# Exploring the impact of the interthalamic adhesion on human cognition: insights from healthy subjects and thalamic stroke patients

Julie P. Vidal, Kévin Rachita, Anaïs Servais, Patrice Péran, Jérémie Pariente, Fabrice Bonneville, Jean-François Albucher, Lola Danet, Emmanuel J. Barbeau

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Julie P. Vidal, Kévin Rachita, Anaïs Servais, Patrice Péran, Jérémie Pariente, et al. Exploring the impact of the interthalamic adhesion on human cognition: insights from healthy subjects and thalamic stroke patients. Journal of Neurology, 2024, 271, pp.5985-5996. 10.1007/s00415-024-12566-z. hal-04756262

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# Exploring the impact of the interthalamic adhesion on human cognition: insights from healthy subjects and thalamic stroke patients

Julie P. Vidal<fnref n="1" />,<fnref n="2" />,✉ Kévin Rachita<fnref n="3" />, Anaïs Servais<fnref n="1" />, Patrice Péran<fnref n="2" />, Jérémie Pariente<fnref n="2" />,<fnref n="3" />, Fabrice Bonneville<fnref n="2" />,<fnref n="3" />, Jean-François Albucher<fnref n="2" />,<fnref n="3" />, Lola Danet<fnref n="2" />,<fnref n="3" />, Emmanuel J. Barbeau<fnref n="1" />

Received: 28 February 2024 / Revised: 27 June 2024 / Accepted: 5 July 2024 / Published online: 17 July 2024
© The Author(s) 2024

## Abstract

The interthalamic adhesion (IA) is a structure that connects the median borders of both thalami. Its anatomical variants and functions remain poorly studied. The main objective of this study was to explore the role of the IA on cognition. 42 healthy subjects and 40 patients with chronic isolated thalamic strokes underwent a neuroimaging and a neuropsychological assessment. The presence, absence, or lesion of the IA and its anatomical variants were evaluated. 76% of participants had an IA, with a higher prevalence among women (92%) than men (61%). The presence or absence of an IA did not affect the neuropsychological performance of healthy subjects nor did the type of IA variant. Across all the tests and when compared to healthy subjects using a Bayesian rmANOVA, patients exhibiting more cognitive impairments were those *without* an IA (n=10, BF₁₀=10,648), while those *with* an IA were more preserved (n=18, BF₁₀=157). More specifically, patients *without* an IA performed more poorly in verbal memory or the Stroop task versus healthy subjects. This was not explained by age, laterality of the infarct, volume or localization of the lesion. Patients *with a lesioned IA* (n=12) presented a similar trend to patients *without* an IA, which could however be explained by a greater volume of lesions. The IA does not appear to play a major role in cognition in healthy subjects, but could play a compensatory role in patients with thalamic lesions.

**Keywords** Thalamus · Interthalamic adhesion · Massa intermedia · Stroke · MRI

## Introduction

The interthalamic adhesion (IA), or massa intermedia, is a midline structure connecting the median border of both thalami across the third ventricle, posterior to the foramen of Monro [1–4]. Intriguingly, the prevalence of the IA within the population varies across MRI studies, ranging from 68 to 98%, with most studies reporting an absence of the IA in around 20% of cases [2, 4–9]. Its typical form in humans is a single and homogenous adherence usually located at the anterosuperior quadrant [1–4]. The IA has anatomical variants: a broad, larger, form in 18% of cases and duplication

which occurs in 2–10% of instances [1, 2, 4, 10–14]. Other rare variants include bilobar, multiple, tubular or rudimental IA seen in less than 3% of subjects [13]. The “kissing thalami” phenomenon occurs when both thalami adhere to one another, preventing proper assessment of whether an IA is present or not [11, 15, 16]. Prevalence of the IA is more common in females (91%) compared to males (83%) [4, 6, 7, 9, 12, 15, 17]. A larger IA is also reported among females versus males [1, 2, 13, 18]. Most studies used T1-weighted MRI scans with a great disparity among methods in the absence of a standardized protocol to evaluate prevalence, anatomical variants or size of the IA.

The reasons for the absence of an IA are debated and include a potential correlation with age [8, 11, 18–21], third ventricle abnormalities [3, 6, 8, 10, 11, 20] and could possibly be related to various neurodevelopmental or psychiatric disorders, such as schizophrenia, borderline personality, major depression or bipolar disorder [9, 11, 17, 20, 22–24]. The absence of an IA could be linked to early neurodevelopmental abnormalities during gestation [9, 21, 24].

<figure><img src="image_3.png" /></figure>

<footnote>Julie P. Vidal
julie.vidal@univ-tlse3.fr</footnote>

<footnote n="1">¹ CerCo (Brain and Cognition Research Center), CNRS, Paul Sabatier University, Toulouse, France</footnote>

<footnote n="2">² ToNiC (Toulouse NeuroImaging Center), INSERM, Paul Sabatier University, Toulouse, France</footnote>

<footnote n="3">³ Neurology Department, Purpan Hospital, Toulouse University Hospital Center, Toulouse, France</footnote>
Due to its limited size, little is known regarding the precise connectivity supported by the IA. Several groups investigated it using diffusion imaging and tractography methods. Damle et al. [25] found that the IA size is associated with anterior thalamic radiations, related to dorsomedian thalamic nuclei and involved in memory [26]. Kochanski et al. [27], using deterministic tractography and the lateral habenula as a seed, reported that some fibers from the stria medullaris cross the IA via anterior thalamic nuclei, some in the direction of the orbitofrontal cortex. When the IA was too small, no crossing fibers were identified, and in the absence of IA, fibers crossed via the posterior commissure leading the authors to suggest the presence of a compensatory pathway. Borghei and colleagues [16] identified widespread connections to the IA, including from the amygdala, hippocampus, entorhinal cortex, insula, medial and lateral orbitofrontal cortices, pericalcarine cortex and cuneus of the occipital lobe. They also showed passage of fibers through the IA to the contralateral hemisphere. Sahin et al. [12] showed that some fibers come from the medial frontal region to the dorsomedial thalamus and from there to the IA. They also reported that fibers from the IA reach the nucleus accumbens, caudate nucleus and fronto-orbital region anteriorly, and the lateral habenula and posterior commissure posteriorly. These results indicate that the IA supports interhemispheric connectivity.

The presence of neuronal cell bodies in the IA is more debated. This debate stems from extensive studies on the IA in mammals, which involve multiple midline nuclei within the IA. In humans, only the reuniens nucleus, part of the median thalamus, may be contained within the IA, but it is smaller and more challenging to delineate. Some studies found neuronal cell bodies in the IA using Nissl-stained material [5] or Golgi material [28] while a recent histological study using hematoxylin–eosin staining pointed towards their absence but identified glial cells hypothesized to be oligodendrocytes surrounding the axons [29].

The role of the IA in human cognition has been a subject of uncertainty for a long time, with some authors considering it as a vestigial part of the brain with no known function [14]. As already mentioned, the fact that the IA is not present in all subjects probably reinforced the idea that it may not play a critical part in cognition. However, a few studies have started to shed light on its potential cognitive significance. The size of the IA was thought to mediate the relationship between age and attention in healthy female subjects [25]. A recent study using healthy subject data from the Human Connectome Project associated the IA absence with inhibition and attention deficits as well as increased negative emotional function [15]. In addition, the absence of the IA among patients with epilepsy was linked to worse performances on verbal memory tests and executive functions [18]. However, as mentioned by the authors, memory

deficits in medial temporal lobe epilepsy patients can also be directly linked to epilepsy. Overall, the role of the IA in human cognition has rarely been investigated using dedicated protocols. This may be due to several factors, including the need for high-quality MRI, which are only recently available, but necessary to identify the IA and to consider its anatomical variants.

In this context, the aim of our study is to clarify the role of the IA in human cognition using a novel approach as assessed in both a group of 45 healthy control subjects and 40 patients with isolated ischemic thalamic stroke. Our general hypothesis was that the IA plays a role in cognition. More specifically, we thought that thalamic stroke patients might reveal the role of the IA in cognition through functional compensation mechanisms. We hypothesized that patients with an IA would produce better performance than patients without an IA on neuropsychological tests. We did not make any specific hypothesis regarding the case of patients with an IA and a thalamic lesion encompassing their IA.

# Materials and methods

## Participants

We collected data from 45 healthy subjects (ages 23–69, median age 52, 20 males) and 40 patients (ages 23–75, median age 54, 25 males) with ischemic thalamic lesions at the chronic stage (91–2674 day post-stroke). These patients were recruited in the Stroke Units at University Hospital of Toulouse between 2011–2013 and 2019–2020.

Patients from two studies were included in order to increase the sample size. The first study was approved by the Institutional Review Board “Comité de Protection des Personnes Sud-Ouest et Outre-Mer no. 2-11-0”. It included 20 patients with a thalamic stroke, younger than 80 years. Marginal extra-thalamic lesions were accepted in this study (this concerned three patients reported in [30] with small lesions extending in surrounding structures of the thalamus). The second study was authorized by the “Comité de Protection des Personnes Ile-de-France IV” (Ethics Committee). It included 20 patients aged below 70 years with at least one stroke lesion visually reaching the dorsomedian nucleus and no extra-thalamic damage. For both studies, recruitment criteria were detection of a first symptomatic thalamic infarct regardless of complaint or neurobehavioral report before onset and no previously known neurovascular, inflammatory or neurodegenerative diseases. The Fazekas and Schmidt score, which assesses white matter lesions, was lower or equal to 2 for all patients. Healthy subjects were volunteers with no known significant health issues. All data

<figure><img src="image_4.png" /></figure>
were acquired after obtaining prior written informed consent
from the participants.

Neuropsychological assessment

All participants underwent the same neuropsychological
examination (at least 3 month post-stroke for patients) which
included: the Free and Cued Selective Reminding test [31]
(verbal anterograde memory); the DMS48 task [32] (visual
anterograde recognition memory); the Stroop test [33] (inhi-
bition); literal and semantic fluencies [33] (executive func-
tions); D2 [34] (attention); digit-symbol test [35] (working
memory); ExaDé confrontation naming test [36] (language)
and three mood and affective scales: the State–Trait Anxi-
ety Inventory [37], Starkstein Apathy Scale [38] and Beck
Depression Inventory Scale [39]. To ensure that the inclu-
sion of patients from two different studies did not affect the
neuropsychological conclusions, a Mann–Whitney *U* test
was conducted to compare their performance on the neu-
ropsychological tests used. No significant difference was
found.

MRI acquisition

For the first 20 patients and 20 healthy subjects, 3D
T1-MPRAGE sequences were acquired on a 3 T scanner
(Philips Achieva) with the following parameters: 1\*1\*1 mm
voxel size, TE = 3.7 ms, TR = 8.2 ms, flip angle = 8°,
FOV = 240\*240, spacing between slices = 0 mm. 3D
T2-FLAIR (Fluid Attenuated Inversion Recovery) sequences
parameters were: 1\*1\*1 mm voxel size, TE = 338 ms,
TR = 8000 ms, TI = 2400 ms, FOV = 240\*240, spac-
ing between slices = 0 mm. For the next 20 patients and
25 healthy subjects, 3D T1-MPRAGE sequences were
acquired on a 3 T scanner (Philips Achieva) with the fol-
lowing parameters: 0.9\*0.9\*1 mm voxel size, TE = 8.1 ms,
TR = 3.7 ms, flip angle = 8°, FOV = 256\*256, spac-
ing between slices = 0 mm. 3D T2-FLAIR sequences
parameters were: 1\*1\*1 mm voxel size, TE = 343 ms,
TR = 8000 ms, TI = 2400 ms, FOV = 240\*240, spacing
between slices = 0 mm.

IA and IA variants identification protocol

Two raters (JV, KR) independently assessed the presence or
absence of the IA, its anatomical variants and if the lesion
involved the IA among patients. A standardized protocol
was set up on MRIcron [40] with a standardized zoom (3)
and contrast value (2000) adapted to the MRI sequence type
(Fig. 1). MRI sequences are reoriented to MNI152 orienta-
tion using FSL (FMRIB Software Library, fslreorient2std)
to ease the identification of the anterior and posterior com-
missure and avoid any confusion with a potential IA. First,

<figure><img src="image_5.png" /><figcaption>**Fig. 1** Standardized protocol to study the IA. This protocol aims to identify the prevalence of the IA, an eventual thalamic lesion extending into it and to characterize its anatomical form using the MRIcron software</figcaption></figure>

the reviewer examined the axial slices from the bottom to
the top. An IA was deemed present if a structure connecting
both thalami was observed on at least one slice between the
anterior and the posterior commissures. Then, this presence
had to be confirmed both on coronal and sagittal slices and
in case of doubt, the FLAIR sequences were used. In this
aim, FLAIR sequences were coregistered to the T1w images
with a rigid transformation (9 degrees of freedom) using
FLIRT (FMRIB's Linear Image Registration Tool) [41]. In
the event of kissing thalami, partial volume, or discordance
between the two raters after attempts to reach a consensus,
the subject was excluded from analyses. An IA was identi-
fied as damaged if at least one voxel of the lesion extended
into it. An extended video protocol to characterize the IA is
publicly available [https://doi.org/10.13140/RG.2.2.35022.
47689] and a training dataset can be sent on request.

Regarding anatomical variants of the IA, we followed the
suggestions provided by Tsutsumi et al., 2021 [13]. More
specifically, the IA was characterized as a broad form when
it adhered to at least 1/3 of both thalami lengths on axial
slices or 1/3 of their heights on coronal slices. The two raters
did not have difficulty reaching agreement except in one case
of possible bilobar IA.

Lesion location

Lesions were manually segmented on the native T1w images
by two independent investigators (JV, LD) using MRIcron
software. Both native images and their corresponding lesions
were normalized on the Montreal Neurological Institute
(MNI) template and localized using the digitized Morel's
atlas [42]. The volume (mm³) of the normalized lesion in
each nucleus and mammillothalamic tract per patient was
then computed. Nuclei were gathered into nuclear groups
(anterior, posterior, lateral, median) using Morel's reparti-
tion [43]. If a lesion reached the mammillothalamic tract
(MTT) with a volume greater than 5mm³, the MTT was
<table><caption>**Table 1** Demographical data of all subjects</caption><thead><tr><th rowspan="2"></th><th colspan="2">Healthy subjects (n=42)</th><th colspan="3">Patients (n=40)</th></tr><tr><th>With IA</th><th>Without IA</th><th>Intact IA</th><th>Damaged IA</th><th>Absent IA</th></tr></thead><tbody><tr><th>N (women)</th><td>32 (20)</td><td>10 (3)</td><td>18 (19)</td><td>12 (6)</td><td>10 (0)</td></tr><tr><th>Mean age (SD, min, max)</th><td>47.9 (15.2, 20, 69)</td><td>54.1 (5.9, 42, 62)</td><td>48.4 (13.2, 23, 69)</td><td>54.8 (18.9, 24, 75)</td><td>51.6 (13, 25, 74)</td></tr><tr><th>Mean years of study (SD, min, max)</th><td>13.4 (3.7, 5, 21)</td><td>13.8 (3.1, 9, 17)</td><td>12.1 (3.2, 5, 17)</td><td>12.8 (4.3, 4, 17)</td><td>12.5 (2.7, 9, 17)</td></tr></tbody></table>

<figure><img src="image_6.png" /><figcaption>**Table 2** Frequency of the absence or presence of the IA and its different anatomical variants among healthy subjects (n=42), patients (n=40) and all subjects (n=82)</figcaption></figure>

<table><thead><tr><th></th><th>One</th><th>Broad</th><th>Double</th><th>Bilobar</th><th>Absent</th></tr></thead><tbody><tr><th>Healthy subjects</th><td>20 (48%)</td><td>6 (14%)</td><td>3 (7%)</td><td>3 (7%)</td><td>10 (24%)</td></tr><tr><th>Patients</th><td>14 (36%)</td><td>4 (10%)</td><td>7 (18%)</td><td>4 (10%)</td><td>10 (25%)</td></tr><tr><th>All subjects</th><td>34 (42%)</td><td>10 (12%)</td><td>10 (12%)</td><td>7 (10%)</td><td>20 (24%)</td></tr></tbody></table>

The prevalence of IA variants among patients was computed on 39 patients due to disagreement between the two raters for 1 subject

note how close the mammillothalamic tract (in pink) is to the IA.

The prevalence of the IA and its anatomical variants are presented in Table 2 (see also Fig. 3). The IA was absent in 24% of all participants. The IA absence was more frequent among men (39%) than women (8%) (BF₁₀ independent multinomial test = 51). We found moderate evidence favoring the absence of an age effect (BF₁₀ t test = 0.38) or education (BF₁₀ t test = 0.27). In addition, no impact of age (BF₁₀ ANOVA = 0.19, education (BF₁₀ ANOVA = 0.16) or gender (BF₁₀ independent multinomial = 0.29) on the distribution of the variants was

evidenced, neither across all subjects nor within healthy subjects or patient subgroups. Prevalence of the IA did not differ between the groups of patients and healthy subjects (BF₁₀ independent multinomial = 0.23).

An IA-related lesion was identified among 12 patients (Fig. 4). For those with a double IA, two patients had one damaged IA while the other one was preserved (Online Resource 2).

The mean lesion volume differed between the groups of patients (BF₁₀ ANOVA = 6.7; IA intact: 285 ± 258 mm³; IA damaged: 604 ± 323 mm³; IA absent: 327 ± 201 mm³) and was higher among patients with a damaged IA than in patients with an intact IA (post-hoc BF₁₀ t test = 8). However, laterality of infarcts (BF₁₀ independent multinomial test = 0.85) and the number of patients with a disrupted mammillothalamic tract (intact IA: 2; damaged IA: 5; IA absent: 3; BF₁₀ independent multinomial = 0.88) were not different between the 3 subgroups of patients. Locations of infarcts were also distributed identically using the mean lesioned volume per nuclear group (BF₁₀ rmANOVA = 0.31). Therefore, the neuropsychological impact specifically associated with the location of thalamic lesions can be considered negligible when comparing the three groups of patients. Those lesions were mainly located in the median and lateral
<figure><img src="image_7.png" /><figcaption>**Fig. 3** Illustration of the different anatomical variants of the IA or illustration of its absence in single healthy subjects. White arrows indicate the IA location</figcaption></figure>

<figure><img src="image_8.png" /><figcaption>**Fig. 4** T1w axial slice for each of the 12 patients with a thalamic lesion reaching the IA (white arrows)</figcaption></figure>

<figure><img src="image_9.png" /></figure>
<figure><img src="image_10.png" /></figure>

<figure><img src="image_11.png" /><figcaption>**Fig. 5** A Posterior distributions of the mean z-score per group to the neuropsychological tests used in the rmANOVA. BF₁₀ results are from the post-hoc *t* test on the group factor against the healthy subject group. Error bars represent 95% confidence intervals. B Mean z-scores per group per neuropsychological subtests used in the rmANOVA. FCSRT 3 Total Recall (3TR), literal fluencies (Lit.), semantic fluencies (Sem.), DMS48 (set 2), D2 (GZ-F), digit-symbol</figcaption></figure>

(Digit), Stroop (interferences minus denomination). C Boxplots of the FCSRT 3 Total Recall, Stroop (I–D), Semantic fluency and Confrontation naming test by groups. BF₁₀ results are from an ANOVA followed by a post-hoc *t* test. A black *x* indicates a lesion to the mammillothalamic tract and a “B” indicates a bilateral thalamic lesion. Groups: Healthy subjects (n=42), Intact IA (n=18), Damaged IA (n=12), Absent IA (n=10)
Discussion

In this study, the IA was absent in 24% of the subjects. Women had a higher prevalence of IA (92%) compared to men (61%) while no effect of age was evidenced. These results are in line with the previous existing literature [4, 6, 7, 9, 12, 15, 17]. We also observed several IA variants from the most typical to the most unusual (Fig. 3) although these variants are usually not studied. In this context, the IA appears an intriguing brain structure since the reasons for such an overall variability are unclear.

Another mystery relates to the functional role of the IA. The literature is very scarce regarding any contribution to cognition which appears to contradict recent findings that the IA may be a white matter tract [12, 47]. In our study, the presence or absence of an IA had no significant effect on the performance across all neuropsychological tests in healthy subjects. An interpretation of these results suggests that the IA plays no part or only has a marginal significance in cognition among the healthy population. This position can be supported by the idea that 20–25% of the population do not have an IA, implying that it is not necessary for any critical cognitive function. It is worth mentioning however that the role of several nuclei in the thalamus such as the mediodorsal nucleus are in fact poorly understood [48]. Another interpretation is therefore that without a suitable theory about the role of the IA, we did not use the appropriate tests to assess its contribution.

Given this situation, we aimed to test the role of the IA in patients with isolated thalamic strokes. We thought that the presence of an IA could be a protective factor against cognitive impairment through post-stroke functional reorganization. In contrast, we hypothesized that patients *without* an IA would show the most severe impairment. The results of this study confirm these predictions as the group of patients *with* an IA was the least severely impaired compared to the group of healthy subjects while the group of patients *without* an IA was the performed the most poorly during the general analysis on all tests combined (Fig. 5A). The group of patients *with* an IA and a lesion extending in it showed an intermediary profile of cognitive impairment between the two other groups of patients.

Follow-up analyses on the neuropsychological tests showed that patient performance was not affected on all tests. This was expected as not all the tests are sensitive enough to be impaired by thalamic lesions. Tests that were more impacted were those with a strong verbal component (the verbal memory task FCSRT, semantic fluency and confrontation naming) in accordance with patient lesion placements which were mostly left-sided (28 left, 6 right, 6 bilateral) and the known role of the left thalamus in lexical selection [49]. Patients also produced poor results on

the Stroop test which strongly depends on the frontal lobes. This also appears to tally with the overall pattern of patient lesions which mainly encompassed the mediodorsal but also ventrolateral thalamus [48].

The patients *without* an IA performed worse than the patients *with* an IA compared to the group of healthy subjects on both the verbal memory task and the Stroop test. Focusing on the verbal memory task, where the largest differences were observed, we obtained similar results (though with lower $BF_{10}$) after removing outliers, or patients with mammillothalamic tract lesions, which are known to impair memory. Assessing the semantic fluency task, the reverse trend was observed (patients *with* an IA were more impaired than patients without an IA compared to healthy subjects) but for much lower $BF_{10}$ differences. Importantly, these effects could not be accounted for by age, laterality of the infarct, nor volume of the lesion. Strengthening these results, the location of lesions was similarly distributed in the different nuclear groups among the three groups of patients (cf. 3.1 Neuroimaging Analyses). This enables us to mitigate the neuropsychological impacts of lesions in specific thalamic nuclei when interpreting these results. In addition, we did not find evidence of disparities between the groups in terms of anxiety or depression that could explain the results.

The case of thalamic lesions extending into the IA is more ambiguous. A similar trend of deficits than patients *without* an IA was observed in patients with a lesioned IA but could be due to larger lesions or a higher prevalence of concomitant lesions to the mammillothalamic tract. Additionally, it is possible that complete disruption of the IA is necessary to induce deficits as a partial lesion may preserve some fibers and allow potential compensation by the opposite thalamus. Moreover, variations in IA anatomy may affect connectivity: a broad variant may support robust connectivity while standard and double variants may have thinner connections, limiting the number of crossing fibers [26].

The absence of an IA could thus be a prognosis of poor neuropsychological outcomes following thalamic strokes. These findings also lead to the hypothesis that the IA may play a role in compensatory mechanisms rather than having a specific part in cognition. In the absence of an IA, the cognitive circuits in healthy subjects otherwise depending on this structure may be supported by other midline structures such as the anterior and posterior commissures or the corpus callosum, potentially explaining the absence of neuropsychological differences between healthy subjects with and without an IA. However, in the case of a thalamic lesion, IA-related circuitry may become important to support compensatory mechanisms, resulting in the lower neuropsychological deficits observed in patients with a preserved IA. If confirmed, accurate identification of the IA could be crucial. It would become especially important for microsurgical and endoscopic approaches to the third ventricle and pineal
region. For instance, in the microsurgical resection of tumors in the third ventricle, preserving the IA could minimize the risk of neuropsychological deficits.

Overall, these results require further exploration and extensive research on patients with isolated thalamic strokes. More specifically, clinical studies from the acute phase along with functional imaging could give some insights about eventual compensatory mechanisms leveraging the IA after a stroke. A limitation of our finding is that we did not actually find evidence in favor of differences between the groups of patients using the Bayesian analyses we conducted. This can be interpreted as resulting from a lack of power since the number of patients without an IA was rather low (n = 10 patients). A thalamic stroke is a rare event, an absent IA represents a minority of the population and strokes affecting the IA are even rarer. Despite those limitations, by combining two different studies conducted in our laboratory, we gathered one of the largest cohorts concerning chronic isolated thalamic infarcts associated with neuropsychological assessment. In addition, the variability of such neuropsychological investigations, due to various factors even if we tried to control them, such as age, educational level, concomitant mammillothalamic tract lesions, IA anatomical variants, exact location of lesions and volume of the lesion, increase the levels of variance that can only be fulfilled by larger groups of subjects. Finally, the IA is a little structure, hard to identify on structural MRI commonly acquired in clinical routine. There is little literature on its connectivity or cognitive functions, which makes it difficult to test solid hypotheses.

In general, the wide variation observed in the literature regarding the size, prevalence, function and connectivity of the IA could be attributed to the lack of standardization in MRI procedures. These discrepancies encompass differences in MRI acquisition parameters. For instance, thicker slices, poor resolution especially in DTI images and inter-slice gaps are all factors that can result in missing a narrow IA and lead to a higher rate of IA absence [24]. Results about the IA incidence using MRI can also contrast with postmortem findings because of the inherent tissue processing that could lead to an IA rupture, artificially decreasing its prevalence [17, 24, 50]. The protocol designed for this study aims to establish an initial standardized MRI protocol for the IA investigations, serving as a foundational framework for further enhancement.

In this study, we explored the role of the interthalamic adhesion (IA) in cognition, particularly in the context of thalamic strokes. Our results indicate that the presence of an IA may serve as a protective factor against cognitive impairments post-stroke, potentially due to its involvement

in compensatory mechanisms. Patients with an IA showed less severe cognitive impairments compared to those without an IA, supporting our hypothesis that the IA may contribute to cognitive resilience. Furthermore, our findings emphasize the importance of accurate IA identification in clinical settings, as it could inform surgical strategies to minimize neuropsychological deficits. This work provides a framework for future research on the IA's role in human cognition.

**Supplementary Information** The online version contains supplementary material available at https://doi.org/10.1007/s00415-024-12566-z.

**Acknowledgements** We would like to thank Hélène Gros, Nathalie Vayssière and the MRI Research Center for their help in MRI acquisition.

**Funding** Open access funding provided by Université Toulouse III - Paul Sabatier.

## Declarations

**Conflicts of interest** The authors have no conflicts of interest relevant to this manuscript to disclose.

**Ethical standard** Patients from two studies were included in order to increase the sample size. The first study was approved by the Institutional Review Board “Comité de Protection des Personnes Sud-Ouest et Outre-Mer no. 2-11-0”. It included 20 patients with a thalamic stroke, younger than 80 years. Marginal extra-thalamic lesions were accepted in this study (this concerned three patients reported in [30] with small lesions extending in surrounding structures of the thalamus). The second study was authorized by the “Comité de Protection des Personnes Ile-de-France IV” (Ethics Committee).

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