Helen Barbas - Academia.edu (original) (raw)

Papers by Helen Barbas

Research paper thumbnail of Sleep spindles in primates: modelling the effects of distinct laminar thalamocortical connectivity in core, matrix, and reticular thalamic circuits

bioRxiv (Cold Spring Harbor Laboratory), Apr 29, 2022

Research paper thumbnail of Characteristics of the contingent negative variation in patients suffering from specific phobias

PubMed, Oct 1, 1978

The essential clinical feature of phobic neurosis is the anticipatory fear of certain objects and... more The essential clinical feature of phobic neurosis is the anticipatory fear of certain objects and situations. Since an important factor in the generation of the contingent negative variation (CNV) is the anticipation of the imperative stimulus, records of CNVs were used as an indicator of electrocortical activity in a group of 14 patients suffering from specific phobias. After clinical evaluation, a CNV to a picture of a nondisturbing object was obtained. The amplitude of the CNV and duration of the PINV (postimperative negative variation) were taken as reference values against which response to the phobic objects were evaluated. Reaction time was automatically measured between the period of S2 and the button press. Significant differences, viz., larger CNV amplitude, longer PINV duration, and shorter reaction time, were found with phobogenic than with nondisturbing stimuli. After behavioral recovery with behavior therapy, no differences were noted in the CNVs obtained with the presentation of non-disturbing and the ones that were phobogenic stimuli. The significance of the results for an understanding of phobic neurosis and behavior therapy are discussed.

Research paper thumbnail of Emotional intensity can enrich or degrade memories: impact of the amygdalar pathway on hippocampus through inhibitory neurons

bioRxiv (Cold Spring Harbor Laboratory), Mar 19, 2022

Research paper thumbnail of Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing

The Journal of Neuroscience, Mar 28, 2023

Research paper thumbnail of From Circuit Principles to Human Psychiatric Disorders

Biological Psychiatry, Mar 1, 2023

Research paper thumbnail of Visual Attention Decits in Schizophrenia Can Arise From Inhibitory Dysfunction in Thalamus or Cortex

Computational Psychiatry, 2018

Research paper thumbnail of Parallel Development of Chromatin Patterns, Neuron Morphology, and Connections: Potential for Disruption in Autism

Frontiers in Neuroanatomy, 2018

Research paper thumbnail of Relationship of Prefrontal Connections to Inhibitory Systems in Superior Temporal Areas in the Rhesus Monkey

Research paper thumbnail of Serial Prefrontal Pathways Are Positioned to Balance Cognition and Emotion in Primates

The Journal of Neuroscience, Sep 28, 2020

Research paper thumbnail of Mechanisms for the Approach/Avoidance Decision Applied to Autism

Trends in Neurosciences, Jul 1, 2019

Research paper thumbnail of The prefrontal cortex, pathological anxiety, and anxiety disorders

Neuropsychopharmacology, Aug 16, 2021

Anxiety is experienced in response to threats that are distal or uncertain, involving changes in ... more Anxiety is experienced in response to threats that are distal or uncertain, involving changes in one’s subjective state, autonomic responses, and behavior. Defensive and physiologic responses to threats that involve the amygdala and brainstem are conserved across species. While anxiety responses typically serve an adaptive purpose, when excessive, unregulated, and generalized, they can become maladaptive, leading to distress and avoidance of potentially threatening situations. In primates, anxiety can be regulated by the prefrontal cortex (PFC), which has expanded in evolution. This prefrontal expansion is thought to underlie primates’ increased capacity to engage high-level regulatory strategies aimed at coping with and modifying the experience of anxiety. The specialized primate lateral, medial, and orbital PFC sectors are connected with association and limbic cortices, the latter of which are connected with the amygdala and brainstem autonomic structures that underlie emotional and physiological arousal. PFC pathways that interface with distinct inhibitory systems within the cortex, the amygdala, or the thalamus can regulate responses by modulating neuronal output. Within the PFC, pathways connecting cortical regions are poised to reduce noise and enhance signals for cognitive operations that regulate anxiety processing and autonomic drive. Specialized PFC pathways to the inhibitory thalamic reticular nucleus suggest a mechanism to allow passage of relevant signals from thalamus to cortex, and in the amygdala to modulate the output to autonomic structures. Disruption of specific nodes within the PFC that interface with inhibitory systems can affect the negative bias, failure to regulate autonomic arousal, and avoidance that characterize anxiety disorders.

Research paper thumbnail of The Cortical Spectrum: a robust structural continuum in primate cerebral cortex revealed by histological staining and magnetic resonance imaging

High-level characterizations of the primate cerebral cortex sit between two extremes: on one end ... more High-level characterizations of the primate cerebral cortex sit between two extremes: on one end the cortical mantle is seen as a mosaic of structurally and functionally unique areas, and on the other it is seen as a uniform six-layered structure in which functional differences are defined solely by extrinsic connections. Neither of these extremes captures the crucial neuroanatomical finding: that the cortex exhibits systematic gradations in architectonic structure. These gradations have been shown to predict cortico-cortical connectivity, which in turn suggests powerful ways to ground connectomics in anatomical structure, and by extension cortical function. A challenge to more widespread use of this concept is the labor-intensive and invasive nature of histological staining, which is the primary means of recognizing anatomical gradations. Here we show that a novel computational analysis technique can be used to derive a coarse-grained picture of cortical variation. For each of 78 c...

Research paper thumbnail of Serial Prefrontal Pathways Are Positioned to Balance Cognition and Emotion in Primates

The Journal of Neuroscience, 2020

The delicate balance among primate prefrontal networks is necessary for homeostasis and behaviora... more The delicate balance among primate prefrontal networks is necessary for homeostasis and behavioral flexibility. Dorsolateral prefrontal cortex (dlPFC) is associated with cognition, while the most ventromedial subgenual cingulate area 25 (A25) is associated with emotion and emotional expression. Yet A25 is weakly connected with dlPFC, and it is unknown how the two regions communicate. In rhesus monkeys of both sexes, we investigated how these functionally distinct areas may interact through pregenual anterior cingulate area 32 (A32), which is strongly connected with both. We found that dlPFC innervated the deep layers of A32, while A32 innervated all layers of A25, mostly targeting spines of excitatory neurons. Approximately 20% of A32 terminations formed synapses on inhibitory neurons in A25, notably the powerful parvalbumin inhibitory neurons in the deep layers, and the disinhibitory calretinin neurons in the superficial layers. By innervating distinct inhibitory microenvironments ...

Research paper thumbnail of Pathways for Memory, Cognition and Emotional Context: Hippocampal, Subgenual Area 25, and Amygdalar Axons Show Unique Interactions in the Primate Thalamic Reuniens Nucleus

The Journal of Neuroscience, 2021

The reuniens nucleus (RE) is situated at the most ventral position of the midline thalamus. In ra... more The reuniens nucleus (RE) is situated at the most ventral position of the midline thalamus. In rats and mice RE is distinguished by bidirectional connections with the hippocampus and medial prefrontal cortex (mPFC) and a role in memory and cognition. In primates, many foundational questions pertaining to RE remain unresolved. We addressed these issues by investigating the composition of the rhesus monkey RE in both sexes by labeling for GABA, a marker of inhibitory neurons, and for the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR), which label thalamic excitatory neurons that project to cortex. As in rats and mice, the macaque RE was mostly populated by CB and CR neurons, characteristic of matrix-dominant nuclei, and had bidirectional connections with hippocampus and mPFC area 25 (A25). Unlike rodents, we found GABAergic neurons in the monkey RE and a sparser but consistent population of core-associated thalamocortical PV neurons. RE had stronger con...

Research paper thumbnail of Anterior Cingulate Pathways May Affect Emotions Through Orbitofrontal Cortex

Cerebral Cortex, Sep 20, 2016

Research paper thumbnail of The inevitable inequality of cortical columns

Frontiers in Systems Neuroscience

The idea of columns as an organizing cortical unit emerged from physiologic studies in the sensor... more The idea of columns as an organizing cortical unit emerged from physiologic studies in the sensory systems. Connectional studies and molecular markers pointed to widespread presence of modular label that necessitated revision of the classical concept of columns. The general principle of cortical systematic variation in laminar structure is at the core of cortical organization. Systematic variation can be traced to the phylogenetically ancient limbic cortices, which have the simplest laminar structure, and continues through eulaminate cortices that show sequential elaboration of their six layers. Connections are governed by relational rules, whereby columns or modules with a vertical organization represent the feedforward mode of communication from earlier- to later processing cortices. Conversely, feedback connections are laminar-based and connect later- with earlier processing areas; both patterns are established in development. Based on studies in primates, the columnar/modular pa...

Research paper thumbnail of Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 17, 2017

The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala... more The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons...

Research paper thumbnail of Cortical connections position primate area 25 as a keystone for interoception, emotion, and memory

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 22, 2018

The structural and functional integrity of subgenual cingulate area 25 (A25) is crucial for emoti... more The structural and functional integrity of subgenual cingulate area 25 (A25) is crucial for emotional expression and equilibrium. A25 has a key role in affective networks, and its disruption has been linked to mood disorders, but its cortical connections have yet to be systematically or fully studied. Using neural tracers in rhesus monkeys, we found that A25 was densely connected with other ventromedial and posterior orbitofrontal areas associated with emotions and homeostasis. A moderate pathway linked A25 with frontopolar area 10, an area associated with complex cognition, which may regulate emotions and dampen negative affect. Beyond the frontal lobe, A25 was connected with auditory association areas and memory-related medial temporal cortices, and with the interoceptive-related anterior insula. A25 mostly targeted the superficial cortical layers of other areas, where broadly dispersed terminations comingled with modulatory inhibitory or disinhibitory microsystems, suggesting a d...

Research paper thumbnail of Neural interaction between the basal forebrain and functionally distinct prefrontal cortices in the rhesus monkey

Research paper thumbnail of The Laminar Pattern of Connections between Prefrontal and Anterior Temporal Cortices in the Rhesus Monkey is Related to Cortical Structure and Function

Research paper thumbnail of Sleep spindles in primates: modelling the effects of distinct laminar thalamocortical connectivity in core, matrix, and reticular thalamic circuits

bioRxiv (Cold Spring Harbor Laboratory), Apr 29, 2022

Research paper thumbnail of Characteristics of the contingent negative variation in patients suffering from specific phobias

PubMed, Oct 1, 1978

The essential clinical feature of phobic neurosis is the anticipatory fear of certain objects and... more The essential clinical feature of phobic neurosis is the anticipatory fear of certain objects and situations. Since an important factor in the generation of the contingent negative variation (CNV) is the anticipation of the imperative stimulus, records of CNVs were used as an indicator of electrocortical activity in a group of 14 patients suffering from specific phobias. After clinical evaluation, a CNV to a picture of a nondisturbing object was obtained. The amplitude of the CNV and duration of the PINV (postimperative negative variation) were taken as reference values against which response to the phobic objects were evaluated. Reaction time was automatically measured between the period of S2 and the button press. Significant differences, viz., larger CNV amplitude, longer PINV duration, and shorter reaction time, were found with phobogenic than with nondisturbing stimuli. After behavioral recovery with behavior therapy, no differences were noted in the CNVs obtained with the presentation of non-disturbing and the ones that were phobogenic stimuli. The significance of the results for an understanding of phobic neurosis and behavior therapy are discussed.

Research paper thumbnail of Emotional intensity can enrich or degrade memories: impact of the amygdalar pathway on hippocampus through inhibitory neurons

bioRxiv (Cold Spring Harbor Laboratory), Mar 19, 2022

Research paper thumbnail of Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing

The Journal of Neuroscience, Mar 28, 2023

Research paper thumbnail of From Circuit Principles to Human Psychiatric Disorders

Biological Psychiatry, Mar 1, 2023

Research paper thumbnail of Visual Attention Decits in Schizophrenia Can Arise From Inhibitory Dysfunction in Thalamus or Cortex

Computational Psychiatry, 2018

Research paper thumbnail of Parallel Development of Chromatin Patterns, Neuron Morphology, and Connections: Potential for Disruption in Autism

Frontiers in Neuroanatomy, 2018

Research paper thumbnail of Relationship of Prefrontal Connections to Inhibitory Systems in Superior Temporal Areas in the Rhesus Monkey

Research paper thumbnail of Serial Prefrontal Pathways Are Positioned to Balance Cognition and Emotion in Primates

The Journal of Neuroscience, Sep 28, 2020

Research paper thumbnail of Mechanisms for the Approach/Avoidance Decision Applied to Autism

Trends in Neurosciences, Jul 1, 2019

Research paper thumbnail of The prefrontal cortex, pathological anxiety, and anxiety disorders

Neuropsychopharmacology, Aug 16, 2021

Anxiety is experienced in response to threats that are distal or uncertain, involving changes in ... more Anxiety is experienced in response to threats that are distal or uncertain, involving changes in one’s subjective state, autonomic responses, and behavior. Defensive and physiologic responses to threats that involve the amygdala and brainstem are conserved across species. While anxiety responses typically serve an adaptive purpose, when excessive, unregulated, and generalized, they can become maladaptive, leading to distress and avoidance of potentially threatening situations. In primates, anxiety can be regulated by the prefrontal cortex (PFC), which has expanded in evolution. This prefrontal expansion is thought to underlie primates’ increased capacity to engage high-level regulatory strategies aimed at coping with and modifying the experience of anxiety. The specialized primate lateral, medial, and orbital PFC sectors are connected with association and limbic cortices, the latter of which are connected with the amygdala and brainstem autonomic structures that underlie emotional and physiological arousal. PFC pathways that interface with distinct inhibitory systems within the cortex, the amygdala, or the thalamus can regulate responses by modulating neuronal output. Within the PFC, pathways connecting cortical regions are poised to reduce noise and enhance signals for cognitive operations that regulate anxiety processing and autonomic drive. Specialized PFC pathways to the inhibitory thalamic reticular nucleus suggest a mechanism to allow passage of relevant signals from thalamus to cortex, and in the amygdala to modulate the output to autonomic structures. Disruption of specific nodes within the PFC that interface with inhibitory systems can affect the negative bias, failure to regulate autonomic arousal, and avoidance that characterize anxiety disorders.

Research paper thumbnail of The Cortical Spectrum: a robust structural continuum in primate cerebral cortex revealed by histological staining and magnetic resonance imaging

High-level characterizations of the primate cerebral cortex sit between two extremes: on one end ... more High-level characterizations of the primate cerebral cortex sit between two extremes: on one end the cortical mantle is seen as a mosaic of structurally and functionally unique areas, and on the other it is seen as a uniform six-layered structure in which functional differences are defined solely by extrinsic connections. Neither of these extremes captures the crucial neuroanatomical finding: that the cortex exhibits systematic gradations in architectonic structure. These gradations have been shown to predict cortico-cortical connectivity, which in turn suggests powerful ways to ground connectomics in anatomical structure, and by extension cortical function. A challenge to more widespread use of this concept is the labor-intensive and invasive nature of histological staining, which is the primary means of recognizing anatomical gradations. Here we show that a novel computational analysis technique can be used to derive a coarse-grained picture of cortical variation. For each of 78 c...

Research paper thumbnail of Serial Prefrontal Pathways Are Positioned to Balance Cognition and Emotion in Primates

The Journal of Neuroscience, 2020

The delicate balance among primate prefrontal networks is necessary for homeostasis and behaviora... more The delicate balance among primate prefrontal networks is necessary for homeostasis and behavioral flexibility. Dorsolateral prefrontal cortex (dlPFC) is associated with cognition, while the most ventromedial subgenual cingulate area 25 (A25) is associated with emotion and emotional expression. Yet A25 is weakly connected with dlPFC, and it is unknown how the two regions communicate. In rhesus monkeys of both sexes, we investigated how these functionally distinct areas may interact through pregenual anterior cingulate area 32 (A32), which is strongly connected with both. We found that dlPFC innervated the deep layers of A32, while A32 innervated all layers of A25, mostly targeting spines of excitatory neurons. Approximately 20% of A32 terminations formed synapses on inhibitory neurons in A25, notably the powerful parvalbumin inhibitory neurons in the deep layers, and the disinhibitory calretinin neurons in the superficial layers. By innervating distinct inhibitory microenvironments ...

Research paper thumbnail of Pathways for Memory, Cognition and Emotional Context: Hippocampal, Subgenual Area 25, and Amygdalar Axons Show Unique Interactions in the Primate Thalamic Reuniens Nucleus

The Journal of Neuroscience, 2021

The reuniens nucleus (RE) is situated at the most ventral position of the midline thalamus. In ra... more The reuniens nucleus (RE) is situated at the most ventral position of the midline thalamus. In rats and mice RE is distinguished by bidirectional connections with the hippocampus and medial prefrontal cortex (mPFC) and a role in memory and cognition. In primates, many foundational questions pertaining to RE remain unresolved. We addressed these issues by investigating the composition of the rhesus monkey RE in both sexes by labeling for GABA, a marker of inhibitory neurons, and for the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR), which label thalamic excitatory neurons that project to cortex. As in rats and mice, the macaque RE was mostly populated by CB and CR neurons, characteristic of matrix-dominant nuclei, and had bidirectional connections with hippocampus and mPFC area 25 (A25). Unlike rodents, we found GABAergic neurons in the monkey RE and a sparser but consistent population of core-associated thalamocortical PV neurons. RE had stronger con...

Research paper thumbnail of Anterior Cingulate Pathways May Affect Emotions Through Orbitofrontal Cortex

Cerebral Cortex, Sep 20, 2016

Research paper thumbnail of The inevitable inequality of cortical columns

Frontiers in Systems Neuroscience

The idea of columns as an organizing cortical unit emerged from physiologic studies in the sensor... more The idea of columns as an organizing cortical unit emerged from physiologic studies in the sensory systems. Connectional studies and molecular markers pointed to widespread presence of modular label that necessitated revision of the classical concept of columns. The general principle of cortical systematic variation in laminar structure is at the core of cortical organization. Systematic variation can be traced to the phylogenetically ancient limbic cortices, which have the simplest laminar structure, and continues through eulaminate cortices that show sequential elaboration of their six layers. Connections are governed by relational rules, whereby columns or modules with a vertical organization represent the feedforward mode of communication from earlier- to later processing cortices. Conversely, feedback connections are laminar-based and connect later- with earlier processing areas; both patterns are established in development. Based on studies in primates, the columnar/modular pa...

Research paper thumbnail of Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 17, 2017

The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala... more The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons...

Research paper thumbnail of Cortical connections position primate area 25 as a keystone for interoception, emotion, and memory

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 22, 2018

The structural and functional integrity of subgenual cingulate area 25 (A25) is crucial for emoti... more The structural and functional integrity of subgenual cingulate area 25 (A25) is crucial for emotional expression and equilibrium. A25 has a key role in affective networks, and its disruption has been linked to mood disorders, but its cortical connections have yet to be systematically or fully studied. Using neural tracers in rhesus monkeys, we found that A25 was densely connected with other ventromedial and posterior orbitofrontal areas associated with emotions and homeostasis. A moderate pathway linked A25 with frontopolar area 10, an area associated with complex cognition, which may regulate emotions and dampen negative affect. Beyond the frontal lobe, A25 was connected with auditory association areas and memory-related medial temporal cortices, and with the interoceptive-related anterior insula. A25 mostly targeted the superficial cortical layers of other areas, where broadly dispersed terminations comingled with modulatory inhibitory or disinhibitory microsystems, suggesting a d...

Research paper thumbnail of Neural interaction between the basal forebrain and functionally distinct prefrontal cortices in the rhesus monkey

Research paper thumbnail of The Laminar Pattern of Connections between Prefrontal and Anterior Temporal Cortices in the Rhesus Monkey is Related to Cortical Structure and Function