Zaghloul, Kareem A.

Abstract Despite promising results, it remains unclear how to optimally target and personalize closed-loop stimulation to ameliorate deficits in memory and other cognitive functions. We hypothesized that evoked connectivity – the measurement of neural pathway activation using single pulses of electrical stimulation – can guide patient-specific selection of stimulation location and parameters for memory. We characterized brain-wide evoked connectivity profiles of stimulation in memory-related brain regions recorded from 81 patients undergoing intracranial monitoring for epilepsy, showing that greater evoked connectivity between the lateral temporal cortex and the broader memory network (including the mesial temporal lobe, limbic regions and prefrontal cortex) corroborates observations of memory improvement by lateral temporal cortex stimulation. We first found that the lateral temporal cortex, compared to other stimulated regions, evokes the greatest and most distributed connectivity response throughout other memory-related regions. Evoked connectivity in downstream regions is greatest when stimulating a previously identified optimal target for memory improvement, bordering white matter at the rostrocaudal center of the middle temporal gyrus. Evoked connectivity corroborates other biomarkers of memory improvement by closed-loop stimulation, including increased resting-state functional connectivity between stimulated and recorded sites and increased modulation of oscillatory power. These results provide insight into the network mechanisms of stimulation for memory and suggest that evoked connectivity can more broadly predict the functional effects of closed-loop stimulation to prospectively guide targeting and parameter selection.

Abstract Scientists debate where, when, and how different visual, orthographic, lexical, and semantic features are involved in visual word recognition. In this study, we investigate intracranial neurophysiology data from 151 patients engaged in reading single words. Using representational similarity analysis, we characterize the neural representation of a hierarchy of word features across the entire cerebral cortex. We find evidence of both feed-forward and feedback processing, with early representation of visual and lexical information in lingual gyrus followed by lexical representation in fusiform gyrus and semantic sensitivity in inferior frontal gyrus, with letter representation emerging later in fusiform gyrus. Furthermore, we observed a variety of anatomically heterogeneous temporal response shapes, and these functional populations had significant feature sensitivity. Taken together, our results demonstrate the early influence of lexical, phonological, and semantic features in visual word recognition and reveal feed-forward, feed-back, and anatomically distributed processing mechanisms that contribute to visual word recognition.

Chronically implantable neurostimulation devices are becoming a clinically viable option for treating patients with neurological disease and psychiatric disorders. Neurostimulation offers the ability to probe and manipulate distributed networks of interacting brain areas in dysfunctional circuits. Here, we use tools from network control theory to examine the dynamic reconfiguration of functionally interacting neuronal ensembles during targeted neurostimulation of cortical and subcortical brain structures. By integrating multimodal intracranial recordings and diffusion-weighted imaging from patients with drug-resistant epilepsy, we test hypothesized structural and functional rules that predict altered patterns of synchronized local field potentials. We demonstrate the ability to predictably reconfigure functional interactions depending on stimulation strength and location. Stimulation of areas with structurally weak connections largely modulates the functional hubness of downstream areas and concurrently propels the brain towards more difficult-to-reach dynamical states. By using focal perturbations to bridge large-scale structure, function, and markers of behavior, our findings suggest that stimulation may be tuned to influence different scales of network interactions driving cognition.

SummaryObjectivesInterictal epileptiform discharges (IEDs) have been linked to memory impairment, but the spatial and temporal dynamics of this relationship remain elusive. In the present study, we aim to systematically characterize the brain areas and times at which IEDs affect memory.MethodsEighty epilepsy patients participated in a delayed free recall task while undergoing intracranial electroencephalography (EEG) monitoring. We analyzed the locations and timing of IEDs relative to the behavioral data in order to measure their effects on memory.ResultsOverall IED rates did not correlate with task performance across subjects (r = 0.03, p = 0.8). However, at a finer temporal scale, within‐subject memory was negatively affected by IEDs during the encoding and recall periods of the task but not during the rest and distractor periods (p < 0.01, p < 0.001, p = 0.3, and p = 0.8, respectively). The effects of IEDs during encoding and recall were stronger in the left hemisphere than in the right (p < 0.05). Of six brain areas analyzed, IEDs in the inferior‐temporal, medial‐temporal, and parietal areas significantly affected memory (false discovery rate < 0.05).SignificanceThese findings reveal a network of brain areas sensitive to IEDs with key nodes in temporal as well as parietal lobes. They also demonstrate the time‐dependent effects of IEDs in this network on memory.