Christopher I. Petkov

Low-intensity transcranial ultrasound stimulation (TUS) is a promising non-invasive technique for brain stimulation and focal neuromodulation. Research with humans and animal models has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on available healthy human participant TUS studies reporting stimulation parameters and outcomes (n = 47 studies, 52 experiments). In initial exploratory analyses with univariate tests, we find that parameters, such as the intensity and continuity of stimulation (duty cycle, DC) show statistical trends towards likely TUS neural enhancement or suppression of function. Machine-learning analyses were limited by the currently small sample size. Given that human TUS sample sizes are expected to increase, predictability on the directionality of TUS effects could improve if a database is available. Therefore, we establish an inTUS database and resource for the systematic reporting of TUS parameters and outcomes to assist in greater precision in TUS use for brain stimulation and neuromodulation. The paper concludes with a selective review of human clinical TUS studies illustrating how hypotheses on the directionality of TUS effects could be developed for empirical testing in the intended clinical application, not limited to the examples provided.

Academic peer review is fundamental for scientific knowledge dissemination, and various initiatives are exploring how the peer review process could be more open, efficient and rewarding. We report an exploratory study where a live community-based review approach was integrated into the editorial workflow of an academic journal (Current Research in Neurobiology; CRNEUR). This study was conducted with five manuscripts ('cases') submitted as preprints, which underwent Live Review-a structured collaborative review session led by PREreview, an organization with the mission to advance equity and openness in scholarly evaluation. With each case, PREreview team members facilitated a 90-min online discussion where registered participants provided real-time discussion and worked together on the online structured peer review document. Authors could join as observers or to answer questions. Participants then volunteered to write up the session notes into a final review and summary statement. Review participants had the option to sign the review. The finalized review was then published on PREreview's open preprint review platform approximately two weeks after the Live Review session, and it was assigned a CC BY 4.0 license and Digital Object Identifier (DOI) linked to the DOI of the reviewed preprint allowing reviewers to be recognized for their contribution. The published review was then incorporated into CRNEUR's editorial workflow to inform editorial decisions and manuscript outcomes. We quantified the speed to first and final editorial decision of the community review (n = 5) in comparison to a larger sample (n = 27) of articles that went through a standard review process at CRNEUR during the same timeframe. First decision times in days after manuscript submission of the Live Reviews were within the Inter Quartile Range (IQR) of the standard review process (community review: median = 75, IQR: 41.3; standard review: median 92, IQR: 41.5), as were final decision times (community review: median 138, IQR: 22.5; standard review: median 211, IQR: 166.0). A survey of the Live Review attendees (n = 13; 30% response rate) on a scale of 1 'Highly Disagree' to 5 'Highly Agree' showed median 'Agree' to 'Highly Agree' scores on several questions including the review being respectful, time efficient and scientifically rigorous (median scores: 5, 4, 4, respectively). The innovative Live Review approach was as efficient as the standard review process in the journal and was rated positively by those surveyed. The small sample size inherent to exploratory studies limits conclusions generalizing to larger sample sizes. We discuss how live, community-based review approaches could be further developed, scaled and sustained.

Despite substantial interest in how neural systems recover over time after acute neurological events, there is a dearth of longitudinal assessment from minutes to months surrounding these events. We compared rare intraoperative recordings in three patients, obtained immediately before and after anterior temporal lobe resection during a semantic prediction task, with longitudinal source-localized electroencephalography (EEG) obtained 2-6 weeks before, and 2 and 6-14 months after surgery. Relative to controls ( n = 20), task performance showed sustained impairment in the two left-hemisphere patients and delayed impact in the right-hemisphere patient. Consistent with theories on ipsilateral and contralateral hemisphere compensation, all patients exhibited bilateral EEG alterations in speech responses and effective connectivity that did not fully recover to pre-operative levels. Direct dataset comparisons of intrinsic neurophysiological biomarkers associated with timescales of processing ( τ _INT ) and excitatory-inhibitory balance (aperiodic slope, χ _SPEC ) showed a striking months-long reduction in rapid neural timescales of processing and gradually increasing aperiodic slope (putatively reflecting increased cortical inhibition or reduced excitation) specifically in the ipsilateral hemisphere of all three patients. Amidst these neurophysiological alterations, semantic task performance did not return to pre-operative levels. These rare longitudinal data advance a mechanistic framework to non-invasively evaluate neurophysiological impact over multiple timeframes in other patient cohorts. Significance statement: We report rare longitudinal recordings obtained minutes to months before and after epilepsy surgery. Using state-of-the-art measures of neurophysiological biomarkers and network dynamics, we observed immediate disruption followed by consistent, longer-lasting alterations in neural excitability and temporal functionality.

There is substantial scientific interest in improving approaches that can enhance cognition through brain stimulation. We implemented a non-invasive focal Transcranial Ultrasound Stimulation (TUS) approach with known longer-lasting post-stimulation effects in two rhesus macaques performing a context-dependent memory-sequencing task implemented on multiple touchscreens within their home units. Consistently in both monkeys, TUS to the anterior – but not posterior – medial temporal lobe enhanced performance under stable memory-sequencing contexts. TUS to the medial prefrontal cortex, on the other hand, selectively improved performance when contexts were unstable and the monkey needed to adapt to both a change in context and temporal sequence. These findings shed new light on fronto-temporal nodes that, when perturbed, can selectively enhance cognitive performance, paving the way for further developing non-invasive approaches to improve cognitive function in humans and to study neural circuits under focal perturbation across species.

Fluid control protocols are widely used in neuroscience to motivate laboratory macaques to engage with behavioural tasks. Despite strong evidence that the physiology of the animals is not compromised by such protocols, fluid control remains controversial due to its potential impact on the psychological well-being of the animals. To address this concern, we investigated the effect of fluid control on the affective state of 23 socially-housed adult macaques (10 females) engaged in neuroscience experiments. The protocol involved up to five consecutive days of fluid control per week, followed by a minimum of two days with unrestricted fluid access. The affective state of the animals was primarily assessed by quantifying the frequency of pharmacologically-validated behavioural indicators of high-arousal negative affect (self-scratching, body shaking, self-grooming). The analysis was subsequently extended to validated behavioural indicators of low-arousal negative affect ( Inactive not alert ) and other behaviours suspected of indicate high-arousal negative affect but lacking proper validation (pacing, yawning). In total, 700 hours of video footage spanning up to seven years of intermittent fluid control per animal were analysed. Despite this extensive dataset, the study found no significant impact of fluid control on average, or any evidence of habituation or sensitization over the years on any of the affective state indicators. Additional results indicate that these null results are not due to a lack of sensitivity, supporting the view that fluid control, as implemented in this study, does not have an adverse impact on the psychological well-being of laboratory macaques. We argue that macaque welfare will be best served by focusing future refinement on other procedures.

Academic peer review is fundamental for scientific knowledge dissemination, and various initiatives are exploring how the peer-review process could be more open, efficient and rewarding. We report five case studies where a live community-based review session was integrated into the editorial workflow of an academic journal (Current Research in Neurobiology; CRNEUR). Five manuscripts, submitted as preprints, underwent Live Review—a structured collaborative review session led by PREreview, an open science project advancing openness in scholarly evaluation. With each case, PREreview team members facilitated a 90-minute online discussion where registered participants provided real-time discussion and worked together on an online structured peer-review document. Authors could join as observers or to answer questions, and journal editors could join as observers. Participants then volunteered to write up the session notes into a final review and summary statement. Review participants had the option to sign the review. The finalized review was then published on PREreview’s open preprint review platform approximately two weeks after the Live Review session. The published review was assigned a Digital Object Identifier (DOI) for participating reviewers to obtain credit for their reviewing effort. The published review was then incorporated into CRNEUR’s editorial process to inform editorial decisions. Results suggest that the speed of this community review can be as rapid as the standard peer-review process for CRNEUR during the same time period, and a small sample size survey of the Live Review pilots attendees showed agreement on several questions including the review being respectful, time efficient and scientifically rigorous. We discuss how live, community-based review approaches could be further developed, scaled and sustained.

The cerebral cortex displays a bewildering diversity of shapes and sizes across and within species. Despite this diversity, we present a universal multi-scale description of primate cortices. We show that all cortical shapes can be described as a set of nested folds of different sizes. As neighbouring folds are gradually merged, the cortices of 11 primate species follow a common scale-free morphometric trajectory, that also overlaps with over 70 other mammalian species. Our results indicate that all cerebral cortices are approximations of the same archetypal fractal shape with a fractal dimension of d_f = 2.5. Importantly, this new understanding enables a more precise quantification of brain morphology as a function of scale. To demonstrate the importance of this new understanding, we show a scale-dependent effect of ageing on brain morphology. We observe a more than fourfold increase in effect size (from two standard deviations to eight standard deviations) at a spatial scale of approximately 2 mm compared to standard morphological analyses. Our new understanding may, therefore, generate superior biomarkers for a range of conditions in the future.

Low-intensity Transcranial Ultrasound Stimulation is a promising non-invasive technique for brain stimulation and focal neuromodulation. Research with humans and animal models has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on available healthy human participant TUS studies reporting stimulation parameters and outcomes ( n = 47 studies, 52 experiments). In initial exploratory analyses with univariate tests, we find that parameters such as the intensity and continuity of stimulation (duty cycle) show statistical trends towards likely TUS neural enhancement or suppression of function. Machine-learning analyses were limited by the currently small sample size. Given that human TUS sample sizes are expected to increase, predictability on the directionality of TUS effects could improve if a database is available. Therefore, we establish an inTUS database and resource for the systematic reporting of TUS parameters and outcomes to assist in greater precision in TUS use for brain stimulation and neuromodulation. The paper concludes with a selective review of human clinical TUS studies illustrating how hypotheses on the directionality of TUS effects could be developed for empirical testing in the intended clinical application, not limited to the examples provided. Highlights: Collated set of hypotheses on using TUS to bias towards neural enhancement or suppression Meta-analysis results identify parameters that may bias directionality of TUS effects inTUS resource established for systematic reporting of TUS parameters and outcomes Selective review of patient TUS studies for enhancing or suppressing neural function

Statistical learning processes are important for language and reading development, and impairments in sequence processing abilities have been identified in language disorders such as dyslexia. Previous research suggests that these deficits may be particularly pronounced in more complex sequence processing tasks. Here, we tested adult dyslexic (n=10) and control (n=18) participants using two different artificial grammars and a suite of language and cognitive tests. The two grammars generated sequences of nonsense words containing either relatively simple adjacent dependencies or more complex nonadjacent dependencies (‘xAB’ and ‘AxB’ respectively, where ‘A’ elements predict ‘B’ elements and ‘x’ elements are uninformative). Participants were initially exposed to legal sequences, before making grammaticality judgements about sequences that were either consistent with or violated the dependencies. The control and dyslexic groups performed equally well, and detected violations of both grammars above chance levels as well as generalising the dependencies to novel vocabularies. However, dyslexic participants responded significantly slower, suggesting some differences in sequence processing, independent of sequence complexity. These results raise questions about whether some of the impairments observed in dyslexia are due to specific sequence processing deficits or may be the result of other difficulties, for example in phonological processing of speech sounds.