Functional imaging trajectories after transient ischemia: a two-patient evidence base surrounded by infarct and haemodynamic literatures

Question: How has task-based fMRI BOLD activation and resting-state or task-based functional connectivity been shown to change longitudinally after transient ischemic events or acute cerebrovascular syndromes without infarction?

Answer

Taken together, the retrieved papers support a narrow and provisional answer: for genuinely non-infarct transient ischemic events, the only direct longitudinal fMRI evidence is a single exploratory study in which acute task-related BOLD hypofunction in the motor network partially normalizes by three months, accompanied by increasing connectivity between the symptomatic-contralateral motor cortex and other sensorimotor regions [1]. Everything more mechanistic is imported from the infarct and haemodynamic literatures, which show that post-injury functional reorganization is non-monotonic, metric-dependent, and concentrated contralaterally in the early phase [2] [13], and that BOLD coherence and evoked-response timing shift in structurally intact but haemodynamically compromised brain [16] [9]. The defensible synthesis is therefore that transient ischemia leaves a detectable, largely reversible functional signature whose direction and anatomical distribution follow the same compensation logic seen after infarction — but that the literature has not yet demonstrated this with adequate samples, resting-state data, or hemodynamic controls.

Acute task hypofunction with partial normalization is the only documented trajectory for DWI-negative TIA, and it rests on two patients

In adults scanned within 24 h of transient anterior-circulation symptoms and excluded for acute DWI lesions, whole-brain and individualized motor-cortex ROI analyses showed reduced bilateral motor-related BOLD responses in the acute phase, with motor cortex activation increasing at 3 months and tending to normalize toward values in non-TIA participants [1]. Connectivity analyses in that study were heterogeneous across the group, but the two confirmed TIA patients showed increased longitudinal connectivity between the motor cortex contralateral to symptoms and other sensorimotor regions, including supplementary motor areas [1]. Six patients contributed longitudinal data and only two had confirmed TIA, so the reported trajectory is an existence proof rather than an estimate of effect size or reproducibility [1].

The same acute suppression appeared in a patient with hypoglycemia, and patients with migraine aura and functional neurological disorder showed less marked longitudinal change, indicating that acute BOLD depression in a suspected-TIA population is not by itself an ischemia-specific signature [1]. This matters for the question as posed: the observed "recovery" of activation cannot yet be attributed to resolution of ischemic dysfunction rather than to resolution of a metabolic or functional mimic [1].

After infarction, resting-state reorganization is non-monotonic and metric-specific, so no single recovery curve transfers to non-infarct events

In the first year after left-hemisphere stroke, three whole-brain resting-state measures diverged: modularity declined steadily and fell below control values by 12 months, hemispheric symmetry was abnormally low at 1 month and rose significantly over the first 6 months to control-comparable levels, and homotopic connectivity followed a U-shape, falling from 1 to 6 months and then rising back toward control values [2]. In patients with exclusively subcortical lesions, acute-phase language-network dynamics at two weeks showed state- and tract-specific hypo- and hyper-connectivity with abnormal topology, and connectivity patterns returned toward healthy-control configuration and re-established domain segregation as language improved by three months and one year [4]. Individual functional connectome fingerprints shifted from the healthy architecture but stabilized within three weeks, after which system-specific reorganization continued, with an initial increase in connectivity within sensory and attention systems followed by decline across higher-level association networks [13]. Structurally, network-diffusion modelling fitted atrophy patterns at 3 and 12 months but performed weakly in the early acute stage, indicating that network-consistent propagation is a late-observable phenomenon [10].

Contralateral and system-specific increases dominate the early phase, consistent with compensatory rebalancing rather than restitution

Across these studies the earliest connectivity change is an increase, not a decrease, on the side opposite the lesion: hemispheric symmetry recovery over the first 6 months after unilateral stroke [2], early increases within sensory and attention systems before later association-network decline [13], and rising contralateral motor-to-sensorimotor coupling in the TIA patients [1]. In childhood stroke, children without hemiparesis were more likely to retain an ipsilesional activation pattern while children with hemiparesis more often showed bilateral or contralesional patterns, with greater tract-weighted functional connectivity strength when moving the affected hand in the better-outcome group [6]. Direction-resolved structure-function analyses in mice likewise found increased contralesional-to-ischemic coupling of primary motor cortex after cortical stroke, changes that did not simply correspond to regional lesion involvement [14]. In acute-to-chronic traumatic brain injury, functional hyperconnectivity was present initially and declined over time while remaining above control levels, whereas cortical structural hypoconnectivity persisted [12].

Haemodynamic and neurovascular changes in structurally intact brain can mimic or mask neuronal reorganization

In asymptomatic unilateral internal carotid artery stenosis, interhemispheric BOLD coherence was significantly diminished at approximately 0.1 Hz across canonical resting-state networks while ultra-slow coherence was preserved, with the reduction most pronounced in watershed areas and accompanied by lateralized cerebral blood volume [16]. In CADASIL, fast BOLD fMRI revealed significant changes in the amplitude and timing of evoked responses indicating early neurovascular impairment unrelated to anatomical lesions [9]. Task-evoked BOLD deactivations can occur alongside stable or even increased glucose consumption, so negative responses in particular cannot be read as reductions in neural metabolism [7]. Together these findings mean that reduced activation or coherence after a transient ischemic event may index vascular rather than neuronal recovery, a confound the TIA literature has not yet addressed [1] [16].

Task activity and connectivity predict different recovery windows, and recruitment of domain-general cortex is not an established mechanism

In longitudinal aphasia imaging, early recovery was independently predicted by acute and subacute activity and connectivity, whereas later improvement was predicted by activity alone; subacute connectivity from multiple-demand to language regions predicted early recovery while acute multiple-demand activity predicted long-term outcome [3]. Progressive activation increase within left-hemisphere language regions over 9 to 71 months, reaching normative range, has been documented alongside behavioural gains long after stroke [8]. Against a strong remapping account, precision fMRI in chronic aphasia found the language and multiple-demand networks remained robustly dissociated, with no evidence of multiple-demand takeover [5]. Recovery mechanisms are also lesion-specific: internal capsule infarcts in rodents produced delayed recovery without long-term ipsilesional cortical reorganization, unlike cortical lesions [15].

Conflicts and gaps

The literature disagrees on the sign of acute change: reduced task activation is reported in suspected TIA [1], whereas post-infarct and post-TBI resting-state studies emphasise early hyperconnectivity and contralateral increases [13] [12], and no study has measured both modalities in the same non-infarct patients. Whether normalization is complete is unresolved: modularity never returns to control levels at 12 months while symmetry and homotopic connectivity do [2]. The compensatory interpretation of contralesional recruitment is contradicted by the finding that preserved functional connectivity without intact neural substrate does not reflect genuine preservation [11]. Most importantly, no retrieved study provides resting-state connectivity data in DWI-negative TIA, none separates neuronal from neurovascular contributions in that population, and the sole direct study is unpowered, single-centre, and includes heterogeneous mimics [1].

What would change the answer

A prospective cohort of DWI-negative TIA with imaging at hyperacute (<24 h), one week, one month, three months, and twelve months, combining task fMRI, resting-state fMRI, and arterial spin labelling or CO2-calibrated cerebrovascular reactivity in the same session would separate neuronal from haemodynamic normalization [16] [9]. Individualized precision-functional localizers and connectome fingerprinting would give single-subject reliable estimates rather than group averages [5] [13]. Mandatory mimic arms — migraine aura, functional neurological disorder, hypoglycemia — would establish specificity, and normative deviation metrics or multivariate cross-validated prediction would test whether acute functional signatures forecast later impairment as they do after infarction [1] [3].

References

[1] Charbonnier, G., Bonnet, L., Comte, A., Medeiros de Bustos, E., Lesourd, M.. "Longitudinal changes in motor network activity and connectivity in patients with suspected Transcient Ischemic Attack: an exploratory fMRI study". medRxiv. 2026-10-19T00:00:00.000Z. URL: https://doi.org/10.64898/2026.10.13.26365278

[2] Tao, Y., Schnur, T. T., Ding, J., Martin, R., Rapp, B.. "Longitudinal changes in functional connectivity networks in the first year following stroke". bioRxiv. 2025-03-13T00:00:00.000Z. URL: https://doi.org/10.1101/2025.03.10.642404

[3] Bruera, A., Jiang, Z., Saur, D., Stockert, A., Hartwigsen, G.. "Changes in Neural Dynamics of Brain Activity and Connectivity Independently Predict Post-Stroke Aphasia Recovery". bioRxiv. 2026-09-20T00:00:00.000Z. URL: https://doi.org/10.64898/2026.09.17.751646

[4] Zhong, T., Chen, Q., Guo, X., Yang, J., Gao, X., Hu, Z., Liu, J., Li, J., Liu, J., Wang, Y., Qu, Z., Li, W., Li, Z., Li, W., Huang, Y., Chen, J., Wen, H., Yuan, B., Gao, H.. "The Disruption and Normalization of Cortical Language Network Dynamics After Post-Stroke White Matter Disconnection". bioRxiv. 2025-08-28T00:00:00.000Z. URL: https://doi.org/10.1101/2025.08.25.672078

[5] Billot, A., Varkanitsa, M., Jhingan, N., Carvalho, N., Falconer, I., Small, H., Ryskin, R., Blank, I., Fedorenko, E., Kiran, S.. "Language comprehension in chronic aphasia relies on the language network, not the Multiple Demand network". medRxiv. 2026-03-18T00:00:00.000Z. URL: https://doi.org/10.64898/2026.03.16.26348460

[6] Curnow, S. R., Chen, J., Warren, A. E., Beare, R., MacKay, M. T., Yang, J. Y.. "Motor network activation and white matter connectivity patterns are related to clinical outcomes after childhood stroke.". medRxiv. 2024-12-11T00:00:00.000Z. URL: https://doi.org/10.1101/2024.12.09.24317592

[7] Blazey, T., Lee, J. J., Snyder, A. Z., Raichle, M. E., An, H., Goyal, M. S., Vlassenko, A. G.. "Task-evoked deactivations: dissociation between BOLD fMRI and FDG". bioRxiv. 2026-05-18T00:00:00.000Z. URL: https://doi.org/10.64898/2026.05.14.725188

[8] Chang, E. H. T., Laks, A. B., Shattuck, K., DeMarco, A. T., Turkeltaub, P. E.. "Dispelling the Plateau Assumption: Case-Based Evidence for Language Recovery in Chronic-Post Stroke Aphasia". bioRxiv. 2026-10-08T00:00:00.000Z. URL: https://doi.org/10.64898/2026.10.03.755714

[9] Boido, D., Ressam, C., Perez, V., Beranger, B., Clary, M., Aydin, A.-K., Ledemberg, J., Abbas, T., Fernandes, F., Riviere, D., Sun, Z. Y., Mangin, J.-F., Charpak, S., Chabriat, H.. "FAST BOLD FMRI REVEALS THE SPATIOTEMPORAL COMPLEXITY OF NEUROVASCULAR COUPLING ALTERATIONS IN CEREBRAL SMALL VESSEL DISEASE". bioRxiv. 2026-06-15T00:00:00.000Z. URL: https://doi.org/10.64898/2026.06.14.732126

[10] Yang, J., Gao, Y., Yang, L., Jiang, Y., Wan, B., Bayrak, S., Liang, X., Valk, S. L., Corbetta, M., Gong, G.. "Structural brain networks shape individual-level progression of brain atrophy after stroke". bioRxiv. 2026-05-12T00:00:00.000Z. URL: https://doi.org/10.64898/2026.05.08.723677

[11] Junca, A., Martin, I., Deco, G., Patow, G. A.. "Preserved but not functional: growth biology shapes connectivity resilience in meningioma and glioma". bioRxiv. 2026-05-20T00:00:00.000Z. URL: https://doi.org/10.64898/2026.05.17.725702

[12] Radanovic, A., Jamison, K. W., Kang, Y., Shah, S., Kuceyeski, A.. "Longitudinal multimodal neuroimaging after traumatic brain injury". bioRxiv. 2025-04-07T00:00:00.000Z. URL: https://doi.org/10.1101/2025.04.04.647315

[13] Santoro, A., Lucatelli, A., Windel, F., Lugli, B., Preti, M. G., Fleury, L., Petruso, F., Beanato, E., Van De Ville, D., Hummel, F. C., Amico, E.. "Individual connectome fingerprints reveal early stabilization and long-term circuit remodeling after stroke". bioRxiv. 2026-03-31T00:00:00.000Z. URL: https://doi.org/10.64898/2026.03.27.714711

[14] Mahani, F. S. N., Hoehn, M., Fink, G. R., Aswendt, M.. "Structure-function coupling reveals hemisphere-specific network reorganization after stroke". bioRxiv. 2026-09-24T00:00:00.000Z. URL: https://doi.org/10.64898/2026.09.18.752042

[15] Cettina, P. E., Guggenmos, D. J., Sivakumar, S. S., Murphy, M. D., Barbay, H. S., Nudo, R. J., Bundy, D. T.. "Absence of cortical reorganization following an internal capsule stroke in rodents". bioRxiv. 2025-11-03T00:00:00.000Z. URL: https://doi.org/10.1101/2025.10.31.685962

[16] Choi, S., Hoffmann, G., Schneider, S., Kaczmarz, S., Yu, X., Preibisch, C., Sorg, C.. "Resting-state fMRI coherence is selectively diminished around 0.1 Hz, particularly inside watershed areas, in patients with unilateral carotid artery stenosis". bioRxiv. 2025-12-26T00:00:00.000Z. URL: https://doi.org/10.1101/2025.06.12.659378

How this survey was made

This survey answers one question: “How has task-based fMRI BOLD activation and resting-state or task-based functional connectivity been shown to change longitudinally after transient ischemic events or acute cerebrovascular syndromes without infarction?”

We keep our own collection of recent preprints and refresh it every day from bioRxiv, medRxiv, arXiv, PsyArXiv, SocArXiv and ChemRxiv. For each survey, we search that collection for recent work and keep the strongest matches: papers that use the same terms as the question, and papers on the same topic in different words.

The text was written from the titles and abstracts of those papers; the full texts were not read. Statements that draw on a particular paper are marked with a number in brackets. The reference list just above is the 16 papers whose work this text draws on, chosen from the 137 papers those searches returned; the rest of the shortlist is not printed. It is not a complete review of everything published on the question.

Treat this as a starting point and a reading list, not a peer-reviewed review. The searches behind this survey ran on October 22, 2026 and covered work from the previous two years.