LSD-induced changes in the functional connectivity of distinct thalamic nuclei.

The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD intake alters the thalamocortical coupling in a nucleus-specific manner. Structural and resting-state functional Magnetic Resonance Imaging (MRI) data were acquired in a placebo-controlled study on subjects exposed to acute LSD administration. Structural MRI was used to parcel the thalamus into its constituent nuclei based on individual anatomy. Nucleus-specific changes of resting-state functional MRI (rs-fMRI) connectivity were mapped using a seed-based approach. LSD intake selectively increased the thalamocortical functional connectivity (FC) of the ventral complex, pulvinar, and non-specific nuclei. Functional coupling was increased between these nuclei and sensory cortices that include the somatosensory and auditory networks. The ventral and pulvinar nuclei also exhibited increased FC with parts of the associative cortex that are dense in serotonin type 2A receptors. These areas are hyperactive and hyper-connected upon LSD intake. At subcortical levels, LSD increased the functional coupling among the thalamus's ventral, pulvinar, and non-specific nuclei, but decreased the striatal-thalamic connectivity. These findings unravel some LSD effects on the modulation of subcortical-cortical circuits and associated behavioral outputs.

Cerebral blood flow patterns in preterm and term neonates assessed with pseudo-continuous arterial spin labeling perfusion MRI.

In preterm (PT) infants, regional cerebral blood flow (CBF) disturbances may predispose to abnormal brain maturation even without overt brain injury. Therefore, it would be informative to determine the spatial distribution of grey matter (GM) CBF in PT and full-term (FT) newborns at term-equivalent age (TEA) and to assess the relationship between the features of the CBF pattern and both prematurity and prematurity-related brain lesions. In this prospective study, we obtained measures of CBF in 66 PT (51 without and 15 with prematurity-related brain lesions) and 38 FT newborns through pseudo-continuous arterial spin labeling (pCASL) MRI acquired at TEA. The pattern of GM CBF was characterized by combining an atlas-based automated segmentation of structural MRI with spatial normalization and hierarchical clustering. The effects of gestational age (GA) at birth and brain injury on the CBF pattern were investigated. We identified 4 physiologically-derived clusters of brain regions that were labeled Fronto-Temporal, Parieto-Occipital, Insular-Deep GM (DGM) and Sensorimotor, from the least to the most perfused. We demonstrated that GM perfusion was associated with GA at birth in the Fronto-Temporal and Sensorimotor clusters, positively and negatively, respectively. Moreover, the presence of periventricular leukomalacia was associated with significantly increased Fronto-Temporal GM perfusion and decreased Insular-DGM perfusion, while the presence of germinal matrix hemorrhage appeared to mildly decrease the Insular-DGM perfusion. Prematurity and prematurity-related brain injury heterogeneously affect brain perfusion. ASL MRI may, therefore, have strong potential as a noninvasive tool for the accurate stratification of individuals at risk of domain-specific impairment.

Effects of a narrative template on memory for the time of movie scenes: automatic reshaping is independent of consolidation.

Memory for time is influenced by reconstructive processes, but the underlying mechanisms remain unclear. The present study investigated whether the effect of schematic prior knowledge on temporal memory for movie scenes, produced by the incomplete presentation (cut) of the movie at encoding, is modulated by cut position, retention interval, and task repetition. In a timeline positioning task, participants were asked to indicate when short video clips extracted from a previously encoded movie occurred on a horizontal timeline that represented the video duration. In line with previous findings, removing the final part of the movie resulted in a systematic underestimation of clips' position as a function of their proximity to the missing part. Further experiments demonstrate that the direction of this automatic effect depends on which part of the movie is deleted from the encoding session, consistent with the inferential structure of the schema, and does not depend on consolidation nor reconsolidation processes, at least within the present experimental conditions. We propose that the observed bias depends on the automatic influence of reconstructive processes on judgments about the time of occurrence, based on prior schematic knowledge.

Long-term memory for movie details: selective decay for verbal information at one week.

Mnemonic representations of complex events are multidimensional, incorporating information about objects and characters, their interactions and their spatial-temporal context. The present study investigated the degree to which detailed verbal information (i.e., dialogues), as well as semantic and spatiotemporal (i.e., "what", "where", and "when") elements of episodic memories for movies, are forgotten over the course of a week. Moreover, we tested whether the amount of dimension-specific forgetting differed as a function of the participant's age. In a mixed design, younger and middle-aged participants were asked to watch a ∼90 min movie and provide yes/no answers to detailed questions about different dimensions of the presented material after 1, 3 days, and 1 week. The results indicate that memory decay mainly affects the verbal dimension, both in terms of response accuracy and confidence. Instead, detailed information about objects/characters' features and spatiotemporal context seems to be relatively preserved, despite a general decrease in response confidence. Furthermore, younger adults were in general more accurate and confident than middle-aged participants, although, again, the verbal dimension exhibited a significant age-related difference. We propose that this selective forgetting depends on the progressive advantage of visual compared to auditory/verbal information in memory for complex events.

The effect of different brain lesions on the reorganization of language functions within the dominant hemisphere assessed with task-based BOLD-fMRI.

BACKGROUND AND PURPOSE: Language reorganization has been described in brain lesions with respect to their location and timing, but little is known with respect to their etiology. We used fMRI to investigate the effects of different types of left hemisphere lesions (GL = gliomas, TLE = temporal lobe epilepsy and CA = cavernous angioma) on the topographic intra-hemispheric language plasticity, also considering their location. METHODS: Forty-seven right-handed patients with 3 different left hemisphere lesions (16 GL, 15 TLE and 16 CA) and 17 healthy controls underwent BOLD fMRI with a verb-generation task. Euclidean distance was used to measure activation peak shifts among groups with respect to reference Tailarach coordinates of Inferior Frontal Gyrus, Superior Temporal Sulcus and Temporo-Parietal Junction. Mixed-model ANOVAs were used to test for differences in activation peak shifts. RESULTS: Significant activation peak shifts were found in GL patients with respect both to HC and other groups (TLA and CA). In addition, in the same group of patients a significant effect of tumor location (anterior or posterior) was detected. CONCLUSIONS: We demonstrated that intra-hemispheric language plasticity is influenced by the type of lesion affecting the left hemisphere and that fMRI is especially valuable in the preoperative assessment of such reorganization in glioma patients.

Alpha rhythm modulations in the intraparietal sulcus reflect decision signals during item recognition.

Theoretical work and empirical observations suggest a contribution of regions along the intraparietal sulcus to the process of evidence accumulation during episodic memory retrieval. In the present study, we recorded magnetoencephalographic signals in a group of healthy human participants to test whether the pattern of oscillatory modulations in the lateral parietal lobe is consistent with the mnemonic accumulator hypothesis. To this aim, the dynamic properties and the spatial distribution of MEG oscillatory power modulations were investigated during an item recognition task in which the amount of evidence for old vs. new memory decisions was manipulated across three levels. A data-driven approach was employed to identify brain nodes where oscillatory activity was sensitive to both retrieval success and the amount of evidence for old decisions. The analysis identified three nodes in the left lateral parietal lobe where the event-related desynchronization (ERD) in the alpha frequency band showed both effects. Further analyses revealed that the alpha ERD in the intraparietal sulcus, but not in other parietal nodes: i. showed modulation of duration in response to the amount of evidence for both old and new decisions, ii. was behaviorally significant, and iii. more accurately tracked the subjective memory judgment rather than the objective memory status. The present findings provide support for a recent anatomical-functional model of the parietal involvement in episodic memory retrieval and suggest that the alpha ERD in the intraparietal sulcus might represent a neural signature of the evidence accumulation process during simple memory-based decisions.

The contribution of the human posterior parietal cortex to episodic memory.

The posterior parietal cortex (PPC) is traditionally associated with attention, perceptual decision making and sensorimotor transformations, but more recent human neuroimaging studies support an additional role in episodic memory retrieval. In this Opinion article, we present a functional-anatomical model of the involvement of the PPC in memory retrieval. Parietal regions involved in perceptual attention and episodic memory are largely segregated and often show a push-pull relationship, potentially mediated by prefrontal regions. Moreover, different PPC regions carry out specific functions during retrieval - for example, representing retrieved information, recoding this information based on task demands, or accumulating evidence for memory decisions.

Altered Medial Prefrontal Connectivity in Parkinson's Disease Patients with Somatic Symptoms.

BACKGROUND: The high co-occurrence of somatic symptom disorder (SSD) in Parkinson's disease (PD) patients suggests overlapping pathophysiology. However, little is known about the neural correlates of SSD and their possible interactions with PD. Existing studies have shown that SSD is associated with reduced task-evoked activity in the medial prefrontal cortex (mPFC), a central node of the default-mode network (DMN). SSD is also associated with abnormal γ-aminobutyric acid (GABA) content, a marker of local inhibitory tone and regional hypoactivity, in the same area when SSD co-occurs with PD. OBJECTIVES: To disentangle the individual and shared effects of SSD and PD on mPFC neurotransmission and connectivity patterns and help disclose the neural mechanisms of comorbidity in the PD population. METHODS: The study cohort included 18 PD patients with SSD (PD + SSD), 18 PD patients, 13 SSD patients who did not exhibit neurologic disorders, and 17 healthy subjects (HC). Proton magnetic resonance (MR) spectroscopy evaluated GABA levels within a volume of interest centered on the mPFC. Resting-state functional MR imaging investigated the region's functional connectivity patterns. RESULTS: Compared to HC or PD groups, the mPFC of SSD subjects exhibited higher GABA levels and connectivity. Higher mPFC connectivity involved DMN regions in SSD patients without PD and regions of the executive and attentional networks (EAN) in patients with PD comorbidity. CONCLUSIONS: Aberrant reconfigurations of connectivity patterns between the mPFC and the EAN are distinct features of the PD + SSD comorbidity. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Spectral signature of attentional reorienting in the human brain.

As we move in the environment, attention shifts to novel objects of interest based on either their sensory salience or behavioral value (reorienting). This study measures with magnetoencephalography (MEG) different properties (amplitude, onset-to-peak duration) of event-related desynchronization/synchronization (ERD/ERS) of oscillatory activity during a visuospatial attention task designed to separate activity related to reorienting vs. maintaining attention to the same location, controlling for target detection and response processes. The oscillatory activity was measured both in fMRI-defined regions of interest (ROIs) of the dorsal attention (DAN) and visual (VIS) networks, previously defined as task-relevant in the same subjects, or whole-brain in a pre-defined set of cortical ROIs encompassing the main brain networks. Reorienting attention (shift cues) as compared to maintaining attention (stay cues) produced a temporal sequence of ERD/ERS modulations at multiple frequencies in specific anatomical regions/networks. An early (∼330 ms), stronger, transient theta ERS occurred in task-relevant (DAN, VIS) and control networks (VAN, CON, FPN), possibly reflecting an alert/reset signal in response to the cue. A more sustained, behaviorally relevant, low-beta band ERD peaking ∼450 ms following shift cues (∼410 for stay cues) localized in frontal and parietal regions of the DAN. This modulation is consistent with a control signal re-routing information across visual hemifields. Contralateral vs. ipsilateral shift cues produced in occipital visual regions a stronger, sustained alpha ERD (peak ∼470 ms) and a longer, transient high beta/gamma ERS (peak ∼490 ms) related to preparatory visual modulations in advance of target occurrence. This is the first description of a cascade of oscillatory processes during attentional reorienting in specific anatomical regions and networks. Among these processes, a behaviorally relevant beta desynchronization in the FEF is likely associated with the control of attention shifts.

Multi-band MEG signatures of BOLD connectivity reorganization during visuospatial attention.

The functional architecture of the resting brain, as measured with the blood oxygenation level-dependent functional connectivity (BOLD-FC), is slightly modified during task performance. In previous work, we reported behaviorally relevant BOLD-FC modulations between visual and dorsal attention regions when subjects performed a visuospatial attention task as compared to central fixation (Spadone et al., 2015). Here we use magnetoencephalography (MEG) in the same group of subjects to identify the electrophysiological correlates of the BOLD-FC modulation found in our previous work. While BOLD-FC topography, separately at rest and during visual attention, corresponded to neuromagnetic Band-Limited Power (BLP) correlation in the alpha and beta bands (8-30 Hz), BOLD-FC modulations evoked by performing the visual attention task (Spadone et al. 2015) did not match any specific oscillatory band BLP modulation. Conversely, following the application of an orthogonal spatial decomposition that identifies common inter-subject co-variations, we found that attention-rest BOLD-FC modulations were recapitulated by multi-spectral BLP-FC components. Notably, individual variability of alpha connectivity between Frontal Eye Fields and visual occipital regions, jointly with decreased interaction in the Visual network, correlated with visual discrimination accuracy. In summary, task-rest BOLD connectivity modulations match multi-spectral MEG BLP connectivity.

Distinct effects of prematurity on MRI metrics of brain functional connectivity, activity, and structure: Univariate and multivariate analyses.

Premature birth affects the developmental trajectory of the brain during a period of intense maturation with possible lifelong consequences. To better understand the effect of prematurity on brain structure and function, we performed blood-oxygen-level dependent (BOLD) and anatomical magnetic resonance imaging (MRI) at 40 weeks of postmenstrual age on 88 newborns with variable gestational age (GA) at birth and no evident radiological alterations. We extracted measures of resting-state functional connectivity and activity in a set of 90 cortical and subcortical brain regions through the evaluation of BOLD correlations between regions and of fractional amplitude of low-frequency fluctuation (fALFF) within regions, respectively. Anatomical information was acquired through the assessment of regional volumes. We performed univariate analyses on each metric to examine the association with GA at birth, the spatial distribution of the effects, and the consistency across metrics. Moreover, a data-driven multivariate analysis (i.e., Machine Learning) framework exploited the high dimensionality of the data to assess the sensitivity of each metric to the effect of premature birth. Prematurity was associated with bidirectional alterations of functional connectivity and regional volume and, to a lesser extent, of fALFF. Notably, the effects of prematurity on functional connectivity were spatially diffuse, mainly within cortical regions, whereas effects on regional volume and fALFF were more focal, involving subcortical structures. While the two analytical approaches delivered consistent results, the multivariate analysis was more sensitive in capturing the complex pattern of prematurity effects. Future studies might apply multivariate frameworks to identify premature infants at risk of a negative neurodevelopmental outcome.

Choice-predictive activity in parietal cortex during source memory decisions.

Neurobiological research has classically focused on perceptual decision-making, although many real-life decisions are based on information that is not currently available but stored in long-term memory. Previous studies have suggested that the lateral parietal cortex encodes decision-related signals during item recognition judgments. In the present fMRI study, we employed a parametric manipulation of evidence for source memory judgments and tested several hypotheses concerning memory decision signals in parietal cortex. As expected, the mean BOLD signal in several parietal regions was modulated by decision evidence. An analysis of the locally distributed pattern of activity, moreover, identified a parietal cluster showing significant choice-predictive activity even at the lowest level of decision evidence, with decoding accuracy that increased as a function of evidence. Decoding patterns were consistent across subjects as shown by a leave-one-subject-out classification analysis. Finally, we found that the pattern of choice-predictive activity in parietal lobe was temporally correlated with that observed in medial temporal regions traditionally associated with long-term memory functions. The present findings are consistent with a general role of lateral parietal regions located around the intraparietal sulcus in representing a decision variable for memory-based decisions.

Task and Regions Specific Top-Down Modulation of Alpha Rhythms in Parietal Cortex.

Alpha (8-12 Hz) power desynchronization is strongly associated to visual perception but has been observed in a large variety of tasks, indicating a general role in task anticipation. We previously reported in human observers that interference by repetitive transcranial magnetic stimulation (rTMS) of core regions of the dorsal attention network (DAN) disrupts both anticipatory alpha desynchronization and performance during a visuospatial attention (VSA) task. Here, we test the hypothesis that alpha desynchronization is task specific, and can be selectively modulated by interfering with activity in different higher-order parietal regions. We contrast the effects of rTMS on alpha rhythms and behavior on 2 different tasks: a VSA and a semantic decision task, by targeting the posterior intraparietal sulcus (pIPS), a core region of the DAN, or the angular gyrus (AG), a core region of the default mode network (DMN). We found that both performance and anticipatory alpha desynchronization were affected by stimulation of IPS only during VSA, and of AG only during semantic decisions. These findings indicate the existence of multiple dedicated parietal channels for the modulation of anticipatory alpha rhythms, which in turn reflect task-specific modulation of excitability in human parieto-occipital cortex.

Dynamic reorganization of human resting-state networks during visuospatial attention.

Fundamental problems in neuroscience today are understanding how patterns of ongoing spontaneous activity are modified by task performance and whether/how these intrinsic patterns influence task-evoked activation and behavior. We examined these questions by comparing instantaneous functional connectivity (IFC) and directed functional connectivity (DFC) changes in two networks that are strongly correlated and segregated at rest: the visual (VIS) network and the dorsal attention network (DAN). We measured how IFC and DFC during a visuospatial attention task, which requires dynamic selective rerouting of visual information across hemispheres, changed with respect to rest. During the attention task, the two networks remained relatively segregated, and their general pattern of within-network correlation was maintained. However, attention induced a decrease of correlation in the VIS network and an increase of the DAN→VIS IFC and DFC, especially in a top-down direction. In contrast, within the DAN, IFC was not modified by attention, whereas DFC was enhanced. Importantly, IFC modulations were behaviorally relevant. We conclude that a stable backbone of within-network functional connectivity topography remains in place when transitioning between resting wakefulness and attention selection. However, relative decrease of correlation of ongoing "idling" activity in visual cortex and synchronization between frontoparietal and visual cortex were behaviorally relevant, indicating that modulations of resting activity patterns are important for task performance. Higher order resting connectivity in the DAN was relatively unaffected during attention, potentially indicating a role for simultaneous ongoing activity as a "prior" for attention selection.

Dynamics of EEG rhythms support distinct visual selection mechanisms in parietal cortex: a simultaneous transcranial magnetic stimulation and EEG study.

Using repetitive transcranial magnetic stimulation (rTMS), we have recently shown a functional anatomical distinction in human parietal cortex between regions involved in maintaining attention to a location [ventral intraparietal sulcus (vIPS)] and a region involved in shifting attention between locations [medial superior parietal lobule (mSPL)]. In particular, while rTMS interference over vIPS impaired target discrimination at contralateral attended locations, interference over mSPL affected performance following shifts of attention regardless of the visual field (Capotosto et al., 2013). Here, using rTMS interference in conjunction with EEG recordings of brain rhythms during the presentation of cues that indicate to either shift or maintain spatial attention, we tested whether this functional anatomical segregation involves different mechanisms of rhythm synchronization. The transient inactivation of vIPS reduced the amplitude of the expected parieto-occipital low-α (8-10 Hz) desynchronization contralateral to the cued location. Conversely, the transient inactivation of mSPL, compared with vIPS, reduced the high-α (10-12 Hz) desynchronization induced by shifting attention into both visual fields. Furthermore, rTMS induced a frequency-specific delay of task-related modulation of brain rhythms. Specifically, rTMS over vIPS or mSPL during maintenance (stay cues) or shifting (shift cues) of spatial attention, respectively, caused a delay of α parieto-occipital desynchronization. Moreover, rTMS over vIPS during stay cues caused a delay of δ (2-4 Hz) frontocentral synchronization. These findings further support the anatomo-functional subdivision of the dorsal attention network in subsystems devoted to shifting or maintaining covert visuospatial attention and indicate that these mechanisms operate in different frequency channels linking frontal to parieto-occipital visual regions.

Hyperconnectivity of the dorsolateral prefrontal cortex following mental effort in multiple sclerosis patients with cognitive fatigue.

OBJECTIVE: To investigate the dynamic temporal changes of brain resting-state functional connectivity (RS-FC) following mental effort in multiple sclerosis (MS) patients with cognitive fatigue (CF). METHODS: Twenty-two MS patients, 11 with (F) and 11 without CF, and 12 healthy controls were included. Separate RS-FC scans were acquired on a 3T MR scanner immediately before (t0), immediately after (t1) and 30 minutes after (t2) execution of the paced auditory serial addition test (PASAT), a cognitively demanding task. Subjectively perceived CF after PASAT execution was also assessed. RS-FC changes were investigated by using a data-driven approach (the Intrinsic Connectivity Contrast-power), complemented by a priori defined regions of interest analyses. RESULTS: The F-group patients experienced stronger RS-FC at t2 between the left superior frontal gyrus (L-SFG) and occipital, frontal and temporal areas, which increased over time after PASAT execution. In the F-group patients, the L-SFG was hyperconnected at t1 with the left caudate nucleus and hypoconnected at t2 with the left anterior thalamus. These variations were correlated with both subjectively perceived and clinically assessed CF, and-for the left thalamus-with PASAT performance. CONCLUSION: The development of cortico-cortical and cortico-subcortical hyperconnectivity following mental effort is related to CF symptoms in MS patients.

Memory accumulation mechanisms in human cortex are independent of motor intentions.

Previous studies on perceptual decision-making have often emphasized a tight link between decisions and motor intentions. Human decisions, however, also depend on memories or experiences that are not closely tied to specific motor responses. Recent neuroimaging findings have suggested that, during episodic retrieval, parietal activity reflects the accumulation of evidence for memory decisions. It is currently unknown, however, whether these evidence accumulation signals are functionally linked to signals for motor intentions coded in frontoparietal regions and whether activity in the putative memory accumulator tracks the amount of evidence for only previous experience, as reflected in "old" reports, or for both old and new decisions, as reflected in the accuracy of memory judgments. Here, human participants used saccadic-eye and hand-pointing movements to report recognition judgments on pictures defined by different degrees of evidence for old or new decisions. A set of cortical regions, including the middle intraparietal sulcus, showed a monotonic variation of the fMRI BOLD signal that scaled with perceived memory strength (older > newer), compatible with an asymmetrical memory accumulator. Another set, including the hippocampus and the angular gyrus, showed a nonmonotonic response profile tracking memory accuracy (higher > lower evidence), compatible with a symmetrical accumulator. In contrast, eye and hand effector-specific regions in frontoparietal cortex tracked motor intentions but were not modulated by the amount of evidence for the effector outcome. We conclude that item recognition decisions are supported by a combination of symmetrical and asymmetrical accumulation signals largely segregated from motor intentions.

Anatomical segregation of visual selection mechanisms in human parietal cortex.

Visual selection requires mechanisms for representing object salience and for shifting the focus of processing to novel objects. It is not clear from computational or neural models whether these operations are performed within the same or different brain regions. Here, we use repetitive transcranial magnetic stimulation to briefly interfere with neural activity in individually localized regions of human posterior parietal cortex (PPC) that are putatively involved in attending to contralateral locations or shifting attention between locations. Stimulation over right ventral intraparietal sulcus impaired target discrimination at contralateral locations, whereas stimulation over right medial superior parietal lobule impaired target discrimination after a shift of attention regardless of its location. This double dissociation is consistent with neuroimaging studies and indicates that mechanisms of visual selection are partly anatomically segregated in human PPC.

Domain-general signals in the cingulo-opercular network for visuospatial attention and episodic memory.

We investigated the functional properties of a previously described cingulo-opercular network (CON) putatively involved in cognitive control. Analyses of common fMRI task-evoked activity during perceptual and episodic memory search tasks that differently recruited the dorsal attention (DAN) and default mode network (DMN) established the generality of this network. Regions within the CON (anterior insula/frontal operculum and anterior cingulate/presupplementary cortex) displayed sustained signals during extended periods in which participants searched for behaviorally relevant information in a dynamically changing environment or from episodic memory in the absence of sensory stimulation. The CON was activated during all phases of both tasks, which involved trial initiation, target detection, decision, and response, indicating its consistent involvement in a broad range of cognitive processes. Functional connectivity analyses showed that the CON flexibly linked with the DAN or DMN regions during perceptual or memory search, respectively. Aside from the CON, only a limited number of regions, including the lateral pFC, showed evidence of domain-general sustained activity, although in some cases the common activations may have reflected the functional-anatomical variability of domain-specific regions rather than a true domain generality. These additional regions also showed task-dependent functional connectivity with the DMN and DAN, suggesting that this feature is not a specific marker of cognitive control. Finally, multivariate clustering analyses separated the CON from other frontoparietal regions previously associated with cognitive control, indicating a unique fingerprint. We conclude that the CON's functional properties and interactions with other brain regions support a broad role in cognition, consistent with its characterization as a task control network.

The role of interoceptive awareness in shaping the relationship between desire thinking and cigarette consumption.

Interoception, the ability to sense and interpret bodily sensations, has recently emerged as a crucial factor in substance use disorders, including smoking. However, the role of interoceptive awareness in tobacco use remains poorly understood. The relationship between interoceptive ability and addictive behavior is complex, and attempting to conceptualize it as a linear association is unlikely to fully capture the complexity of the mechanisms underlying cravings and urges. We hypothesized that the role played by interoceptive awareness in tobacco use is deeply linked to desire thinking, that is, the conscious and voluntary cognitive process orienting to prefigure images, information, and memories about positive target-related experiences. Desire thinking is typically observed in addiction, where it may contribute to interpreting specific bodily sensations, such as the perceived need for a cigarette. From this perspective, the physiological impact and inclination toward desire thinking contribute to a higher daily cigarette consumption, particularly in situations of low interoceptive awareness. To test this hypothesis, we assessed the physiological activation, the tendency toward desire thinking about smoking, cigarette consumption, and the interoceptive abilities of smoking volunteers. Through a moderation analysis, we showed that desire thinking about smoking predicts a higher number of cigarettes per day in individuals with lower interoceptive awareness (p < .05). These findings suggest that the relationship between desire thinking and interoceptive awareness is a fundamental component of tobacco use, highlighting the importance of taking into account the bodily feedback deriving from the cognitive representation of smoking in addiction research and therapy.