Common framework for linear regression

Mounting evidence suggests that the right cerebellum contributes to verbal working memory, but the functional role of this contribution remains unclear. In an established theory of motor control, the cerebellum is thought to predict sensory consequences of movements through an internal "forward model." Here, we hypothesize a similar predictive process can generalize to cerebellar non-motor function, and that the right cerebellum plays a predictive role that is beneficial for rapidly engaging the phonological loop in verbal working memory. To test this hypothesis, double-pulse transcranial magnetic stimulation (TMS) was administered over either the right cerebellum or right occipital lobe (control site), on half the trials, to interrupt the rehearsal of a 6-letter sequence. We found that cerebellar stimulation resulted in greater errors in participants' report of the letter in the current position. Additional analyses revealed that immediately after cerebellar TMS, participants were more likely to use out of date information to predict the next letter in the sequence. This pattern of errors is consistent with TMS causing a temporary disruption of state estimation and cerebellar forward model function, leading to prediction errors in the phonological loop.

2018

Neuropsychologia, 2009

The dorsolateral prefrontal cortex (dlPFC) plays an important role in working memory, including the control of memory-guided response. In this study, with 24 subjects, we used high frequency repetitive transcranial magnetic stimulation (rTMS) to evaluate the role of the dlPFC in memoryguided response to two different types of spatial working memory tasks: one requiring a recognition decision about a probe stimulus (operationalized with a yes/no button press), another requiring direct recall of the memory stimulus by moving a cursor to the remembered location. In half the trials, randomly distributed, rTMS was applied to the dlPFC and in a separate session, the superior parietal lobule (SPL), a brain area implicated in spatial working memory storage. A 10-Hz (3 sec., 110% of motor threshold) train of TMS was delivered at the onset of the response period. We found that only dlPFC rTMS significantly affected performance, with rTMS of right dlPFC decreasing accuracy on delayed-recall trials, and rTMS of left and right dlPFC decreasing and enhancing accuracy, respectively, on delayed-recognition trials. These findings confirm that the dlPFC plays an important role in memory-guided response, and suggest that the nature of this role varies depending on the processes required for making a response.

Journal of Cognitive Neuroscience, 2006

& Understanding the contributions of the prefrontal cortex (PFC) to working memory is central to understanding the neural bases of high-level cognition. One question that remains controversial is whether the same areas of the dorsolateral PFC (dlPFC) that participate in the manipulation of information in working memory also contribute to its short-term retention (STR). We evaluated this question by first identifying, with functional magnetic resonance imaging (fMRI), brain areas involved in manipulation. Next, these areas were targeted with repetitive transcranial magnetic stimulation (rTMS) while subjects performed tasks requiring only the STR or the STR plus manipulation of information in working memory. fMRI indicated that manipulation-related activity was independent of retention-related activity in both the PFC and superior parietal lobule (SPL). rTMS, however, yielded a different pattern of results. Although rTMS of the dlPFC selectively disrupted manipulation, rTMS of the SPL disrupted manipulation and STR to the same extent. rTMS of the postcentral gyrus (a control region) had no effect on performance. The implications of these results are twofold. In the PFC, they are consistent with the view that this region contributes more importantly to the control of information in working memory than to its STR. In the SPL, they illustrate the importance of supplementing the fundamentally correlational data from neuroimaging with a disruptive method, which affords stronger inference about structure-function relations. &

NeuroImage, 2005

Load-dependent and practice-related changes in neocortical and cerebellar structures involved in verbal working memory (VWM) were investigated using functional MRI (fMRI) and a two alternative forced choice Sternberg paradigm. Using working memory loads ranging from 2 to 6 letters, regions exhibiting linear and quadratic trends in load-dependent activations were identified. Behaviorally, reaction time measurements revealed significant linear increases with increasing memory load, and significant decreases with increased task practice. Brain activations indicated a preponderance of linear load-dependent responses in both superior (lobule VI/Crus I) and inferior (lobule VIIB/ VIIIA) cerebellar hemispheres, as well as in areas of neocortex including left precentral (BA 6), inferior frontal (BA 47), parahippocampal (BA 35), inferior parietal (BA 40), cingulate (BA 32), and right inferior and middle frontal (BA 46/47) regions. Fewer voxels exhibited quadratic without linear trends with the most prominent of these activations located in left inferior parietal (BA 40), precuneus, and parahippocampal regions. Analysis of load  session interactions revealed that right inferior cerebellar and left inferior parietal activations increased with practice, as did the correlations between activation in each region with reaction time, suggesting that changes in this cerebro-cerebellar network underlie practice-related increases in efficiency of VWM performance. These results replicate and extend our previous findings of fMRI activation in the cerebellum during VWM, and demonstrate predominately linear increases in cerebro-cerebellar activation with increasing memory load as well as changes in network function with increased task proficiency.

Frontiers in Neurology

Visual working memory (VWM), the core process inherent to many advanced cognitive processes, deteriorates with age. Elderly individuals usually experience defects in the processing of VWM. The dorsolateral prefrontal cortex is a key structure for the top-down control of working memory processes. Many studies have shown that repeated transcranial magnetic stimulation (rTMS) improves VWM by modulating the excitability of neurons in the target cortical region, though the underlying neural mechanism has not been clarified. Therefore, this study sought to assess the characteristics of brain memory function post-rTMS targeting the left dorsolateral prefrontal cortex. The study stimulated the left dorsolateral prefrontal cortex in elderly individuals by performing a high-frequency rTMS protocol and evaluated behavioral performance using cognitive tasks and a VWM task. Based on the simultaneously recorded electroencephalogram signals, event-related potential and event-related spectral pertu...

Journal of Neuroscience, 2008

It is a fundamental question whether the medial temporal lobe (MTL) supports only long-term memory encoding, or contributes to working memory (WM) processes as well. Recent data suggest that the MTL is activated whenever multiple items or item features are being maintained in WM. This may rely on interactions between the MTL or the prefrontal cortex (PFC) and content-specific areas in the inferior temporal (IT) cortex. Here, we investigated the neural mechanism through which the MTL, PFC, and IT cortex interact during WM maintenance. First, we quantified phase synchronization of intracranial EEG data in epilepsy patients with electrodes in both regions. Second, we used directional coupling analysis to study whether oscillatory activity in the IT cortex drives the MTL or vice versa. Finally, we investigated functional connectivity in functional magnetic resonance imaging data of healthy subjects with seeds in the MTL and PFC. With increasing load, EEG phase synchronization between the IT cortex and anterior parahippocampal gyrus and within the MTL increased. Coupling was bidirectional in all load conditions, but changed toward an increased top-down (anterior parahippocampal gyrus 3 IT) coupling in the high gamma range (51-75 Hz) with increasing load. Functional connectivity between the MTL seed and the visual association cortex increased with load, but activity within the MTL and the PFC correlated with fewer voxels, suggesting that more specific neural networks were engaged. These data indicate that WM for multiple items depends on an increased strength of top-down control of activity within the IT cortex by the MTL.