Precision Light for the Treatment of Psychiatric Disorders

Abstract

Circadian timekeeping can be reset by brief flashes of light using stimulation protocols thousands of times shorter than those previously assumed to be necessary for traditional phototherapy. These observations point to a future where flexible architectures of nanosecond-, microsecond-, and millisecond-scale light pulses are compiled to reprogram the brain's internal clock when it has been altered by psychiatric illness or advanced age. In the current review, we present a chronology of seminal experiments that established the synchronizing influence of light on the human circadian system and the efficacy of prolonged bright-light exposure for reducing symptoms associated with seasonal affective disorder. We conclude with a discussion of the different ways that precision flashes could be parlayed during sleep to effect neuroadaptive changes in brain function. This article is a contribution to a special issue on Circadian Rhythms in Regulation of Brain Processes and Role in Psychiatric Disorders curated by editors Shimon Amir, Karen Gamble, Oliver Stork, and Harry Pantazopoulos.

Figure 1

Phase response curve to light. The pacemaker's timekeeping responses to light are modeled by a sinusoidal PRC. Ostensibly, the PRC documents how the brain's clock shifts the body's activities so that they are always in register with the temporal beacons of sunset and sunrise. Light falling later-than-expected in the early evening is perceived as an extension of the sunset. Any significant illumination here will trigger a phase delay of a person's physiology and behavior so that they can continue to be active while the sun is still out (or perceived to still be out). On the other hand, light falling earlier-than-expected in the very late evening is perceived as the leading edge of a sunrise. Any significant illumination in this region will trigger a phase advance of a person's physiology and behavior so that they can arouse from sleep earlier to greet the sunrise (or the brain's estimate of where in the night's duration the sunrise should occur). By convention, delays in a PRC to light are plotted with negative values, while advances are plotted with positive values. In many, but not all instances, phase shifts commensurate in magnitude (hours) with the difference in timing between the photic stimulation and the onsets/offsets of a light schedule define the PRC amplitude. Shown in red are conditions whose symptoms could benefit from readjustments in circadian timekeeping. Targeting phototherapy to the shallow area of the delay zone can correct the advances often seen in people with bipolar disorder [87, 88]. Targeting phototherapy to the shallow area of the advance zone—right before a person wakes up—can offset the delays that often characterize those with seasonal affective disorder [85, 86].

Box 1