Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brainbehavior relationships in stroke.stroke | functional connectivity | interhemispheric | memory | language A lthough structural damage from stroke is focal, remote dysfunction can occur in regions of the brain distant from the area of damage (1, 2). The set of regions that are directly damaged or indirectly affected is embedded within a larger functional network that is in dynamic balance with other networks in the brain. This framework posits that a lesion in a single location in the brain has the ability to disrupt brain functions far beyond the lesion boundaries (3-5).Numerous correlates of remote physiological dysfunction have been proposed, including abnormal task recruitment of contralesional brain areas (6-8), disruption of metabolism (9) or regional cerebral blood flow (10, 11), and more recently disruption of signal coherence (12-15).However, there is only a limited understanding of how remote physiological dysfunction is related to lesion topography (14, 16). Moreover, the behavioral relevance of reported physiological changes is unclear. Although some studies have reported significant correlation with behavioral impairment, the total amount of behavioral variance explained is unknown. Finally, because mechanisms of remote dysfunction have typically been examined in relatively small groups of individuals, their generalization at the population level is unknown. As a result, physiological measures of brain function are not used in the evaluation and treatment of stroke victims.More traditional lesion-symptom mapping studies have also used statistical methods to relate lesion topography to the severity of different behavioral deficits (17,18). An implicit assumption of these studies is that the strength of association between structural damage and behavior is the same irrespective of the behavior that is measured. However, it is also possi...

SUMMARY We examined the contribution of the amygdala to value signals within orbital (OFC) and medial (MFC) prefrontal cortex. On each trial, monkeys chose between two stimuli that were associated with different quantities of reward. In intact monkeys, as expected, neurons in both OFC and MFC signaled the reward quantity associated with stimuli. Contrasted with MFC, OFC contained a larger proportion of neurons encoding reward quantity and did so with faster response latencies. Removing the amygdala eliminated these differences, mainly by decreasing value coding in OFC. Similar decreases occurred in OFC immediately before and after reward delivery. Although the amygdala projects to both OFC and MFC, these findings show that it has its greatest influence over reward-value coding in OFC. Importantly, amygdala lesions did not abolish value coding in OFC, which shows that OFC’s representations of the value of objects, choices and outcomes depends, in large part, on other sources.

Background Nonhuman primates (NHPs) are a valuable research model because of their behavioral, physiological and neuroanatomical similarities to humans. In the absence of language, autonomic activity can provide crucial information about cognitive and affective states during single-unit recording, inactivation and lesion studies. Methods standardized for use in humans are not easily adapted to NHPs and detailed guidance has been lacking. New Method We provide guidance for monitoring heart rate and pupil size in the behavioral neurophysiology setting by addressing the methodological issues, pitfalls and solutions for NHP studies. The methods are based on comparative physiology to establish a rationale for each solution. We include examples from both electrophysiological and lesion studies. Results Single-unit recording, pupil responses and heart rate changes represent a range of decreasing temporal resolution, a characteristic that impacts experimental design and analysis. We demonstrate the unexpected result that autonomic measures acquired before and after amygdala lesions are comparable despite disruption of normal autonomic function. Comparison with Existing Methods Species and study design differences can render standard techniques used in human studies inappropriate for NHP studies. We show how to manage data from small groups typical of NHP studies, data from the short behavioral trials typical of neurophysiological studies, issues associated with longitudinal studies, and differences in anatomy and physiology. Conclusions Autonomic measurement to infer cognitive and affective states in NHP is neither off-the-shelf nor onerous. Familiarity with the issues and solutions will broaden the use of autonomic signals in NHP single unit and lesion studies.

Spatial attention is the cognitive function that coordinates the selection of visual stimuli with appropriate behavioral responses. Recent studies have reported that phase-amplitude coupling (PAC) of low and high frequencies covaries with spatial attention, but differ on the direction of covariation and the frequency ranges involved. We hypothesized that distinct phase-amplitude frequency pairs have differentiable contributions during tasks that manipulate spatial attention. We investigated this hypothesis with electrocorticography (ECoG) recordings from participants who engaged in a cued spatial attention task. To understand the contribution of PAC to spatial attention we classified cortical sites by their relationship to spatial variables or behavioral performance. Local neural activity in spatial sites was sensitive to spatial variables in the task, while local neural activity in behavioral sites correlated with reaction time. We found two PAC frequency clusters that covaried with different aspects of the task. During a period of cued attention, delta-phase/high-gamma (DH) PAC was sensitive to cue direction in spatial sites. In contrast, theta-alpha-phase/beta-low-gamma-amplitude (TABL) PAC robustly correlated with future reaction times in behavioral sites. Finally, we investigated the origins of TABL PAC and found it corresponded to behaviorally relevant, sharp waveforms, which were also coupled to a low frequency rhythm. We conclude that TABL and DH PAC correspond to distinct mechanisms during spatial attention tasks and that sharp waveforms are elements of a coupled dynamical process.