synchronization of these brain oscillations is feasible with the application of a novel brain stimulation technique , transcranial alternating current stimulation ( tacs ) , in which alternating current of specified frequency entrains and enhances the brain rhythms to the corresponding frequency .
previous studies suggested that working memory and executive function deficits in schizophrenia are associated with reduced low- and high - frequency electroencephalogram ( eeg ) activity .
exogenously synchronizing the dorsolateral prefrontal cortex and posterior parietal cortex in phase with tacs frequency has been shown to enhance the working memory performance in healthy subjects .
application of theta frequency ( 38 hz ) stimulation over parietal region can increase the working memory load , and gamma frequency ( > 30 hz ) stimulation over frontal region can enhance the working memory processing .
tacs , given its potential to modulate brain oscillations , is postulated to be useful in enhancing the working memory in patients with schizophrenia . moreover
, the effect of tacs is known to be dependent on the state of the brain .
application of a brain stimulation with the subject being concurrently engaged in a neuropsychological or a psychophysiological task is called  online  stimulation . a cognitive task known to activate a specific brain region ( e.g. , working memory task and prefrontal cortex ) has been shown to change its susceptibility to neuromodulation ; hence , application of tacs to this brain region ( i.e. , prefrontal cortex ) while it is engaged in a working memory task can potentially result in resonated effects .
thus , further enhancement of neuromodulation in targeted brain region is feasible with  online tacs . 
apart from a recent case report in obsessive compulsive disorder , we are unaware of any other description on the application of tacs in psychiatric population . moreover , there has been no report on the feasibility of  online  tacs in any psychiatric disorder . given the complexity of online tacs , in this report , we describe the successful application of this neuromodulatory paradigm in a schizophrenia patient who had significant cognitive deficits .
p is a right - handed , 35-year - old male with an engineering degree diagnosed with paranoid schizophrenia ( diagnostic and statistical manual of mental disorders 4 edition ) with illness duration of 8 years .
his symptoms were under partial remission with olanzapine 15 mg / day except for occasional auditory hallucinations .
however , he reported significant cognitive deficits ( digit symbol substitution test  203 s for 100 digits ; animal fluency test  8/min ; computerized n - back test 
the patient as well as his primary caregiver was provided with adequate information regarding the tacs procedure , and a video of the related procedural implementation was also shown ; following this , the patient agreed to participate in the tacs sessions .
we adhered to the ethical principles for medical research involving human subjects as per the world medical association declaration of helsinki ( http://www.wma.net/en/30publications/10policies/b3/ ) .
the electrodes ( 35 cm ) were placed at the left dorsolateral prefrontal cortex ( f3 ) and the left posterior parietal region ( p3 ) according to 1020 system .
two online tacs sessions ( first session with theta frequency and second session with gamma frequency ) were administered with an inter - session interval of 48 h using standard equipment ( neuroconn dc stimulator plus , http://www.neuroconn.de/dc-stimulator_plus_en/ ) [ figure 1a ] . during tacs , the subject performed computerized sternberg 's task that was presented using e - prime software ( https://www.pstnet.com/eprime.cfm ) . in this task ,
the patient was shown random sequence of numbers ( in sets of 2 or 4 consisting of a random combination of numbers from 0 to 9 ) .
each display sequence was followed by a blank screen for 2 s , following which a target numerical in red color was presented .
( left arrow and right arrows in key board ) to indicate whether the target digit has been presented in the preceding sequence set .
once the patient responds , feedback will be given with  or  signs to indicate the correct and incorrect responses , respectively [ figure 1b ] .
the patient was familiarized with the sternberg 's task before the tacs session ; cognitive task was initiated after 2 min of initiation of tacs session . during the 20 min tacs session ,
the patient performed the sternberg 's task for 15 min ( 3 blocks of 5 min each with 1 min gap between each block ) .
( b ) schematic representation of sternberg 's task during transcranial alternating current stimulation sessions baseline eeg was acquired , and peak alpha frequency of 11 was noted in the posterior electrodes ( o1 , o2 , p3 , p4 , pz , po7 , and po8 ) . as per the previous description , individual - specific stimulating theta frequency was determined to be 6 hz ( stimulating theta frequency = individual peak alpha frequency 5 ) . to determine the threshold of current strength , we applied tacs stimulation starting with 1 ma and increased the current strength stepwise by 0.25 ma up to a maximum of 2 ma . for every level of selected current strength ,
the stimulation was applied for 1 min ( ramping up and down for 100 cycles ) .
since the patient was able to tolerate all the levels of current strength , 20 min of sinusoidal tacs was given at 6 hz frequency at 2 ma current intensity without dc offset , a 0 relative phase , and impedance kept below 15 k. the intensity was gradually ramped up for initial 100 cycles ( ~16 s ) and similarly ramped down during the termination to minimize the adverse effects .
side effects were assessed using a structured questionnaire ; except for tolerable mild pricking sensation during the sessions .
the second session of tacs was given after 48 h with a stimulation frequency of 40 hz . while determining threshold current intensity as described above , at levels above 1.5 ma , the patient experienced phosphenes left eye > right eye as well pricking sensations at the skin underneath the electrodes .
hence , gamma tacs ( 40 hz frequency ) at 1 ma was administered for 20 min ; all other parameters were kept similar to that of theta tacs session .
the patient tolerated the session well with flickering sensation during the initiation and only mild pricking sensations during the stimulation .
no other side effects such as pressure sensations were noted during or following the gamma tacs session . during both the tacs sessions ,
the patient was able to perform the sternberg 's task with fair attentiveness and without cognitive fatigue ; this was ascertained using a 10-point likert scale .
the effect of tacs was assessed with computerized numerical n - back ( 0- , 1- , and 2-back ) test and dual ( position and color ) 2-back test before the initiation and 20-min after the termination of each tacs session .
we noticed improved accuracy of responses in 1- , 2- , and dual 2-back tests after theta tacs session ( pre - tacs accuracy of 86.1% , 80.5% , and 9.5% ; post - tacs accuracy - 94.4% , 86.1% , and 16% , respectively ) .
performances in gamma sessions remained unchanged in 1- , 2- , and dual 2-back tests ( pre - tacs accuracy of 93.05% , 81.94% , and 25.5% ; post - tacs accuracy of 91.66% , 77.78% , and 25% , respectively ) .
baseline eeg was acquired , and peak alpha frequency of 11 was noted in the posterior electrodes ( o1 , o2 , p3 , p4 , pz , po7 , and po8 ) . as per the previous description , individual - specific stimulating theta frequency was determined to be 6 hz ( stimulating theta frequency = individual peak alpha frequency 5 ) . to determine the threshold of current strength , we applied tacs stimulation starting with 1 ma and increased the current strength stepwise by 0.25 ma up to a maximum of 2 ma . for every level of selected current strength ,
the stimulation was applied for 1 min ( ramping up and down for 100 cycles ) .
since the patient was able to tolerate all the levels of current strength , 20 min of sinusoidal tacs was given at 6 hz frequency at 2 ma current intensity without dc offset , a 0 relative phase , and impedance kept below 15 k. the intensity was gradually ramped up for initial 100 cycles ( ~16 s ) and similarly ramped down during the termination to minimize the adverse effects .
side effects were assessed using a structured questionnaire ; except for tolerable mild pricking sensation during the sessions .
the second session of tacs was given after 48 h with a stimulation frequency of 40 hz . while determining threshold current intensity as described above , at levels above 1.5 ma , the patient experienced phosphenes left eye > right eye as well pricking sensations at the skin underneath the electrodes .
hence , gamma tacs ( 40 hz frequency ) at 1 ma was administered for 20 min ; all other parameters were kept similar to that of theta tacs session .
the patient tolerated the session well with flickering sensation during the initiation and only mild pricking sensations during the stimulation .
no other side effects such as pressure sensations were noted during or following the gamma tacs session . during both the tacs sessions ,
the patient was able to perform the sternberg 's task with fair attentiveness and without cognitive fatigue ; this was ascertained using a 10-point likert scale .
the effect of tacs was assessed with computerized numerical n - back ( 0- , 1- , and 2-back ) test and dual ( position and color ) 2-back test before the initiation and 20-min after the termination of each tacs session .
we noticed improved accuracy of responses in 1- , 2- , and dual 2-back tests after theta tacs session ( pre - tacs accuracy of 86.1% , 80.5% , and 9.5% ; post - tacs accuracy - 94.4% , 86.1% , and 16% , respectively ) .
performances in gamma sessions remained unchanged in 1- , 2- , and dual 2-back tests ( pre - tacs accuracy of 93.05% , 81.94% , and 25.5% ; post - tacs accuracy of 91.66% , 77.78% , and 25% , respectively ) .
this case report offers preliminary support to the feasibility of implementing both theta- and gamma - online tacs in schizophrenia .
given that tacs has the potential to modulate various perceptual and cognitive abnormalities in psychiatric population , it has promising applications in schizophrenia as well .
however , we need systematic studies to optimize several tacs parameters ( e.g. , montage positions , stimulation frequency , current intensity , stimulation duration , state during the stimulation [ resting / performing task / sleeping ] , and phase difference across the stimulation sites ) .
importantly , these parameters are also related to tolerance and different side effects associated with tacs .
existing literature suggests that like other noninvasive brain stimulation techniques , tacs is safe and well tolerated ; the potential side effects involve skin perceptions , pressure sensations , and phosphenes , which are usually mild and tolerable .
this is in tune with the observation that our patient was able to perform the task during the stimulation ( online tacs ) , which encourages further systematic studies in schizophrenia .
similarly , we also observed an improvement in accuracy in dual 2-back tasks than in other tasks .
though the potential confounding influence of practice effect is a possibility , the task differential improvement ( i.e. , dual 2-back alone showing the improvement ) as well as stimulation frequency - specific change ( i.e. , improvement occurring with theta , but not gamma frequency ) in cognitive performance argues against this ; however , definitive interpretations on such effects can be done with examination of larger number of subjects in a sham - controlled design that involves multiple sessions . in summary , this case report highlights the feasibility and potential utility of online tacs as a new therapeutic tool in schizophrenia and this needs further systematic evaluation .
noninvasiveness , safety , and ease of administration of tacs , in addition to this being a relatively less - expensive tool , make it a promising avenue toward targeting different symptom profiles including cognition in several psychiatric disorders including schizophrenia .
this work is supported by the department of science and technology ( government of india ) research grant ( sr / csi/158/2012 ) to gv and indian council of medical research young scientist research grant ( dhr / hrd / young scientist / type - vi(2)/2015 ) to vs. ab is supported by the welcome trust / dbt india alliance .
this work is supported by the department of science and technology ( government of india ) research grant ( sr / csi/158/2012 ) to gv and indian council of medical research young scientist research grant ( dhr / hrd / young scientist / type - vi(2)/2015 ) to vs. ab is supported by the welcome trust / dbt india alliance .
 abnormalities in resting and event - related brain oscillations are known to be associated with cognitive deficits in schizophrenia . 
 transcranial alternating current stimulation ( tacs ) modulates these rhythms across the neuronal circuits and could have a potential therapeutic role in psychiatric disorders . in this report , we describe , for the first time , application of online tacs in a schizophrenia patient with working memory deficits . 
 this case report supports the feasibility and potential utility of online tacs in schizophrenia , which needs further systematic research . 
INTRODUCTION
CASE REPORT
Theta transcranial alternating current stimulation
Gamma transcranial alternating current stimulation
DISCUSSION
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Conflicts of interest