Biology subjects

Brissenden, J. A.

Publications and source records attributed to Brissenden, J. A..

7 recordsLinked to original sources

bioRxiv2026

Frontal stimulation reshapes SCAN connectivity and improves motor function in Parkinson's disease

Parkinson's disease is a neurodegenerative disorder with characteristic motor deficits of bradykinesia and impaired coordination, and non-motor deficits affecting cognitive abilities such as attention and executive functions. Recent evidence suggests that some canonical motor deficits in Parkinson's disease (e.g., freezing of gait) are associated with abnormalities in frontal cortical processing typically thought to underlie executive functions such as cognitive control. The evidence from human research linking frontal cognitive disruption and motor deficits in people with Parkinson's disease is correlational. Individuals with cognitive impairments often also display gait and balance deficits, but causal evidence remains lacking. We combined non-invasive brain stimulation with functional MRI (fMRI) to ascertain whether dorsolateral prefrontal cortex (DLPFC) exerts a causal influence modulating motor function and to test the hypothesis that an excitatory stimulation protocol applied to a cognitive control network can improve motor performance in Parkinson disease. Participants with Parkinson's disease performed a precision force-tracking task shown to track with gait impairment while undergoing functional neuroimaging scans. On half of trials, participants were required to simultaneously perform a cognitively demanding 2-back working memory task to tax attentional systems. Following the initial baseline scan, participants returned for three separate counterbalanced sessions that combined transcranial magnetic stimulation (TMS) in the form of theta burst stimulation (TBS) with fMRI. Just prior to task performance, participants received either excitatory (intermittent TBS) or inhibitory (continuous TBS) stimulation protocols over right DLPFC. In the third session, participants received stimulation to a control site outside the cognitive and motor areas implicated in our task. Our within-subjects experimental design allowed us to examine the effects of stimulation on motor behavior, the influence of cognitive load on motor behavior, and the neural systems supporting cognitive control and motor execution. Consistent with our hypothesis, excitatory stimulation of DLPFC improved motor performance in a precision force-tracking task as indexed by reduced tracking error and smoother movement execution. These effects emerged preferentially under dual-task conditions when cognitive demands were high. Our results show that this improved motor performance coincides with reductions in functional connectivity not only between the stimulation site and primary motor cortex, but also within the recently described somato-cognitive action network (SCAN) thought to support action planning and whole-body movement coordination. We conclude that frontal cognitive control systems play a causal role in modulating movement in Parkinson's disease and suggest that targeting these systems with non-invasive interventions may enhance motor function.

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bioRxiv2026

Cerebellar perturbation impairs human working memory and degrades spatial tuning throughout cortex

Working memory, the transient maintenance and manipulation of information, is fundamental to human cognition. While working memory is typically thought to rely on frontoparietal cortex, the cerebellum communicates with association cortex through closed-loop cerebro-cerebellar pathways and is well positioned to influence cortical dynamics supporting cognition. It is currently unknown whether cerebellar processing is causally necessary for the maintenance of visual information and whether cortical population coding is dependent on cerebellum. We combined functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) of frontal, parietal, and cerebellar cortex in humans. Using a generative model of population receptive fields, we show that cerebellar perturbation impairs spatial working memory recall and broadly degrades cortical spatial tuning. Direct comparisons revealed dissociable effects on population coding: cerebellar perturbation preferentially reduced stimulus-specific gain in early visual cortex, parietal perturbation preferentially suppressed stimulus-independent visual responses, and frontal perturbation preferentially increased response variability across higher-order visual, parietal, and frontal regions. These findings demonstrate that intact cerebellar function is necessary for maintaining cortical working memory representations and that cerebellar, parietal, and frontal nodes support working memory fidelity via distinct mechanisms.

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bioRxiv2025

Combined Auditory, Tactile, and Visual fMRI Reveals Sensory-Biased and Supramodal Working Memory Regions in Human Frontal Cortex

Selectivity for sensory modality characterizes distinct subregions of the human brain, well beyond the primary sensory cortices. We previously identified frontal and posterior cortical regions that are preferentially recruited for visual vs. auditory attention and working memory (WM). Here, we extend our approach to include tactile cognition and to characterize cortical regions recruited by WM in each of three sensory modalities. The joint organization of visual-selective, auditory-selective, tactile-selective, and supramodal WM recruitment within individual subjects has not been fully investigated previously. Male and female human subjects participated in a blocked fMRI task requiring them to perform N-back WM judgements in auditory, visual, or tactile (haptic) modalities. We confirmed our prior reports of multiple visual-biased and auditory-biased frontal lobe regions. We also observed several bilateral tactile-selective regions abutting previously described visual- and auditory-selective regions, including dorsal and ventral precentral sulcus, the postcentral sulcus, and the anterior intraparietal sulcus. Several cortical regions were recruited by WM in all three sensory modalities in individual subjects, including precentral sulcus, inferior frontal sulcus, intraparietal sulcus, anterior insula and pre-supplementary motor area. Supramodal regions exhibited substantial overlap with visual-biased regions in frontal and parietal cortex and comparatively little overlap with tactile- or auditory-biased regions. Lastly, resting-state analyses revealed that auditory-, visual- and tactile-selective WM regions segregate into modality-specific networks that span frontal and posterior cortex. Together, these results shed light on the functional organization of sensory-selective and supramodal regions supporting higher-order cognition. SIGNIFICANCE STATEMENTUsing within-subject fMRI analyses of three different sensory modalities, we identify the fine-scale architecture of sensory-biased and supramodal working memory structures within human frontal cortex. Sixteen bilateral frontal lobe regions are identified: five auditory-biased, four visual-biased, two tactile-biased, and five multiple-demand / supramodal regions. These parcels are largely distinct with the notable exception that the visual-biased regions each partially overlap with supramodal regions, suggesting a tight link between visual and supramodal working memory representations. Sensory-biased frontal lobe regions form modality-specific networks with traditionally-identified posterior sensory cortical regions. The findings demonstrate a pervasive role for sensory modality in the functional organization of frontal cortex and offer a fine-scale parcellation of the human frontal lobe regions supporting working memory.

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bioRxiv2024

Errors of attention adaptively warp spatial memory

Adaptation is the process by which we adjust internal models of the body, world, and mind in response to sensory feedback. While adaptation is studied extensively in the context of motor control, there is limited evidence that cognitive functions such as working memory are subject to the same error-driven adaptive control mechanism. To examine the possibility that internal spatial representations undergo adaptation, we had participants perform a task that interleaved a perceptual discrimination task and a spatial working memory task. Perceptual discrimination trials (85% of trials) presented an initial peripheral cue to exogenously capture attention, immediately followed by a displaced target stimulus. This sequence of events served to repeatedly induce a covert attentional allocation error. Interleaved spatial working memory trials (15% of trials) presented a stimulus at a pseudorandom peripheral location followed by a delay interval. On half of the working memory trials, the stimulus was surreptitiously presented at the same location as the initial attentional cue. We found that as attentional errors accumulated over the course of the experiment, participants spatial recall shifted to counteract the attentional error. The magnitude of this shift was proportional to the number of induced errors. Recall performance rapidly recovered following the offset of error trials. Multiple control experiments ruled out alternative explanations for these results, such as oculomotor confounds and attentional biases unrelated to error. These findings indicate that the computational mechanisms governing the adaptation of motor commands appear to similarly serve to adjust and calibrate spatial cognition.

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bioRxiv2021

Reward influences the allocation but not the availability of resources in visual working memory

Visual working memory possesses strict capacity constraints which place limits on the availability of resources for encoding and maintaining information. Studies have shown that prospective rewards improve performance on visual working memory tasks, but it remains unclear whether rewards increase total resource availability or rather influence the allocation of resources without affecting availability. Participants performed a continuous report visual working memory task with oriented grating stimuli. On each trial, participants were presented with a priority cue, which signaled the item most likely to be probed, and a reward cue, which signaled the magnitude of a performance-contingent reward. We showed that rewards decreased recall error for cued items and increased recall error for non-cued items. We further demonstrated that rewards produced a tradeoff in the probability of successfully encoding a cued versus a non-cued item rather than a tradeoff in recall precision or the probability of binding errors. Lastly, we showed that rewards only affected resource allocation when participants were given the opportunity to engage proactive control prior to encoding. These findings indicate that rewards influence the flexible allocation of resources during selection and encoding in visual working memory, but do not augment total capacity.

neuroscience↗

bioRxiv2021

Extended frontal networks for visual and auditory working memory

Working memory (WM) supports the persistent representation of transient sensory information. Visual and auditory stimuli place different demands on WM and recruit different brain networks. Separate auditory- and visual-biased WM networks extend into the frontal lobes, but several challenges confront attempts to parcellate human frontal cortex, including fine-grained organization and between-subject variability. Here, we use differential intrinsic functional connectivity from two visual-biased and two auditory-biased frontal structures to identify additional candidate sensory-biased regions in frontal cortex. We then examine direct contrasts of task fMRI during visual vs. auditory 2-back WM to validate those candidate regions. Three visual-biased and five auditory-biased regions are robustly activated bilaterally in the frontal lobes of individual subjects (N=14, 7 women). These regions exhibit a sensory preference during passive exposure to task stimuli, and that preference is stronger during WM. Hierarchical clustering analysis of intrinsic connectivity among novel and previously identified bilateral sensory-biased regions confirms that they functionally segregate into visual and auditory networks, even though the networks are anatomically interdigitated. We also observe that the fronto-temporal auditory WM network is highly selective and exhibits strong functional connectivity to structures serving non-WM functions, while the fronto-parietal visual WM network hierarchically merges into the multiple-demand cognitive system.

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bioRxiv2021

Predicted Utility Modulates Working Memory Fidelity in the Brain

The predicted utility of information stored in working memory (WM) is hypothesized to influence the strategic allocation of WM resources. Prior work has shown that when information is prioritized, it is remembered with greater precision relative to other remembered items. However, these paradigms often complicate interpretation of the effects of predicted utility on item fidelity due to a concurrent memory load. Likewise, no fMRI studies have examined whether the predicted utility of an item modulates fidelity in the neural representation of items during the memory delay without a concurrent load. In the current study, we used fMRI to investigate whether predicted utility influences fidelity of WM representations in the brain. Using a generative model multivoxel analysis approach to estimate the quality of remembered representations across predicted utility conditions, we observed that items with greater predicted utility are maintained in memory with greater fidelity, even when they are the only item being maintained. Further, we found that this pattern follows a parametric relationship where more predicted utility corresponded to greater fidelity. These precision differences could not be accounted for based on a redistribution of resources among already-remembered items. Rather, we interpret these results in terms of a gating mechanism that allows for pre-allocation of resources based on predicted value alone. This evidence supports a theoretical distinction between resource allocation that occurs as a result of load and resource pre-allocation that occurs as a result of predicted utility.

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