Human fear-related motor neurocircuitry

doi:10.1016/j.neuroscience.2007.09.048

Neuroscience

Volume 150, Issue 1, 30 November 2007, Pages 1-7

https://doi.org/10.1016/j.neuroscience.2007.09.048 Get rights and content

Abstract

Using functional magnetic resonance imaging and an experimental paradigm of instructed fear, we observed a striking pattern of decreased activity in primary motor cortex with increased activity in dorsal basal ganglia during anticipation of aversive electrodermal stimulation in 42 healthy participants. We interpret this pattern of activity in motor neurocircuitry in response to cognitively-induced fear in relation to evolutionarily-conserved responses to threat that may be relevant to understanding normal and pathological fear in humans.

Section snippets

Participants

Forty-two healthy, right-handed participants (mean age: 28 [std 6]; 16 women) underwent fMRI scanning as part of this study, which was approved by the Weill-Cornell Institutional Review Board.

Dial-up procedure

Immediately prior to scanning, each participant determined the level of electrodermal stimulation to be received during the scan session via a standardized dial-up procedure in which stimulations to the left wrist were increased gradually to a level of intensity experienced by that individual as

SCR and debriefing questionnaire

Analysis of 14 skin conductance tracings (seven traces [out of 21] could not be analyzed due to excessive artifact or no detectable SCRs) revealed significantly larger SCR magnitudes during threat as compared with safety, t(13)=3.23, P=0.007 (two-tailed), Cohen’s d=1.07.

Responses to the post-scan debriefing question “How did you feel when seeing each of the two colors?” were available for 38/42 participants. Thirty-three of 38 participants (86.8%) reported feeling anxious or fearful about

Discussion

Results indicate that brain regions traditionally considered to be involved mainly in motor behavior (dorsal basal ganglia and primary motor cortex) respond robustly and consistently to an experimentally-induced state of conscious fear, while threat-related amygdalar activity is limited to the earliest portion of the experiment. Actual movement is an unlikely explanation for findings because no experimental condition required any motor response. That the experimental paradigm produced

Conclusion

The role of cortical and subcortical neurocircuitry in evolutionarily-conserved motor and other responses to perceived danger deserves additional translational study in animals models, in healthy humans, and in patients suffering from fear-related disorders.

Acknowledgments

This research was supported by NIH grants P50MH058911 and 5R01MH061825. We are grateful to Jude Allen, Josefino Borja, and Wolfgang Engelien for their help with this project.

References (27)

M.L. Boshuisen et al.
rCBF differences between panic disorder patients and control subjects during anticipatory anxiety and rest
Biol Psychiatry
(2002)
P. Chua et al.
A functional anatomy of anticipatory anxiety
Neuroimage
(1999)
S. Grillner et al.
Mechanisms for selection of basic motor programs: roles for the striatum and pallidum
Trends Neurosci
(2005)
C. Grillon et al.
A review of the modulation of the startle reflex by affective states and its application in psychiatry
Clin Neurophysiol
(2003)
H. Gu et al.
Single-shot interleaved z-shim EPI with optimized compensation for signal losses due to susceptibility-induced field inhomogeneity at 3 T
Neuroimage
(2002)
M. Javanmard et al.
Neuroanatomic correlates of CCK-4-induced panic attacks in healthy humans: a comparison of two time points
Biol Psychiatry
(1999)
A. Lieberman
Are freezing of gait (FOG) and panic related?
J Neurol Sci
(2006)
J.B.J.B. Nitschke et al.
Functional neuroanatomy of aversion and its anticipation
Neuroimage
(2006)
N. Tzourio-Mazoyer et al.
Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain
Neuroimage
(2002)
K.J. Worsley et al.
A general statistical analysis for fMRI data
Neuroimage
(2002)

D.H. Zald

The human amygdala and the emotional evaluation of sensory stimuli

Brain Res Brain Res Rev

(2003)

G.E. Alexander et al.

Parallel organization of functionally segregated circuits linking basal ganglia and cortex

Annu Rev Neurosci

(1986)

D.C. Blanchard et al.

Human defensive behaviors to threat scenarios show parallels to fear- and anxiety-related defense patterns of non-human mammals

Neurosci Biobehav Rev

(2001)

Cited by (72)

Anti-Hebbian plasticity in the motor cortex promotes defensive freezing
2023, Current Biology
Regional brain activity often decreases from baseline levels in response to external events, but how neurons develop such negative responses is unclear. To study this, we leveraged the negative response that develops in the primary motor cortex (M1) after classical fear learning. We trained mice with a fear conditioning paradigm while imaging their brains with standard two-photon microscopy. This enabled monitoring changes in neuronal responses to the tone with synaptic resolution through learning. We found that M1 layer 5 pyramidal neurons (L5 PNs) developed negative tone responses within an hour after conditioning, which depended on the weakening of their dendritic spines that were active during training. Blocking this form of anti-Hebbian plasticity using an optogenetic manipulation of CaMKII activity disrupted negative tone responses and freezing. Therefore, reducing the strength of spines active at the time of memory encoding leads to negative responses of L5 PNs. In turn, these negative responses curb M1’s capacity for promoting movement, thereby aiding freezing. Collectively, this work provides a mechanistic understanding of how area-specific negative responses to behaviorally relevant cues can be achieved.
Interactions across emotional, cognitive and subcortical motor networks underlying freezing of gait
2023, NeuroImage: Clinical
Freezing of gait (FOG) is a gait disorder affecting patients with Parkinson’s disease (PD) and related disorders. The pathophysiology of FOG is unclear because of its phenomenological complexity involving motor, cognitive, and emotional aspects of behavior. Here we used resting-state functional MRI to retrieve functional connectivity (FC) correlated with the New FOG questionnaire (NFOGQ) reflecting severity of FOG in 67 patients with PD. NFOGQ scores were correlated with FCs in the extended basal ganglia network (BGN) involving the striatum and amygdala, and in the extra-cerebellum network (CBLN) involving the frontoparietal network (FPN). These FCs represented interactions across the emotional (amygdala), subcortical motor (BGN and CBLN), and cognitive networks (FPN). Using these FCs as features, we constructed statistical models that explained 40% of the inter-individual variances of FOG severity and that discriminated between PD patients with and without FOG. The amygdala, which connects to the subcortical motor (BGN and CBLN) and cognitive (FPN) networks, may have a pivotal role in interactions across the emotional, cognitive, and subcortical motor networks. Future refinement of the machine learning-based classifier using FCs may clarify the complex pathophysiology of FOG further and help diagnose and evaluate FOG in clinical settings.
The brain correlates of hostile attribution bias and their relation to the displaced aggression
2022, Journal of Affective Disorders
Hostile attribution bias (HAB) has been considered as a risk factor of various types of psychosocial adjustment problem, and contributes to displaced aggression (DA). The neural basis of HAB and the underlying mechanisms of how HAB predicts DA remain unclear.
The current study used degree centrality (DC) and resting-sate functional connectivity (RSFC) to investigate the functional connection pattern related to HAB in 503 undergraduate students. Furthermore, the “Decoding” was used to investigate which psychological components the maps of the RSFC-behavior may be related to. Finally, to investigate whether and how the RSFC pattern, HAB predicts DA, we performed mediation analyses.
We found that HAB was negatively associated with DC in bilateral temporal poles (TP) and positively correlated with DC in the putamen and thalamus; Moreover, HAB was negatively associated with the strength of functional connectivity between TP and brain regions in the theory of mind network (ToM), and positively related to the strength of functional connectivity between the thalamus and regions in the ToM network. The “Decoding” showed the maps of the RSFC-behavior may involve the theory mind, autobiographic, language, comprehension and working memory. Mediation analysis further showed that HAB mediated the relationship between some neural correlates of the HAB and DA.
The current results need to be further tested by experimental methods or longitudinal design in further studies.
These findings shed light on the neural underpinnings of HAB and provide a possible mediation model regarding the relationships among RSFC pattern, HAB, and displaced aggression.
Brain activation elicited by acute stress: An ALE meta-analysis
2022, Neuroscience and Biobehavioral Reviews
Stress abounds in daily life and is closely related to psychiatric disease. Less is known about the neural basis for the gender differences in stress, and the common and specific neural mechanism for physiological and psychosocial stress. The current study obtained 141 stress-oriented neuroimaging experiments from 126 eligible articles and sorted them into nine types of neuroimaging datasets based on the combination of stress (general, physiological or psychosocial) and gender (overall, male or female). An activation likelihood estimation (ALE) meta-analysis was conducted on each dataset to detect the spatial convergence of activations. A hierarchical clustering analysis was also conducted to uncover the relationship between the stress-induced paradigms and spatial distribution of brain activations. We found that the physiological stress and psychosocial stress showed common activation in the bilateral anterior insula and brainstem, but different activation likelihood in the bilateral insula, thalami, middle cingulate cortex, left fusiform gyri, and left amygdala. Men were more likely to activate the bilateral thalami during physiological stress, whereas women were more likely to activate the left amygdala during psychosocial stress. The activation patterns are more consistent among different physiological stress paradigms than psychosocial stress paradigms. Our results suggest that physiological stress and psychosocial stress activate common brain regions for movement and attentional regulation but different brain regions for sensory and affective processing.
Facing yourself – A note on self-image
2021, Journal of Economic Behavior and Organization
The concern for a positive self-image is a central assumption in a large class of signaling models. In this paper, we exogenously vary the impact of self-image concerns by manipulating self-directed attention and study the impact on moral behavior. The choice context in the experiment is whether subjects inflict a painful electric shock on another subject to receive a monetary reward. In the main treatment, subjects see their own face on the decision screen in a real-time video feed. In three control conditions, subjects see either no video at all or a neutral video, or they see themselves in a mirror. We find that increasing self-awareness significantly reduces the fraction of subjects inflicting pain. The finding emphasizes the importance of self-image concerns for moral decision making with implications for theory as well as practical applications to promote socially desirable outcomes.
Threat bias and resting state functional connectivity of the amygdala and bed nucleus stria terminalis
2020, Journal of Psychiatric Research
Previous research has distinguished the activations of the amygdala and bed nucleus of stria terminalis (BNST) during threat-related contingencies. However, how intrinsic connectivities of the amygdala and BNST relate to threat bias remains unclear. Here, we investigated how resting state functional connectivity (rsFC) of the amygdala and BNST in healthy controls (HC) and patients with anxiety-related disorders (PAD) associate with threat bias in a dot-probe task.
Imaging and behavioral data of 30 PAD and 83 HC were obtained from the Nathan Kline Institute - Rockland sample and processed according to published routines. All imaging results were evaluated at voxel p < 0.001 and cluster p < 0.05, FWE corrected in SPM.
PAD and HC did not show differences in whole brain rsFC with either the amygdala or BNST. In linear regressions threat bias was positively correlated with amygdala-thalamus/anterior cingulate cortex (ACC) rsFC in HC but not PAD, and with BNST-caudate rsFC in PAD but not HC. Slope tests confirmed group differences in the correlations between threat bias and amygdala-thalamus/ACC as well as BNST-caudate rsFC.
As only half of the patients included were diagnosed with comorbid anxiety, the current findings need to be considered with the clinical heterogeneity and require replication in populations specifically with anxiety disorders.
Together, these results suggest amygdala and BNST connectivities as new neural markers of anxiety disorders. Whereas amygdala-thalamus/ACC rsFC support adaptive regulation of threat response in the HC, BNST-caudate rsFC may reflect maladaptive neural processes that are dominated by anticipatory anxiety.

View all citing articles on Scopus

View full text

Rapid reportHuman fear-related motor neurocircuitry

Abstract

Section snippets

Participants

Dial-up procedure

SCR and debriefing questionnaire

Discussion

Conclusion

Acknowledgments

Biol Psychiatry

Neuroimage

Trends Neurosci

Clin Neurophysiol

Neuroimage

Biol Psychiatry

J Neurol Sci

Neuroimage

Neuroimage

Neuroimage

Brain Res Brain Res Rev

Parallel organization of functionally segregated circuits linking basal ganglia and cortex

Annu Rev Neurosci

Human defensive behaviors to threat scenarios show parallels to fear- and anxiety-related defense patterns of non-human mammals

Neurosci Biobehav Rev

Rapid report
Human fear-related motor neurocircuitry