Disinhibition of Primitive Reflexes in Attention Deficit and Hyperactivity Disorder: Insight Into Specific Mechanisms in Girls and Boys

Objective: Cognitive and motor disintegration and other functional disturbances in various neuropsychiatric disorders may be related to inhibitory deficits that may manifest as a persistence or re-expression of primitive reflexes and few recent data suggest that these deficits may occur in Attention Deficit and Hyperactivity Disorder (ADHD).Methods: We have tested a hypothesis to which extent ADHD symptoms and balance deficits are related to persisting primitive reflexes, such as Asymmetric Tonic Neck Reflex (ATNR) and Symmetric Tonic Neck Reflex (STNR) in 80 medication-naïve children with ADHD (40 boys and 40 girls) in the school age (8–11 years) and compared these data with a control group of 60 children (30 boys and 30 girls).Results: These data show new finding that ADHD symptoms and balance deficits are strongly and specifically associated with persistent ATNR in girls and STNR in boys.Conclusions: These results provide first evidence in medical literature that ADHD in girls and boys is specifically related to distinguished neurological developmental mechanisms related to disinhibition of primitive reflexes.

Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome

The alteration of excitatory–inhibitory (E–I) balance has been implicated in various neurological and psychiatric diseases, including autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder that is the most common known cause of ASD. Understanding the molecular and physiological features of FXS is thought to enhance our knowledge of the pathophysiology of ASD. Accumulated evidence implicates deficits in the inhibitory circuits in FXS that tips E–I balance toward excitation. Deficits in interneurons, the main source of an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have been reported in FXS, including a reduced number of cells, reduction in intrinsic cellular excitability, or weaker synaptic connectivity. Manipulating the interneuron activity ameliorated the symptoms in the FXS mouse model, which makes it reasonable to conceptualize FXS as an interneuronopathy. While it is still poorly understood how the developmental profiles of the inhibitory circuit go awry in FXS, recent works have uncovered several developmental alterations in the functional properties of interneurons. Correcting disrupted E–I balance by potentiating the inhibitory circuit by targeting interneurons may have a therapeutic potential in FXS. I will review the recent evidence about the inhibitory alterations and interneuron dysfunction in ASD and FXS and will discuss the future directions of this field.

Reaction time intra-individual variability reveals inhibitory deficits in single- and multiple-domain amnestic mild cognitive impairment

Objectives Amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer’s disease and other dementias, is characterized by episodic memory impairment. Recent evidence has shown inhibitory control deficits in aMCI, but the extent of these deficits across inhibitory domains (i.e., response inhibition and interference control) and aMCI subtypes (i.e., single- versus multiple-domain) remains unclear. Few studies have included response time intra-individual variability (RT IIV) in these efforts. The aim of this study was to compare response inhibition and interference control between aMCI subtypes using measures of accuracy, mean RT, and RT IIV. Method We report data from 34 individuals with single-domain aMCI (sdaMCI, 66–86 years), 20 individuals with multiple-domain aMCI (mdaMCI, 68–88 years), and 52 healthy controls (64–88 years) who completed tasks of response inhibition (Go-NoGo) and interference control (Flanker). Group differences in accuracy, mean RT, and RT IIV were examined for both tasks. Results Individuals with mdaMCI had higher RT IIV than the other groups on both tasks. In RT IIV, we observed an interference control deficit in mdaMCI and sdaMCI relative to healthy controls, a finding not observed through accuracy or mean RT. Discussion RT IIV may detect subtle differences in inhibition deficits between aMCI subtypes that may not be evident with conventional behavioral measures. Findings support the supplementary use of RT IIV when assessing early executive function deficits.

Spinal Inhibitory Interneurons: Gatekeepers of Sensorimotor Pathways

The ability to sense and move within an environment are complex functions necessary for the survival of nearly all species. The spinal cord is both the initial entry site for peripheral information and the final output site for motor response, placing spinal circuits as paramount in mediating sensory responses and coordinating movement. This is partly accomplished through the activation of complex spinal microcircuits that gate afferent signals to filter extraneous stimuli from various sensory modalities and determine which signals are transmitted to higher order structures in the CNS and to spinal motor pathways. A mechanistic understanding of how inhibitory interneurons are organized and employed within the spinal cord will provide potential access points for therapeutics targeting inhibitory deficits underlying various pathologies including sensory and movement disorders. Recent studies using transgenic manipulations, neurochemical profiling, and single-cell transcriptomics have identified distinct populations of inhibitory interneurons which express an array of genetic and/or neurochemical markers that constitute functional microcircuits. In this review, we provide an overview of identified neural components that make up inhibitory microcircuits within the dorsal and ventral spinal cord and highlight the importance of inhibitory control of sensorimotor pathways at the spinal level.

Auditory Gating in Hearing Loss

Background Sensory gating is a measure used to evaluate inhibitory deficits underlying neurological disorders. However, the effects of hearing loss (HL), thought to decrease inhibition, remain unknown on gating function. Purpose The goal of this study was to investigate gating performance in HL. Research Design This was a prospective, cross-sectional study with independent group comparison and correlational design. Study Sample Eleven adults (mean age/standard deviation = 47.546 ± 7.967 years) with normal hearing (NH) and 11 adults (mean age/standard deviation = 56.273 ± 13.871 years) with mild–moderate high-frequency HL. Data Collection and Analysis Cortical auditory evoked potentials (CAEPs) were recorded in response to tonal pairs via high-density electroencephalography. The CAEP response to the second tone in the pair (S2) was compared with the response to the first tone in the pair (S1) within groups. Amplitude gating indices were compared between groups and correlated with auditory behavioral measures. Current density reconstructions were performed to estimate cortical gating generators. Results Amplitude gating indices were decreased and correlated with elevated auditory thresholds. Gating generators in temporal, frontal, and prefrontal regions were localized in the NH group, while HL gating was localized in mainly temporal and parietal areas. Conclusions Reduced inhibition may be associated with compensatory cortical gating networks in HL and should be considered when utilizing gating in clinical populations.