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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.

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.

Although evidence suggests that patients with left hemisphere strokes and nonfluent aphasia who receive 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the intact right inferior frontal gyrus experience persistent benefits in naming, it remains unclear whether the effects of rTMS in these patients generalize to other language abilities. We report a subject with chronic nonfluent aphasia who showed stable deficits of elicited propositional speech over the course of five years, and received 1200 pulses of 1 Hz rTMS daily for 10 days at a site identified as being optimally responsive to rTMS in this patient. Consistent with prior studies there was improvement in object naming, with a statistically significant improvement in action naming. Improvement was also demonstrated in picture description at 2, 6, and 10 months after rTMS with respect to the number of narrative words and nouns, sentence length, and use of closed class words. Compared to his baseline performance, the patient showed significant improvement on the Western Aphasia Battery subscale for spontaneous speech. These findings suggest that manipulation of the intact contralesional cortex in patients with nonfluent aphasia may result in language benefits that generalize beyond naming to include other aspects of language production.

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.

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 ten, 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 yr. 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 14-18 pictures, post-TMS (2 mo. to 43 mo. post-TMS). His longest phrase length (Cookie Theft picture) improved from 3 words pre-TMS, to 5-6 words post-TMS.Pre-TMS (1.5 yr. 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 1 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 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 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. NIH Public Access

No abstract

This study sought to discover if an optimum 1 cm2 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, 1 Hz 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.