Transcranial Photobiomodulation Treatment: Significant Improvements in Four Ex-Football Players with Possible Chronic Traumatic Encephalopathy.

Background: Chronic traumatic encephalopathy, diagnosed postmortem (hyperphosphorylated tau), is preceded by traumatic encephalopathy syndrome with worsening cognition and behavior/mood disturbances, over years. Transcranial photobiomodulation (tPBM) may promote improvements by increasing ATP in compromised/stressed cells and increasing local blood, lymphatic vessel vasodilation. Objective: Aim 1: Examine cognition, behavior/mood changes Post-tPBM. Aim 2: MRI changes - resting-state functional-connectivity MRI: salience, central executive, default mode networks (SN, CEN, DMN); magnetic resonance spectroscopy, cingulate cortex. Methods: Four ex-players with traumatic encephalopathy syndrome/possible chronic traumatic encephalopathy, playing 11- 16 years, received In-office, red/near-infrared tPBM to scalp, 3x/week for 6 weeks. Two had cavum septum pellucidum. Results: The three younger cases (ages 55, 57, 65) improved 2 SD (p < 0.05) on three to six neuropsychological tests/subtests at 1 week or 1 month Post-tPBM, compared to Pre-Treatment, while the older case (age 74) improved by 1.5 SD on three tests. There was significant improvement at 1 month on post-traumatic stress disorder (PTSD), depression, pain, and sleep. One case discontinued narcotic pain medications and had reduced tinnitus. The possible placebo effect is unknown. At 2 months Post-tPBM, two cases regressed. Then, home tPBM was applied to only cortical nodes, DMN (12 weeks); again, significant improvements were seen. Significant correlations for increased SN functional connectivity (FC) over time, with executive function, attention, PTSD, pain, and sleep; and CEN FC, with verbal learning/memory, depression. Increased n-acetyl-aspartate (NAA) (oxygen consumption, mitochondria) was present in anterior cingulate cortex (ACC), parallel to less pain and PTSD. Conclusion: After tPBM, these ex-football players improved. Significant correlations of increased SN FC and CEN FC with specific cognitive tests and behavior/mood ratings, plus increased NAA in ACC support beneficial effects from tPBM.

Transcranial Photobiomodulation to Improve Cognition in Gulf War Illness.

Introduction: Approximately 25-30% of veterans deployed to Kuwait, 1990-91, report persistent multi-symptom Gulf War Illness (GWI) likely from neurotoxicant exposures. Photobiomodulation (PBM) in red/near-infrared (NIR) wavelengths is a safe, non-invasive modality shown to help repair hypoxic/stressed cells. Red/NIR wavelengths are absorbed by cytochrome C oxidase in mitochondria, releasing nitric oxide (increasing local vasodilation), and increasing adenosine tri-phosphate production. We investigated whether PBM applied transcranially could improve cognition, and health symptoms in GWI. Materials and Methods: Forty-eight (40 M) participants completed this blinded, randomized, sham-controlled trial using Sham or Real, red/NIR light-emitting diodes (LED) applied transcranially. Fifteen, half-hour transcranial LED (tLED) treatments were twice a week (7.5 weeks, in-office). Goggles worn by participant and assistant maintained blinding for visible red. Pre-/Post- testing was at Entry, 1 week and 1 month post- 15th treatment. Primary outcome measures were neuropsychological (NP) tests; secondary outcomes, Psychosocial Questionnaires, including PTSD. Results: Primary Analyses (all participants), showed improvement for Real vs. Sham, for Digit Span Forwards (p < 0.01); and a trend for Trails 4, Number/Letter Sequencing (p < 0.10). For secondary outcomes, Real group reported more improvement on the SF-36V Plus, Physical Component Score (p < 0.08). Secondary Analyses included only subjects scoring below norm (50%ile) at Entry, on specific NP test/s. Real and Sham improved at 1 week after 15th treatment; however, at 1 month, only those receiving Real improved further: Digit Span Total, Forwards and Backwards; Trails 4, Number/Letter Sequencing; California Verbal Learning Test-II, long delay free recall; Continuous Performance Test-II, False Alarm Rate; and Color-Word Interference, Stroop, Trial 3, Inhibition; Sham group worsened, toward Entry values. Only those with more post-traumatic stress disorder (PTSD) symptomatology at Entry, receiving Real, continued to have additional PTSD reduction at 1 month; Sham regressed. Conclusion: This study was underpowered (n = 48), with large heterogeneity at Entry. This likely contributed to significance or trend to significance, for only two of the NP tests (Digit Span Forwards; Trails 4, Number/Letter Sequencing) and only one general health measure, the SF-36V Plus, Physical Component Score. More subjects receiving Real, self-reported increased concentration, relaxation and sleep. Controlled studies with newer, transcranial LED home treatment devices are warranted; this is expected to increase enrollment. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01782378.

Increased Functional Connectivity Within Intrinsic Neural Networks in Chronic Stroke Following Treatment with Red/Near-Infrared Transcranial Photobiomodulation: Case Series with Improved Naming in Aphasia.

Objective: To examine effects of four different transcranial, red/near-infrared (NIR), light-emitting diode (tLED) protocols on naming ability in persons with aphasia (PWA) due to left hemisphere (LH) stroke. This is the first study to report beneficial effects from tLED therapy in chronic stroke, and parallel changes on functional magnetic resonance imaging (fMRI). Materials and methods: Six PWA, 2-18 years poststroke, in whom 18 tLED treatments were applied (3 × /week, 6 weeks) using LED cluster heads: 500 mW, red (633 nm) and NIR (870 nm), 22.48 cm2, 22.2 mW/cm2. Results: After Protocol A with bilateral LED placements, including midline, at scalp vertex over left and right supplementary motor areas (L and R SMAs), picture naming was not improved. P1 underwent pre-/postovert, picture-naming task-fMRI scans; P2 could not. After Protocol A, P1 showed increased activation in LH and right hemisphere, including L and R SMAs. After Protocol B with LEDs only on ipsilesional, LH side, naming ability significantly improved for P1 and P2; the fMRI scans for P1 then showed activation only on the ipsilesional LH side. After Protocol C with LED placements on ipsilesional LH side, plus one midline placement over mesial prefrontal cortex (mPFC) at front hairline, a cortical node of the default mode network (DMN), P3 and P4 had only moderate/poor response, and no increase in functional connectivity on resting-state functional-connectivity MRI. After Protocol D, however, with LED placements on ipsilesional LH side, plus over two midline nodes of DMN, mPFC, and precuneus (high parietal) simultaneously, P5 and P6 each had good response with significant increase in functional connectivity within DMN, p < 0.0005; salience network, p < 0.0005; and central executive network, p < 0.05. Conclusions: NIR photons can affect surface brain cortex areas subjacent to where LEDs are applied on the scalp. Improved naming ability was present with optimal Protocol D. Transcranial photobiomodulation may be an additional noninvasive therapy for stroke.

Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to Improve Cognition in Chronic Traumatic Brain Injury.

OBJECTIVE: We review the general topic of traumatic brain injury (TBI) and our research utilizing transcranial photobiomodulation (tPBM) to improve cognition in chronic TBI using red/near-infrared (NIR) light-emitting diodes (LEDs) to deliver light to the head. tPBM improves mitochondrial function increasing oxygen consumption, production of adenosine triphosphate (ATP), and improving cellular energy stores. Nitric oxide is released from the cells increasing regional blood flow in the brain. Review of published studies: In our previously published study, 11 chronic TBI patients with closed-head TBI caused by different accidents (motor vehicle accident, sports-related, improvised explosive device blast injury) and exhibiting long-lasting cognitive dysfunction received 18 outpatient treatments (Monday, Wednesday, Friday for 6 weeks) starting at 10 months to 8 years post-TBI. LED therapy is nonthermal, painless, and noninvasive. An LED-based device classified as nonsignificant risk (FDA cleared) was used. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm2) was applied for 9 min 45 sec (13 J/cm2) using 11 locations on the scalp: midline from front-to-back hairline and bilaterally on frontal, parietal, and temporal areas. Testing was performed before and after transcranial LED (tLED; at 1 week, 1 month, and at 2 months after the 18th treatment) and showed significant improvements in executive function and verbal memory. There were also fewer post-traumatic stress disorder (PTSD) symptoms reported. Ongoing studies: Ongoing, current studies involve TBI patients who have been treated with tLED using either 26 J/cm2 per LED location on the head or treated with intranasal only (iLED) using red (633 nm) and NIR (810 nm) diodes placed into the nostrils. The NIR iLED is hypothesized to deliver photons to the hippocampus, and the red 633 nm iLED is believed to increase melatonin. Results have been similar to the previously published tLED study. Actigraphy sleep data showed increased time asleep (on average one additional hour per night) after the 18th tLED or iLED treatment. LED treatments may be performed in the home. Sham-controlled studies with veterans who have cognitive dysfunction from Gulf War Illness, blast TBI, and TBI/PTSD are currently ongoing.

Language improvements after TMS plus modified CILT: Pilot, open-protocol study with two, chronic nonfluent aphasia cases.

PURPOSE: The purpose of this study was to investigate: 1) the feasibilty of administering a modified CILT (mCILT) treatment session immediately after TMS; and 2) if this combined therapy could improve naming and elicited propositional speech in chronic, nonfluent aphasia. METHODS: Two chronic stroke patients with nonfluent aphasia (mild-moderate and severe) each received twenty minutes of rTMS to suppress the right pars triangularis, followed immediately by three hours of mCILT (5 days/week, 2 weeks). (Each patient had received TMS alone, 2-6 years prior.) Language evaluations were performed pre- TMS+mCILT, and post- at 1-2 months, and 6 or 16 months. RESULTS: Both patients showed significant improvements in naming pictures, and elicited propositional speech at 1-2 months post- TMS+mCILT. The improved naming was still present at 6 months post- TMS+mCILT for P2; but not at 16 months post- TMS+mCILT for P1. CONCLUSIONS: It is feasible to administer mCILT for three hours immediately after a TMS session. It is unknown if the significant improvements in naming pictures, and elicited propositional speech were associated with the second series of TMS, or this first series of mCILT, or a combination of both. A larger, sham controlled clinical trial is warranted.

Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study.

This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26-62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm(2)) was applied for 10 min to each of 11 scalp placements (13 J/cm(2)). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest that placebo-controlled studies are warranted.

Transcranial magnetic stimulation and aphasia rehabilitation.

Repetitive transcranial magnetic stimulation (rTMS) has been reported to improve naming in chronic stroke patients with nonfluent aphasia since 2005. In part 1, we review the rationale for applying slow, 1-Hz, rTMS to the undamaged right hemisphere in chronic nonfluent aphasia patients after a left hemisphere stroke; and we present a transcranial magnetic stimulation (TMS) protocol used with these patients that is associated with long-term, improved naming post-TMS. In part 2, we present results from a case study with chronic nonfluent aphasia where TMS treatments were followed immediately by speech therapy (constraint-induced language therapy). In part 3, some possible mechanisms associated with improvement after a series of TMS treatments in stroke patients with aphasia are discussed.

TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia.

This study sought to discover if an optimum 1 cm(2) area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions.

Research with rTMS in the treatment of aphasia.

This review of our research with rTMS to treat aphasia contains four parts: Part 1 reviews functional brain imaging studies related to recovery of language in aphasia with emphasis on nonfluent aphasia. Part 2 presents the rationale for using rTMS to treat nonfluent aphasia patients (based on results from functional imaging studies). Part 2 also reviews our current rTMS treatment protocol used with nonfluent aphasia patients, and our functional imaging results from overt naming fMRI scans, obtained pre- and post- a series of rTMS treatments. Part 3 presents results from a pilot study where rTMS treatments were followed immediately by constraint-induced language therapy (CILT). Part 4 reviews our diffusion tensor imaging (DTI) study that examined white matter connections between the horizontal, midportion of the arcuate fasciculus (hAF) to different parts within Broca's area (pars triangularis, PTr; pars opercularis, POp), and the ventral premotor cortex (vPMC) in the RH and in the LH. Part 4 also addresses some of the possible mechanisms involved with improved naming and speech, following rTMS with nonfluent aphasia patients.

Horizontal portion of arcuate fasciculus fibers track to pars opercularis, not pars triangularis, in right and left hemispheres: a DTI study.

The arcuate fasciculus (AF) is a white matter pathway traditionally considered to connect left Broca's area with posterior language zones. We utilized diffusion tensor imaging (DTI) in eight healthy subjects (5 M) to track pathways in the horizontal mid-portion of the AF (hAF) to subregions of Broca's area - pars triangularis (PTr) and pars opercularis (POp); and to ventral premotor cortex (vPMC) in the right and left hemispheres (RH, LH). These pathways have previously been studied in the LH, but not in the RH. Only 1/8 subjects showed fiber tracts between PTr and hAF in the RH (also, only 1/8 in the LH). In contrast to PTr, 5/8 subjects showed fiber tracts between POp and hAF in the RH (8/8 in the LH). Fiber tracts for vPMC were similar to those of POp, where 7/8 subjects showed fiber tracts between vPMC and hAF in the RH (8/8 in the LH). Our designated hAF could have included some of the superior longitudinal fasciculus (SLF) III, because it is difficult to separate the two fiber bundles. The SLF III has been previously reported to connect supramarginal gyrus with POp and vPMC in the LH. Thus, although the present DTI study showed almost no pathways between PTr and hAF in the RH (and in the LH), robust pathways were observed between POp and/or vPMC with hAF in the RH (and in LH). These results replicate previous studies for the LH, but are new, for the RH. They could contribute to better understanding of recovery in aphasia.

Improved language in a chronic nonfluent aphasia patient after treatment with CPAP and TMS.

OBJECTIVE: To present pretreatment and post-treatment language data for a nonfluent aphasia patient who received 2 treatment modalities: (1) continuous positive airway pressure (CPAP) for his sleep apnea, starting 1-year poststroke; and (2) repetitive transcranial magnetic brain stimulation (TMS), starting 2 years poststroke. BACKGROUND: Language data were acquired beyond the spontaneous recovery period of 3 to 6 months poststroke onset. CPAP restores adequate oxygen flow throughout all stages of sleep, and may improve cognition. A series of slow, 1 Hz repetitive TMS treatments to suppress a posterior portion of right pars triangularis has been shown to improve phrase length and naming in chronic nonfluent aphasia. METHOD: The Boston Diagnostic Aphasia Examination and Boston Naming Test were administered pre-CPAP, and after 2 to 5 months of CPAP. These same tests were administered pre-TMS, and at 3 and 6 months post-TMS, and again 2.4 years later. RESULTS: Post-CPAP testing showed increased Phrase Length, Auditory Comprehension, and naming Animals and Tools/Implements (Boston Diagnostic Aphasia Examination). Testing at 3 and 6 months post-TMS showed significant increase in Phrase Length, Auditory Comprehension, and Boston Naming Test compared with pre-TMS. These gains were retained at 2.4 years post-TMS. CPAP use continued throughout. CONCLUSIONS: Physiologic treatment interventions may promote language recovery in chronic aphasia.

Research with transcranial magnetic stimulation in the treatment of aphasia.

Repetitive transcranial magnetic stimulation (rTMS) has been used to improve language behavior, including naming, in stroke patients with chronic, nonfluent aphasia. Part 1 of this article reviews functional imaging studies related to language recovery in aphasia. Part 2 reviews the rationale for using rTMS to treat nonfluent aphasia (based on functional imaging) and presents our current rTMS protocol. We present language results from our rTMS studies as well as imaging results from overt naming functional MRI scans obtained before and after a series of rTMS treatments. Part 3 presents results from a pilot study in which rTMS treatments were followed immediately by constraint-induced language therapy. Part 4 reviews our diffusion tensor imaging study examining the possible connectivity of the arcuate fasciculus to different parts of Broca's area (pars triangularis, pars opercularis) and to the ventral premotor cortex. The potential role of mirror neurons in the right pars opercularis and ventral premotor cortex in aphasia recovery is discussed.

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.

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.

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 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.

Overt propositional speech in chronic nonfluent aphasia studied with the dynamic susceptibility contrast fMRI method.

This study examined activation levels in the left (L) supplementary motor area (SMA) and the right (R) SMA (separately), and activation in nine R perisylvian language homologues during overt, propositional speech in chronic nonfluent aphasia patients. Previous functional imaging studies with a variety of chronic aphasia patients have reported activation in these regions during different language tasks, however, overt propositional speech has not been examined. In the present research, four nonfluent aphasia patients were studied during overt elicited propositional speech at 4-9 years post-single L hemisphere stroke, which spared the SMA. The dynamic susceptibility contrast (DSC) method of functional MRI was used to calculate relative cerebral blood volume (relCBV) for cortical regions of interest (ROIs) during the first-pass bolus of gadolinium during two conditions: (1) pattern (silent viewing of checkerboard patterns) and (2) story (overt, elicited propositional speech describing sequential pictures, which formed a story). During the story condition, controls had significantly higher relCBV in L SMA than in R SMA; aphasics, however, had significantly higher relCBV in R SMA than in L SMA. During the pattern condition, no significant differences were observed between the L SMA and the R SMA for either controls or aphasics. In addition, aphasics had significantly higher relCBV in the R sensorimotor mouth during story than pattern. This R sensorimotor mouth relCBV was also significantly higher in aphasics than controls during story, and the two groups did not differ during pattern. The overall mean relCBV for the nine R perisylvian ROIs was significantly higher for aphasics than controls during both story and pattern. These results suggest that poor modulation, including possible over-activation of R sensorimotor mouth and other R perisylvian language homologues may underlie in part, the hesitant, poorly articulated, agrammatic speech associated with nonfluent 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.