An anxious patient tends to see the world as a dangerous place, one full of threats. This predisposition is extreme in people with post-traumatic stress disorder (PTSD), who continuously over interpret harmless events in their environment as representing severe threats. Our current theories of anxiety assume some level of unconscious processing of the environment that biases some individuals towards sensing danger.

Recent neurobiological research by Eric Kandel, winner of a Nobel Prize for his work on memory, supports this view of brain function (Neuron 2004;44:1043-55). This research focused on the amygdala, a bilateral structure in the temporal lobe, which has proved to be crucial in the processing of emotional reactions, particularly determining and coding the emotional significance of external stimuli. The amygdala has neural connections to the thalamus, hypothalamus and the cortex. It releases hormones and neuromodulators that can alter cognitive processing in the cortex.

Anxious “by nature”?

Kandel’s researchers studied 2 groups of people — normal controls and a group with high trait anxiety, as measured by a standardized scale (Spielberger). The scale identified people who are anxious “by nature,” not just those in a state of anxiety at the time of the study. Such people experience chronic states of tension and apprehension. Psychiatrists think that trait anxiety results from the interaction of genome, epigenome and developmental experience in the life history of an individual. The investigators used high-resolution fMRI (functional magnetic resonance imaging), which allowed them to visualize 2 distinct regions in the amygdala — the dorsal area (DA) and the basolateral region (BLA).

While they were being scanned, subjects were shown photographs of faces in a state of fear (a technique that’s been shown to reliably activate the amygdala). Then they were shown photos of neutral faces, with flashes of fearful countenances presented too quickly for conscious perception. This was confirmed when subjects didn’t report seeing any frightened faces.

Reactions to the unseen

When both groups clearly saw the fearful faces and processed them consciously, the DA region in all subjects became activated. The 2 groups exhibited a significant difference, however, when they processed unconsciously perceived photos of frightened faces. Those with high trait anxiety showed marked activation of their BLA, while those with normal trait anxiety had no activation of either area of the amygdala. In normal subjects, the briefly flashed photos were below the threshold that causes activation of the amygdala. In the people with high trait anxiety, unconscious information processing, when inaccessible to regulation by conscious processes, was very vulnerable to bias whose magnitude appeared to be determined by their level of trait anxiety, i.e. the greater the base level of anxiety, the greater the activation seen. These findings confirm that unconscious mental processes add underlying biases to our information processing. These results are consistent with both psychoanalytic and cognitive models of the mind, which postulate that there’s an automatic “bottom up” processing of threat that’s independent of conscious attention.

Other research has demonstrated that cortical — “top down” — processing can modulate anxiety reactions (Neuron 2006;51: 871-82). Indeed, research shows that in PTSD patients, there’s reduced activity of inhibitory areas of the cerebral cortex, presumably allowing unmodulated intensity of unconscious processing bias to prevail, giving rise to the exhausting, persistent, intense anxiety of that disorder.

Medications can modify these processes, at least temporarily; we don’t know if enduring changes are possible, though. Some psychotherapy studies have shown reduction of measured trait anxiety as a treatment endpoint. We don’t yet understand whether psychotherapy can alter the underlying trait anxiety or whether it serves to extend the conscious regulation of responses. This work promises to make way for more biologically based research into psychotherapy. If he’d been able to see these results, Freud would likely have been pleased.