What happens in the brain during an anxiety attack?

Brain Activity During Anxiety Attacks

During an anxiety attack, the brain experiences a complex interplay of neural circuits involving hyperactivation of the amygdala and dysregulation of prefrontal cortex control, leading to both psychological and physiological manifestations of fear and stress. 1

Key Neural Circuits Involved

• The amygdala becomes hyperactive during anxiety attacks, serving as the brain's primary fear processing center that triggers the body's alarm system 1
• The prefrontal cortex (PFC), which normally regulates emotional responses, shows decreased functional connectivity with the amygdala, reducing its ability to control fear responses 1, 2
• The hypothalamus activates the sympathoexcitatory neural circuits, leading to the physical symptoms of anxiety through the hypothalamic-pituitary-adrenal (HPA) axis 1, 3
• The hippocampus, involved in memory processing and contextual fear, shows altered functioning during anxiety states 1, 4

Neurochemical Changes

• Sympathoexcitatory neural circuits undergo disinhibition, resulting in increased catecholamine (adrenaline and noradrenaline) release 1, 3
• The neurotransmitter balance shifts with alterations in:
  • GABA (inhibitory) signaling, which is often reduced 5
  • Glutamate (excitatory) transmission, which may be increased 5
  • Serotonin and norepinephrine regulation, which becomes dysregulated 6

Functional Connectivity Disruptions

• Reduced connectivity between the right amygdala and right superior frontal gyrus, anterior cingulate cortex, and supramarginal gyrus occurs in anxiety disorders 2
• Decreased functional connectivity between the left amygdala and subgenual cingulate cortex correlates with reduced heart rate variability, linking cognitive and autonomic symptoms 2
• The balance between habitual and goal-directed behavior is altered, with increased habit formation associated with hyperactivation of the caudate nucleus 1

Autonomic Nervous System Response

• After threat detection, the prefrontal cortex and amygdala regulate heart rate through a pathway involving:
  • The nucleus ambiguus
  • The dorsal nucleus of the vagus nerve
  • The vagus nerve itself, which connects to the sinoatrial node of the heart 1
• This activation leads to the classic "fight-or-flight" response with increased heart rate, blood pressure, and respiratory rate 1
• In some cases, parasympathetic activation may occur, leading to fear-induced bradycardia (slowing of heart rate) 1

Inflammatory Processes

• Anxiety states activate microglia (brain immune cells), leading to neuroinflammation 1
• Pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α become elevated, contributing to anxiety symptoms 1, 3
• The ATP-P2X7 receptor pathway in microglia activates the NLRP3 inflammasome, further promoting inflammation 1

Structural Changes with Chronic Anxiety

• Chronic anxiety and stress can lead to:
  • Reduced volume and functionality of the hippocampus and medial prefrontal cortex 3, 4
  • Decreased hippocampal neurogenesis 3
  • Dendritic retraction in both hippocampus and prefrontal cortex 3, 4
  • Alterations in brain-derived neurotrophic factor (BDNF) expression, affecting neuroplasticity 5

Clinical Implications

• These neurobiological changes explain the common symptoms experienced during anxiety attacks, including racing heart, chest pain, sweating, dizziness, and fear of losing control 6
• The disruption in prefrontal-amygdala circuitry explains why logical thinking becomes difficult during anxiety attacks 2, 4
• Effective treatments for anxiety target these neural mechanisms:
  • Cognitive-behavioral therapy increases right ventrolateral prefrontal cortex activation, improving control over anxiety responses 7, 4
  • Medications like SSRIs and benzodiazepines modulate neurotransmitter systems involved in anxiety circuitry 6

Understanding these brain mechanisms helps explain why anxiety attacks feel so overwhelming and why they involve both psychological and physical symptoms that reinforce each other in a vicious cycle 2, 4.