Identification of a Common Neurobiological Substrate for Mental Illness

Goodkind, Madeleine S.; Eickhoff, Simon B.; Oathes, Desmond J.; Jiang, Ying; Chang, Andrew; Jones-Hagata, Laura B.; Ortega, Brissa N.; Zaiko, Yevgeniya V.; Roach, Erika L.; Korgaonkar, Mayuresh S.; Grieve, Stuart M.; Galatzer‐Levy, Isaac R.; Fox, Peter T.; Etkin, Amit

doi:10.1001/jamapsychiatry.2014.2206

Cited by 1,200 publications

(1,058 citation statements)

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“…associated with the lesion or pharmacological studies by directly establishing a causal role of dACC neural activities on attentional behavior. Our study supports the possibility that the changes in dACC observed in many psychiatric disorders (Bush et al, 1999;Goodkind et al, 2015) can causally contribute to cognitive dysfunction. As far as we are aware, this is the first study that directly demonstrates that dACC neurons play a causal role in attention processing in mice.…”

Section: Discussionsupporting

confidence: 86%

“…Furthermore, the dACC is hypoactivated in patients with attention-deficit/hyperactivity disorder during an attention task (Bush et al, 1999). Shrinkage of the dACC that is commonly observed in multiple psychiatric disordersincluding schizophrenia, bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety-correlates with poor executive functioning including sustained attention (Goodkind et al, 2015). Electrophysiologic singleunit recording in both primates and rodents also demonstrate dACC activity during attention tasks, specifically in anticipation of oncoming task-relevant visual cues (Johnston et al, 2007;Totah et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse

Koike

Demars

Short

et al. 2015

Neuropsychopharmacol

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Attention is disrupted commonly in psychiatric disorders, yet mechanistic insight remains limited. Deficits in this function are associated with dorsal anterior cingulate cortex (dACC) excitotoxic lesions and pharmacological disinhibition; however, a causal relationship has not been established at the cellular level. Moreover, this association has not yet been examined in a genetically tractable species such as mice. Here, we reveal that dACC neurons causally contribute to attention processing by combining a chemogenetic approach that reversibly suppresses neural activity with a translational, touchscreen-based attention task in mice. We virally expressed inhibitory hM4Di DREADD (designer receptor exclusively activated by a designer drug) in dACC neurons, and examined the effects of this inhibitory action with the attention-based five-choice serial reaction time task. DREADD inactivation of the dACC neurons during the task significantly increased omission and correct response latencies, indicating that the neuronal activities of dACC contribute to attention and processing speed. Selective inactivation of excitatory neurons in the dACC not only increased omission, but also decreased accuracy. The effect of inactivating dACC neurons was selective to attention as response control, motivation, and locomotion remain normal. This finding suggests that dACC excitatory neurons play a principal role in modulating attention to task-relevant stimuli. This study establishes a foundation to chemogenetically dissect specific cell-type and circuit mechanisms underlying attentional behaviors in a genetically tractable species.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse

Koike

Demars

Short

et al. 2015

Neuropsychopharmacol

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“…These include executive function and action such as expressed in the goals being pursued, affect and autobiographical memory, defining the foundations of autonoetic experience. Neglect is a multifaceted pathology due to a distributed network destabilization of the thalamo-cortical system; the same holds for other deficits of consciousness including schizophrenia [219]. Hence, there is no convincing evidence to depart from the multi-scale network interpretation of consciousness advocated here.…”

Section: Discussionmentioning

confidence: 73%

Synthetic consciousness: the distributed adaptive control perspective

Verschure

2016

Phil. Trans. R. Soc. B

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One contribution of 13 to a theme issue 'The major synthetic evolutionary transitions'. Understanding the nature of consciousness is one of the grand outstanding scientific challenges. The fundamental methodological problem is how phenomenal first person experience can be accounted for in a third person verifiable form, while the conceptual challenge is to both define its function and physical realization. The distributed adaptive control theory of consciousness (DACtoc) proposes answers to these three challenges. The methodological challenge is answered relative to the hard problem and DACtoc proposes that it can be addressed using a convergent synthetic methodology using the analysis of synthetic biologically grounded agents, or quale parsing. DACtoc hypothesizes that consciousness in both its primary and secondary forms serves the ability to deal with the hidden states of the world and emerged during the Cambrian period, affording stable multi-agent environments to emerge. The process of consciousness is an autonomous virtualization memory, which serializes and unifies the parallel and subconscious simulations of the hidden states of the world that are largely due to other agents and the self with the objective to extract norms. These norms are in turn projected as value onto the parallel simulation and control systems that are driving action. This functional hypothesis is mapped onto the brainstem, midbrain and the thalamo-cortical and cortico-cortical systems and analysed with respect to our understanding of deficits of consciousness. Subsequently, some of the implications and predictions of DACtoc are outlined, in particular, the prediction that normative bootstrapping of conscious agents is predicated on an intentionality prior. In the view advanced here, human consciousness constitutes the ultimate evolutionary transition by allowing agents to become autonomous with respect to their evolutionary priors leading to a post-biological Anthropocene.This article is part of the themed issue 'The major synthetic evolutionary transitions'.

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“…In contrast, neuroimaging has not so far been very successful in aiding differential diagnosis of disorders in terms of current diagnostic categories. A recent large meta-analysis identified a set of regions in which structural abnormalities were consistently associated with psychiatric disorders, but found very little specificity for individual disorders 56 , consistent with the notion that current diagnostic distinctions are not biologically realistic categories.…”

Section: Brain Disordersmentioning

confidence: 83%