SLT over five 20-minute daily sessions in 45 chronic stroke patients. EEG and DTI were used to explore treatment-mediated neuroplastic mechanisms. The primary outcome measures were linguistic skills evaluated by the Western Aphasia Battery-Revised before and after the intervention.ResultsCompared to sham (SLT + placebo), tDCS patients improved significantly more in aphasia quotient, auditory verbal comprehension, and spontaneous speech. While tDCS improved both expressive and receptive domains, sham only improved expressive language. EEG showed recovery in both groups to rely predominantly on the contralesional side, particularly the right middle temporal area (T4). While tDCS induced recovery correlated with changes in the faster frequencies (e.g., alpha, beta), sham mediated recovery correlated with changes in the slower frequencies (e.g., theta, delta). Furthermore, reduced beta coherence between T3 and T4 was associated with repetition gains specific to tDCS. Furthermore, improved spontaneous speech in tDCS was associated with decreased mean diffusivity in superior cerebellar peduncle. Given this region’s connectivity with contralateral cortical regions, this finding extends and aligns with the EEG signatures of neuroplasticity in right-lateralized cortical regions, highlighting the role of cerebro-cerebellar connections in language recovery.ConclusionsOur findings support the use of anodal Broca’s tDCS for enhancing both expressive and receptive language domains in chronic aphasia. To the best of our knowledge, this study represents the first multimodal neuroimaging (EEG, DTI) study to uncover mechanistic differences between tDCS and behavioral mediated aphasia recovery, and the first to identify a cerebellar white matter marker of language recovery following tDCS.Clinical Trial Registrationhttp://www.clinicaltrials.gov[NCT03699930]
- Published
- 2023
14. Down but not out: drugs that enhance delta oscillations but preserve consciousness
- Author
-
Joel Frohlich, Pedro Mediano, Francesco Bavato, and Alireza Gharabaghi
- Abstract
Delta (1 – 4 Hz) EEG/MEG activity is generally indicative of loss of consciousness and cortical down states, particularly when it is diffuse and high amplitude. Remarkably, however, drug challenge studies of several diverse classes of pharmacological agents—including antiepileptics, GABA-B-ergics, anticholinergics, and psychedelic tryptamines—demonstrate that participants appear to be neurophysiologically “down” (EEG activity resembling cortical down states) even when they are not psychologically “out” (unconscious). Of those substances that are safe to use in healthy volunteers, some may be highly valuable research tools for investigating which neural activity patterns are sufficient for consciousness or its absence.
- Published
- 2023
15. The complexity of event-related MEG signals decreases with maturation in human fetuses and newborns
- Author
-
Joel Frohlich, Julia Moser, Pedro A. M. Mediano, Hubert Preissl, and Alireza Gharabaghi
- Abstract
It is unknown how cortical entropy or “complexity”, a marker of consciousness, evolves in early human development. To test the hypothesis that the entropy of cortical signals increases approaching birth, we conducted the first ever study to relate fetal cortical entropy to maturation. MEG recordings were obtained from a sample of fetuses and newborns with prior evidence of perceptual consciousness. Using cortical responses to auditory irregularities, we computed several measures of signal entropy. Despite our hypothesis, cortical entropy significantly decreased with maturation in fetuses and newborns, with the strongest effect occurring with 4 – 10 Hz permutation entropy in both groups. Decreases in permutation entropy were driven by amplitude changes in both fetuses and newborns, whereas phase and its interaction with amplitude drove increases in entropy, possibly related to consciousness. These results lay groundwork both for future measures of perinatal consciousness and new in utero estimates of risk for neurodevelopmental disorders.TeaserEven as birth nears, a neural marker of consciousness decreases with gestational age in late fetal development and continues to decline after birth.
- Published
- 2022
16. Electrophysiological Abnormalities in Angelman Syndrome Correlate With Symptom Severity
- Author
-
Marius Keute, Wen-Hann Tan, Lynne M. Bird, Joerg F. Hipp, and Joel Frohlich
- Subjects
medicine.medical_specialty ,RC435-571 ,Clinical scales ,Audiology ,Electroencephalography ,Neurodegenerative ,Bayley Scales of Infant Development ,Article ,Epilepsy ,Neurodevelopmental disorder ,Clinical Research ,Angelman syndrome ,Behavioral and Social Science ,medicine ,UBE3A ,2.1 Biological and endogenous factors ,EEG ,Toddler ,Aetiology ,Pediatric ,Psychiatry ,medicine.diagnostic_test ,business.industry ,Neurosciences ,General Medicine ,medicine.disease ,Vineland Adaptive Behavior Scale ,Brain Disorders ,Mental Health ,Neurological ,business ,Biomarkers - Abstract
Background Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by the absence of functional UBE3A in neurons. Excess low-frequency oscillations as measured with electroencephalography (EEG) have been identified as a characteristic finding, but the relationship of this EEG finding to the symptomatology of AS and its significance in the pathophysiology of AS remain unknown. Methods We used correlations and machine learning to investigate the cross-sectional and longitudinal relationship between EEG spectral power and motor, cognitive, and language skills (Bayley Scales of Infant and Toddler Development, Third Edition); adaptive behavior (Vineland Adaptive Behavior Scales, Second Edition); AS-specific symptoms (AS Clinical Severity Scale); and the age of epilepsy onset in a large sample of children (age: 1–18 years) with AS due to a chromosomal deletion of 15q11-q13 (45 individuals with 72 visits). Results We found that after accounting for age differences, participants with stronger EEG delta-band abnormality had earlier onset of epilepsy and lower performance scores across symptom domains including cognitive, motor, and communication. Combing spatial and spectral information beyond the delta frequency band increased the cross-sectional association with clinical severity on average by approximately 45%. Furthermore, we found evidence for longitudinal correlations of EEG delta-band power within several performance domains, including the mean across Bayley Scales of Infant and Toddler Development, Third Edition, scores. Conclusions Our results show an association between EEG abnormalities and symptom severity in AS, underlining the significance of the former in the pathophysiology of AS. Furthermore, our work strengthens the rationale for using EEG as a biomarker in the development of treatments for AS, a concept that may apply more generally to neurodevelopmental disorders.
- Published
- 2021
17. Functional connectivity during language processing in 3‐month‐old infants at familial risk for autism spectrum disorder
- Author
-
Andrew Marin, Aaron Scheffler, Xuan Amelia Tran, Nicole M. McDonald, Joel Frohlich, Mirella Dapretto, Damla Şentürk, Erin Nosco, Abigail Dickinson, Shafali S. Jeste, and Christopher Kure Liu
- Subjects
Longitudinal study ,medicine.medical_specialty ,Autism Spectrum Disorder ,Alpha (ethology) ,Audiology ,Electroencephalography ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Longitudinal Studies ,Toddler ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,business.industry ,General Neuroscience ,Brain ,Infant ,Coherence (statistics) ,medicine.disease ,Language development ,Autism spectrum disorder ,Autism ,business ,030217 neurology & neurosurgery - Abstract
Auditory statistical learning (ASL) plays a role in language development and may lay a foundation for later social communication impairment. As part of a longitudinal study of infant siblings, we asked whether electroencephalography (EEG) measures of connectivity during ASL at 3 months of age-differentiated infants who showed signs of autism spectrum disorder (ASD) at age 18 months. We measured spectral power and phase coherence in the theta (4-6 Hz) and alpha (6-12 Hz) frequency bands within putative language networks. Infants were divided into ASD-concern (n = 14) and No-ASD-concern (n = 49) outcome groups based on their ASD symptoms at 18 months, measured using the Autism Diagnostic Observation Scale Toddler Module. Using permutation testing, we identified a trend toward reduced left fronto-central phase coherence at the electrode pair F9-C3 in both theta and alpha frequency bands in infants who later showed ASD symptoms at 18 months. Across outcome groups, alpha coherence at 3 months correlated with greater word production at 18 months on the MacArthur-Bates Communicative Development Inventory. This study introduces signal processing and analytic tools that account for the challenges inherent in infant EEG studies, such as short duration of recordings, considerable movement artifact, and variable volume conduction. Our results indicate that connectivity, as measured by phase coherence during 2.5 min of ASL, can be quantified as early as 3 months and suggest that early alternations in connectivity may serve as markers of resilience for neurodevelopmental impairments.
- Published
- 2020
18. Properties of beta oscillations in Dup15q syndrome
- Author
-
Damla Şentürk, Joel Frohlich, Shafali S. Jeste, Lawrence T. Reiter, Vidya Saravanapandian, Carly Hyde, Edwin H. Cook, Joerg F. Hipp, Peyman Golshani, and Aaron Scheffler
- Subjects
medicine.medical_specialty ,Neurology ,Cognitive Neuroscience ,Dup15q syndrome ,Autism ,Audiology ,Dup15q ,Electroencephalography ,Pathology and Forensic Medicine ,lcsh:RC321-571 ,03 medical and health sciences ,Epilepsy ,GABA ,0302 clinical medicine ,Intellectual Disability ,medicine ,Humans ,0501 psychology and cognitive sciences ,EEG ,Child ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,medicine.diagnostic_test ,business.industry ,Research ,05 social sciences ,Neurodevelopmental disorders ,UBE3A ,Neuropsychology ,Infant ,Reproducibility of Results ,medicine.disease ,Vineland Adaptive Behavior Scale ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Biomarker (medicine) ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Biomarkers ,050104 developmental & child psychology ,Follow-Up Studies - Abstract
BackgroundDuplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism, intellectual disability, hypotonia, and epilepsy. The 15q region harbors genes critical for brain development, particularlyUBE3Aand a cluster of gamma-aminobutyric acid type A receptor (GABAAR) genes. We recently described an electrophysiological biomarker of the syndrome, characterized by excessive beta oscillations (12–30 Hz), resembling electroencephalogram (EEG) changes induced by allosteric modulation of GABAARs. In this follow-up study, we tested a larger cohort of children with Dup15q syndrome to comprehensively examine properties of this EEG biomarker that would inform its use in future clinical trials, specifically, its (1) relation to basic clinical features, such as age, duplication type, and epilepsy; (2) relation to behavioral characteristics, such as cognition and adaptive function; (3) stability over time; and (4) reproducibility of the signal in clinical EEG recordings.MethodsWe computed EEG power and beta peak frequency (BPF) in a cohort of children with Dup15q syndrome (N= 41, age range 9–189 months). To relate EEG parameters to clinical (study 1) and behavioral features (study 2), we examined age, duplication type, epilepsy, cognition, and daily living skills (DLS) as predictors of beta power and BPF. To evaluate stability over time (study 3), we derived the intraclass correlation coefficients (ICC) from beta power and BPF computed from children with multiple EEG recordings (N= 10, age range 18–161 months). To evaluate reproducibility in a clinical setting (study 4), we derived ICCs from beta power computed from children (N= 8, age range 19–96 months), who had undergone both research EEG and clinical EEG.ResultsThe most promising relationships between EEG and clinical traits were found using BPF. BPF was predicted both by epilepsy status (R2= 0.11,p= 0.038) and the DLS component of the Vineland Adaptive Behavior Scale (R2= 0.17,p= 0.01). Beta power and peak frequency showed high stability across repeated visits (beta power ICC = 0.93, BPF ICC = 0.92). A reproducibility analysis revealed that beta power estimates are comparable between research and clinical EEG (ICC = 0.94).ConclusionsIn this era of precision health, with pharmacological and neuromodulatory therapies being developed and tested for specific genetic etiologies of neurodevelopmental disorders, quantification and examination of mechanistic biomarkers can greatly improve clinical trials. To this end, the robust beta oscillations evident in Dup15q syndrome are clinically reproducible and stable over time. With future preclinical and computational studies that will help disentangle the underlying mechanism, it is possible that this biomarker could serve as a robust measure of drug target engagement or a proximal outcome measure in future disease modifying intervention trials.
- Published
- 2020
19. Consciousness is supported by near-critical slow cortical electrodynamics
- Author
-
Daniel Toker, Ioannis Pappas, Janna D. Lendner, Joel Frohlich, Diego M. Mateos, Suresh Muthukumaraswamy, Robin Carhart-Harris, Michelle Paff, Paul M. Vespa, Martin M. Monti, Friedrich T. Sommer, Robert T. Knight, and Mark D’Esposito
- Subjects
Cerebral Cortex ,Brain Mapping ,Epilepsy ,Multidisciplinary ,Quantitative Biology::Neurons and Cognition ,Consciousness ,1.1 Normal biological development and functioning ,Physics::Medical Physics ,Neurosciences ,anesthesia ,psychedelics ,Neurodegenerative ,Brain Disorders ,Electrophysiological Phenomena ,Clinical Research ,Underpinning research ,Animals ,Humans ,criticality - Abstract
Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, we empirically identify a mathematically specific critical point near which waking cortical oscillatory dynamics operate, which is known as the edge-of-chaos critical point, or the boundary between stability and chaos. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magnetoencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of low-frequency cortical electric oscillations away from this critical point; conversely, we show that psychedelics may increase the information richness of cortical activity by tuning low-frequency cortical oscillations closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC) and show that assessing the proximity of slow cortical oscillatory electrodynamics to the edge-of-chaos critical point may be useful as an index of consciousness in the clinical setting.
- Published
- 2021
20. Neural oscillations track recovery of consciousness in acute traumatic brain injury patients
- Author
-
Joel Frohlich, Julia S. Crone, Micah A. Johnson, Evan S. Lutkenhoff, Norman M. Spivak, John Dell'Italia, Joerg F. Hipp, Vikesh Shrestha, Jesús E. Ruiz Tejeda, Courtney Real, Paul M. Vespa, and Martin M. Monti
- Subjects
Neurology ,Radiological and Ultrasound Technology ,Consciousness ,Brain Injuries ,Brain Injuries, Traumatic ,Consciousness Disorders ,Humans ,Radiology, Nuclear Medicine and imaging ,Electroencephalography ,Neurology (clinical) ,Anatomy - Abstract
Electroencephalography (EEG), easily deployed at the bedside, is an attractive modality for deriving quantitative biomarkers of prognosis and differential diagnosis in severe brain injury and disorders of consciousness (DOC). Prior work by Schiff has identified four dynamic regimes of progressive recovery of consciousness defined by the presence or absence of thalamically-driven EEG oscillations. These four predefined categories (ABCD model) relate, on a theoretical level, to thalamocortical integrity and, on an empirical level, to behavioral outcome in patients with cardiac arrest coma etiologies. However, whether this theory-based stratification of patients might be useful as a diagnostic biomarker in DOC and measurably linked to thalamocortical dysfunction remains unknown. In this work, we relate the reemergence of thalamically-driven EEG oscillations to behavioral recovery from traumatic brain injury (TBI) in a cohort of N = 38 acute patients with moderate-to-severe TBI and an average of 1 week of EEG recorded per patient. We analyzed an average of 3.4 hr of EEG per patient, sampled to coincide with 30-min periods of maximal behavioral arousal. Our work tests and supports the ABCD model, showing that it outperforms a data-driven clustering approach and may perform equally well compared to a more parsimonious categorization. Additionally, in a subset of patients (N = 11), we correlated EEG findings with functional magnetic resonance imaging (fMRI) connectivity between nodes in the mesocircuit-which has been theoretically implicated by Schiff in DOC-and report a trend-level relationship that warrants further investigation in larger studies.
- Published
- 2021
21. Consciousness is supported by near-critical cortical electrodynamics
- Author
-
Joel Frohlich, Diego M. Mateos, Daniel Toker, Paul M. Vespa, Michelle Paff, Ioannis Pappas, Suresh D. Muthukumaraswamy, Martin M. Monti, Robin L. Carhart-Harris, Mark D'Esposito, Friedrich T. Sommer, Robert T. Knight, and Lendner Jd
- Subjects
medicine.diagnostic_test ,media_common.quotation_subject ,Unconsciousness ,Information processing ,Disorders of consciousness ,Electroencephalography ,medicine.disease ,medicine.anatomical_structure ,Critical point (thermodynamics) ,Quantum electrodynamics ,Cortex (anatomy) ,medicine ,medicine.symptom ,Consciousness ,Psychology ,Electrocorticography ,media_common - Abstract
Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition, and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, for the first time, we empirically identify the specific critical point near which conscious cortical dynamics operate as the edge-of-chaos critical point, or the boundary between periodicity/stability and chaos/instability. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magne-toencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, GABAergic anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of cortical dynamics away from this critical point; conversely, we show that psychedelics may increase the information-richness of cortical activity by tuning cortical electrodynamics closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC), and show that assessing the proximity of cortical electrodynamics to the edge-of-chaos critical point may be clinically useful as a new biomarker of consciousness.Significance StatementWhat changes in the brain when we lose consciousness? One possibility is that the loss of consciousness corresponds to a transition of the brain’s electric activity away from edge-of-chaos criticality, or the knife’s edge in between stability and chaos. Recent mathematical developments have produced novel tools for testing this hypothesis, which we apply for the first time to cortical recordings from diverse brain states. We show that the electric activity of the cortex is indeed poised near the boundary between stability and chaos during conscious states and transitions away from this boundary during unconsciousness, and that this transition disrupts cortical information processing.
- Published
- 2021
22. Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes
- Author
-
Joel Frohlich, Lynne M. Bird, Benjamin D. Philpot, Hannah Purtell, Omar Khwaja, Joerg F. Hipp, Wen-Hann Tan, Pilar Garcés, Shafali S. Jeste, Meghan T. Miller, Michael S. Sidorov, Maria-Clemencia Hernandez, Alexander Rotenberg, Michelle L. Krishnan, and Marius C. Hoener
- Subjects
0301 basic medicine ,Adolescent ,Genotype ,GABRA5 ,Electroencephalography ,03 medical and health sciences ,Chromosome 15 ,0302 clinical medicine ,Neurodevelopmental disorder ,Angelman syndrome ,medicine ,UBE3A ,Humans ,Theta Rhythm ,Child ,Biological Psychiatry ,Cerebral Cortex ,Genetics ,biology ,medicine.diagnostic_test ,Infant ,medicine.disease ,Brain Waves ,Phenotype ,030104 developmental biology ,Delta Rhythm ,Child, Preschool ,biology.protein ,Angelman Syndrome ,Beta Rhythm ,030217 neurology & neurosurgery - Abstract
Background Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by either disruptions of the gene UBE3A or deletion of chromosome 15 at 15q11-q13, which encompasses UBE3A and several other genes, including GABRB3, GABRA5, GABRG3, encoding gamma-aminobutyric acid type A receptor subunits ( β 3, α 5, γ 3). Individuals with deletions are generally more impaired than those with other genotypes, but the underlying pathophysiology remains largely unknown. Here, we used electroencephalography (EEG) to test the hypothesis that genes other than UBE3A located on 15q11-q13 cause differences in pathophysiology between AS genotypes. Methods We compared spectral power of clinical EEG recordings from children (1–18 years of age) with a deletion genotype (n = 37) or a nondeletion genotype (n = 21) and typically developing children without Angelman syndrome (n = 48). Results We found elevated theta power (peak frequency: 5.3 Hz) and diminished beta power (peak frequency: 23 Hz) in the deletion genotype compared with the nondeletion genotype as well as excess broadband EEG power (1–32 Hz) peaking in the delta frequency range (peak frequency: 2.8 Hz), shared by both genotypes but stronger for the deletion genotype at younger ages. Conclusions Our results provide strong evidence for the contribution of non-UBE3A neuronal pathophysiology in deletion AS and suggest that hemizygosity of the GABRB3-GABRA5-GABRG3 gene cluster causes abnormal theta and beta EEG oscillations that may underlie the more severe clinical phenotype. Our work improves the understanding of AS pathophysiology and has direct implications for the development of AS treatments and biomarkers.
- Published
- 2019
23. Consciousness among delta waves: a paradox?
- Author
-
Martin M. Monti, Joel Frohlich, and Daniel Toker
- Subjects
0301 basic medicine ,Electromagnetic theories of consciousness ,Consciousness ,media_common.quotation_subject ,Disorders of consciousness ,Unconsciousness ,Electroencephalography ,03 medical and health sciences ,0302 clinical medicine ,Level of consciousness ,medicine ,Humans ,Slow-wave sleep ,media_common ,Epilepsy ,medicine.diagnostic_test ,Brain ,medicine.disease ,Delta wave ,030104 developmental biology ,Delta Rhythm ,Neurology (clinical) ,medicine.symptom ,Psychology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
A common observation in EEG research is that consciousness vanishes with the appearance of delta (1–4 Hz) waves, particularly when those waves are high amplitude. High amplitude delta oscillations are frequently observed in states of diminished consciousness, including slow wave sleep, anaesthesia, generalized epileptic seizures, and disorders of consciousness, such as coma and the vegetative state. This strong correlation between loss of consciousness and high amplitude delta oscillations is thought to stem from the widespread cortical deactivation that occurs during the ‘down states’ or troughs of these slow oscillations. Recently, however, many studies have reported the presence of prominent delta activity during conscious states, which casts doubt on the hypothesis that high amplitude delta oscillations are an indicator of unconsciousness. These studies include work in Angelman syndrome, epilepsy, behavioural responsiveness during propofol anaesthesia, postoperative delirium, and states of dissociation from the environment such as dreaming and powerful psychedelic states. The foregoing studies complement an older, yet largely unacknowledged, body of literature that has documented awake, conscious patients with high amplitude delta oscillations in clinical reports from Rett syndrome, Lennox-Gastaut syndrome, schizophrenia, mitochondrial diseases, hepatic encephalopathy, and non-convulsive status epilepticus. At the same time, a largely parallel body of recent work has reported convincing evidence that the complexity or entropy of EEG and magnetoencephalographic signals strongly relates to an individual’s level of consciousness. Having reviewed this literature, we discuss plausible mechanisms that would resolve the seeming contradiction between high amplitude delta oscillations and consciousness. We also consider implications concerning theories of consciousness, such as integrated information theory and the entropic brain hypothesis. Finally, we conclude that false inferences of unconscious states can be best avoided by examining measures of electrophysiological complexity in addition to spectral power.
- Published
- 2020
24. Author response for 'Functional connectivity during language processing in 3‐month‐old infants at familial risk for autism spectrum disorder'
- Author
-
Joel Frohlich, Xuan Amelia Tran, Abigail Dickinson, Aaron Scheffler, Nicole M. McDonald, Andrew Marin, Mirella Dapretto, Shafali S. Jeste, Damla Şentürk, Erin Nosco, and Christopher Kure Liu
- Subjects
Autism spectrum disorder ,business.industry ,Functional connectivity ,medicine ,Familial risk ,medicine.disease ,business ,Clinical psychology - Published
- 2020
25. High-voltage, diffuse delta rhythms coincide with wakeful consciousness and complexity in Angelman syndrome
- Author
-
John Dell'Italia, Joerg F. Hipp, Martin M. Monti, Lynne M. Bird, Micah A. Johnson, and Joel Frohlich
- Subjects
medicine.medical_specialty ,Neurology ,media_common.quotation_subject ,theories and models ,Experimental and Cognitive Psychology ,Neurodegenerative ,Basic Behavioral and Social Science ,Rhythm ,Angelman syndrome ,Behavioral and Social Science ,medicine ,disorders of consciousness ,AcademicSubjects/SCI02139 ,media_common ,Pediatric ,Epilepsy ,states of consciousness ,neurology ,Neurosciences ,medicine.disease ,Brain Disorders ,Philosophy ,Psychiatry and Mental health ,Clinical Psychology ,Neurological ,Neurology (clinical) ,Consciousness ,Sleep Research ,Corrigendum ,Psychology ,Neuroscience ,Research Article ,sleep and dreaming - Abstract
Abundant evidence from slow wave sleep, anesthesia, coma, and epileptic seizures links high-voltage, slow electroencephalogram (EEG) activity to loss of consciousness. This well-established correlation is challenged by the observation that children with Angelman syndrome (AS), while fully awake and displaying volitional behavior, display a hypersynchronous delta (1–4 Hz) frequency EEG phenotype typical of unconsciousness. Because the trough of the delta oscillation is associated with down-states in which cortical neurons are silenced, the presence of volitional behavior and wakefulness in AS amidst diffuse delta rhythms presents a paradox. Moreover, high-voltage, slow EEG activity is generally assumed to lack complexity, yet many theories view functional brain complexity as necessary for consciousness. Here, we use abnormal cortical dynamics in AS to assess whether EEG complexity may scale with the relative level of consciousness despite a background of hypersynchronous delta activity. As characterized by multiscale metrics, EEGs from 35 children with AS feature significantly greater complexity during wakefulness compared with sleep, even when comparing the most pathological segments of wakeful EEG to the segments of sleep EEG least likely to contain conscious mentation and when factoring out delta power differences across states. These findings (i) warn against reverse inferring an absence of consciousness solely on the basis of high-amplitude EEG delta oscillations, (ii) corroborate rare observations of preserved consciousness under hypersynchronization in other conditions, (iii) identify biomarkers of consciousness that have been validated under conditions of abnormal cortical dynamics, and (iv) lend credence to theories linking consciousness with complexity.
- Published
- 2020
26. Emergence of consciousness and complexity amidst diffuse delta rhythms: the paradox of Angelman syndrome
- Author
-
Joerg F. Hipp, Joel Frohlich, Micah A. Johnson, John Dell'Italia, Martin M. Monti, and Lynne M. Bird
- Subjects
medicine.diagnostic_test ,media_common.quotation_subject ,Unconsciousness ,Electroencephalography ,medicine.disease ,Sleep in non-human animals ,Complex dynamics ,Rhythm ,Angelman syndrome ,medicine ,Wakefulness ,medicine.symptom ,Consciousness ,Psychology ,media_common ,Cognitive psychology - Abstract
Numerous theories link consciousness to informationally rich, complex neural dynamics. This idea is challenged by the observation that children with Angelman syndrome (AS), while fully conscious, display a hypersynchronous electroencephalogram (EEG) phenotype typical of information-poor dynamics associated with unconsciousness. If informational complexity theories are correct, then sufficiently complex dynamics must still exist during wakefulness and exceed that observed in sleep despite pathological delta (1 – 4 Hz) rhythms in children with AS. As characterized by multiscale metrics, EEGs from 35 children with AS feature significantly greater complexity during wakefulness compared with sleep, even when comparing the most pathological segments of wakeful EEG to the segments of sleep EEG least likely to contain conscious experiences, and when factoring out delta power differences across states. These findings support theories linking consciousness with complexity and warn against reverse inferring an absence of consciousness solely on the basis of clinical readings of EEG.
- Published
- 2019
- Full Text
- View/download PDF
27. Mechanisms underlying the EEG biomarker in Dup15q syndrome
- Author
-
Joerg F. Hipp, Joel Frohlich, Carly Hyde, Scott Huberty, Richard W. Olsen, Peyman Golshani, Shafali S. Jeste, Lawrence T. Reiter, Vidya Saravanapandian, Carrie E. Bearden, Stormy J. Chamberlain, Andrei Irimia, and Charlotte DiStefano
- Subjects
Male ,Autism ,Dup15q syndrome ,Electroencephalography ,Bioinformatics ,lcsh:RC346-429 ,Cohort Studies ,Fathers ,GABA ,0302 clinical medicine ,Receptors ,2.1 Biological and endogenous factors ,EEG ,Aetiology ,Child ,GABRG3 ,Pediatric ,0303 health sciences ,biology ,medicine.diagnostic_test ,Neurodevelopmental disorders ,3. Good health ,Psychiatry and Mental health ,Phenotype ,Mental Health ,Autism spectrum disorder ,GABRA5 ,Female ,Human ,Adult ,Midazolam ,Intellectual and Developmental Disabilities (IDD) ,Clinical Sciences ,Dup15q ,Chromosomes ,03 medical and health sciences ,Developmental Neuroscience ,Clinical Research ,Intellectual Disability ,GABRB3 ,medicine ,UBE3A ,Genetics ,Humans ,Molecular Biology ,lcsh:Neurology. Diseases of the nervous system ,030304 developmental biology ,Chromosome Aberrations ,Chromosomes, Human, Pair 15 ,business.industry ,GABA-A ,Research ,Pair 15 ,Neurosciences ,Receptors, GABA-A ,medicine.disease ,Brain Disorders ,biology.protein ,business ,Genomic imprinting ,030217 neurology & neurosurgery ,Biomarkers ,Developmental Biology - Abstract
Background Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz). Both paternal Dup15q syndrome cases displayed beta power comparable to the reference cohort. Conclusions Our results suggest a critical role for GABAergic transmission in the Dup15q syndrome beta EEG phenotype, which cannot be explained by UBE3A dysfunction alone. If this mechanism is confirmed, the phenotype may be used as a marker of GABAergic pathology in clinical trials for Dup15q syndrome. Electronic supplementary material The online version of this article (10.1186/s13229-019-0280-6) contains supplementary material, which is available to authorized users.
- Published
- 2019
28. Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome
- Author
-
Stormy J. Chamberlain, Andrei Irimia, Joel Frohlich, Joerg F. Hipp, Carly Hyde, Shafali S. Jeste, Lawrence T. Reiter, Peyman Golshani, Carrie E. Bearden, Charlotte DiStefano, Richard W. Olsen, Scott Huberty, and Vidya Saravanapandian
- Subjects
medicine.medical_specialty ,Statement (logic) ,Clinical Sciences ,Dup15q ,Electroencephalography ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,medicine ,Psychiatry ,Molecular Biology ,lcsh:Neurology. Diseases of the nervous system ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,business.industry ,Neuropsychology ,Neurosciences ,Correction ,Human genetics ,Psychiatry and Mental health ,Biomarker (medicine) ,business ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Following publication of the original article [1], we have been notified that the Ethics statement of the articles should be changed. The Ethics statement now reads
- Published
- 2019
29. Autism Imaging and Devices
- Author
-
Joel Frohlich, Esube Bekele, Giorgia Michelini, Adel Elmaghraby, and Annukka Lindell
- Subjects
Autism spectrum disorder ,medicine ,medicine.disease ,Psychology ,Twin study ,Clinical psychology - Published
- 2017
30. Chapter 13 Imaging brain connectivity in autism spectrum disorder
- Author
-
Robert Coben, Iman Mohammad-Rezazadeh, Joel Frohlich, Joseph Jurgiel, and Giorgia Michelini
- Subjects
03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,05 social sciences ,medicine ,Autism ,0501 psychology and cognitive sciences ,Audiology ,Psychology ,medicine.disease ,Spectrum (topology) ,030217 neurology & neurosurgery ,050105 experimental psychology - Published
- 2016
31. Reviewing the ketamine model for schizophrenia
- Author
-
Joel Frohlich and John D. Van Horn
- Subjects
Dopamine ,Synaptic pruning ,Phencyclidine ,Receptors, N-Methyl-D-Aspartate ,Article ,mental disorders ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Age of Onset ,Dopamine hypothesis of schizophrenia ,gamma-Aminobutyric Acid ,Pharmacology ,Dopaminergic ,medicine.disease ,Psychiatry and Mental health ,medicine.anatomical_structure ,nervous system ,Schizophrenia ,Disinhibition ,NMDA receptor ,Ketamine ,Schizophrenic Psychology ,medicine.symptom ,Psychology ,Neuroscience ,medicine.drug - Abstract
The observation that antagonists of the N-methyl-D-aspartate receptor (NMDAR), such as phencyclidine (PCP) and ketamine, transiently induce symptoms of acute schizophrenia had led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. The glutamate hypothesis can explain negative and cognitive symptoms of schizophrenia better than the dopamine hypothesis, and has the potential to explain dopamine dysfunction itself. The pharmacological and psychomimetic effects of ketamine, which is safer for human subjects than phencyclidine, are herein reviewed. Ketamine binds to a variety of receptors, but principally acts at the NMDAR, and convergent genetic and molecular evidence point to NMDAR hypofunction in schizophrenia. Furthermore, NMDAR hypofunction can explain connectional and oscillatory abnormalities in schizophrenia in terms of both weakened excitation of inhibitory γ-aminobutyric acidergic (GABAergic) interneurons that synchronize cortical networks and disinhibition of principal cells. Individuals with prenatal NMDAR aberrations might experience the onset of schizophrenia towards the completion of synaptic pruning in adolescence, when network connectivity drops below a critical value. We conclude that ketamine challenge is useful for studying the positive, negative, and cognitive symptoms, dopaminergic and GABAergic dysfunction, age of onset, functional dysconnectivity, and abnormal cortical oscillations observed in acute schizophrenia.
- Published
- 2013
32. Inferring Brain Signals Synchronicity from a Sample of EEG Readings
- Author
-
Shafali S. Jeste, Charlotte DiStefano, Qian Li, Catherine A. Sugar, Donatello Telesca, Damla Şentürk, and Joel Frohlich
- Subjects
FOS: Computer and information sciences ,Statistics and Probability ,Computer science ,Brain activity and meditation ,Sample (statistics) ,Electroencephalography ,01 natural sciences ,Statistics - Applications ,Article ,010104 statistics & probability ,Synchronicity ,0502 economics and business ,Consensus clustering ,medicine ,Applications (stat.AP) ,0101 mathematics ,050205 econometrics ,Heterogeneous sample ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Pattern recognition ,Spectral clustering ,ComputingMethodologies_PATTERNRECOGNITION ,Artificial intelligence ,Statistics, Probability and Uncertainty ,business - Abstract
Inferring patterns of synchronous brain activity from a heterogeneous sample of electroencephalograms (EEG) is scientifically and methodologically challenging. While it is intuitively and statistically appealing to rely on readings from more than one individual in order to highlight recurrent patterns of brain activation, pooling information across subjects presents non-trivial methodological problems. We discuss some of the scientific issues associated with the understanding of synchronized neuronal activity and propose a methodological framework for statistical inference from a sample of EEG readings. Our work builds on classical contributions in time-series, clustering and functional data analysis, in an effort to reframe a challenging inferential problem in the context of familiar analytical techniques. Some attention is paid to computational issues, with a proposal based on the combination of machine learning and Bayesian techniques.
- Published
- 2016
33. Brain connectivity in autism spectrum disorder
- Author
-
Joel Frohlich, Sandra K. Loo, Iman Mohammad-Rezazadeh, and Shafali S. Jeste
- Subjects
0301 basic medicine ,Autism Spectrum Disorder ,Intellectual and Developmental Disabilities (IDD) ,graph theory ,Autism ,1.1 Normal biological development and functioning ,Clinical Sciences ,Electroencephalography ,Brain mapping ,Article ,03 medical and health sciences ,Typically developing ,0302 clinical medicine ,Underpinning research ,2.3 Psychological ,Neural Pathways ,Behavioral and Social Science ,medicine ,Humans ,Aetiology ,Clinical phenotype ,Intellectual and Developmental Disabilities ,Pediatric ,Brain Mapping ,Neurology & Neurosurgery ,medicine.diagnostic_test ,Functional connectivity ,brain connectivity ,Neurosciences ,Brain ,medicine.disease ,Magnetic Resonance Imaging ,Brain Disorders ,Brain region ,030104 developmental biology ,Mental Health ,Neurology ,Autism spectrum disorder ,Neurological ,Cognitive Sciences ,Neurology (clinical) ,social and economic factors ,Psychology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Purpose of reviewMany studies have reported that individuals with autism spectrum disorder (ASD) have different brain connectivity patterns compared with typically developing individuals. However, the results of more recent studies do not unanimously support the traditional view in which individuals with ASD have lower connectivity between distant brain regions and increased connectivity within local brain regions. In this review, we discuss different methods for measuring brain connectivity and how the use of different metrics may contribute to the lack of convergence of investigations of connectivity in ASD.Recent findingsThe discrepancy in brain connectivity results across studies may be due to important methodological factors, such as the connectivity measure applied, the age of patients studied, the brain region(s) examined, and the time interval and frequency band(s) in which connectivity was analyzed.SummaryWe conclude that more sophisticated electroencephalography analytic approaches should be utilized to more accurately infer causation and directionality of information transfer between brain regions, which may show dynamic changes of functional connectivity in the brain. Moreover, further investigations of connectivity with respect to behavior and clinical phenotype are needed to probe underlying brain networks implicated in core deficits of ASD.
- Published
- 2016
34. Ketamine and the Dissociatives
- Author
-
John D. Van Horn and Joel Frohlich
- Subjects
Psychosis ,medicine.drug_class ,medicine.disease ,Dissociative ,Dizocilpine ,chemistry.chemical_compound ,Monoamine neurotransmitter ,Nicotinic agonist ,nervous system ,chemistry ,Dopamine ,mental disorders ,medicine ,Psychology ,Neurotransmitter ,Neuroscience ,Phencyclidine ,medicine.drug - Abstract
Dissociative agents—uncompetitive N -methyl- d -aspartate receptor (NMDAR) antagonists—such as ketamine, phencyclidine, and dizocilpine are known to transiently induce positive, negative, and cognitive symptoms of schizophrenia in healthy adults. Herein, we conclude that dissociative drug challenge accurately models neurotransmitter dysfunction, excitotoxicity, neurodegeneration, age of onset, gamma band aberrations, and electroencephalogram signal complexity observed in schizophrenia. Furthermore, dissociative drugs bind to a host of other receptors (e.g., sigma, opioid, dopamine D 2 , cholinergic) and thus transcend NMDAR hypofunction models of schizophrenia. Principal effects of dissociative agents are mediated by blockade of NMDARs expressed by gamma-aminobutyric acid (GABA)ergic interneurons, resulting in disruptions of gamma oscillations and disinhibition of glutamatergic and cholinergic afferents, triggering patterns of excitotoxic neurodegeneration seen in schizophrenia. Future work should seek to understand the extent to which ketamine and other dissociative drugs might effect psychomimesis through action at muscarinic, nicotinic, opioid, and sigma-1 receptors, as well as monoamine transporters.
- Published
- 2016
35. List of Contributors
- Author
-
Renata Rigacci Abdalla, Tomohiro Abekawa, Przemysław Adamczyk, Wendy Adams, Peter H. Addy, Yukio Ago, María Álvaro-Bartolomé, Martina Andellini, Matthew E. Andrzejewski, Gustavo A. Angarita, Mariana Angoa-Pérez, John H. Anneken, Luís Antunes, Yalda Hosseinzadeh Ardakani, Mustafa Aydin, Nima Badri, Ram C. Bajpai, Daniel José Barbosa, Alfonso Barrós-Loscertales, Debasish Basu, Benjamin Becker, Jacob T. Beckley, Pablo García Bermejo, Laís F. Berro, Amanda L. Blaker, Ede Bodoki, Krzysztof Borowiak, Scott E. Bowen, Patricia A. Broderick, Berit Brogaard, Giovana Brolese, T.M. Brunt, T. Buchborn, Eduardo R. Butelman, Raul Caetano, Sónia Campos, Sofija V. Canavan, João Paulo Capela, Manolo Carta, Félix Carvalho, Lucia Carvelli, Briony J. Catlow, Young-Tae Chang, Himanshu K. Chaturvedi, Lela Chilachava, Aree Choodum, Shannon J. Clough, Vanessa Coelho-Santos, Ana Maria Coimbra, Stuart A. Collins, Bru Cormand, Albert Dahan, Elias Dakwar, Antonio Dávalos E., Cor de Jong, Maria de Lourdes Bastos, Marc R. Del Bigio, Teresa Dembińska, Ugur Deveci, D.C. Dieterich, Boukje Dijkstra, Dean E. Dluzen, Margarita L. Dubocovich, Carlos García Esperón, Chun-Kai Fang, Vahid Farnia, Luís Félix, Noelia Fernàndez-Castillo, Daniel Flack, Elisabeth Frauger, Joel Frohlich, Daniela F. Fukushiro, Daniel A. García, M. Julia García-Fuster, Jesús A. García-Sevilla, Eric L. Garland, Dimitria Electra Gatzia, Lia Gelazonia, Abhishek Ghosh, Roy Gigengack, Senobar Golshani, Joana Gonçalves, Javier González-Maeso, Ingmar Gorman, David K. Grandy, G. Grecksch, Alissa M. Greer, Gary A. Gudelsky, Casey Guillot, Joshua M. Gulley, Yoko Hagino, Robert M. Hallock, Emily R. Hankosky, James B. Hanks, Carl Hart, H.W.W. Hasselmann, Hirotake Hida, Sarah E. Hodges, Nicole Holder, André W. Hollais, V. Höllt, Jiri Horacek, Matthew O. Howard, Fleur Margaret Howells, Skye Hsin-Hsien Yeh, Mei Huang, Anthony J. Hutchinson, Jeng-Jong Hwang, Kazutaka Ikeda, Jennifer E. Iudicello, Ahmad Jalloh, Bardia Jamali, Nadezhda Japaridze, Eiichi Jodo, Chantele Joordens, Rasmon Kalayasiri, Rama Kamal, Etsuko Kamegaya, Tadahiro Katayama, Adam W. Keasling, Ruri Kikura-Hanajiri, Matthew Kirkpatrick, Béla Kiss, Rita Kočárová, Saurabh S. Kokane, Mary Jeanne Kreek, Peter R. Kufahl, Donald M. Kuhn, Takeshi Kumazawa, Snezana Kusljic, Krzysztof Łabuz, Maryse Lapeyre-Mestre, Ronaldo Ramos Laranjeira, Andrew J. Lawrence, Byung Dae Lee, Ricardo Alexandre Leitão, L. Stan Leung, Chiang-Shan R. Li, Meng Li, Qing Lin, Felicia Loghin, Elena López-Cancio M., Jennifer Lyke, Michael Lyvers, Scott Macdonald, Clarice Sandi Madruga, Michael Maes, Timothy J. Maher, Jingyi Ma, Chitra D. Mandyam, Claudia Mardones, Gina Martin, Luciana Massaro, Toshio Matsuda, M.T.B. McMaster, Richard H. Melloni, Herbert Y. Meltzer, Joëlle Micallef, Maria Mironidou-Tzouveleki, Masayoshi Mishina, Sandro Mitsuhiro, Christian Montag, Elisabeth Moore, Erin E. Morgan, Peter T. Morgan, Satoshi Morimoto, Thomas R. Morrison, Anna Moszczynska, Akihiro Mouri, Antonio Napolitano, Nichole M. Neugebauer, Niamh NicDaeid, Charles D. Nichols, Martin Nizama-Valladolid, Yukihiro Noda, Nicole A. Northrop, M. Foster Olive, Rory D. Ostrow, Linda C.J. Oudejans, Tomas Palenicek, Arvind Pandey, Mariusz Papp, Ioannis D. Passos, Madan Kumar Paudel, Maria A. Perillo, Christina J. Perry, Nataša Petronijević, Siripan Phattanarudee, Ilana Pinsky, Nino Pochkhidze, Anca Pop, Marianne Possa, Barbara Potocka-Banaś, Boris B. Quednow, Nevena V. Radonjić, Lakshmi Rajagopal, Marta Ribasés, Lesley A. Ricci, Carola Vergara Rosales, Mohammad-Reza Rouini, Juan Sanchez-Ramos, Renan Santos-Baldaia, Siddharth Sarkar, Kaori Sasaki-Tabata, Naomi Sato, Tomonori Sato, Wakako Sawada, Silvia Bassani Schuch, Setsuko Sekita, Eduardo Alvear Serrano, Behjat Sheikholeslami, Osamu Shirota, Ana Paula Silva, Nicola Simola, Derek P. Simon, Ichiro Sora, Anne Orgler Sordi, Mitchell G. Spring, Katarzyna Stebelska, Haruhiko Sugimura, Yoshiaki Suzuki, Kazuhiro Takuma, Hiroyuki Tanaka, Meshkat Torkamanian, Pasarapa Towiwat, Anahí V. Turina, Filip Tyls, J.G.C. van Amsterdam, W. van den Brink, Maarten van den Buuse, John Darrell Van Horn, Martijn van Noorden, Monique van Velzen, Carlos Venâncio, Dietrich von Baer, Lisia von Diemen, Martin Walter, Fang Wang, Erica Weber, Petr Winkler, Steven Paul Woods, John J. Woodward, Chun-Fu Wu, Raphael Wuo-Silva, Wang Xu, Bryan K. Yamamoto, Hideko Yamamoto, Toshifumi Yamamoto, Jing-Yu Yang, Duanting Zhai, Mzia Zhvania, and Jordan K. Zjawiony
- Published
- 2016
36. Electrophysiological biomarkers of diagnosis and outcome in neurodevelopmental disorders
- Author
-
Joel Frohlich, Shafali S. Jeste, and Sandra K. Loo
- Subjects
Treatment response ,Pediatric Research Initiative ,Child Development Disorders ,Intellectual and Developmental Disabilities (IDD) ,Developmental Disabilities ,Autism ,Clinical Sciences ,autism spectrum disorder ,Electroencephalography ,Outcome (game theory) ,behavioral disciplines and activities ,Article ,Clinical biomarker ,Intervention (counseling) ,mental disorders ,medicine ,Attention deficit hyperactivity disorder ,Animals ,Humans ,Attention Deficit Disorder ,Intellectual and Developmental Disabilities ,Pervasive ,Pediatric ,screening and diagnosis ,Neurology & Neurosurgery ,medicine.diagnostic_test ,Prevention ,Neurosciences ,biomarkers ,medicine.disease ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,Clinical trial ,Detection ,Treatment Outcome ,attention deficit hyperactivity disorder ,Mental Health ,Neurology ,Child Development Disorders, Pervasive ,Autism spectrum disorder ,Attention Deficit Disorder with Hyperactivity ,Attention Deficit Disorder (ADD) ,Cognitive Sciences ,Neurology (clinical) ,Psychology ,Biomarkers ,Clinical psychology ,4.2 Evaluation of markers and technologies - Abstract
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Purpose of review The heterogeneity in clinical presentation and outcome in neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) autism spectrum disorder (ASD) necessitates the identification and validation of biomarkers that can guide diagnosis, predict developmental outcomes, and monitor treatment response. Electrophysiology holds both practical and theoretical advantages as a clinical biomarker in neurodevelopmental disorders, and considerable effort has been invested in the search for electroencephalography (EEG) biomarkers in ADHD and ASD. Recent findings Here, we discuss the major themes in the evaluation of biomarkers and then review studies that have applied EEG to better inform diagnosis, focusing on the controversy surrounding the theta:beta ratio in ADHD; prediction of risk, highlighting recent studies of infants at high risk for ASD; and treatment monitoring, presenting new efforts in the redefinition of outcome measures in clinical trials of ASD treatment. Summary We conclude that insights gained from EEG studies will contribute significantly to a more mechanistic understanding of these disorders and to the development of biomarkers that can assist with diagnosis, prognosis, and intervention. There is a need, however, to utilize approaches that accommodate, rather than ignore, diagnostic heterogeneity and individual differences.
- Published
- 2015
37. Trajectory of frequency stability in typical development
- Author
-
Andrei Irimia, Shafali S. Jeste, and Joel Frohlich
- Subjects
medicine.medical_specialty ,Self-organized criticality ,Brain activity and meditation ,Cognitive Neuroscience ,Poison control ,Audiology ,Electroencephalography ,Development ,Medical and Health Sciences ,Article ,Cohort Studies ,Executive Function ,Behavioral Neuroscience ,Cellular and Molecular Neuroscience ,Metastability ,Cognition ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Child ,Preschool ,Balance (ability) ,medicine.diagnostic_test ,Psychology and Cognitive Sciences ,Cognitive flexibility ,Neuropsychology ,Brain ,Experimental Psychology ,Biomarker ,Dynamics ,Psychiatry and Mental health ,Neurology ,Child, Preschool ,Neurology (clinical) ,Psychology ,Biomarkers - Abstract
© 2014, Springer Science+Business Media New York. This work explores a feature of brain dynamics, metastability, by which transients are observed in functional brain data. Metastability is a balance between static (stable) and dynamic (unstable) tendencies in electrophysiological brain activity. Furthermore, metastability is a theoretical mechanism underlying the rapid synchronization of cell assemblies that serve as neural substrates for cognitive states, and it has been associated with cognitive flexibility. While much previous research has sought to characterize metastability in the adult human brain, few studies have examined metastability in early development, in part because of the challenges of acquiring adequate, noise free continuous data in young children. To accomplish this endeavor, we studied a new method for characterizing the stability of EEG frequency in early childhood, as inspired by prior approaches for describing cortical phase resets in the scalp EEG of healthy adults. Specifically, we quantified the variance of the rate of change of the signal phase (i.e., frequency) as a proxy for phase resets (signal instability), given that phase resets occur almost simultaneously across large portions of the scalp. We tested our method in a cohort of 39 preschool age children (age =53 ± 13.6 months). We found that our outcome variable of interest, frequency variance, was a promising marker of signal stability, as it increased with the number of phase resets in surrogate (artificial) signals. In our cohort of children, frequency variance decreased cross-sectionally with age (r = −0.47, p = 0.0028). EEG signal stability, as quantified by frequency variance, increases with age in preschool age children. Future studies will relate this biomarker with the development of executive function and cognitive flexibility in children, with the overarching goal of understanding metastability in atypical development.
- Published
- 2014
38. A Quantitative Electrophysiological Biomarker of Duplication 15q11.2-q13.1 Syndrome
- Author
-
Scott Huberty, Damla Şentürk, Shafali S. Jeste, Lawrence T. Reiter, Joel Frohlich, Edwin H. Cook, Charlotte DiStefano, Peyman Golshani, Raman Sankar, Vidya Saravanapandian, and Ronald L. Thibert
- Subjects
Male ,0301 basic medicine ,Pathology ,Neurology ,Autism Spectrum Disorder ,Physiology ,Social Sciences ,lcsh:Medicine ,Electroencephalography ,Audiology ,Biochemistry ,Epilepsy ,0302 clinical medicine ,Medicine and Health Sciences ,Psychology ,Child ,lcsh:Science ,Cerebral Cortex ,Clinical Neurophysiology ,Brain Mapping ,Multidisciplinary ,medicine.diagnostic_test ,Electrodiagnosis ,Drugs ,Electrophysiology ,Bioassays and Physiological Analysis ,Brain Electrophysiology ,Autism spectrum disorder ,Child, Preschool ,Medical genetics ,Female ,Genetic Oscillators ,Anticonvulsants ,Anatomy ,Research Article ,medicine.medical_specialty ,Adolescent ,Imaging Techniques ,Neurophysiology ,Neuroimaging ,Dup15q ,Research and Analysis Methods ,Clinical neurophysiology ,Young Adult ,03 medical and health sciences ,Diagnostic Medicine ,Intellectual Disability ,Genetics ,medicine ,Humans ,Chromosome Aberrations ,Pharmacology ,Clinical Genetics ,Chromosomes, Human, Pair 15 ,Scalp ,Electrophysiological Techniques ,lcsh:R ,Infant ,Biology and Life Sciences ,Repeated measures design ,medicine.disease ,030104 developmental biology ,Developmental Psychology ,lcsh:Q ,Head ,Biomarkers ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Background Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism spectrum disorder (ASD). A distinct electrophysiological (EEG) pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome. Methods In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11), age-and-IQ-matched children with ASD (n = 10) and age-matched typically developing (TD) children (n = 9) and computed relative power in 6 frequency bands for 9 regions of interest (ROIs). Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27) across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions. Results In the first study, spontaneous beta1 (12–20 Hz) and beta2 (20–30 Hz) power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1–4 Hz) was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1). In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome. Conclusions Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome.
- Published
- 2016
39. Brain connectivity in autism spectrum disorder.
- Author
-
Mohammad-Rezazadeh I, Frohlich J, Loo SK, and Jeste SS
- Subjects
- Autism Spectrum Disorder diagnosis, Autism Spectrum Disorder pathology, Brain pathology, Humans, Magnetic Resonance Imaging methods, Neural Pathways pathology, Autism Spectrum Disorder physiopathology, Brain physiopathology, Brain Mapping, Neural Pathways physiopathology
- Abstract
Purpose of Review: Many studies have reported that individuals with autism spectrum disorder (ASD) have different brain connectivity patterns compared with typically developing individuals. However, the results of more recent studies do not unanimously support the traditional view in which individuals with ASD have lower connectivity between distant brain regions and increased connectivity within local brain regions. In this review, we discuss different methods for measuring brain connectivity and how the use of different metrics may contribute to the lack of convergence of investigations of connectivity in ASD., Recent Findings: The discrepancy in brain connectivity results across studies may be due to important methodological factors, such as the connectivity measure applied, the age of patients studied, the brain region(s) examined, and the time interval and frequency band(s) in which connectivity was analyzed., Summary: We conclude that more sophisticated electroencephalography analytic approaches should be utilized to more accurately infer causation and directionality of information transfer between brain regions, which may show dynamic changes of functional connectivity in the brain. Moreover, further investigations of connectivity with respect to behavior and clinical phenotype are needed to probe underlying brain networks implicated in core deficits of ASD.
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.