Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulators

OBJECTIVE: To compare changes in regional cerebral blood flow (rCBF), using positron emission tomography (PET), during chronic and acute sacral neuromodulation (SN). SN is an effective long-term treatment for chronic urge incontinence due to urinary bladder hyperactivity, as sensory nerves, spinal and supraspinal structures are probably responsible for the action of SN. It is not known which brain areas are involved, and the optimum benefit of SN is not immediate, suggesting that induced plasticity of the brain is necessary. PATIENTS AND METHODS: Brain activity was measured in two groups: 12 urge incontinent patients (11 women and one man; mean age 52 years) in whom an implanted unilateral S3 nerve neurostimulator had been effective for >6 months (mean time after implantation 4.5 years); and eight urge incontinent patients (seven women and one man; mean age 49 years) in whom the neurostimulator was activated for the first time in the PET scanner. RESULTS: During SN in chronically implanted patients, there were significant decreases in rCBF in the middle part of the cingulate gyrus, the ventromedial orbitofrontal cortex, midbrain and adjacent midline thalamus, and rCBF increases in the dorsolateral prefrontal cortex. During acute SN in newly implanted patients, there were significant decreases in rCBF the medial cerebellum, and increases in the right postcentral gyrus cortex, the right insular cortex and the ventromedial orbitofrontal cortex. Group analysis between chronic and newly implanted patients showed significant differences in the associative sensory cortex, premotor cortex and the cerebellum, all three involved in learning behaviour. CONCLUSIONS: These findings suggests that chronic SN influences, presumably via the spinal cord, brain areas previously implicated in detrusor hyperactivity, awareness of bladder filling, the urge to void and the timing of micturition. Furthermore, SN affects areas involved in alertness and awareness. Acute SN modulates predominantly areas involved in sensorimotor learning, which might become less active during the course of chronic SN.     

Connection patterns distinguish 3 regions of human parietal cortex

Three regions of the macaque inferior parietal lobule and adjacent lateral intraparietal sulcus (IPS) are distinguished by the relative strengths of their connections with the superior colliculus, parahippocampal gyrus, and ventral premotor cortex. It was hypothesized that connectivity information could therefore be used to identify similar areas in the human parietal cortex using diffusion-weighted imaging and probabilistic tractography. Unusually, the subcortical routes of the 3 projections have been reported in the macaque, so it was possible to compare not only the terminations of connections but also their course. The medial IPS had the highest probability of connection with the superior colliculus. The projection pathway resembled that connecting parietal cortex and superior colliculus in the macaque. The posterior angular gyrus and the adjacent superior occipital gyrus had a high probability of connection with the parahippocampal gyrus. The projection pathway resembled the macaque inferior longitudinal fascicle, which connects these areas. The ventral premotor cortex had a high probability of connection with the supramarginal gyrus and anterior IPS. The connection was mediated by the third branch of the superior longitudinal fascicle, which interconnects similar regions in the macaque. Human parietal areas have anatomical connections resembling those of functionally related macaque parietal areas.     

Dorsal posterior parietal rTMS affects voluntary orienting of visuospatial attention

Patients with lesions in posterior parietal cortex (PPC) are relatively unimpaired in voluntarily directing visual attention to different spatial locations, while many neuroimaging studies in healthy subjects suggest dorsal PPC involvement in this function. We used an offline repetitive transcranial magnetic stimulation (rTMS) protocol to study this issue further. Ten healthy participants performed a cue-target paradigm. Cues prompted covert orienting of spatial attention under voluntary control to either a left or right visual field position. Targets were flashed subsequently at the cued or uncued location, or bilaterally. Following rTMS over right dorsal PPC, (i) the benefit for target detection at cued versus uncued positions was preserved irrespective of cueing direction (left- or rightward), but (ii) leftward cueing was associated with a global impairment in target detection, at all target locations. This reveals that leftward orienting was still possible after right dorsal PPC stimulation, albeit at an increased overall cost for target detection. In addition, rTMS (iii) impaired left, but (iv) enhanced right target detection after rightward cueing. The finding of a global drop in target detection during leftward orienting with a spared, relative detection benefit at the cued (left) location (i-ii) suggests that right dorsal PPC plays a subsidiary rather than pivotal role in voluntary spatial orienting. This finding reconciles seemingly conflicting results from patients and neuroimaging studies. The finding of attentional inhibition and enhancement occurring contra- and ipsilaterally to the stimulation site (iii-iv) supports the view that spatial attention bias can be selectively modulated through rTMS, which has proven useful to transiently reduce visual hemispatial neglect.     

The interaction of brain regions during visual search processing as revealed by transcranial magnetic stimulation

Although it has long been known that right posterior parietal cortex (PPC) has a role in certain visual search tasks, and human motion area V5 is involved in processing tasks requiring attention to motion, little is known about how these areas may interact during the processing of a task requiring the speciality of each. Using transcranial magnetic stimulation (TMS), this study first established the specialization of each area in the form of a double dissociation; TMS to right PPC disrupted processing of a color/form conjunction and TMS to V5 disrupted processing of a motion/form conjunction. The key finding of this study is, however, if TMS is used to disrupt processing of V5 at its critical time of activation during the motion/form conjunction task, concurrent disruption of right PPC now has a significant effect, where TMS at PPC alone does not. Our findings challenge the conventional interpretation of the role of right PPC in conjunction search and spatial attention.     

Control of object-based attention in human cortex

Visual attention is a mechanism by which observers select relevant or important information from the current visual array. Previous investigations have focused primarily on the ability to select a region of space for further visual analysis. These studies have revealed a distributed frontoparietal circuit that is responsible for the control of spatial attention. However, vision must ultimately represent objects and in real scenes objects often overlap spatially; thus attention must be capable of selecting objects and their properties nonspatially. Little is known about the neural basis of object-based attentional control. In two experiments, human observers shifted attention between spatially superimposed faces and houses. Event-related functional magnetic resonance imaging (fMRI) revealed attentional modulation of activity in face- and house-selective cortical regions. Posterior parietal and frontal regions were transiently active when attention was shifted between spatially superimposed perceptual objects. The timecourse of activity provides insight into the functional role that these brain regions play in attentional control processes.     

Cortical mechanisms for shifting and holding visuospatial attention

Access to visual awareness is often determined by covert, voluntary deployments of visual attention. Voluntary orienting without eye movements requires decoupling attention from the locus of fixation, a shift to the desired location, and maintenance of attention at that location. We used event-related functional magnetic resonance imaging to dissociate these components while observers shifted attention among 3 streams of letters and digits, one located at fixation and 2 in the periphery. Compared with holding attention at the current location, shifting attention between the peripheral locations was associated with transient increases in neural activity in the superior parietal lobule (SPL) and frontal eye fields (FEF), as in previous studies. The supplementary eye fields and separate portions of SPL and FEF were more active for decoupling attention from fixation than for shifting attention to a new location. Large segments of precentral sulcus (PreCS) and posterior parietal cortex (PPC) were more active when attention was maintained in the periphery than when it was maintained at fixation. We conclude that distinct subcomponents of the dorsal frontoparietal network initiate redeployments of covert attention to new locations and disengage attention from fixation, while sustained activity in lateral regions of PPC and PreCS represents sustained states of peripheral attention.     

Mental visual synthesis is originated in the fronto-temporal network of the left hemisphere

Mental visual synthesis is the capacity for experiencing, constructing, or manipulating 'mental imagery'. To investigate brain networks involved in mental visual synthesis, brain activity was measured in right-handed healthy volunteers during mental imagery tasks, in which the subjects were instructed to imagine a novel object, that does not exist in the real world, by composing it from two visually presented words associated with a real object or two achromatic line drawings of a real object, using functional magnetic resonance imaging (fMRI). Both tasks activated the same areas in the inferior frontal and inferior temporal cortices of the left hemisphere. Our results indicate that the source of mental visual synthesis may be formed by activity of a brain network consisting of these areas, which are also involved in semantic operations and visual imagery.     

The different neural correlates of action and functional knowledge in semantic memory: an FMRI study

Previous reports suggest that the internal organization of semantic memory is in terms of different "types of knowledge," including "sensory" (information about perceptual features), "action" (motor-based knowledge of object utilization), and "functional" (abstract properties, as function and context of use). Consistent with this view, a specific loss of action knowledge, with preserved functional knowledge, has been recently observed in patients with left frontoparietal lesions. The opposite pattern (impaired functional knowledge with preserved action knowledge) was reported in association with anterior inferotemporal lesions. In the present study, the cerebral representation of action and functional knowledge was investigated using event-related analysis of functional magnetic resonance imaging data. Fifteen subjects were presented with pictures showing pairs of manipulable objects and asked whether the objects within each pair were used with the same manipulation pattern ("action knowledge" condition) or in the same context ("functional knowledge" condition). Direct comparisons showed action knowledge, relative to functional knowledge, to activate a left frontoparietal network, comprising the intraparietal sulcus, the inferior parietal lobule, and the dorsal premotor cortex. The reverse comparison yielded activations in the retrosplenial and the lateral anterior inferotemporal cortex. These results confirm and extend previous neuropsychological data and support the hypothesis of the existence of different types of information processing in the internal organization of semantic memory.     

Recruitment of periventricular parietal regions in processing cluttered point-light biological motion

Recent findings point to the existence of a cortical-subcortical parietal network that drives attention-related integration of features and elements. Here we ask whether the functioning of this network might be modulated by early periventricular lesions. To this end, a cohort of adolescents who were born premature with different severity of bilateral periventricular leukomalacia (PVL) and two groups of matched peers (term-born adolescents and former preterms with normal MRI scan) were shown a set of impoverished point-light stimuli. Observers had to detect a point-light walker embedded in an array of distracters mimicking the motion of the target's dots. Patients exhibited higher susceptibility to distortions caused by distracters. In patients only, sensitivity to the point-light figure highly correlates not just with performance on additionally administered feature integration tasks but also on visual attention-demanding IQ tasks. Moreover, the sensitivity index, as well as the values of both IQ factors, decreases with an increase in the volumetric PVL extent in the parieto-occipital region. No relationship was found between these variables and the lesion extent in the frontal or temporal periventricular regions. The data suggest that visual integration and attention in processing cluttered point-light displays are intimately connected. Most importantly, periventricular parieto-occipital regions might be part of a distributed network recruited in deployment of the posterior attentional system. The functioning of this system seems to be vulnerable to bilateral periventricular damage even if it occurs very early in brain development.     

Functional architecture of retinotopy in visual association cortex of behaving monkey

While the receptive field properties of single neurons in the inferior parietal cortex have been quantitatively described from numerous electrical measurements, the visual topography of area 7a and the adjacent dorsal prelunate area (DP) remains unknown. This lacuna may be a technical byproduct of the difficulty of reconstructing tens to hundreds of penetrations, or may be the result of varying functional retinotopic architectures. Intrinsic optical imaging, performed in behaving monkey for extended periods of time, was used to evaluate retinotopy simultaneously at multiple positions across the cortical surface. As electrical recordings through an implanted artificial dura are difficult, the measurement and quantification of retinotopy with long-term recordings was validated by imaging early visual cortex (areas V1 and V2). Retinotopic topography was found in each of the three other areas studied within a single day's experiment. However, the ventral portion of DP (DPv) had a retinotopic topography that varied from day to day, while the more dorsal aspects (DPd) exhibited consistent retinotopy. This suggests that the dorsal prelunate gyrus may consist of more than one visual area. The retinotopy of area 7a also varied from day to day. Possible mechanisms for this variability across days are discussed as well as its impact upon our understanding of the representation of extrapersonal space in the inferior parietal cortex.     

Differential parahippocampal and retrosplenial involvement in three types of visual scene recognition

Human observers can quickly and accurately interpret the meaning of complex visual scenes. The neural mechanisms underlying this ability are largely unexplored. We used functional magnetic resonance imaging to measure cortical activity while subjects identified briefly presented scenes as specific familiar locations ("Houston Hall"), general place categories ("kitchen"), or general situational categories ("party"). Scene-responsive voxels in the parahippocampal place area (PPA) and retrosplenial cortex (RSC) were highly sensitive to recognition level when identifying scenes, responding more strongly during location identification than during place category or situation identification. In contrast, the superior temporal sulcus, cingulate sulcus, and supermarginal gyrus displayed the opposite pattern, responding more strongly during place category and situation identification. Consideration of results from 4 experiments suggests that the PPA represents the visuospatial structure of individual scenes, whereas RSC supports processes that allow scenes to be localized within a larger extended environment. These results suggest that different scene identification tasks tap distinct cortical networks. In particular, we hypothesize that the PPA and RSC are critically involved in the identification of specific locations but play a less central role in other scene recognition tasks.     

Agraphia after awake surgery for brain tumor: new insights into the anatomo-functional network of writing

Background

Controversy still exists about neural basis underlying writing and its relation with the sites subserving oral language. Our objective is to study functional areas involved in writing network, based on the observations of different postoperative writing disorders in a population of patients without preoperative agraphia.

Methods

We analyzed the postoperative agraphia profiles in 15 patients who underwent surgery for cerebral LGGs in functional language areas, using electrical mapping under local anesthesia. These profiles were then correlated to the sites of the lesions, shown by preoperative cerebral imaging.

Results

Our findings showed that (1) spoken language and writing functions could be dissociated, and that (2) writing is subserved, at least partially, by a network of 5 areas located in the dominant hemisphere for language: the superior parietal region, the supramarginalis gyrus, the second and third frontal convolutions, the supplementary motor area, and the insula. Each of these areas seems to have a different role in writing, which will be detailed in this article. However, among the patients, only those with lesions of the supplementary motor area did not recover from agraphia in the postoperative period (in 50% of cases).

Conclusions

On the basis of these results, and in the light of the recent literature, we discuss the relevance of each area in this anatomo-functional network as well as the clinical implications of such better knowledge of the neural basis of writing, especially for brain surgery and functional rehabilitation.     

Changes in fMRI activation following rehabilitation of reading and visual processing deficits in subjects with traumatic brain injury

In this case series fMRI was used to examine activation patterns during presentation of a reading comprehension (RC) task in three adult subjects with a history of severe traumatic brain injury (TBI). These subjects received cognitive rehabilitation therapy (CRT) for visual processing and acquired reading deficits. fMRI and neuropsychological testing occurred pre- and post-rehabilitation. The study's objective was to evaluate the neurobiological changes using fMRI occurring with CRT and to compare these results to repeat fMRI in matched control subjects. While improvements in neuropsychological testing occurred post-CRT, diffuse and variable activation patterns in the subjects with TBI were still demonstrated when compared to the control subjects repeat imaging. Multiple networks exist to accomplish the complex task of sentence reading and rehabilitation of the cognitive components of reading, such as visual processing; in subjects with TBI, can alter the activation pattern demonstrated during reading comprehension in subjects many years post-injury. This is the first demonstration of changes in network activation patterns post-CRT in patients with severe, chronic TBI on an fMRI task shown to have imaging stability in a normal control sample.     

Impairment of gaze-centered updating of reach targets in bilateral parietal-occipital damaged patients

Recent studies have suggested that internal updating of visuospatial targets in humans occurs in gaze-centered coordinates and takes place in the parietal and extrastriate cortices. We explored how information for reaching is updated in two patients with bilateral lesions in these areas. Subjects performed two visuomotor tasks: (i) a fixation reaching task, which began with the appearance of one of five fixation positions (varying eye positions) followed by a central reaching target. Subjects reached to the target while fixating on the presented fixation position (relative to gaze the target was always presented in the periphery); and (ii) a saccade reaching task, in which subjects foveated on the central reaching target, then made a saccade to the presented fixation position before reaching to the central target. In both tasks, subjects reached to targets after a 500 or 5000 ms delay. Gaze-centered updating predicts similarities in reaching errors between fixation and saccade trials. Control subjects showed evidence for gaze-centered updating during both 500 and 5000 ms delay conditions. In contrast, patient AT, who had extensive occipital-parietal damage, only showed signs of gaze-centered representation after 5 s. Patient IG, with a more focal lesion in the parietal cortices, showed partial updating in gaze-centered coordinates when reaching with the small memory delay but recovered a complete gaze-centered representation after the longer delay. This suggests that patients with bilateral occipital-parietal lesions may rely on non-gaze-centered frames to store immediate target locations in reaching space but, given enough time, this information may be rerouted to access other gaze-centered motor cortical mechanisms.     

Brain processing of the signals ascending through unmyelinated C fibers in humans: an event-related functional magnetic resonance imaging study

Event-related functional magnetic resonance imaging was usedto investigate brain processing of the signals ascending fromperipheral C and A fibers evoked by phasic laser stimuli onthe right hand in humans. The stimulation of both C and A nociceptorsactivated the bilateral thalamus, bilateral secondary somatosensorycortex, right (ipsilateral) middle insula, and bilateral Brodmann'sarea (BA) 24/32, with the majority of activity found in theposterior portion of the anterior cingulate cortex (ACC). However,magnitude of activity in the right (ipsilateral) BA32/8/6, includingdorsal parts in the anterior portion of the ACC (aACC) and pre-supplementarymotor area (pre-SMA), and the bilateral anterior insula wassignificantly stronger following the stimulation of C nociceptorsthan A nociceptors. It was concluded that the activation ofC nociceptors, related to second pain, evokes different brainprocessing from that of A nociceptors, related to first pain,probably due to the differences in the emotional and motivationalaspects of either pain, which are mainly related to the aACC,pre-SMA, and anterior insula.