Transcranial electric stimulation (TES) is an emerging technique, developed to non-invasively modulate brain function. However, the spatiotemporal distribution of the intracranial electric fields induced by TES remains poorly understood. In particular, it is unclear how much current actually reaches the brain, and how it distributes across the brain. Lack of this basic information precludes a firm mechanistic understanding of TES effects. In this study we directly measure the spatial and temporal characteristics of the electric field generated by TES using stereotactic EEG (s-EEG) electrode arrays implanted in cebus monkeys and surgical epilepsy patients. We found a small frequency dependent decrease (10%) in magnitudes of TES induced potentials and negligible phase shifts over space. Electric field strengths were strongest in superficial brain regions with maximum values of about 0.5 mV/mm. Our results provide crucial information of the underlying biophysics in TES applications in humans and the optimization and design of TES stimulation protocols. In addition, our findings have broad implications concerning electric field propagation in non-invasive recording techniques such as EEG/MEG.

Hippocampal sharp-wave ripples (SWRs) constitute one of the most synchronized activation events in the brain and play a critical role in offline memory consolidation. Yet their cognitive content and function during awake, conscious behavior remains unclear. We directly examined this question using intracranial recordings in human patients engaged in episodic free recall of previously viewed photographs. Our results reveal a content-selective increase in hippocampal ripple rate emerging 1 to 2 seconds prior to recall events. During recollection, high-order visual areas showed pronounced SWR-coupled reemergence of activation patterns associated with recalled content. Finally, the SWR rate during encoding predicted subsequent free-recall performance. These results point to a role for hippocampal SWRs in triggering spontaneous recollections and orchestrating the reinstatement of cortical representations during free episodic memory retrieval.

Whereas the neurophysiology of respiration has traditionally focused on automatic brain stem processes, higher brain mechanisms underlying the cognitive aspects of breathing are gaining increasing interest. Therapeutic techniques have used conscious control and awareness of breathing for millennia with little understanding of the mechanisms underlying their efficacy. Using direct intracranial recordings in humans, we correlated cortical and limbic neuronal activity as measured by the intracranial electroencephalogram (iEEG) with the breathing cycle. We show this to be the direct result of neuronal activity, as demonstrated by both the specificity of the finding to the cortical gray matter and the tracking of breath by the gamma-band (40-150 Hz) envelope in these structures. We extend prior observations by showing the iEEG signal to track the breathing cycle across a widespread network of cortical and limbic structures. We further demonstrate a sensitivity of this tracking to cognitive factors by using tasks adapted from cognitive behavioral therapy and meditative practice. Specifically, volitional control and awareness of breathing engage distinct but overlapping brain circuits. During volitionally paced breathing, iEEG-breath coherence increases in a frontotemporal-insular network, and during attention to breathing, we demonstrate increased coherence in the anterior cingulate, premotor, insular, and hippocampal cortices. Our findings suggest that breathing can act as an organizing hierarchical principle for neuronal oscillations throughout the brain and detail mechanisms of how cognitive factors impact otherwise automatic neuronal processes during interoceptive attention. NEW & NOTEWORTHY Whereas the link between breathing and brain activity has a long history of application to therapy, its neurophysiology remains unexplored. Using intracranial recordings in humans, we show neuronal activity to track the breathing cycle throughout widespread cortical/limbic sites. Volitional pacing of the breath engages frontotemporal-insular cortices, whereas attention to automatic breathing modulates the cingulate cortex. Our findings imply a fundamental role of breathing-related oscillations in driving neuronal activity and provide insight into the neuronal mechanisms of interoceptive attention.