Biology subjects

Dickey, C. W.

Publications and source records attributed to Dickey, C. W..

5 recordsLinked to original sources

bioRxiv2026

Transcranial magnetic stimulation to the dorsolateral prefrontal cortex modulates single-neuron activity in humans

Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an FDA-cleared treatment for depression, yet how cortical stimulation influences single neurons in deep brain circuits remains unknown. Using intracranial microelectrode recordings in four neurosurgical patients, we resolved single-neuron spikes as early as 8 ms from 185 single neurons after single-pulse left dlPFC TMS. TMS elicited time-locked firing responses in 46% of neurons across deep cortical and subcortical structures bilaterally. TMS facilitated putative interneuron spiking in striato-thalamic regions from [~]8 ms, peaking at [~]80-100 ms, and lasting to [~]1000 ms, while suppressing putative pyramidal cell spiking with a delayed and slower time course. Trial-by-trial single-neuron modulations were positively correlated with cortico-striato-thalamic network activity and anti-correlated with limbic network activity. These findings reveal that dlPFC TMS facilitates inhibitory firing in executive control networks while suppressing limbic excitatory drive, providing a cellular mechanism for how cortical stimulation modulates distributed brain networks.

neuroscience↗

bioRxiv2022

Cortico-cortical and hippocampo-cortical co-rippling are facilitated by thalamo-cortical spindles and upstates, but not by thalamic ripples

The co-occurrence of brief [~]90Hz oscillations (co-ripples) may be important for integrating information across the neocortex and hippocampus and, therefore, essential for sleep consolidation, and cognition in general. However, how such co-ripples are synchronized is unknown. We tested if cortico-cortical and hippocampal-cortical ripple co-occurrences are due to the simultaneous direct propagation of thalamic ripples, and/or if they are coordinated by lower frequency thalamic waves. Using human intracranial recordings, we found that ripples are generated in the anterior and posterior thalamus during local spindles on the down-to-upstate transition in non-rapid eye movement sleep, with similar characteristics as cortical and hippocampal ripples. However, thalamic ripples only infrequently co-occur or phase-lock, with cortical and hippocampal ripples. In contrast, thalamo-cortical spindles and upstates were strongly coordinated with cortico-cortical and hippocampo-cortical co-rippling. Thus, while thalamic ripples may not directly drive multiple cortical or hippocampal sites at ripple frequency, thalamo-cortical spindles and upstates may provide the input necessary for spatially distributed co-rippling to integrate information in the cortex. Significance StatementWidespread networks of [~]90 Hz oscillations, called "ripples," have recently been identified in humans and may help to bind information in the cortex and hippocampus for memory. However, it is not known whether the thalamus generates ripples, and if so whether they, or other thalamic waves, coordinate networks of co-occurring cortical and hippocampal ripples. Here, we show that the human thalamus generates [~]90 Hz ripples during NREM sleep. While thalamic ripples do not appear to directly synchronize ripple co-occurrence in the cortex and hippocampus, our data provide evidence that propagating thalamo-cortical spindles and upstates organize these networks. Thus, the thalamus projects slower frequency waves that modulate higher frequency hippocampo-cortical oscillatory networks for memory in humans.

neuroscience↗

bioRxiv2021

Cortical ripples provide the conditions for consolidation during NREM sleep in humans

Hippocampal ripples index the reconstruction of spatiotemporal neuronal firing patterns essential for the consolidation of memories in the cortex during non-rapid eye movement sleep (NREM). Recently, cortical ripples in humans have been shown to enfold the replay of neuron firing patterns during cued recall. Here, using intracranial recordings from 18 patients (12 female), we show that cortical ripples also occur during NREM in humans, with similar density, oscillation frequency ([~]90 Hz), duration, and amplitude to waking. Ripples occurred in all cortical regions with similar characteristics, unrelated to putative hippocampal connectivity, and were less dense and robust in higher association areas. Putative pyramidal and interneuron spiking phase-locked to cortical ripples during NREM, with phase delays consistent with ripple generation through pyramidal-interneuron feedback. Cortical ripples were smaller in amplitude than hippocampal ripples, but were similar in density, frequency, and duration. Cortical ripples during NREM typically occurred just prior to the upstate peak, often during spindles. Upstates and spindles have previously been associated with memory consolidation, and we found that cortical ripples grouped co-firing between units within the window of spike-timing-dependent plasticity. Thus, human NREM cortical ripples are: ubiquitous and stereotyped with a tightly focused oscillation frequency; similar to hippocampal ripples; associated with upstates and spindles; and associated with unit co-firing. These properties are consistent with cortical ripples possibly contributing to memory consolidation and other functions during NREM in humans. Significance StatementIn rodents, hippocampal ripples organize replay during sleep to promote memory consolidation in the cortex, where ripples also occur. However, evidence for cortical ripples in human sleep is limited, and their anatomical distribution and physiological properties are unexplored. Here, using human intracranial recordings, we demonstrate that ripples occur throughout the cortex during waking and sleep with highly stereotyped characteristics. During sleep, cortical ripples tend to occur during spindles on the down-to-upstate transition, and thus participate in a sequence of sleep waves that is important for consolidation. Furthermore, cortical ripples organize single unit spiking with timing optimal to facilitate plasticity. Therefore, cortical ripples in humans possess essential physiological properties to support memory and other cognitive functions.

neuroscience↗

bioRxiv2021

Widespread ripples synchronize human cortical activity

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such binding of different components of mental events into unified representations occurs is unknown. The binding-bysynchrony theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations ( ripples) occur in the hippocampus and cortex, and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ~70ms duration 90Hz ripples often couple (within {+/-}500ms), co-occur ([≥]25ms overlap), and crucially, phase-lock (have consistent phase-lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phaselocking increases with more cortical sites co-rippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase-lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical co-ripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and co-ripples increase high-frequency correlations between areas, suggesting synchronized unit-spiking facilitating information exchange. Co-occurrence, phasesynchrony, and high-frequency correlation are maintained with little decrement over very long distances (25cm). Hippocampo-cortico-cortical co-ripples appear to possess the essential properties necessary to support binding-by-synchrony during memory retrieval, and perhaps generally in cognition. Significance StatementDifferent elements of a memory, or any mental event, are encoded in locations distributed across the cortex. A prominent hypothesis proposes that widespread networks are integrated with bursts of synchronized high-frequency oscillations called ripples, but evidence is limited. Here, using recordings inside the human brain, we show that ripples occur simultaneously in multiple lobes in both cortical hemispheres, and the hippocampus, generally during sleep and waking, and especially during memory recall. Ripples phase-lock local cell firing, and phase-synchronize with little decay between locations separated by up to 25cm, enabling long-distance integration. Indeed, co-rippling sites have increased correlation of very high-frequency activity which reflects cell firing. Thus, ripples may help bind information across the cortex in memory and other mental events.

neuroscience↗

bioRxiv2020

Travelling spindles create necessary conditions for spike-timing-dependent plasticity in humans

Sleep spindles facilitate memory consolidation in the cortex during mammalian non-rapid eye movement (NREM) sleep. In rodents, phase-locked firing during spindles may facilitate spike-timing-dependent plasticity (STDP) by grouping pre- and post-synaptic cell firing within [~]25ms. Currently, microphysiological evidence in humans for conditions conducive for STDP during spindles is absent. We analyzed local field potentials and supragranular unit spiking during spindles from 10x10 arrays of microelectrodes at 400{micro}m pitch in humans. We found strong tonic and phase-locked increases in firing and co-firing within 25ms during spindles. Co-firing, spindle co-occurrence, and spindle coherence were greatest between sites within [~]2mm, and high co-firing of units on different electrodes was largely restricted to moments of high spindle coherence between those electrodes. Spindles propagated at [~]0.23m/s in distinct patterns, with correlated cell co-firing sequences. These results suggest that spindles may organize spatiotemporal patterns of neuronal co-firing which promote memory consolidation during NREM sleep.

neuroscience↗