Different Effect Sizes of Motor Skill Training Combined with Repetitive Transcranial versus Trans-Spinal Magnetic Stimulation in Healthy Subjects.

Repetitive transcranial magnetic stimulation (rTMS) is used to enhance motor training (MT) performance. The use of rTMS is limited under certain conditions, such as after a stroke with severe damage to the corticospinal tract. This raises the question as to whether repetitive trans-spinal magnetic stimulation (rSMS) can also be used to improve MT. A direct comparison of the effect size between rTMS and rSMS on the same MT is still lacking. Before conducting the study in patients, we determined the effect sizes of different stimulation approaches combined with the same motor training in healthy subjects. Two experiments (E1 and E2) with 96 subjects investigated the effect size of combining magnetic stimulation with the same MT. In E1, high-frequency rTMS, rSMS, and spinal sham stimulation (sham-spinal) were applied once in combination with MT, while one group only received the same MT (without stimulation). In E2, rTMS, rSMS, and sham-spinal were applied in combination with MT over several days. In all subjects, motor tests and motor-evoked potentials were evaluated before and after the intervention period. rTMS had the greatest effect on MT, followed by rSMS and then sham-spinal. Daily stimulation resulted in additional training gains. This study suggests that rSMS increases excitability and also enhances MT performance. This current study provides a basis for further research to discover whether patients who cannot be treated effectively with rTMS would benefit from rSMS.

Understanding the concept of a novel tool requires interaction of the dorsal and ventral streams.

The left hemisphere tool-use network consists of the dorso-dorsal, ventro-dorsal, and ventral streams, each with distinct computational abilities. In the dual-loop model, the ventral pathway through the extreme capsule is associated with conceptual understanding. We performed a learning experiment with fMRI to investigate how these streams interact when confronted with novel tools. In session one, subjects observed pictures and video sequences in real world action of known and unknown tools and were asked whether they knew the tools and whether they understood their function. In session two, video sequences of unknown tools were presented again, followed again by the question of understanding their function. Different conditions were compared to each other and effective connectivity (EC) in the tool-use network was examined. During concept acquisition of an unknown tool, EC between dorsal and ventral streams was found posterior in fusiform gyrus and anterior in inferior frontal gyrus, with a functional interaction between BA44d and BA45. When previously unknown tools were presented for a second time, EC was prominent only between dorsal stream areas. Understanding the concept of a novel tool requires an interaction of the ventral stream with the dorsal streams. Once the concept is acquired, dorsal stream areas are sufficient.

Accelerated brain ageing in sepsis survivors with cognitive long-term impairment.

In the last years, cognitive impairment was emphasized to be a prominent long-term sequelae of sepsis. The level of cognitive impairment is comparable with that in mild cognitive impairment (MCI) patients. Whether sepsis survivors also show a comparable brain atrophy is still unclear. For the analysis of brain atrophy, a novel method named brain age gap estimation (BrainAGE) was used. In this analysis approach, an algorithm identifies age-specific atrophy across the whole brain and calculates a BrainAGE score in years. In case of accelerated brain atrophy, the BrainAGE score is increased in comparison to the healthy age reference group, indicating a difference in estimated chronological age. 20 survivors of severe sepsis (longer than 2 years post sepsis) with persistent cognitive deficits were investigated with a battery of neuropsychological tests. Their MRI images were compared to an age- and sex-matched control group. Sepsis survivors showed a significant higher BrainAGE score of 4.5 years compared to healthy controls. We also found a close relationship between the BrainAGE score and severity of cognitive impairment (a higher BrainAGE score was associated with more severe cognitive impairment). Consequently, sepsis survivors with persistent cognitive impairment showed an accelerated brain ageing, which was closely associated with the severity of cognitive impairment (similar to MCI patients).

Anatomy of brain lesions after stroke predicts effectiveness of mirror therapy.

To improve clinical outcome, one longstanding goal in treating stroke patients has been an individual therapy based on functional and anatomical knowledge of the single patient. Therefore, in this study brain imaging of 36 chronic stroke patients was analyzed to identify parameters predicting clinical recovery. T1-weighted MRI was acquired to assess the lesion; functional MRI was used to visualize existing resources; DTI for the integrity of the corticospinal tract (CST) and long association tracts. These data were related to the clinical course. All patients were treated intensively with the mirror therapy (MT) only. After the training period, we analyzed which patient's feature would predict a beneficial course. Patients as a group improved after MT, but according to the fMRI activation of primary sensorimotor cortex (SMC), they could be divided in two groups with very diverging clinical outcome: those with ipsilesional SMC activation showed a noticeable increase of clinical scores, accompanied with ipsilesional activation in the frontal projection areas of the dorsal and ventral streams during action observation in fMRI. Those with contralesional SMC activation had lesions affecting both the dorsal and ventral stream and did not benefit from MT. The outcome for this therapy was not related to affection of CST. This study demonstrates that only in patients in which dorsal and ventral streams are not affected and therefore an interaction between these streams in post- and prerolandic regions is possible, MT can induce clinical improvement. Consequently, knowledge of the anatomical lesion can predict the beneficial course of MT.

[Optimized Transition from Inpatient Stroke Rehabilitation to Home Care - Current Practice and Analysis of Factors Influencing Transition]. / Optimierung der Überleitung von der stationären in die ambulante Gesundheitsversorgung nach Schlaganfall (OpTheraS).

OBJECTIVE: To identify factors influencing the current transition practice and to generate aspects to improve transition. METHODS: Expert interviews and group discussions with health care professionals; a scoping review and a standardized interview with stroke patients 6 weeks after discharge via telephone. RESULTS: 14 expert interviews and 3 group discussions (n=18) were conducted. Factors influencing transition at home were communication of professionals between and within settings, social support and role behavior of stroke patients. The interviews (n=110) revealed realization of recommendations towards consultations of medical specialists of 37%, and of outpatient therapies up to 86%. The scoping review included 7 systematic reviews, 21 randomised trials and 5 controlled trials to patient education, information and counselling, Early Supported Discharge models, stroke liaison services, team conferences and integrated care pathways. CONCLUSION: A structured approach is needed which has to consider the complexity of the transition process.

Facial motor and non-motor disabilities in patients with central facial paresis: a prospective cohort study.

Although central facial paresis (CFP) is a major symptom of stroke, there is a lack of studies on the motor and non-motor disabilities in stroke patients. A prospective cohort study was performed at admission for inpatient rehabilitation and discharge of post-stroke phase of 112 patients (44% female, median age: 64 years, median Barthel index: 70) with CFP. Motor function was evaluated using House-Brackmann grading, Sunnybrook grading and Stennert Index. Automated action unit (AU) analysis was performed to analyze mimic function in detail. Non-motor function was assessed using the Facial Disability Index (FDI) and the Facial Clinimetric Evaluation (FaCE). Median interval from stroke to rehabilitation was 21 days. Rehabilitation lasted 20 days. House-Brackmann grading was ≥ grade III for 79% at admission. AU activation in the lower face was significantly lower in patients with right hemispheric infarction compared to left hemispheric infarction (all p < 0.05). Median total FDI and FaCE score were 46.5 and 69, respectively. Facial grading and FDI/FaCE scores improved during inpatient rehabilitation (all p < 0.05). There was a significant increase of the activation of AU12 (Zygomaticus major muscle), AU13 (Levator anguli oris muscle), and AU24 (Orbicularis oris muscle) during inpatient rehabilitation (all p < 0.05). Multivariate analysis revealed that activation of AU10 (Levator labii superioris), AU12, AU17 (Depressor labii), and AU 38 (Nasalis) were independent predictors for better quality of life. These results demonstrate that CFP has a significant impact on patient's quality of life. Therapy of CFP with focus on specific AUs should be part of post-stroke rehabilitation.

Boosting the Motor Outcome of the Untrained Hand by Action Observation: Mirror Visual Feedback, Video Therapy, or Both Combined-What Is More Effective?

Action observation (AO) allows access to a network that processes visuomotor and sensorimotor inputs and is believed to be involved in observational learning of motor skills. We conducted three consecutive experiments to examine the boosting effect of AO on the motor outcome of the untrained hand by either mirror visual feedback (MVF), video therapy (VT), or a combination of both. In the first experiment, healthy participants trained either with MVF or without mirror feedback while in the second experiment, participants either trained with VT or observed animal videos. In the third experiment, participants first observed video clips that were followed by either training with MVF or training without mirror feedback. The outcomes for the untrained hand were quantified by scores from five motor tasks. The results demonstrated that MVF and VT significantly increase the motor performance of the untrained hand by the use of AO. We found that MVF was the most effective approach to increase the performance of the target effector. On the contrary, the combination of MVF and VT turns out to be less effective looking from clinical perspective. The gathered results suggest that action-related motor competence with the untrained hand is acquired by both mirror-based and video-based AO.

The Dual-Loop Model and the Human Mirror Neuron System: an Exploratory Combined fMRI and DTI Study of the Inferior Frontal Gyrus.

The inferior frontal gyrus (IFG) is active during both goal-directed action and while observing the same motor act, leading to the idea that also the meaning of a motor act (action understanding) is represented in this "mirror neuron system" (MNS). However, in the dual-loop model, based on dorsal and ventral visual streams, the MNS is thought to be a function of the dorsal steam, projecting to pars opercularis (BA44) of IFG, while recent studies suggest that conceptual meaning and semantic analysis are a function of ventral connections, projecting mainly to pars triangularis (BA45) of IFG. To resolve this discrepancy, we investigated action observation (AO) and imitation (IMI) using fMRI in a large group of subjects. A grasping task (GR) assessed the contribution from movement without AO. We analyzed connections of the MNS-related areas within IFG with postrolandic areas with the use of activation-based DTI. We found that action observation with imitation are mainly a function of the dorsal stream centered on dorsal part of BA44, but also involve BA45, which is dorsally and ventrally connected to the same postrolandic regions. The current finding suggests that BA45 is the crucial part where the MNS and the dual-loop system interact.

The ventral fiber pathway for pantomime of object use.

The current concept of a dual loop system of brain organization predicts a domain-general dual-pathway architecture involving dorsal and ventral fiber connections. We investigated if a similar dichotomy of brain network organization applies for pantomime (P) and imitation of meaningless gestures (I). Impairments of these tasks occur after left hemispheric brain lesions causing apraxia. Isolated impairments and double-dissociations point towards an anatomical segregation. Frontal and parietal areas seem to contribute differently. A special role of the inferior frontal gyrus and underlying fiber pathways was suggested recently. Using a combined fMRI/DTI-approach, we compared the fiber pathway architecture of left hemispheric frontal, temporal and parietal network components of pantomime and imitation. Thereby, we separated object effects from pantomime-specific effects. P and I both engage a fronto-temporo-parietal network of cortical areas interconnected by a dorsal fiber system (superior longitudinal fascicle) for direct sensory-motor interactions. The pantomime-specific effect additionally involved the triangular part of the inferior frontal gyrus, the middle temporal gyrus, the inferior parietal cortex and the intraparietal sulcus, interconnected by ventral fibers of the extreme capsule, likely related to higher-order conceptual and semantic operations. We discuss this finding in the context of the dual loop model and recent anatomical concepts.

Long-term sequelae of severe sepsis: cognitive impairment and structural brain alterations - an MRI study (LossCog MRI).

BACKGROUND: The number of patients with cognitive impairment after sepsis or septic shock is high. However, the underlying neurophysiological basis of sepsis induced cognitive impairment is not fully understood. METHODS/DESIGN: This is a prospective, controlled observational study. We are in the process of recruiting 25 survivors of severe sepsis or septic shock who will be investigated with functional MRI (fMRI), T1-weighted MRI und Diffusion Tensor Imaging (DTI) as well as Magnetoencephalography (MEG). Furthermore, patients will undergo neuropsychological evaluation using the DemTect and the clock drawing tests. In addition, verbal and declarative memory is assessed by the Verbal Learning and Memory Test. The primary aim is to determine the volumetry of the amygdala and the hippocampus. The secondary aim is to analyze the relationship between cognitive tests and MEG, and the (f)MRI results. Moreover, a between-group comparison will be evaluated to an age-matched group of healthy controls. DISCUSSION: In a previous MEG study, we observed a significant slowing of the prominent background activity in sepsis survivors and hepatic encephalopathy patients in particular shortly after discharge from the ICU. Intriguingly, the rhythmic brain activity after visual flickering stimulation was altered in sepsis survivors in comparison to age-matched healthy volunteers. We propose that this desynchronization is based on affected underlying neuronal responses between various interconnected brain regions. The current project will analyze whether the modifications are related to a damage of the fibers connecting different brain regions or to a disturbance of the functional interaction between different brain regions or even due to an atrophy of certain brain regions. TRIAL REGISTRATION: "Langzeitfolgen nach schwerer Sepsis: Kognitive Beeinträchtigungen und strukturelle Veränderungen am Gehirn, eine MRT Studie"; German Clinical Trials Register (DRKS00005484).

Action semantics and movement characteristics engage distinct processing streams during the observation of tool use.

The cortical motor system follows a modular organization in which different features of executed movements are supported by distinct streams. Accordingly, different levels of action recognition, such as movement characteristics or action semantics may be processed within distinct networks. The present study aimed to differentiate areas related to the analysis of action features involving semantic knowledge from regions concerned with the evaluation of movement characteristics determined by structural object properties. To this end, the assessment of (i) tool-associated actions in relation to semantically, but not functionally inappropriate recipients (factor "Semantics"), and the evaluation of (ii) tool-associated movements performed with awkward versus correct hand postures (factor "Hand") were experimentally manipulated in an fMRI study with an event-related 2 × 2 factorial design. The videos used as stimuli displayed actions performed with the right hand in third-person perspective. Conjunction analysis of all four experimental conditions showed that observing videos depicting tool-related actions compared to rest was associated with widespread bilateral activity within the frontal lobes, inferior and superior parietal lobules, parts of the temporal lobes, as well as the occipital lobes. Viewing actions executed with incorrect compared to correct hand postures (factor "Hand") elicited significantly more activity within right primary sensory cortex (Brodmann area 2) and superior parietal lobule. Conversely, tool-associated actions displayed after semantically incorrect compared to correct recipients elicited higher activation within a left-lateralized network comprising the ventro-lateral prefrontal cortex (VLPFC), parts of the intraparietal sulcus and the angular gyrus (AG), as well as the supplementary motor area (SMA) and pre-SMA. Probabilistic diffusion tensor imaging-based tractography revealed two distinct fiber connections between AG and the frontal activation: A dorsal pathway via the superior longitudinal fascicle to the caudal part of VLPFC and a ventral pathway reaching the more rostral parts of VLPFC via the extreme capsule. The task-dependent relative modulation of activity within these brain networks composed of activated cortical areas connected by specific white matter tracts may indicate that the assessment of semantic action features relies on both dorso-ventral and ventral processing streams, whereas the analysis of hand postures with respect to objects depends on areas within the dorso-dorsal stream.

Action imagery combined with action observation activates more corticomotor regions than action observation alone.

BACKGROUND AND PURPOSE: Both action observation (AO) and action imagery have been proposed as therapeutic options for stroke rehabilitation. Currently, it is not clear to what extent their underlying neuronal mechanisms differ from each other and whether one of these therapeutic options might be preferable for this purpose. METHODS: Twenty-six neurologically healthy subjects were investigated using functional magnetic resonance imaging during AO alone and during AO with additional action imagery of video clips showing simple, object-related hand actions. RESULTS: The blood oxygenation level dependent (BOLD) signal induced by AO increased in a bihemispheric, symmetrical network of areas including the occipital, superior, and inferior parietal cortex, dorsal and ventral premotor regions, and the prefrontal cortex. The addition of imagery to the AO elicited additional activation in both cerebellar hemispheres, caudate nucleus, ventral and dorsal premotor cortex, inferior parietal cortex, and the supplementary motor area. DISCUSSION AND CONCLUSION: These data reveal more profound activations of the motor system during AO in conjunction with imagery than during AO alone. These results may have important implications for neurorehabilitation and motor learning.

Ventral and dorsal fiber systems for imagined and executed movement.

Although motor imagery is an entirely cognitive process, it shows remarkable similarity to overt movement in behavioral and physiological studies. In concordance, brain imaging studies reported shared fronto-parietal sensorimotor networks commonly engaged by both tasks. However, differences in prefrontal and parietal regions point toward additional cognitive mechanisms in the context of imagery. Within the perspective of a general dichotomization into dorsal and ventral processing streams in the brain, the question arises whether motor imagery and overt movement could differentially involve the dorsal or ventral system. Therefore, we combined fMRI and DTI data of 20 healthy subjects to analyze the anatomical characteristics of connecting fronto-parietal association pathways of imagined and overt movements. We found a dichotomy of fiber pathways into dorsal and ventral systems: the superior longitudinal fascicle (SLF II-III) was found to connect frontal and parietal regions involved in both overt and imagined movements, whereas a ventral tract via the extreme/external capsule (EmC/EC) connects cortical regions specific for motor imagery that were situated more anteriorly and posteriorly. We suppose that motor imagery-related kinesthetic emulations are embedded into dorsal sensorimotor networks, and imagery-specific cognitive functions are implemented in the ventral system. These findings have implications for models of motor cognition.

Association of activity changes in the primary sensory cortex with successful motor rehabilitation of the hand following stroke.

BACKGROUND: Previous studies demonstrated a posterior shift of activation toward the primary sensory cortex (S1) following stroke; however, any relationship between this posterior shift and clinical outcome measures for the affected hand function were unclear. OBJECTIVE: The authors investigated the possible role of S1 in motor recovery. METHODS: Assuming that previous studies examined inhomogeneous groups of patients, the authors selected participants with chronic stroke who had moderate hand paresis, normal sensory examination and somatosensory-evoked potentials, and no lesion within the S1, thalamus, or brain stem. Constraint-induced movement therapy (CIMT) was used to train the impaired hand. To relate fMRI (functional MRI) activation changes from baseline to post-CIMT, a correlation analysis was performed with changes of the Wolf Motor Function Test (WMFT) as a test for the hand function. RESULTS: A close relationship was found between increases in hand function and peak changes in activation within the ipsilesional S1. With a better outcome, greater increases in activation within the S1 were evident (P < .03; r = 0.73). CONCLUSION: In selected patients, the sensory network influences training-induced motor gains. This predictive knowledge of plasticity when applying CIMT may suggest strategies to enhance the effect of therapy, such as the addition of electrical stimulation to enhance S1 excitability.

Functional plasticity induced by mirror training: the mirror as the element connecting both hands to one hemisphere.

BACKGROUND: Mirror therapy (MT) is a promising therapeutic approach in stroke patients with severe hand paresis. OBJECTIVE: The ipsilateral (contralesional) primary sensorimotor cortex (SMC) and the mirror neuron system have been suggested to play decisive roles in the MT network. The present study investigated its underlying neural plasticity. METHODS: Two groups of healthy participants (n = 13 in each group) performed standardized fine motor tasks moving pegs and marbles (20 min/d for 4 days) with their right hand with either a mirror (mirror training group, MG) or a nonreflective board (control training group, CG) positioned orthogonally in front of them. The number of items moved by each hand was tested after each training session. Functional MRI (fMRI) was acquired before and after the training procedure to investigate the mirror training (MTr)-specific network by the analysis of the factors Time and Group. RESULTS: The hand performance test of the trained right hand did not differ between the 2 groups. The untrained left hand improved significantly more in the MG compared with the CG. fMRI analysis of action observation and imitation of grasping tasks demonstrated MTr-specific activation changes within the right dorsal and left ventral premotor cortex as well as in the left SMC (SMC(left)). Analysis of functional and effective connectivity showed a MTr-specific increase of functional coupling between each premotor region and the left supplementary motor area, which in turn showed an increased functional interaction with the ipsilateral SMC(left). CONCLUSIONS: MTr remodels the motor system by functionally connecting hand movement to the ipsilateral SMC. On a system level, it leads to interference of the neural circuit related to motor programming and observation of the trained hand with the illusionary movement of the untrained hand.

Dynamic gray matter changes within cortex and striatum after short motor skill training are associated with their increased functional interaction.

Gray matter (GM) changes have been described after short learning tasks that lasted for 7 days or after external stimulation that lasted for 5 days. However, the early time course of training-dependent GM changes is still unknown. We investigated whether shorter motor training sessions (four times of 30 min training) would induce GM changes. Therefore, T1-weighted MRIs were acquired daily. Because reported GM changes were induced by learning, a close relationship was assumed between the functional activity and the GM changes. Therefore, fMRI was performed in addition to daily T1-weighted MRIs. At the end of the four training sessions (at time point "post"), the test results of the trained motor skill were associated with an increase of GM in secondary cortical motor areas (dPMC(right), dPMC(left), SMA(left) and the right inferior parietal lobule, IPL(right)). The earliest time point at which a GM change was detected was 1day before in the right ventral striatum (by contrasting daily T1-weighted MRI vs. baseline). To analyze whether this very early GM change within the right ventral striatum is associated with those GM changes at time point post (which were associated with motor skill performance), their functional connectivity was investigated over the time period of motor skill training. This analysis revealed an increase of functional coupling between these regions (striatum and cortex) over the training days. The current data demonstrate training-induced short GM plasticity is paralleled by their temporally dynamical process of functional interaction between the cortex and the striatum in response to a motor skill training.

Activation changes in sensorimotor cortex during improvement due to CIMT in chronic stroke.

PURPOSE: The integrity of the pyramidal tract (PT) does not seem to influence clinical improvement after two weeks of Constraint-Induced Movement Therapy (CIMT). However, when PT is intact, improvement is associated with a decrease of fMRI-activation in primary sensorimotor cortex (SMC) and when affected, with an increase of activation in SMC. The aim was to observe the long-term effect of CIMT, depending on the integrity of the PT, and to correlate improvement with changes in fMRI-activation. SUBJECTS AND METHODS: Twelve new chronic stroke patients were treated with CIMT and integrity of PT was measured with transcranial magnetic stimulation. Before therapy, after therapy, and after 6 months, changes in motor function were correlated with differential and percent fMRI signal changes. RESULTS: All patients improved after two weeks of therapy, but only those with intact PT maintained improvement after 6 months. When PT was intact, improvement correlated with first a decrease of activation in SMC and after 6 months with an increase. When PT was affected, improvement consistently correlated with an increase in a lateral extension of SMC. Percent changes of activation were surrounded by differential changes. CONCLUSIONS: An intact PT might be advantageous for lasting improvement after CIMT and subregions in the SMC seem to behave differently during recovery.

Age-independent activation in areas of the mirror neuron system during action observation and action imagery. A fMRI study.

PURPOSE: Recent studies have found age-related BOLD signal changes in several areas of the human brain. We investigated whether such changes also occur in brain areas involved in the processing of motor action observation and imagery. METHODS: Functional magnetic resonance imaging with an experimental paradigm in which motor acts had to be observed and/or imagined from a first person perspective was performed in twenty-six subjects. RESULTS: In line with previous work action observation and imagery induced BOLD signal increases in similar areas, predominantly in the premotor and parietal cortex. In contrast to young subjects the elderly displayed a stronger activity in most activated brain areas indicative of compensatory activity for the age-related decline of neural structures. Importantly, activity in the ventrolateral premotor cortex and inferior parietal cortex, seminal areas of the mirror neuron system, did not exhibit activity changes as a function of age. CONCLUSION: These findings suggest that activity within the mirror neuron system is not age dependent and provide a neural basis for therapeutical interventions and novel rehabilitation treatments such as video therapy.

The longitudinal changes of BOLD response and cerebral hemodynamics from acute to subacute stroke. A fMRI and TCD study.

BACKGROUND: By mapping the dynamics of brain reorganization, functional magnetic resonance imaging MRI (fMRI) has allowed for significant progress in understanding cerebral plasticity phenomena after a stroke. However, cerebro-vascular diseases can affect blood oxygen level dependent (BOLD) signal. Cerebral autoregulation is a primary function of cerebral hemodynamics, which allows to maintain a relatively constant blood flow despite changes in arterial blood pressure and perfusion pressure. Cerebral autoregulation is reported to become less effective in the early phases post-stroke. This study investigated whether any impairment of cerebral hemodynamics that occurs during the acute and the subacute phases of ischemic stroke is related to changes in BOLD response. We enrolled six aphasic patients affected by acute stroke. All patients underwent a Transcranial Doppler to assess cerebral autoregulation (Mx index) and fMRI to evaluate the amplitude and the peak latency (time to peak-TTP) of BOLD response in the acute (i.e., within four days of stroke occurrence) and the subacute (i.e., between five and twelve days after stroke onset) stroke phases. RESULTS: As patients advanced from the acute to subacute stroke phase, the affected hemisphere presented a BOLD TTP increase (p = 0.04) and a deterioration of cerebral autoregulation (Mx index increase, p = 0.046). A similar but not significant trend was observed also in the unaffected hemisphere. When the two hemispheres were grouped together, BOLD TTP delay was significantly related to worsening cerebral autoregulation (Mx index increase) (Spearman's rho = 0.734; p = 0.01). CONCLUSIONS: The hemodynamic response function subtending BOLD signal may present a delay in peak latency that arises as patients advance from the acute to the subacute stroke phase. This delay is related to the deterioration of cerebral hemodynamics. These findings suggest that remodeling the fMRI hemodynamic response function in the different phases of stroke may optimize the detection of BOLD signal changes.