Biology subjects

Grafman, J.

Publications and source records attributed to Grafman, J..

6 recordsLinked to original sources

bioRxiv2026

Non-invasive Neuromodulation Targeting Approach by Mapping Stimulations and Lesions That Modify Visual Memory

Therapeutic brain stimulation is believed to target specific networks, but targeting approaches for memory remain debated. For other symptoms, neuromodulation targets have been localized by mapping connectivity of lesions and stimulation sites to specific symptoms. This approach has yielded networks for global memory, but it remains unclear whether it applies to specific types of memory. Here, we mapped connectivity of stimulation sites, lesions, and atrophy patterns associated with different memory types. We included 544 individuals across three datasets: transcranial magnetic stimulation (N=262), penetrating head trauma (N=169), and ischemic stroke (N=113). We identified a network preferentially connected to lesions and stimulation sites specifically associated with changes in visual memory. Of note, the direction of this effect was inverted depending on whether lesions or stimulation occurred at younger age or an older age, consistent with prior results. This age effect was replicated in an independent dataset of patients with preclinical Alzheimers disease (N=1240). To examine neuromodulation targets, we computed electrical field models for potential TMS sites that overlap with the networks derived from each stimulation or lesion dataset; the resulting targets intersected with established targets that demonstrated efficacy for treating memory impairment - precuneus, cortical-hippocampal network, and dorsolateral prefrontal cortex - with peak intersection at medial posterior parietal lobe, angular gyrus, and left anterior middle frontal gyrus, respectively. Future head-to-head clinical trials are needed to systematically compare these proposed neuromodulation targets against each other. One Sentence SummaryNeuromodulation targets for visual memory diverge by age at the time of injury or stimulation.

neuroscience↗

bioRxiv2026

Causal Evidence for the Neural Underpinnings of Subjective Happiness

Happiness is a central but poorly localized dimension of human experience, and causal evidence linking discrete brain regions to subjective happiness is scarce. We tested whether focal brain damage modulates self-reported happiness by measuring Subjective Happiness Scale (SHS) scores in 131 male veterans with penetrating traumatic brain injury (pTBI) and 33 matched healthy controls (HC), and by applying voxel-based lesion-symptom mapping within anatomically pre-defined brain regions. Overall, individuals with pTBI reported higher SHS scores than HC. VLSM identified two lesion clusters associated with increased happiness after injury: a small cluster in the right anterior cingulate cortex and a larger cluster in the right orbitofrontal cortex. These results provide causal evidence that right frontal circuitry--notably the ACC and OFC--modulates subjective happiness, challenging current accounts of motivational and emotional processing and pointing to targeted neural substrates for understanding and potentially modulating human happiness.

neuroscience↗

bioRxiv2026

Focal brain stimulation sites that modify autonomic arousal map to a convergent brain circuit and potential therapeutic target

Causal modulation of autonomic outflow could yield new therapeutic targets for autonomic hyperactivation. We employed three natural experiments in which different brain regions were targeted using transcranial magnetic stimulation (TMS) (n=139 sites, n=14 individuals), deep brain stimulation (n=392 sites, n=58 individuals), or low-intensity focused ultrasound (n=46 sites, n=23 individuals) with subsequent autonomic measurements. Using a human connectome database (n=1000) as a wiring diagram, we identified a convergent brain circuit that, when focally modulated, transiently reduces autonomic arousal. This circuit significantly resembled previously reported causal circuits for posttraumatic stress disorder (PTSD) and anxiety. In independent datasets, TMS to the autonomic arousal circuit reduced laboratory startle in healthy volunteers (n=28), lesions to this circuit reduced exaggerated startle in PTSD (n=193), and TMS to this circuit reduced anxiety-related autonomic symptoms in patients with clinically significant anxiety (n=30). Thus, the convergent circuit may serve as a potential neuromodulation target for autonomic hyperactivation.

neuroscience↗

bioRxiv2025

Risky Choices After Frontal Brain Injury: Differential Effects in Self vs Other-Decision Contexts

Frontal lobe integrity is crucial for assessing risk and making informed decisions. This study investigated how frontal lobe lesions affect the computational mechanisms underlying risky choice, particularly when decisions impact oneself versus another person. A Patient Group of 20 individuals with frontal cortex damage and a Control Group of 20 matched individuals performed a gambling task, making accept/reject decisions on mixed-outcome gambles for themselves ("Self") or an anonymous other ("Other"). We provide a mechanistic account of choice behavior using Prospect Theory, the leading behavioral model of decision-making under risk, to quantify parameters for utility curvature, loss aversion, and probability weighting. Behaviorally, the Patient Group accepted significantly more disadvantageous gambles for themselves than did the Control Group yet showed a trend toward greater caution when choosing for others. Prospect Theory modeling revealed a specific computational phenotype for this behavior. Compared to the Control Group, the Patient Group exhibited significantly more pronounced utility curvature (lower , {beta}) and more linear, less distorted probability weighting (higher {gamma}). While patients also showed a trend toward lower loss aversion ({lambda}), this difference was not statistically significant. This combination of altered utility and probability processing explains their paradoxical risk-seeking. These findings suggest that frontal cortex damage disrupts the computation of subjective value, leading to a distinctive decision-making profile marked by altered utility curvature and reduced sensitivity to outcome magnitudes. This computational characterization deepens our understanding of frontal lobe contributions to decision-making and can inform targeted rehabilitation strategies.

neuroscience↗

bioRxiv2024

Evidence for distinct networks underlying symptom clusters of posttraumatic stress disorder

BackgroundClinical and psychometric evidence has long supported a multidimensional model of PTSD, with symptom subcategories derived from factor analytic methods. Although research on the biological bases of PTSD as a unitary construct is profuse, comparatively few studies have examined the neural mechanisms underlying subcategories of PTSD symptoms. The present study aimed to provide the first evidence of causal relationships between brain structure and PTSD symptom subcategories, using a lesion-behavior mapping approach. MethodsUsing a group of male combat veterans with focal penetrating traumatic brain injuries (n = 177), we determined the effects of focal damage on the PTSD symptom subcategories of hyperarousal, avoidance, and re-experiencing. ResultsOur findings revealed two distinct networks that underlie symptom subcategories of PTSD: (1) an amygdala-ventromedial prefrontal cortex network underlying hyperarousal and avoidance symptoms, in which amygdala damage acts as a risk factor for the development of these symptoms, while vmPFC damage acts as a protective factor against the same symptoms; and (2) a hippocampal network underlying re-experiencing and avoidance, in which hippocampal damage acts as a protective factor against these symptoms. ConclusionsThe present study provides novel insights regarding the causal role of key brain regions in the heterogeneous expression of PTSD symptoms. Results not only contribute to a more complete picture of the neural mechanisms underlying PTSD, but may also aid in the future development of individualized therapeutic strategies that target specific symptom profiles.

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bioRxiv2023

A neural network for religious fundamentalism derived from patients with brain lesions

Religious fundamentalism, characterized by rigid adherence to a set of beliefs putatively revealing inerrant truths, is ubiquitous across cultures and has a global impact on society. Understanding the psychological and neurobiological processes producing religious fundamentalism may inform a variety of scientific, sociological, and cultural questions. Research indicates that brain damage can alter religious fundamentalism. However, the precise brain regions involved with these changes remain unknown. Here, we analyzed brain lesions associated with varying levels of religious fundamentalism in two large datasets from independent laboratories. Lesions associated with greater fundamentalism were connected to a specific brain network with nodes in the right orbitofrontal, dorsolateral prefrontal, and inferior parietal lobes. This fundamentalism network was strongly right hemisphere lateralized and highly reproducible across the independent datasets (r = 0.82) with cross-validations between datasets. To explore the relationship of this network to lesions previously studied by our group, we tested for similarities to twenty-one lesion-induced conditions. Lesions associated with confabulation and criminal behavior showed a similar connectivity pattern as lesions associated with greater fundamentalism. Moreover, lesions associated with poststroke pain showed a similar connectivity pattern as lesions associated with lower fundamentalism. These findings are consistent with hemispheric specializations in reasoning and lend insight into previously observed epidemiological associations with fundamentalism, such as cognitive rigidity and outgroup hostility.

neuroscience↗