Multi-day rTMS exerts site-specific effects on functional connectivity but does not influence associative memory performance

Hendrikse, Joshua; Coxon, James P.; Thompson, Sarah R.; Suo, Chao; Fornito, Alex; Yücel, Murat; Rogasch, Nigel C.

doi:10.1016/j.cortex.2020.08.028

Cited by 19 publications

(26 citation statements)

References 45 publications

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“…Alternatively, the lack of changes in functional connectivity might reflect a site-specific property of the DLPFC. Site-specific changes in functional connectivity have been reported following rTMS (Cocchi et al, 2016; Castrillon et al, 2020; Hendrikse et al, 2020a), with certain studies reporting divergent changes in connectivity when identical forms of stimulation were applied across different cortical regions (Cocchi et al, 2016; Castrillon et al, 2020). Overall, this evidence suggests that the effects of rTMS on functional connectivity are highly variable and may not follow frequency-dependent conventions (e.g., reduced connectivity following 1 Hz rTMS and cTBS), particularly when stimulation is applied to non-motor regions.…”

Section: Discussionmentioning

confidence: 99%

“…However, in this study, we observed no change in local neural activity or GABA concentration, suggesting that cTBS may not have induced the significant local effects on DLPFC activity to influence connectivity across a wider network-scale. Further, personalised methods may not always enhance the reproducibility of rTMS effects (Hendrikse et al, 2020a). Finally, our working memory assessments occurred approximately 30-40 mins after stimulation.…”

Section: Discussionmentioning

confidence: 99%

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No evidence for changes in GABA concentration, functional connectivity, or working memory following continuous theta burst stimulation over dorsolateral prefrontal cortex

Thapa¹,

Hendrikse²,

Thompson³

et al. 2021

Preprint

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Continuous theta burst stimulation (cTBS) is thought to reduce cortical excitability and modulate functional connectivity, possibly by altering cortical inhibition at the site of stimulation. However, most evidence comes from the motor cortex and it remains unclear whether similar effects occur following stimulation over other brain regions. We assessed whether cTBS over left dorsolateral prefrontal cortex altered gamma aminobutyric acid (GABA) concentration, functional connectivity and brain dynamics at rest, and brain activation and memory performance during a working memory task. Seventeen healthy individuals participated in a randomised, sham-controlled, cross-over experiment. Before and after either real or sham cTBS, magnetic resonance spectroscopy was obtained at rest to measure GABA concentrations, whereas functional magnetic resonance imaging (fMRI) was recorded at rest and during an n-back working memory task to measure functional connectivity, brain dynamics (low-frequency fluctuations), and task-related patterns of brain activity. We could not find evidence for changes in GABA concentration (P=0.66, Bayes factor [BF10]=0.07), resting-state functional connectivity (P(FWE)>0.05), resting-state low-frequency fluctuations (P=0.88, BF10=0.04), blood-oxygen level dependent activity during the n-back task (P(FWE) >0.05), or working memory performance (P=0.13, BF10=0.05) following real or sham cTBS. Our findings add to a growing body of literature suggesting the effects of cTBS are highly variable between individuals and question the notion that cTBS is a universal 'inhibitory' paradigm.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

No evidence for changes in GABA concentration, functional connectivity, or working memory following continuous theta burst stimulation over dorsolateral prefrontal cortex

Thapa¹,

Hendrikse²,

Thompson³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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“…By targeting a DMN component functionally connected to hippocampus, many researchers have applied rTMS to improve hippocampal-dependent memory function. In particular, Voss and colleagues have frequently demonstrated success using a paradigm involving 20 Hz rTMS to left AG at 100% RMT [12,13,[51][52][53][54]57,59]. The only significant source of heterogeneity within the application of this paradigm was the number of rTMS sessions applied.…”

Section: Rtms Of Other Frontal Lobe Areasmentioning

confidence: 99%

“…In one study, Freedberg and colleagues observed that both three or four sessions of rTMS to left AG resulted in similar RSFC changes as when five stimulation sessions were applied, but did not assess changes in memory [59]. Surprisingly, Hendrikse and colleagues reported finding no significant cognitive benefit following four rTMS sessions [51]. To explore this potential minimum threshold, a dose-finding study was carried out by Freedberg and colleagues and discovered that a minimum of 5 rTMS sessions was required for significant change in RSFC reliably [50].…”

Section: Rtms Of Other Frontal Lobe Areasmentioning

confidence: 99%

Stimulating Memory: Reviewing Interventions Using Repetitive Transcranial Magnetic Stimulation to Enhance or Restore Memory Abilities

2021

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Human memory systems are imperfect recording devices that are affected by age and disease, but recent findings suggest that the performance of these systems may be modifiable through interventions using non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS). The translational potential of these rTMS interventions is clear: memory problems are the most common cognitive complaint associated with healthy aging, while pathological conditions such as Alzheimer’s disease are often associated with severe deficits in memory. Therapies to improve memory or treat memory loss could enhance independence while reducing costs for public health systems. Despite this promise, several important factors limit the generalizability and translational potential of rTMS interventions for memory. Heterogeneity of protocol design, rTMS parameters, and outcome measures present significant challenges to interpretation and reproducibility. However, recent advances in cognitive neuroscience, including rTMS approaches in addition to a new understanding of functional brain networks and related insights, may offer methodological tools necessary to design new interventional studies with enhanced experimental rigor, improved reproducibility, and greater likelihood of successful translation to clinical settings. In this review, we first discuss the current state of the literature on memory modulation with rTMS, then offer a commentary on developments in cognitive neuroscience that are relevant to rTMS interventions, and finally close by offering several recommendations for the design of future investigations using rTMS to modulate human memory performance.

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“…To assess the intrarater reliability of manual traced images, each subject's hippocampi were retraced from a structural T1‐weighted structural image acquired 1 week after the experimental assessment. T1‐images acquired at this follow‐up time point were acquired in the context of a separate study investigating the effects of 4 days of repetitive transcranial magnetic stimulation (rTMS) on functional connectivity (see Hendrikse et al, 2020). The tracer was blinded to MRI assessment time points and hypotheses pertaining to this study.…”

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confidence: 99%

Regular aerobic exercise is positively associated with hippocampal structure and function in young and middle‐aged adults

et al. 2021

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Regular exercise has numerous benefits for brain health, including the structure and function of the hippocampus. The hippocampus plays a critical role in memory function, and is altered in a number of psychiatric disorders associated with memory impairments (e.g., depression and schizophrenia), as well as healthy aging. While many studies have focused on how regular exercise may improve hippocampal integrity in older individuals, less is known about these effects in young to middle‐aged adults. Therefore, we assessed the associations of regular exercise and cardiorespiratory fitness with hippocampal structure and function in these age groups. We recruited 40 healthy young to middle‐aged adults, comprised of two groups (n = 20) who self‐reported either high or low levels of exercise, according to World Health Organization guidelines. We assessed cardiorespiratory fitness using a graded exercise test (VO2max) and hippocampal structure via manual tracing of T1‐weighted magnetic resonance images. We also assessed hippocampal function using magnetic resonance spectroscopy to derive estimates of N‐acetyl‐aspartate concentration and hippocampal‐dependent associative memory and pattern separation tasks. We observed evidence of increased N‐acetyl‐aspartate concentration and associative memory performance in individuals engaging in high levels of exercise. However, no differences in hippocampal volume or pattern separation capacity were observed between groups. Cardiorespiratory fitness was positively associated with left and right hippocampal volume and N‐acetyl‐aspartate concentration. However, no associations were observed between cardiorespiratory fitness and associative memory or pattern separation. Therefore, we provide evidence that higher levels of exercise and cardiorespiratory fitness are associated with improved hippocampal structure and function. Exercise may provide a low‐risk, effective method of improving hippocampal integrity in an early‐to‐mid‐life stage.

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Multi-day rTMS exerts site-specific effects on functional connectivity but does not influence associative memory performance

Cited by 19 publications

References 45 publications

No evidence for changes in GABA concentration, functional connectivity, or working memory following continuous theta burst stimulation over dorsolateral prefrontal cortex

No evidence for changes in GABA concentration, functional connectivity, or working memory following continuous theta burst stimulation over dorsolateral prefrontal cortex

Stimulating Memory: Reviewing Interventions Using Repetitive Transcranial Magnetic Stimulation to Enhance or Restore Memory Abilities

Regular aerobic exercise is positively associated with hippocampal structure and function in young and middle‐aged adults

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