Dynamic network structure of interhemispheric coordination.

Fifty years ago Gazzaniga and coworkers published a seminal article that discussed the separate roles of the cerebral hemispheres in humans. Today, the study of interhemispheric communication is facilitated by a battery of novel data analysis techniques drawn from across disciplinary boundaries, including dynamic systems theory and network theory. These techniques enable the characterization of dynamic changes in the brain's functional connectivity, thereby providing an unprecedented means of decoding interhemispheric communication. Here, we illustrate the use of these techniques to examine interhemispheric coordination in healthy human participants performing a split visual field experiment in which they process lexical stimuli. We find that interhemispheric coordination is greater when lexical information is introduced to the right hemisphere and must subsequently be transferred to the left hemisphere for language processing than when it is directly introduced to the language-dominant (left) hemisphere. Further, we find that putative functional modules defined by coherent interhemispheric coordination come online in a transient manner, highlighting the underlying dynamic nature of brain communication. Our work illustrates that recently developed dynamic, network-based analysis techniques can provide novel and previously unapproachable insights into the role of interhemispheric coordination in cognition.

Fronto-cerebellar circuits and eye movement control: a diffusion imaging tractography study of human cortico-pontine projections.

A possible role of the cerebellum in cognitive function might be revealed through its anatomical connections with specific regions of the cerebral cortex. To understand the kind of information transmitted between the cortex and cerebellum, we studied the connections from six subdivisions of frontal and prefrontal cortex using diffusion imaging tractography. Cortico-pontine fibers travel through the cerebral peduncles and reach the cerebellum by way of a synaptic link in the pontine nuclei. In 19 human data sets, we tracked connections between the cerebral peduncle and left hemispheric masks of the superior frontal gyrus (SFG), precentral gyrus (PcG), middle frontal gyrus (MFG), orbital frontal cortex, and two regions of inferior frontal gyrus, including pars opercularis and pars triangularis. Cortico-pontine fibers arose from the PcG, the caudal/medial SFG and a small region of the MFG in a majority of the subjects analyzed. While these regions do have known roles in cognitive and executive functions, all three are strongly associated with the planning and execution of eye movements. Connections from more ventral prefrontal cortex were negligible, indicating that these regions are only sparsely represented in the circuit. Based on this pattern of connectivity, it is likely that the prefrontal connections to the cerebellum are involved in covert motor operations and the control of eye movements.

Cortical projection topography of the human splenium: hemispheric asymmetry and individual differences.

The corpus callosum is the largest white matter pathway in the human brain. The most posterior portion, known as the splenium, is critical for interhemispheric communication between visual areas. The current study employed diffusion tensor imaging to delineate the complete cortical projection topography of the human splenium. Homotopic and heterotopic connections were revealed between the splenium and the posterior visual areas, including the occipital and the posterior parietal cortices. In nearly one third of participants, there were homotopic connections between the primary visual cortices, suggesting interindividual differences in splenial connectivity. There were also more instances of connections with the right hemisphere, indicating a hemispheric asymmetry in interhemispheric connectivity within the splenium. Combined, these findings demonstrate unique aspects of human interhemispheric connectivity and provide anatomical bases for hemispheric asymmetries in visual processing and a long-described hemispheric asymmetry in speed of interhemispheric communication for visual information.

Overt naming fMRI pre- and post-TMS: Two nonfluent aphasia patients, with and without improved naming post-TMS.

Two chronic, nonfluent aphasia patients participated in overt naming fMRI scans, pre- and post-a series of repetitive transcranial magnetic stimulation (rTMS) treatments as part of a TMS study to improve naming. Each patient received 10, 1-Hz rTMS treatments to suppress a part of R pars triangularis. P1 was a 'good responder' with improved naming and phrase length; P2 was a 'poor responder' without improved naming. Pre-TMS (10 years poststroke), P1 had significant activation in R and L sensorimotor cortex, R IFG, and in both L and R SMA during overt naming fMRI (28% pictures named). At 3 mo. post-TMS (42% named), P1 showed continued activation in R and L sensorimotor cortex, R IFG, and in R and L SMA. At 16 mo. post-TMS (58% named), he also showed significant activation in R and L sensorimotor cortex mouth and R IFG. He now showed a significant increase in activation in the L SMA compared to pre-TMS and at 3 mo. post-TMS (p < .02; p < .05, respectively). At 16 mo. there was also greater activation in L than R SMA (p < .08). At 46 mo. post-TMS (42% named), this new LH pattern of activation continued. He improved on the Boston Naming Test from 11 pictures named pre-TMS, to scores ranging from 14 to 18 pictures, post-TMS (2-43 mo. post-TMS). His longest phrase length (Cookie Theft picture) improved from three words pre-TMS, to 5-6 words post-TMS. Pre-TMS (1.5 years poststroke), P2 had significant activation in R IFG (3% pictures named). At 3 and 6 mo. post-TMS, there was no longer significant activation in R IFG, but significant activation was present in R sensorimotor cortex. On all three fMRI scans, P2 had significant activation in both the L and R SMA. There was no new, lasting perilesional LH activation across sessions for this patient. Over time, there was little or no change in his activation. His naming remained only at 1-2 pictures during all three fMRI scans. His BNT score and longest phrase length remained at one word, post-TMS. Lesion site may play a role in each patient's fMRI activation pattern and response to TMS treatment. P2, the poor responder, had an atypical frontal lesion in the L motor and premotor cortex that extended high, near brain vertex, with deep white matter lesion near L SMA. P2 also had frontal lesion in the posterior middle frontal gyrus, an area important for naming (Duffau et al., 2003); P1 did not. Additionally, P2 had lesion inferior and posterior to Wernicke's area, in parts of BA 21 and 37, whereas P1 did not. The fMRI data of our patient who had good response following TMS support the notion that restoration of the LH language network is linked in part, to better recovery of naming and phrase length in nonfluent aphasia.

Cerebellum: connections and functions.

In addition to its role in motor control, reflex adaptation, and motor learning, three sorts of evidence have been put forward to support the idea that the cerebellum may also be involved in cognition. Patients with cerebellar lesions are reported to have deficits in performing one or another cognitive task. The cerebellum is often seen to be activated when normal subjects perform such tasks. There are connections to and from areas of the prefrontal cortex that may be involved in cognition. In this paper, we review the anatomical evidence to support the claim. We suggest that there are only minor connections with cognitive areas of the cerebral cortex and that some of the imaging evidence may reflect the cerebellum's role in the control of eye movements rather than cognition.

Neuroimaging techniques offer new perspectives on callosal transfer and interhemispheric communication.

The brain relies on interhemispheric communication for coherent integration of cognition and behavior. Surgical disconnection of the two cerebral hemispheres has granted numerous insights into the functional organization of the corpus callosum (CC) and its relationship to hemispheric specialization. Today, technologies exist that allow us to examine the healthy, intact brain to explore the ways in which callosal organization relates to normal cognitive functioning and cerebral lateralization. The CC is organized in a topographical manner along its antero-posterior axis. Evidence from neuroimaging studies is revealing with greater specificity the function and the cortical projection targets of the topographically organized callosal subregions. The size, myelination and density of fibers in callosal subregions are related to function of the brain regions they connect: smaller fibers are slow-conducting and connect higher-order association areas; larger fibers are fast-conducting and connect visual, motor and secondary somotosensory areas. A decrease in fiber size and transcallosal connectivity might be related to a reduced need for interhemispheric communication due, in part, to increased intrahemispheric connectivity and specialization. Additionally, it has been suggested that lateralization of function seen in the human brain lies along an evolutionary continuum. Hemispheric specialization reduces duplication of function between the hemispheres. The microstructure and connectivity patterns of the CC provide a window for understanding the evolution of hemispheric asymmetries and lateralization of function. Here, we review the ways in which converging methodologies are advancing our understanding of interhemispheric communication in the normal human brain.

Overt naming in aphasia studied with a functional MRI hemodynamic delay design.

The purpose of this study was to develop a functional MRI method to examine overt speech in stroke patients with aphasia. An fMRI block design for overt picture naming was utilized which took advantage of the hemodynamic response delay where increased blood flow remains for 4-8 s after the task [(Friston, K.J., Jezzard, P., Turner, R., 1994. Analysis of functional MRI time-series. Hum. Brain Mapp. 1, 153-171)]. This allowed task-related information to be obtained after the task, minimizing motion artifact from overt speech (Eden, G.F., Joseph, J., Brown, H.E., Brown, C.P., Zeffiro, T.A., 1999. Utilizing hemodynamic delay and dispersion to detect fMRI signal change without auditory interference: the behavior interleaved gradients technique. Magn. Reson. Med. 41, 13-20; Birn, RM., Bandettini, P.A., Cox, R.W., Shaker, R., 1999. Event-related fMRI of tasks involving brief motion. Hum. Brain Mapp. 7, 106-114; Birn, R.M., Cox, R.W., Bandettini, P.A., 2004. Experimental designs and processing strategies for fMRI studies involving overt verbal responses. NeuroImage 23, 1046-1058). Five chronic aphasia patients participated (4 mild-moderate and 1 severe nonfluent/global). The four mild-moderate patients who correctly named 88-100% of the pictures during fMRI, had a greater number of suprathreshold voxels in L supplementary motor area (SMA) than R SMA (P < 0.07). Three of these four mild-moderate patients showed activation in R BA 45 and/or 44; along with L temporal and/or parietal regions. The severe patient, who named no pictures, activated almost twice as many voxels in R SMA than L SMA. He also showed activation in R BA 44, but had remarkably extensive L and R temporal activation. His poor naming and widespread temporal activation may reflect poor modulation of the bi-hemispheric neural network for naming. Results indicate that this fMRI block design utilizing hemodynamic response delay can be used to study overt naming in aphasia patients, including those with mild-moderate or severe aphasia. This method permitted verification that the patients were cooperating with the task during fMRI. It has application for future fMRI studies of overt speech in aphasia.

Improved naming after TMS treatments in a chronic, global aphasia patient--case report.

We report improved ability to name pictures at 2 and 8 months after repetitive transcranial magnetic stimulation (rTMS) treatments to the pars triangularis portion of right Broca's homologue in a 57 year-old woman with severe nonfluent/global aphasia (6.5 years post left basal ganglia bleed, subcortical lesion). TMS was applied at 1 Hz, 20 minutes a day, 10 days, over a two-week period. She received no speech therapy during the study. One year after her TMS treatments, she entered speech therapy with continued improvement. TMS may have modulated activity in the remaining left and right hemisphere neural network for naming.

Improved picture naming in chronic aphasia after TMS to part of right Broca's area: an open-protocol study.

Functional imaging studies with nonfluent aphasia patients have observed "over-activation" in right (R) language homologues. This may represent a maladaptive strategy; suppression may result in language improvement. We applied slow, 1 Hz repetitive transcranial magnetic stimulation (rTMS) to an anterior portion of R Broca's homologue daily, for 10 days in four aphasia patients who were 5-11 years poststroke. Significant improvement was observed in picture naming at 2 months post-rTMS, with lasting benefit at 8 months in three patients. This preliminary, open trial suggests that rTMS may provide a novel treatment approach for aphasia by possibly modulating the distributed, bi-hemispheric language network.

Transcranial magnetic stimulation as a complementary treatment for aphasia.

Functional brain imaging with nonfluent aphasia patients has shown increased cortical activation (perhaps "overactivation") in right (R) hemisphere language homologues. These areas of overactivation may represent a maladaptive strategy that interferes with, rather than promotes, aphasia recovery. Repetitive transcranial magnetic stimulation (rTMS) is a painless, noninvasive procedure that utilizes magnetic fields to create electric currents in discrete brain areas affecting about a 1-cm square area of cortex. Slow frequency, 1 Hz rTMS reduces cortical excitability. When rTMS is applied to an appropriate cortical region, it may suppress the possible overactivation and thus modulate a distributed neural network for language. We provide information on rTMS and report preliminary results following rTMS application to R Broca's area (posterior, R pars triangularis) in four stroke patients with nonfluent aphasia (5-11 years after left hemisphere stroke). Following 10 rTMS treatments, significant improvement in naming pictures was observed. This form of rTMS may provide a novel, complementary treatment for aphasia.

Test-retest reliability of fMRI during nonverbal semantic decisions in moderate-severe nonfluent aphasia patients.

Cortical reorganization in poststroke aphasia is not well understood. Few studies have investigated neural mechanisms underlying language recovery in severe aphasia patients, who are typically viewed as having a poor prognosis for language recovery. Although test-retest reliability is routinely demonstrated during collection of language data in single-subject aphasia research, this is rarely examined in fMRI studies investigating the underlying neural mechanisms in aphasia recovery. The purpose of this study was to acquire fMRI test-retest data examining semantic decisions both within and between two aphasia patients. Functional MRI was utilized to image individuals with chronic, moderate-severe nonfluent aphasia during nonverbal, yes/no button-box semantic judgments of iconic sentences presented in the Computer-assisted Visual Communication (C-ViC) program. We investigated the critical issue of intra-subject reliability by exploring similarities and differences in regions of activation during participants' performance of identical tasks twice on the same day. Each participant demonstrated high intra-subject reliability, with response decrements typical of task familiarity. Differences between participants included greater left hemisphere perilesional activation in the individual with better response to C-ViC training. This study provides fMRI reliability in chronic nonfluent aphasia, and adds to evidence supporting differences in individual cortical reorganization in aphasia recovery.